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Autism may be linked to abnormal immune system characteristics and novel protein fragment

2012-01-18T10:10:00.000-08:00

University of South Florida researchers made the discoveries using mouse models of autism

Tampa, FL (Jan 3, 2012) – Immune system abnormalities that mimic those seen with autism spectrum disorders have been linked to the amyloid precursor protein (APP), reports a research team from the University of South Florida's Department of Psychiatry and the Silver Child Development Center.

The study, conducted with mouse models of autism, suggests that elevated levels of an APP fragment circulating in the blood could explain the aberrations in immune cell populations and function – both observed in some autism patients. The findings were recently published online in the Journal of the Federation of American Societies for Experimental Biology nursing ceus.

The USF researchers concluded that the protein fragment might be both a biomarker for autism and a new research target for understanding the physiology of the disorder.

"Autism affects one in 110 children in the United States today," said research team leader Jun Tan, MD, PhD, professor of psychiatry and the Robert A. Silver Chair, Rashid Laboratory for Developmental Neurobiology at USF's Silver Child Development Center. "While there are reports of abnormal T-cell numbers and function in some persons affected with autism, no specific cause has been identified. The disorder is diagnosed by behavioral observation and to date no associated biomarkers have been identified."

"Not only are there no associated biomarkers, but the prognosis for autism is poor and the costs associated with care are climbing," said Francisco Fernandez, MD, department chair and head of the Silver Center. "The work of Dr. Tan and his team is a start that may lead to earlier diagnosis and more effective treatments."

The amyloid precursor protein is typically the focus of research related to Alzheimer's disease. However, recent scientific reports have identified elevated levels of the particular protein fragment, called, sAPP-α, in the blood of autistic children. The fragment is a well-known growth factor for nerves, and studies imply that it plays a role in T-cell immune responses as well.

To study the autism-related effects of this protein fragment on postnatal neurodevelopment and behavior, Dr. Tan and his team inserted the human DNA sequence coding for the sAPP-α fragment into the genome of a mouse model for autism. While the studies are ongoing, the researchers documented the protein fragment's effects on the immune system of the test mice.

"We used molecular biology and immunohistochemistry techniques to characterize T-cell development in the thymus and also function in the spleen of the test animals," Dr. Tan said. "Then we compared transgenic mice to their wild-type littermates."

The researchers found that increased levels of sAPP-α in the transgenic mice led to increased cytotoxic T-cell numbers. The investigators also discovered subsequent impairment in the recall function of memory T-cells in the test mice, suggesting that the adaptive immune response is negatively affected in the presence of high levels of the protein fragment.

"Our work suggests that the negative effects of elevated sAPP-α on the adaptive immune system is a novel mechanism underlying certain forms of autism," concluded Dr. Tan, who holds the Silver Chair in Developmental Neurobiology. "The findings also add support to the role of sAPP-α in the T-cell response."

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Other researchers involved in the study were Antoinette Bailey, Dr. Huayan Hou, Dr. Demian Obregon, Jun Tian, Dr. Yuyan Zhu, Dr. Qiang Zou, Dr. William Nikolic, Dr. Michael Bengston, Dr. Takashi Mori (Saitama Medical Center/Saitama Medical University, Japan) and Dr. Tanya Murphy.

The work was supported by the Silver Endowment and a grant from the National Institutes of Health/National Institute of Mental Health.

Citation: Aberrant T-lymphocyte development and function in mice overexpressing human secreted amyloid precursor protein-α: implications for autism; A. Bailey, H. Hou, D. Obregon, J. Tian, Y. Zhu, Q. Zou, W. Nikolic, M. Bengston, T. Mori, T. Murphy, J. Tan; The FASEB Journal; published online Nov. 15, 2011.

USF Health's mission is to envision and implement the future of health. It is the partnership of the USF Health Morsani College of Medicine, the College of Nursing, the College of Public Health, the College of Pharmacy, the School of Biomedical Sciences and the School of Physical Therapy and Rehabilitation Sciences; and the USF Physician's Group. The University of South Florida is a global research university ranked 34th in federal research expenditures for public universities.

ELDERLY CAN BE AS FAST AS YOUNG IN SOME BRAIN TASKS, STUDY SHOWS

2012-01-17T12:43:00.000-08:00

COLUMBUS, Ohio – Both children and the elderly have slower response times when they have to make quick decisions in some settings.

But recent research suggests that much of that slower response is a conscious choice to emphasize accuracy over speed.

In fact, healthy older people can be trained to respond faster in some decision-making tasks without hurting their accuracy – meaning their cognitive skills in this area aren’t so different from younger adults.

Roger Ratcliff
“Many people think that it is just natural for older people’s brains to slow down as they age, but we’re finding that isn’t always true,” said Roger Ratcliff, professor of psychology at Ohio State University and co-author of the studies.

“At least in some situations, 70-year-olds may have response times similar to those of 25-year olds.”

Ratcliff and his colleagues have been studying cognitive processes and aging in their lab for about a decade. In a new study published online this month in the journal Child Development, they extended their work to children.

Ratcliff said their results in children are what most scientists would have expected: very young children have slower response times and poorer accuracy compared to adults, and these improve as the children mature.

But the more interesting finding is that older adults don’t necessarily have slower brain processing than younger people, said Gail McKoon, professor of psychology at Ohio State and co-author of the studies.

“Older people don’t want to make any errors at all, and that causes them to slow down. We found that it is difficult to get them out of the habit, but they can with practice,” McKoon said.

Researchers uncovered this surprising finding by using a model developed by Ratcliff that considers both the reaction time and the accuracy shown by participants in speeded tasks. Most models only consider one of these variables.

“If you look at aging research, you find some studies that show older people are not impaired in accuracy, but other studies that show that older people do suffer when it comes to speed. What this model does is look at both together to reconcile the results,” Ratcliff said.

Ratcliff, McKoon and their colleagues have used several of the same experiments in children, young adults and the elderly.

In one experiment, participants are seated in front of a computer screen. Asterisks appear on the screen and the participants have to decide as quickly as possible whether there is a “small” number (31-50) or a “large” number (51-70) of asterisks. They press one of two keys on the keyboard, depending on their answer.

In another experiment, participants are again seated in front of a computer screen and are shown a string of letters. They have to decide whether those letters are a word in English or not. Some strings are easy (the nonwords are a random string of letters) and some are hard (the nonwords are pronounceable, such as “nerse”).

In the Child Development study, the researchers used the asterisk test on second and third graders, fourth and fifth graders, ninth and tenth graders, and college-aged adults. Third graders and college-aged adults participated in the word/nonword test.

The results showed that there was a rise in accuracy and decrease in response time on both tasks from the second and third-graders to the college-age adults.

The younger children took longer than older children and adults to respond in the experiment, Ratcliff said. They, like the elderly, were taking longer to make up their mind. But the younger children were also less accurate than younger adults in this study.

“Younger children are not able to make as good of use of the information they are presented, so they are less accurate,” Ratcliff said. “That improves as they mature.”

Older adults show a different pattern. In a study published in the journal Cognitive Psychology, Ratcliff and colleagues compared college-age subjects, older adults aged 60-74, and older adults aged 75-90. They used the same asterisk and word/nonword tests that were in the Child Development study. They found that there was little difference in accuracy among the groups, even the oldest of participants.

However, the college students had faster response times than did the 60-74 year olds, who were faster than the 75-90 year olds. Continuing Education for Counselors

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“If you look at aging research, you find some studies that show older people are not impaired in accuracy, but other studies that show that older people do suffer when it comes to speed. What this model does is look at both together to reconcile the results.”

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But the slower response times are not all the result of a decline in skills among older adults. In a previous study, the researchers encouraged older adults to go faster on these same tests. When they did, the difference in their response times compared to college-age students decreased significantly.

“For these simple tasks, decision-making speed and accuracy is intact even up to 85 and 90 years old,” McKoon said.

That doesn’t mean there are no effects of aging on decision-making speed and accuracy, Ratcliff said. In a study in the Journal of Experimental Psychology: General, Ratcliff, McKoon and another colleague found (like in studies from other laboratories) that accuracy for “associative memory” does decline as people age. For example, older people were much less likely to remember if they had studied a pair of words together than did younger adults.

But Ratcliff said that, overall, their research suggests there should be greater optimism about the cognitive skills of seniors.

“The older view was that all cognitive processes decline at the same rate as people age,” Ratcliff said.

“We’re finding that there isn’t such a uniform decline. There are some things that older people do nearly as well as young people.”

Ratcliff co-authored the Child Development paper with Jessica Love and John Opfer of Ohio State and Clarissa Thompson of the University of Oklahoma. Ratcliff and McKoon co-authored the Cognitive Psychology and Journal of Experimental Psychology: General papers with Anjali Thapar of Bryn Mawr College.

Some of the research was supported with grants from the National Institute on Aging and the National Institute of Mental Health.

Turning on Dormant Gene May Hold Key for Correcting a Neurodevelopmental Defect

2012-01-12T19:29:00.000-08:00

Finding Shows Therapeutic Potential of Small-Molecule Targeting Strategy

Scientists working in cell culture and in mice have been able to correct the loss of gene activity underlying a rare but severe developmental disorder by turning on a gene that is normally silenced in brain cells. Further testing of the identified compound that activates the gene will determine whether it has potential as a genetically-based treatment for the disorder, Angelman syndrome.

Background

Infants with Angelman syndrome appear normal at birth, but show developmental delays by 6 to 12 months. Features of the disorder include impaired speech, seizures, hyperactivity, and motor difficulties. No effective treatment exists CADC I & II Continuing Education

In the late 1990s, researchers found that the disorder results from changes or deletions in the maternal gene for the enzyme ubiquitin protein ligase E3A (Ube3a). Most genes are inherited in sets of two, one from the mother and one from the father. In some cases, either the maternal or paternal gene is silenced, or prevented from being translated into protein. This normal silencing based on inheritance from a mother or father is called imprinting. The Ube3a gene is an example of genetic imprinting, as the paternal gene is normally silenced in neurons. With the maternal gene out of action, infants with Angelman syndrome lack the enzyme, leading to changes in the brain that underlie the symptoms of the disorder.

This Study

This research is reported online in the journal Nature, and was carried out by scientists at the University of North Carolina School of Medicine at Chapel Hill, led by the labs of Ben Philpot, Bryan Roth, and Mark Zylka. In an effort to restore the absent Ube3a enzyme in neurons, the research team screened thousands of compounds for their ability to “wake up” the paternal Ube3a gene. The investigators used neurons from genetically engineered mice to test whether compounds could activate the gene; the neurons fluoresce if the paternal Ube3a gene is expressed, or translated into protein. The team screened 2,306 candidate small molecules from multiple molecular libraries. If fluorescence was detected, that meant that the test compound activated the Ube3a gene. The screening and access to the molecular libraries was made possible through NIMH’s Psychoactive Drug Screening Program, funded by contract to perform pharmacological and functional screening of novel compounds. Bryan Roth at UNC Chapel Hill is the project director and a coauthor of the Nature paper.

The investigators found that a class of compounds—topoisomerase inhibitors—could unsilence the paternal gene. They chose one, topotecan, and tested it to see whether it could do the same thing in vivo in a mouse. They administered topotecan directly into the brain and later into spinal fluid; in both cases it was able to activate paternal Ube3a. Activation persisted for 12 weeks after delivery of the compound had stopped.

Significance

"This is the first time anyone has used a small molecule to successfully target activation of a disease-relevant gene," said senior author Benjamin Philpot. "The work demonstrates that turning on a dormant gene could represent a therapeutic intervention for Angelman syndrome."

NIMH helped to fund this project and has issued a grant to the UNC team to continue studies of topotecan, initially in mice. Although topotecan is already in use in both children and adults as a cancer chemotherapeutic agent, further testing is essential to determine the dosage of the agent that would be needed to be effective, the best means of administering the medication, and whether side-effects at the necessary dosage level are within a range that make it feasible to use. The authors emphasize that much work remains before this or related agents can or should be used for treatment of this condition.

Reference

Huang, H.-S., Allen, J., Mabb, A., King, I., Miriyala, J., Taylor-Blake, B., Sciaky, N., Dutton, J. Jr., Lee, H.M., Chen, X., Jin, J. Bridges, A., Zylka, M., Roth, B., Philpot, B. Topoisomerase inhibitors unsilence the dormant allele of Ube3a in neurons. Nature. Published online ahead of print December 21, 2011, doi: 10.1038/nature10726.

This image shows Ube3a staining in a neurotypical mouse brain and its absence in the Angelman syndrome model mouse brain.

Source: Ben Philpot, Ph.D., University of North Carolina School of Medicine

Atypical antipsychotic more effective than older drugs in treating childhood mania, but side effects can be serious

2012-01-11T20:05:00.000-08:00

The antipsychotic medication risperidone is more effective for initial treatment of mania in children diagnosed with bipolar disorder compared to other mood stabilizing medications, but it carries the potential for serious metabolic side effects, according to an NIMH-funded study published online ahead of print January 2, 2012, in the Archives of General Psychiatry social worker continuing education

Background

Childhood bipolar disorder is a relatively rare but seriously impairing condition. It is also associated with an increased risk of substance use disorders and suicide. To treat symptoms of mania, a key symptom of the disorder, medications such as mood stabilizers or antipsychotics are often prescribed. However, no prior study has addressed the question of which medication to try first.

In the Treatment of Early Age Mania (TEAM) study, Barbara Geller, M.D., of Washington University in St. Louis, and colleagues randomized 290 children ages 6-15 years diagnosed with bipolar I disorder (having mixed or manic symptoms) to treatment with lithium, divalproex sodium or risperidone for an 8-week trial. None of the children had taken an anti-manic medication before. Lithium has been used to treat bipolar disorder for many years. Divalproex sodium is an anticonvulsant mood stabilizer commonly prescribed to treat bipolar disorder as well. Risperidone is an atypical antipsychotic that has been approved by the U.S. Food and Drug Administration for the treatment of mania in youth age 10 and older.

Results of the Study

After eight weeks, 68.5 percent of the children taking risperidone showed improvement in manic symptoms, compared to 35.6 percent of those taking lithium and 24 percent of those taking divalproex sodium. Overall, 24.7 percent discontinued the trial, but more children taking lithium—32.2 percent—discontinued the trial compared to those taking risperidone (15.7 percent discontinued) or divalproex sodium (26 percent discontinued.)

However, those taking risperidone also gained more weight than those on the other medications—an average of more than 7 lbs compared to around 3 lbs for those taking lithium and 3.7 lbs for those taking divalproex sodium. Those taking risperidone were also more likely to experience other metabolic side effects, such as an increase in cholesterol levels, compared to those on the other medications.

Significance

The researchers concluded that risperidone was significantly more effective than lithium or divalproex sodium for initial treatment of childhood mania. In addition, the children were less likely to discontinue the drug compared to those taking lithium or divalproex sodium, indicating a higher tolerance for it. This finding is consistent with other studies that have compared second-generation antipsychotics like risperidone to placebo in treating childhood mania.

However, the researchers caution that risperidone is associated with adverse metabolic effects that can increase the risk for diabetes and cardiovascular problems. They note that many children responded to low doses of the medication, suggesting that clinicians should be conservative when determining how to dose the medication. A lower dose may minimize the potential for serious side effects. The researchers also caution that because diagnostic measures for childhood bipolar disorder are not always consistent across studies, and because the validity of such a diagnosis in younger children is under debate, TEAM findings may not generalize to patients diagnosed using other measures.

What’s Next

More research is needed to develop safer, more effective interventions for children with early onset bipolar disorder for both initial and longer term treatment.

Reference

Geller B, Luby J, Josh P, Wagner KD, Emslie G, Walkup JT, Axelson DA, Bolhofner K, Robb A, Wolf DV, Riddle MA, Birmaher B, Ryan ND, Severe J, Vitiello B, Tillman R, Lavori P. A randomized controlled trial of risperidone, lithium and divalproex sodium for initial treatment of bipolar I disorder, manic or mixed phase, in children and adolescents. Archives of General Psychiatry. Online ahead of print January 2, 2012.

School absenteeism, mental health problems linked

2012-01-03T12:45:00.000-08:00

School absenteeism is a significant problem, and students who are frequently absent from school more often have symptoms of psychiatric disorders. A new longitudinal study of more than 17,000 youths has found that frequently missing school is associated with a higher prevalence of mental health problems later on in adolescence, and that mental health problems during one year also predict missing additional school days in the following year for students in middle and high school social worker continuing education

The study, published in the journal Child Development, was conducted by researchers at the University of California, Los Angeles (UCLA), the University of Florida, Boston University, the Child and Adolescent Services Research Center, the Oregon Social Learning Center, and Johns Hopkins University.

"We've long known that students who are frequently absent from school are more likely to have symptoms of psychiatric disorders, but less clear is the reason why," says Jeffrey Wood, associate professor of educational psychology and psychiatry at UCLA, who led the study. "These two aspects of youths' adjustment may at times exacerbate one another, leading over the course of time to more of each."

The study found that between grades 2 and 8, students who already had mental health symptoms (such as antisocial behavior or depression) missed more school days over the course of a year than they had in the previous year and than students with few or no mental health symptoms. Conversely, middle and high school students who were chronically absent in an earlier year of the study tended to have more depression and antisocial problems in subsequent years. For example, 8th graders who were absent more than 20 days were more likely to have higher levels of anxiety and depression in 10th grade than were 8th graders who were absent fewer than 20 days.

"The findings can help inform the development of programs to reduce school absenteeism," according to Wood. "School personnel in middle schools and high schools could benefit from knowing that mental health issues and school absenteeism each influence the other over time. Helping students address mental health issues may in turn help prevent the emergence of chronic absenteeism. At the same time, working to help students who are developing a pattern of chronic absenteeism come to school more consistently may help prevent psychiatric problems."

The researchers looked at more than 17,000 children in 1st through 12th grades using three datasets: the National Longitudinal Study of Adolescent Health, a longitudinal study of a nationally representative sample of adolescents in grades 7 to 12; the Johns Hopkins Prevention Intervention Research Center Study, a longitudinal study of classroom-based interventions involving children in grades 1 to 8; and the Linking the Interests of Families and Teachers trial, a longitudinal study of children in grades 1 through 12.

Researchers interviewed students and parents annually or biennially, and they gathered information from school attendance records. In addition, students, parents, and teachers filled out questionnaires.

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The study was funded by the National Institute of Mental Health and the Eunice Kennedy Shriver National Institute of Child Health and Human Development, with cooperative funding from 17 other agencies.

NDAR Federation Creates Largest Source of Autism Research Data to Date

2011-12-15T19:45:00.000-08:00

NIH-funded Database Sets Standard for Collaboration and Data Sharing

Source: NDAR

A data partnership between the National Database for Autism Research (NDAR), and the Autism Genetic Resource Exchange (AGRE) positions NDAR as possibly the largest repository to date of genetic, phenotypic, clinical, and medical imaging data related to research on autism spectrum disorders (ASD)LPC Continuing Education

“The collaboration between AGRE and NDAR exemplifies the efforts of government and stakeholders to work together for a common cause,” said Thomas R. Insel, M.D., director of the National Institute of Mental Health, part of NIH. “NDAR continues to be a leader in the effort to standardize and share ASD data with the research community, and serves as a model to all research communities.”

NDAR is supported by the National Institutes of Health; AGRE is an Autism Speaks program.

NDAR’s mission is to facilitate data sharing and scientific collaboration on a broad scale, providing a shared common platform for autism researchers to accelerate scientific discovery. Built around the concept of federated repositories, NDAR integrates and standardizes data, tools, and computational techniques across multiple public and private autism databases. Through NDAR, researchers can access results from these different sources at the same time, using the rich data set to conduct independent analyses, supplement their own research data, or evaluate the data supporting published journal articles, among many other uses.

Databases previously federated with NDAR include Autism Speaks’ Autism Tissue Program, the Kennedy Krieger Institute’s Interactive Autism Network (IAN), and the NIH Pediatric MRI Data Repository. AGRE currently houses a clinical dataset with detailed medical, developmental, morphological, demographic, and behavioral information from people with ASD and their families.

Approved NDAR users will have access to data from the 25,000 research participants represented in NDAR, as well as 2,500 AGRE families and more than 7,500 participants who reported their own information to IAN.

NDAR is supported by NIMH, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Institute of Neurological Disorders and Stroke, the National Institute of Environmental Health Sciences, and the NIH Center for Information Technology.

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The mission of the NIMH is to transform the understanding and treatment of mental illnesses through basic and clinical research, paving the way for prevention, recovery and cure. For more information, visit the NIMH website.

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit the NIH website.

Suspect Gene Variants Boost PTSD Risk after Mass Shooting

2011-12-06T16:09:00.000-08:00

Profile of Risk Emerging for Trauma-triggered Molecular Scars

College students exposed to a mass shooting were 20-30 percent more likely to later develop post traumatic stress disorder (PTSD) symptoms if they harbored a risk version of a gene, NIMH-funded researchers have discovered. This boost in risk, traced to common variants of the gene that controls recycling of serotonin, was comparable to the risk conferred by close proximity to the shooting – for example, being in the room with the shooter versus just being on campus.

The discovery is the latest of several recently reported that collectively profile heightened biological vulnerability to developing PTSD following trauma – and the molecular scars it leaves in the brain.

For example, early this year, researchers linked high levels of a stress-triggered, estrogen-related hormone to PTSD symptoms in women, with certain versions of the hormone receptor’s gene conferring higher risk. A PET scan study in September traced increased PTSD symptoms to heightened levels of a serotonin receptor. Both studies suggest potential new drug targets for treating the disorder. Evidence is also mounting that trauma – particularly if experienced very early in life – can adversely alter the set-points of gene expression in brain stress circuits and compromise immune and inflammatory system function continuing education for counselors

Gene-by-environment – caught in the act

By chance, researchers at Northern Illinois University (NIU) had already collected data on students’ PTSD symptoms prior to the 2008 murder-suicide that killed six on the Dekalb, Illinois campus.*

“This provided a rare opportunity to pinpoint not just a correlation but a cause – to document that such a tragedy can conspire with a risk gene to produce the disorder,” explained Kerry Ressler, M.D., Ph.D., of Emory University.

NIMH grantees Ressler, NIU’s Holly Orcutt, Ph.D., and colleagues, report on discovery of this gene-by-environment interaction online September 5th 2011 in the Archives of General Psychiatry.

Previous efforts to confirm such an interaction in PTSD had been confounded by lack of data on individuals’ pre-trauma symptoms. Any pre-existing symptoms must be taken into account to establish a common baseline – so that new symptoms that develop can confidently be pegged to the traumatic event.

By chance, before the tragedy, Orcutt’s team had prospectively surveyed PTSD symptoms in more than a thousand NIU undergraduate women, as part of a longitudinal study on predictors of sexual victimization, which can trigger the disorder. Within a few weeks after the tragedy, they seized the opportunity and – with help from a NIMH RAPID grant – conducted follow-up surveys, using the same measures, in subsets of the original sample – and then again after several months – to track symptom changes. Ressler’s team ultimately analyzed saliva samples from 235 women for gene type.

Previous studies had linked PTSD to a version of the gene that codes for the serotonin transporter (SERT), the protein on neurons that recycles the chemical messenger serotonin back into the cell after it is secreted into the synapse. So the researchers focused their genetic analysis on this variation, noting that it is “the most commonly described polymorphism in the psychiatric genetics literature.”

For example, this same site of genetic variation has also been linked to increased risk for anxiety - and, in some studies, increased risk for depression following stressful life events, although the latter findings remain controversial. Some hypothesize that these implicated variants may have less to do with conferring disease risk, per se, than with increased sensitivity to environmental influences more generally.**

Antidepressant medications, serotonin selective reuptake inhibitors (SSRIs), work by blocking SERT, thereby enhancing serotonin activity. SSRIs are the main medication treatment for PTSD.

Everyone inherits two copies of the SERT gene, one from each parent. So people can inherit one or two copies of risk-associated versions that are common in the population. Carrying any combination of these risk versions had been associated with increased risk for PTSD in 8 out of 9 previous studies.

The new study more definitively connects the dots between the environmental trigger and these risk gene types. Among 204 women without prior symptoms, 20 percent of those who showed acute symptoms within a few weeks after the shooting had developed PTSD symptoms when surveyed several months later. Proximity to the shooting and the risk gene types were about equally predictive of increased risk among this group.

These results come at a time of ferment in the field over confidence in gene-by-environment findings. A recent analysis by NIMH grantees of more than 100 such studies over the past decade uncovered what they call “publication bias.” They found that positive new findings were more likely to get published, while direct replications – which tend be less likely to confirm positive new findings – were under-reported. The net effect: an unintentional bias toward false positive reports. Notably, the researchers singled out as a prime example of this bias the scientific literature on serotonin transporter gene-by-environment interactions.

“How we measure environment may be at least as important as how we measure genetics, but to date, little effort has been focused on that,” noted Ressler. “We think that performing prospective studies in populations with shared trauma may be one way to 'hold constant' the environment variable, thus allowing for more clarity in the role of genetics.”

PTSD symptoms of NIU undergraduate women with a risk-associated serotonin transporter gene type (s/s, lG/lG, s/lG) increased 20-30 percent more than in classmates with a protective gene type after the 2008 campus shootings (Time 2). The increased risk was comparable to that conferred by close proximity to the shooting.
Source: Kerry Ressler, M.D., Ph.D., Emory University

Why Women are More Vulnerable

Earlier this year, Ressler and colleagues reported findings that may help to explain why women are twice as likely as men to develop PTSD. They linked PTSD symptoms in women to higher blood levels of what has been dubbed the “master regulator” of the stress response, a hormone called PACAP (pituitary adenyl cyclase-activating peptide).

PTSD symptoms were 5-fold higher in women with above average PACAP levels, compared to women with below average levels. Also in women only, a certain version of the gene that codes for PACAP’s receptor, PAC-1, conferred increased vulnerability. Experiments in rodents confirmed that this variable part of the PAC-1 gene is regulated, in part, by the female hormone estrogen.

This suggests that heightened vulnerability to PTSD in females may be traceable to this brain system critical to proper stress circuit function. Genetic variation in a different pathway may similarly be linked to increased risk for PTSD in men, say the researchers.

Females with higher-than-average levels of the stress-managing hormone PACAP had 5 times more PTSD symptoms than females with lower-than-average levels. By contrast, PACAP levels were unrelated to PTSD symptoms in males. Since the PACAP system is shaped, in part, by the female hormone estrogen, these differences could help to explain why women are twice as likely as men to develop the disorder.
Source: Kerry Ressler, M.D., Ph.D., Emory University

PACAP, “master regulator” of the stress response.
Source: Lee Eiden, Ph.D., NIMH Section on Molecular Neuroscience

Molecular scars

The Emory researchers also found increased methylation – epigenetic regulation of gene expression in response to the environment – in the part of Pac1 associated with PTSD in both women and men. Adverse experiences can induce molecules called methyl groups to attach to DNA and block genes from turning on. This results in enduring changes in the proteins the genes express. These molecular scars can weaken the brain’s defenses against PTSD.

Indeed, methylation increases pervasively in PTSD, according to Ressler and colleagues. Notably, they pinpointed such increases in several genes implicated in inflammatory and immune system abnormalities that go along with PTSD. They also saw abnormalities in immune system chemical messengers, called cytokines. Increased blood levels of one such cytokine TNF-alpha, known to trigger stress response symptoms, correlated with a history of child abuse and cumulative life stresses.

Early trauma may deplete resilience molecule

In September, a NIMH-funded brain imaging study reported that levels of a type of serotonin receptor (1B) were markedly lower in stress circuits of PTSD patients than in others exposed to trauma. This protein on neurons, to which the neurotransmitter binds, plays a pivotal role in stress resilience and antidepressant effect. By contrast, PET scans revealed that people who had experienced trauma but didn’t develop PTSD had only slightly fewer receptors than healthy controls.

NIMH grantee Alexander Neumeister, M.D., of Mount Sinai School of Medicine, and colleagues, traced both the severity of symptoms and the depleted receptors largely to the age at which trauma was first experienced. The earlier the age and the more subsequent trauma exposures, the fewer receptors expressed and the more severe the PTSD symptoms and overlap with depression. The dearth of receptors likely reflects such features of patients’ trauma histories, with those who develop PTSD also having other genetic or environmental vulnerabilities, say the researchers.

Patients with PTSD (right) had significantly fewer serotonin 1B receptors (yellow & red areas) in their brain stress circuits than healthy controls (left). PET scan images show destinations of a radioactive tracer that binds to serotonin 1B receptors. Front of brain is at bottom.
Source: Alexander Neumeister, M.D., Mount Sinai School of Medicine

Possible Uses: Risk profile and treatment targets?

Such epigenetic and genetic signatures of PTSD proneness in blood and brain, together with behavioral measures, may collectively prove useful in profiling a patient’s risk for developing the disorder. Molecules such as PACAP and the serotonin 1B receptor may also hold promise as potential targets of new drugs aimed at correcting specific abnormalities in the affected brain pathways, suggest the researchers.

NIMH RAPID grant helps salvage science from tragedy
2/14/08 Mass shooting on NIU campus
2/19/08 NIU researcher Holly Orcutt, Ph.D., contacts NIMH to discuss how to make the most of her prospectively collected data on PTSD and other parameters to learn from the tragedy.
3/26/08 Orcutt submits a concept for a follow-up study under the NIMH Rapid Assessment Post Impact of Disaster (RAPID) research program announcement – a unique time sensitive mechanism for expediting funding of research grants in response to emergency situations.
5/17/08 Grant application submitted.
6/18/08 Application undergoes peer review.
9/18/08 Grant awarded to NIU and Orcutt.

References

Acute and Posttraumatic Stress Symptoms in a Prospective Gene x Environment Study of a University Campus Shooting. Mercer KB, Orcutt HK, Quinn JF, Fitzgerald CA, Conneely KN, Barfield RT, Gillespie CF, Ressler KJ. Arch Gen Psychiatry. 2011 Sep 5. [Epub ahead of print]
PMID:21893641

A Critical Review of the First 10 Years of Candidate Gene-by-Environment Interaction Research in Psychiatry. Duncan LE, Keller MC. Am J Psychiatry. 2011 Sep 2. [Epub ahead of print]
PMID: 21890791

Post-traumatic stress disorder is associated with PACAP and the PAC1 receptor.
Ressler KJ, Mercer KB, Bradley B, Jovanovic T, Mahan A, Kerley K, Norrholm SD, Kilaru V, Smith AK, Myers AJ, Ramirez M, Engel A, Hammack SE, Toufexis D, Braas KM, Binder EB, May V.Nature. 2011 Feb 24;470(7335):492-7. Erratum in: Nature. 2011 Sep 1;477(7362):120.
PMID:21350482

PACAP: a master regulator of neuroendocrine stress circuits and the cellular stress response.
Stroth N, Holighaus Y, Ait-Ali D, Eiden LE. Ann N Y Acad Sci. 2011 Mar;1220:49-59. doi: 10.1111/j.1749-6632.2011.05904.x. Review. PMID:21388403

The Effect of Early Trauma Exposure on Serotonin Type 1B Receptor Expression Revealed by Reduced Selective Radioligand Binding. Murrough JW, Czermak C, Henry S, Nabulsi N, Gallezot JD, Gueorguieva R, Planeta-Wilson B, Krystal JH, Neumaier JF, Huang Y, Ding YS, Carson RE, Neumeister A. Arch Gen Psychiatry. 2011 Sep;68(9):892-900. PMID:21893657

Differential immune system DNA methylation and cytokine regulation in post-traumatic stress disorder. Smith AK, Conneely KN, Kilaru V, Mercer KB, Weiss TE, Bradley B, Tang Y, Gillespie CF, Cubells JF, Ressler KJ. Am J Med Genet B Neuropsychiatr Genet. 2011 Sep;156(6):700-8. doi: 10.1002/ajmg.b.31212. Epub 2011 Jun 28. PMID:21714072

Psychiatry: A molecular shield from trauma. Stein MB. Nature. 2011 Feb 24;470(7335):468-9. No abstract available. PMID:21350472

*http://en.wikipedia.org/wiki/Northern_Illinois_University_shooting

** http://www.theatlantic.com/magazine/archive/2009/12/the-science-of-success/7761/

HIV Variants in Spinal Fluid May Hold Clues in Development of HIV-related Dementia

2011-12-01T01:18:00.000-08:00

NIMH-funded researchers found two variants of HIV in the cerebrospinal fluid (CSF) of infected study participants that were genetically distinct from the viral variants found in the participants’ blood. The study, published October 6, 2011, in the journal PLoS Pathogens, suggests these CSF variants may help to inform research on the development and treatment of cognitive problems related to HIV infection.

Background

The advent of antiretroviral medications has helped many with HIV to manage the illness effectively. But even with proper treatment, a significant percentage of HIV-infected people develop HIV-associated dementia (HAD) or more mild neurological disorders. Research suggests that some people with HAD harbor variants of HIV in their cerebrospinal fluid (CSF) that may be less responsive to current treatments and thus contribute to cognitive decline. Understanding the role of HIV in HAD may also inform efforts to treat or prevent mild neurocognitive disorders associated with HIV.

To explore this issue, Ronald Swanstrom, Ph.D., of the University of North Carolina at Chapel Hill, and colleagues collected samples of blood and CSF from 11 people with HIV. All samples were collected just before and shortly after the person started antiretroviral therapy. The researchers also had access to additional samples from two of the 11 participants, collected several years prior to their starting treatment ceus for counselors

Results of the Study

The researchers found two variants of HIV in participants’ CSF that were genetically distinct from HIV found in their blood. Among participants diagnosed with HAD, the HIV variants in CSF showed greater genetic differences from the type of HIV in their blood, compared with participants with no HAD symptoms.

HIV typically targets a type of immune cell called T-cells. However, researchers found that one CSF variant replicated in macrophages, a different type of immune cell that typically lives longer than T-cells. In one of the participants with longer-term data, the researchers found evidence of this variant before the participant was diagnosed with HAD. During that time, the participant’s neurological assessments reported only mild impairment. The proportion of macrophage-targeting variants in the CSF increased over time, particularly in the first month after the participant was diagnosed with HAD.

In the other participant with longer-term data, the researchers noted the presence of the second CSF variant, which targeted T-cells, after the participant was diagnosed with HAD. Before the participant was diagnosed with HAD, the T-cell-targeting variant was not present in CSF samples.

Significance

The findings indicate that the genetically distinct variants of HIV in the CSF may each play a role in the development of HAD and related neurological disorders.

According to the researchers, the variant that targets macrophages provides clues to how HIV may evolve in order to replicate in a new cell type. The presence of the T-cell-targeting variant suggests that HIV infection may cause T-cells to migrate into the CSF. If confirmed, this migration would provide an alternative mechanism for maintaining viral replication in the central nervous system, which is associated with neurocognitive impairment.

What’s Next

Examining samples of blood, CSF, and brain tissue from a larger number of HIV- infected people with more mild symptoms of neurocognitive impairment may reveal physiological features that distinguish the two CSF variants identified in the current study. According to the researchers, identifying such features may help predict either current or future neurocognitive impairment and would emphasize the benefits of starting treatment early.

Reference

Schnell G, Joseph S, Spudich S, Price RW, Swanstrom. HIV-1 Replication in the Central nervous System Occurs in Two Distinct Cell Types. PLoS Pathog. 2011 Oct;7(10):e1002286

Training Peers Improves Social Outcomes for Some Kids with ASD

2011-11-28T15:50:00.000-08:00

NIH-funded Study Finds Engaging Peers in Social Skills Intervention May Be More Helpful than Training Children with ASD Directly

Children with autism spectrum disorder (ASD) who attend regular education classes may be more likely to improve their social skills if their typically developing peers are taught how to interact with them than if only the children with ASD are taught such skills. According to a study funded by the National Institutes of Health, a shift away from more commonly used interventions that focus on training children with ASD directly may provide greater social benefits for children with ASD. The study was published online ahead of print on November 28, 2011, in the Journal of Child Psychology and Psychiatry.

"Real life doesn't happen in a lab, but few research studies reflect that," said Thomas R. Insel, director of the National Institute of Mental Health (NIMH), a part of NIH. "As this study shows, taking into account a person’s typical environment may improve treatment outcomes." CEUs for Counselors

The most common type of social skills intervention for children with ASD is direct training of a group of children with social challenges, who may have different disorders and may be from different classes or schools. The intervention is usually delivered at a clinic, but may also be school-based and offered in a one-on-one format. Other types of intervention focus on training peers how to interact with classmates who have difficulty with social skills. Both types of intervention have shown positive results in studies, but neither has been shown to be as effective in community settings.

Connie Kasari, Ph.D., of the University of California, Los Angeles, and colleagues compared different interventions among 60 children, ages 6-11, with ASD. All of the children were mainstreamed in regular education classrooms for at least 80 percent of the school day.

These children were randomly assigned to either receive one-on-one training with an intervention provider or to receive no one-on-one intervention. The children were also randomized to receive a peer-mediated intervention or no peer-mediated intervention. The two-step randomization resulted in four intervention categories, each with 15 children who had ASD:
Child-focused: direct, one-on-one training between the child with ASD and intervention provider to practice specific social skills, such as how to enter a playground game or conversation
Peer-mediated: group training with the intervention provider for three typically developing children from the same classroom as the student with ASD; the affected student did not receive any social skills training. The participating children were selected by study staff and teachers and were taught strategies for engaging students with social difficulties.
Both child-focused and peer-mediated interventions
Neither intervention.

All interventions were given for 20 minutes two times a week for six weeks. A follow-up was conducted 12 weeks after the end of the study. After the follow up phase, all children with ASD who had received neither intervention were re-randomized to one of the other treatment categories.

Children with ASD whose peers received training—including those who may also have received the child-focused intervention—spent less time alone on playgrounds and had more classmates naming them as a friend, compared to participants who received the child-focused interventions. Teachers also reported that students with ASD in the peer-mediated groups showed significantly better social skills following the intervention. However, among all intervention groups, children with ASD showed no changes in the number of peers they indicated as their friends.

At follow-up, children with ASD from the peer-mediated groups continued to show increased social connections despite some of the children having changed classrooms due to a new school year and having new, different peers.

According to the researchers, the findings suggest that peer-mediated interventions can provide better and more persistent outcomes than child-focused strategies, and that child-focused interventions may only be effective when paired with peer-mediated intervention.

In addition to the benefits of peer-mediated interventions, the researchers noted several areas for improvement. For example, peer engagement especially helped children with ASD to be less isolated on the playground, but it did not result in improvement across all areas of playground behavior, such as taking turns in games or engaging in conversations and other joint activities. Also, despite greater inclusion in social circles and more frequent engagement by their peers, children with ASD continued to cite few friendships. Further studies are needed to explore these factors as well as other possible mediators of treatment effects.

The study was supported by NIMH, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Institute of Neurological Disorders and Stroke, and the National Institute on Deafness and Other Communication Disorders through the Studies to Advance Autism Research and Treatment (STAART) network program and received additional funding from the Health Resources and Services Administration (HRSA).

Reference

Kasari C, Rotheram-Fuller E, Locke J, Gulsrud A. Making the Connection Randomized Controlled Trial of Social Skills at School for Children with Autism Spectrum Disorders. J Ch Psychol Psychiatry. 2011 Nov 28. [epub ahead of print]

Clinical Trials Number: NCT00095420

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The mission of the NIMH is to transform the understanding and treatment of mental illnesses through basic and clinical research, paving the way for prevention, recovery and cure. For more information, visit the NIMH website.

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit the NIH website.

Psychologists chase down sleep demons

2011-11-27T21:02:00.000-08:00

What do Moby Dick, the Salem witch trials and alien abductions all have in common? They all circle back to sleep paralysis.

Less than 8 percent of the general population experiences sleep paralysis, but it is more frequent in two groups -- students and psychiatric patients -- according to a new study by psychologists at Penn State and the University of Pennsylvania.

Sleep paralysis is defined as "a discrete period of time during which voluntary muscle movement is inhibited, yet ocular and respiratory movements are intact," the researchers state in the current issue of Sleep Medicine Reviews. Hallucinations may also be present in these transitions to or from sleep.

Alien abductions and incubi and succubi, as well as other demons that attack while people are asleep, are implicated as different cultural interpretations of sleep paralysis. The Salem witch trials are now thought possibly to involve the townspeople experiencing sleep paralysis. And in the 19th-century novel Moby Dick, the main character Ishmael experiences an episode of sleep paralysis in the form of a malevolent presence in the room.

Brian A. Sharpless, clinical assistant professor of psychology and assistant director of the psychological clinic at Penn State, noted that some people who experience these episodes may regularly try to avoid going to sleep because of the unpleasant sensations they experience. But other people enjoy the sensations they feel during sleep paralysis.

"I realized that there were no real sleep paralysis prevalence rates available that were based on large and diverse samples," Sharpless said. "So I combined data from my previous study with 34 other studies in order to determine how common it was in different groups." MHC CEUs

He looked at a total of 35 published studies from the past 50 years to find lifetime sleep paralysis rates. These studies surveyed a total of 36,533 people. Overall he found that about one-fifth of these people experienced an episode at least once. Frequency of sleep paralysis ranged from once in a lifetime to every night.

When looking at specific groups, 28 percent of students reported experiencing sleep paralysis, while nearly 32 percent of psychiatric patients reported experiencing at least one episode. People with panic disorder were even more likely to experience sleep paralysis, and almost 35 percent of those surveyed reported experiencing these episodes. Sleep paralysis also appears to be more common in non-Caucasians.

"Sleep paralysis should be assessed more regularly and uniformly in order to determine its impact on individual functioning and better articulate its relation to other psychiatric and medical conditions," said Sharpless.

He looked at a broad range of samples, and papers were included from many different countries.

People experience three basic types of hallucinations during sleep paralysis -- the presence of an intruder, pressure on the chest sometimes accompanied by physical and/or sexual assault experiences and levitation or out-of-body experiences.

Up to this point there has been little research conducted on how to alleviate sleep paralysis or whether or not people experience episodes throughout their lives.

"I want to better understand how sleep paralysis affects people, as opposed to simply knowing that they experience it," said Sharpless. "I want to see how it impacts their lives." Sharpless hopes to look at relationships between sleep paralysis and post-traumatic stress disorder in the future.

This research was supported in part by the National Institute of Mental Health.

Also working on this research was Jacques P. Barber, professor of psychiatry, University of Pennsylvania.

Diagnoses of autism spectrum disorders vary widely across clinics

2011-11-25T17:23:00.000-08:00

Archives of General Psychiatry study suggests common diagnostic subcategories like asperger syndrome are flawed and provides questionable value

NEW YORK (Nov. 9, 2011) -- To diagnose autism spectrum disorders, clinicians typically administer a variety of tests or scales and use information from observations and parent interviews to classify individuals into subcategories listed in standard psychiatric diagnostic manuals. This process of forming "best-estimate clinical diagnoses" has long been considered the gold standard, but a new study demonstrates that these diagnoses are widely variable across centers, suggesting that this may not be the best method for making diagnoses MHC Continuing Education

"Clinicians at one center may use a label like Asperger syndrome to describe a set of symptoms, while those at another center may use an entirely different label for the same symptoms. This is not a good way to make a diagnosis," says the study's lead investigator, Dr. Catherine Lord, director of the Institute for Brain Development, a partnership of Weill Cornell Medical College, NewYork-Presbyterian Hospital and Columbia University Medical Center. "Autism spectrum disorders are just that -- a spectrum of disorders. Instead of using subcategories, it would be better to simply report the results from agreed-upon tests and scales. This approach would provide more consistent and accurate information about individual patients."

The new study, published on Nov. 7 in the journal Archives of General Psychiatry, adds to previous evidence that standardized diagnostic instruments accurately predict who has autism and will continue to have it over time. It is also in line with recent skepticism about the value of categorical groupings of autism spectrum disorders in standard diagnostic manuals, such as the Diagnostic and Statistical Manual of Mental Disorders – IV – text revision (DSM-IV-TR) and the International Statistical Classification of Diseases. "There has been a lot of controversy about whether there should be separate diagnoses for autism spectrum disorder, especially Asperger syndrome," Dr. Lord says. "Most of the research has suggested that Asperger syndrome really isn't different from other autism spectrum disorders."

In the new study, Dr. Lord and co-author Dr. Eva Petkova, a biostatistician at NYU, studied about 2,100 people between the ages of 4 and 18 who were given a diagnosis of autism spectrum disorder by clinicians at 12 university-based centers. The participants were recruited from the Simons Simplex Collection, a multi-site project aimed at studying de novo genetic variations in families affected by autism spectrum disorders. The clinicians, who are experts in autism spectrum disorders, received training on how to administer and score the same set of cognitive tests and standardized instruments assessing social and communication skills and repetitive behavior, including the Autism Diagnostic Observation Schedule (ADOS) and the Autism Diagnostic Interview -- Revised (ADI-R). However, they received no specific training in making best-estimate clinical diagnoses. They used the DSM-IV-TR to classify individuals into three categories of varying severity: autistic disorder, pervasive developmental disorder -- not otherwise specified (PDD-NOS), and Asperger syndrome.

The researchers found that diagnoses of specific categories of autism spectrum disorder varied dramatically from site to site across the country. For instance, clinicians at one site gave only a diagnosis of autistic disorder, while clinicians at other sites gave that diagnosis to fewer than half of the participants. The proportion of individuals receiving a diagnosis of Asperger syndrome ranged from zero to nearly 21 percent across sites. These site differences were the second most important factor accounting for variation in the diagnoses (after social and communication deficits). However, the individuals with autism spectrum disorders did not vary significantly across sites in terms of their demographic information or developmental and behavioral characteristics, as measured by standardized instruments.

"The labels are pretty meaningless, because people are using the same general terms as if they mean the same thing, when they really don't," Dr. Lord says. "Because clinicians may not be using labels appropriately or diagnosing accurately, they may not be getting a sense of children's strengths and weaknesses and what therapy is best for them."

Clinicians across centers varied in how they weighed different factors and in the thresholds they set to make diagnoses. Although verbal IQ strongly influenced diagnoses at most centers, there were striking differences in the cutoff points used at each site to classify individuals into specific categories. The effect of age on diagnoses, and the specific age cutoff points, also varied dramatically across sites. "This doesn't make sense. You don't want to be told that you have a cold if you're 7 and a bacterial infection if you're 12, when you present with identical symptoms," Dr. Lord says.

The variability in clinical diagnoses could reflect regional differences, Dr. Lord says. For instance, services in some regions may be available only to children with a diagnosis of autistic disorder, but this same diagnosis may be stigmatizing or limit school options in other regions. Clinicians may also vary in how they take into account an individual's level of irritability and hyperactivity when judging the severity of autism spectrum disorder, Dr. Lord adds.

Because of the inconsistencies in best-estimate clinical diagnoses, the use of standard diagnostic manuals to classify individuals into subcategories of autism spectrum disorder should be reconsidered, Dr. Lord says. "It's very important for clinicians to use information from dimensions that directly relate to autism spectrum disorders, in addition to verbal IQ and the level of irritability and hyperactivity," she says. "The take-home message is that there really should be just a general category of autism spectrum disorder, and then clinicians should be able to describe a child's severity on these separate dimensions."

"This is an extremely important paper regarding our understanding of the various components of autism spectrum disorder from a group that has been crucial in defining the features of autism over many years," says Dr. Gerald D. Fischbach, scientific director of the Simons Foundation Autism Research Initiative. "They call attention to quantifiable traits rather than existing diagnostic categories. We are proud to have funded this project and to have gathered the Simons Simplex Collection on which this study is based under Dr. Lord's leadership."

In future research, Dr. Lord will work on improving diagnostic instruments --making them shorter, easier to use, and more appropriate for a wider variety of patients -- and assessing whether certain dimensions are really distinct from one another. This work will build on her previous pioneering efforts in developing these commonly used scales.

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Additional collaborating institutions include Columbia University Medical Center in New York City; the Simons Foundation in New York City; the University of Michigan in Ann Arbor; Emory University School of Medicine in Atlanta, Ga.; Emory University School of Medicine and Marcus Autism Center, Children's Healthcare of Atlanta, Ga.; Children's Hospital of Philadelphia in Pennsylvania; the University of Washington in Seattle; Vanderbilt University Medical Center in Nashville, Tenn.; Harvard Medical School in Boston, Mass.; the University of California, Los Angeles; Montreal Children's Hospital in Quebec, Canada; the University of Missouri in Columbia; Baylor College of Medicine in Houston, Texas; the University of Illinois at Chicago; Cincinnati Children's Hospital Medical Center in Ohio; the University of Minnesota in Minneapolis; and Indiana University in Bloomington.

This research was funded by the Simons Foundation and the National Institute of Mental Health.

Columbia University Medical Center

Columbia University Medical Center provides international leadership in basic, pre-clinical and clinical research, in medical and health sciences education, and in patient care. The Medical Center trains future leaders and includes the dedicated work of many physicians, scientists, public health professionals, dentists, and nurses at the College of Physicians & Surgeons, the Mailman School of Public Health, the College of Dental Medicine, the School of Nursing, the biomedical departments of the Graduate School of Arts and Sciences, and allied research centers and institutions. Established in 1767, Columbia's College of Physicians and Surgeons was the first institution in the country to grant the M.D. degree and is now among the most selective medical schools in the country. Columbia University Medical Center is home to the largest medical research enterprise in New York City and state and one of the largest in the United States. For more information, please visit www.cumc.columbia.edu.

NewYork-Presbyterian Hospital

NewYork-Presbyterian Hospital, based in New York City, is the nation's largest not-for-profit, non-sectarian hospital, with 2,409 beds. The Hospital has nearly 2 million inpatient and outpatient visits in a year, including 12,797 deliveries and 195,294 visits to its emergency departments. NewYork-Presbyterian's 6,144 affiliated physicians and 19,376 staff provide state-of-the-art inpatient, ambulatory and preventive care in all areas of medicine at five major centers: NewYork-Presbyterian Hospital/Weill Cornell Medical Center, NewYork-Presbyterian Hospital/Columbia University Medical Center, NewYork-Presbyterian/Morgan Stanley Children's Hospital, NewYork-Presbyterian/The Allen Hospital and NewYork-Presbyterian Hospital/Westchester Division. One of the most comprehensive health care institutions in the world, the Hospital is committed to excellence in patient care, research, education and community service. NewYork-Presbyterian is the #1 hospital in the New York metropolitan area and is consistently ranked among the best academic medical institutions in the nation, according to U.S.News & World Report. The Hospital has academic affiliations with two of the nation's leading medical colleges: Weill Cornell Medical College and Columbia University College of Physicians and Surgeons. For more information, visit www.nyp.org.

Weill Cornell Medical College

Weill Cornell Medical College, Cornell University's medical school located in New York City, is committed to excellence in research, teaching, patient care and the advancement of the art and science of medicine, locally, nationally and globally. Physicians and scientists of Weill Cornell Medical College are engaged in cutting-edge research from bench to bedside, aimed at unlocking mysteries of the human body in health and sickness and toward developing new treatments and prevention strategies. In its commitment to global health and education, Weill Cornell has a strong presence in places such as Qatar, Tanzania, Haiti, Brazil, Austria and Turkey. Through the historic Weill Cornell Medical College in Qatar, the Medical College is the first in the U.S. to offer its M.D. degree overseas. Weill Cornell is the birthplace of many medical advances -- including the development of the Pap test for cervical cancer, the synthesis of penicillin, the first successful embryo-biopsy pregnancy and birth in the U.S., the first clinical trial of gene therapy for Parkinson's disease, and most recently, the world's first successful use of deep brain stimulation to treat a minimally conscious brain-injured patient. Weill Cornell Medical College is affiliated with NewYork-Presbyterian Hospital, where its faculty provides comprehensive patient care at NewYork-Presbyterian Hospital/Weill Cornell Medical Center. The Medical College is also affiliated with the Methodist Hospital in Houston. For more information, visit weill.cornell.edu.

Older adults in home health care at elevated risk for unsafe meds

2011-11-23T18:23:00.000-08:00

New study shows 40 percent of seniors cared for by a home health agency are taking a prescription that is potentially unsafe or ineffective to them

NEW YORK (Nov. 21, 2011) -- Older adults receiving home health care may be taking a drug that is unsafe or ineffective for someone their age. In fact, nearly 40 percent of seniors receiving medical care from a home health agency are taking at least one prescription medication that is considered potentially inappropriate to seniors, a new study in the Journal of General Internal Medicine has revealed LPC Ceus

The study's researchers, led by Dr. Yuhua Bao, assistant professor of public health at Weill Cornell Medical College, found that home health care patients aged 65 and over are prescribed Potentially Inappropriate Medications, or PIMs, at rates three times higher than patients who visit a medical office. The researchers' data shows that home health care patients are taking 11 medications on average, and that the concurrent use of multiple medications is a strong indicator of the presence of PIMs.

"Elderly patients receiving home health care are usually prescribed medications by a variety of physicians, and it's a great challenge for home health care nurses to deal with prescriptions from many sources," says Dr. Bao.

Still, she sees the home health care model offering potential for improving this situation. "Having a medical professional enter an elderly patient's home is an opportunity to do a proper medication review and reconciliation," Dr. Bao explains.

The study used data from the National Home and Hospice Care Survey, conducted in 2007 by the Centers for Disease Control and Prevention (CDC), which is the most recent nationally representative epidemiological survey of home health patients. The 2002 Beers Criteria, an expert-panel-generated list that itemizes 77 medications or groups of medications considered inappropriate for elderly people, was the basis for the PIMs chosen.

In a review of data of 3,124 home health patients 65 years of age or older, the researchers found 38 percent were taking at least one PIM. Senior patients taking 15 or more medications were five to six times as likely to be prescribed PIMs as patients taking seven or fewer medications. Of those seniors taking at least one PIM, 21 percent were taking 15 or more medications.

According to Dr. Bao, the study, if anything, underestimates the prevalence of PIMs taken by home health patients: The researchers were not able to look at potentially problematic drug-to-drug interactions or drug-and-disease interactions because data were not available.

There is no one reason why PIMs are prevalent in home health care settings. "Anecdotal evidence shows that many physicians are not aware of what is on the PIM list," says Dr. Bao. "In our fragmented health care system, we generally don't have an electronic reference for a patient that lists all medications from different physicians, and there isn't a readily available means for professionals to share essential information. Enhanced physician communication with home health care nurses may help to address the problem, as well as better communication among physicians."

Dr. Bao sees incentives for improvement in communication and care coordination in the implementation of the Patient Protection and Affordable Care Act passed by the U.S. Congress in 2010. "The current payment system doesn't provide incentives to optimize coordination of care," says Dr. Bao. "But when providers in different settings as a group are held responsible for outcomes and costs of care through, for example, an accountable care organization -- a concept promoted in the Affordable Care Act -- this could create an impetus to break the communication barriers that currently exist."

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Co-authors include Huibo Shao, Tara F. Bishop, Bruce R. Schackman and Martha L. Bruce -- all from Weill Cornell Medical College.

The study was funded by the National Institute of Mental Health. The authors do not have conflicts of interest.

Weill Cornell Medical College

Weill Cornell Medical College, Cornell University's medical school located in New York City, is committed to excellence in research, teaching, patient care and the advancement of the art and science of medicine, locally, nationally and globally. Physicians and scientists of Weill Cornell Medical College are engaged in cutting-edge research from bench to bedside, aimed at unlocking mysteries of the human body in health and sickness and toward developing new treatments and prevention strategies. In its commitment to global health and education, Weill Cornell has a strong presence in places such as Qatar, Tanzania, Haiti, Brazil, Austria and Turkey. Through the historic Weill Cornell Medical College in Qatar, the Medical College is the first in the U.S. to offer its M.D. degree overseas. Weill Cornell is the birthplace of many medical advances -- including the development of the Pap test for cervical cancer, the synthesis of penicillin, the first successful embryo-biopsy pregnancy and birth in the U.S., the first clinical trial of gene therapy for Parkinson's disease, and most recently, the world's first successful use of deep brain stimulation to treat a minimally conscious brain-injured patient. Weill Cornell Medical College is affiliated with NewYork-Presbyterian Hospital, where its faculty provides comprehensive patient care at NewYork-Presbyterian Hospital/Weill Cornell Medical Center. The Medical College is also affiliated with the Methodist Hospital in Houston. For more information, visit weill.cornell.edu.

Intervention Shows Promise in Treating Depression Among Preschoolers

2011-11-19T13:06:00.000-08:00

Source: NIMH

A new psychosocial approach shows promise in helping preschoolers with symptoms of depression function better and learn to regulate their emotions, according to an NIMH-funded study published online ahead of print October 31, 2011, in the Journal of Child Psychology and Psychiatry.

Background

Recent studies have shown that symptoms of clinical depression can arise in children as young as 3, and may in fact be an early manifestation of a childhood mood disorder. However, no studies have investigated the best way to treat the disorder among children so young. In addition, many established psychosocial treatments for depression in adults and older youth, such as cognitive behavioral therapy or interpersonal therapy, might not be a good fit to the developmental needs of very young children.

Yet research has shown that very early behavioral interventions can have a significant impact on the trajectory of conduct problems and neuro-developmental disorders like autism or some developmental delays. These findings suggest that very early intervention for a mood disorder could potentially head off depression later in life lpc continuing education

Toward that end, Joan Luby, M.D., of Washington University and colleagues conducted a preliminary pilot study comparing a novel form of psychotherapy called Parent Child Interaction Therapy -Emotion Development (PCIT-ED) with a psycho-educational program. PCIT includes hands-on components aimed at strengthening the parent-child relationship by teaching positive play techniques and coaching parents through the process, and training parents in methods for handling noncompliance and disruptive behavior. PCIT has already been shown to be effective for treating disruptive disorders among preschoolers. The Emotion Development component was designed to help the parent enhance the child’s ability to recognize emotions in self and others and more effectively regulate intense emotions.

The psycho-education program—the control condition—educated parents in small groups about child development. It emphasized emotional and social development but did not include individual coaching or practice sessions with the parents and their children.

The researchers randomly assigned 54 preschoolers (aged 3-7) and their parents to either PCIT-ED or to the psycho-education program. Each program was conducted over a 12-week period.

Results of the Study

After 12 weeks, depression symptoms among the preschoolers significantly declined in both groups. The group receiving PCIT-ED also showed improvements in levels of anxiety, hyperactivity, conduct problems, hostility and inattention, whereas the group receiving the psycho-education program showed improvements in separation anxiety. In addition, the PCIT-ED group showed improvements in a child’s executive functioning and his or her ability to recognize and regulate emotions, compared to the control condition. The PCIT-ED group also reported reduced parenting stress and decreases in maternal depression, whereas the psycho-education group did not.

Significance

The results indicate that PCIT-ED is acceptable to families and may be beneficial. The researchers conclude that a full-scale randomized controlled trial is warranted.

What’s Next

While intriguing, the findings are preliminary only and should be interpreted with caution until further research can be conducted.

Reference

Luby J, Lenze S and Tillman R. A novel early intervention for preschool depression: findings from a pilot randomized controlled trial. Journal of Child Psychology and Psychiatry. Online ahead of print Oct. 31, 2011.

FOCUS ON TESTING HURTS STUDENTS IN HIGH SCHOOL HEALTH CLASSES

2011-11-16T18:27:00.000-08:00

COLUMBUS, Ohio – High school health classes fail to help students refuse sexual advances or endorse safe sex habits when teachers focus primarily on testing knowledge, a new study reveals.

But when teachers emphasized learning the material for its own sake, and to improve health, students had much better responses. In these kinds of classrooms, students had lower intentions of having sex and felt better able to navigate sexual situations.

“A focus on tests doesn’t help students in health classes make healthier choices,” said Eric M. Anderman, lead author of the study and professor of educational psychology at Ohio State University.

Eric Anderman
“In health education, knowledge is not the most important outcome. What we really want to do is change behaviors, and testing is not the way to achieve that.”

The study appears online in the Journal of Research on Adolescence and will be published in a future print edition.

This study is part of a larger 5-year project that is studying HIV and pregnancy prevention in rural communities in Appalachia.

Researchers from Ohio State, the University of Kentucky and George Mason University are collecting data from more than 5,000 students in 32 Appalachian high schools.

For this study, students were surveyed in 9th grade before taking a health class that included information on HIV and pregnancy prevention. They were then surveyed again between four and six weeks after their class, and at the end of 10th grade, about one year later.

After taking the class, students were asked if their teachers had encouraged them to learn the material because they would be tested on it (called an extrinsic focus), or if the teachers encouraged them to truly learn and understand the information because it would be important for their lives (termed a mastery focus).

The researchers then compared these two groups of students on a variety of measures. Overall, the results showed that students in classes with a mastery focus were better off on a variety of health-related measures than were those whose teachers emphasized testing, Anderman said.

One example is the ability to refuse unwanted sexual advances. Findings showed that students in mastery classes reported they were better able to refuse sex 4 to 6 weeks later and even one year later than they were before the class began.

However, those in the extrinsic-focused classes “actually felt less effective at refusing sex after they took the class than they did before,” Anderman said.

Similar results were found when students were asked whether they thought they would wait to have sex.

Four to six weeks after the class, students whose teachers emphasized mastery were more likely to report that they wanted to wait to have sex, although there was no significant effect at a year later. That was not true for those who had extrinsic-focused classes, who were actually less likely to want to wait for sex after taking the class.

“That’s a really scary finding. The class was not having the intended effect when teachers emphasized the tests,” Anderman said.

Students were asked if their teachers had encouraged them to learn the material because they would be tested on it (called an extrinsic focus), or if the teachers encouraged them to truly learn and understand the information because it would be important for their lives (termed a mastery focus)ceus for counselors

Students in the mastery classes reported they felt better able to tell partners they would not have sex without using a condom at both time points after the class. Those in the extrinsic-oriented classes did not at the first follow-up.

Similar results favoring students in mastery-oriented classes occurred when students were asked about communication with parents about sex-related topics, knowledge about sex-related health issues, actual intentions to have sex, and belief about the importance of these health issues and whether they had the ability to learn more.

The results are clear, Anderman said.

“Focusing on knowledge about health does not equate to healthy behavior,” he said. “It’s more important for the students to improve their health than it is to get a 90 percent on a test.”

When students focus on tests, they are thinking about what they need to remember to get a good grade, he said. They are not taking the time to think about why they are learning this information, and why it is important in their life.

“Ideally, in the perfect world, I would say students shouldn’t be tested in health classes. Tests are important in a lot of areas, but health is not one of them,” he said.

“But if you have to have tests, make them minimal and low-pressure. This is not about separating students in terms of ability. It is about getting students to adopt healthy habits.”

Co-authors of the study were DeLeon Gray and Ann O’Connell of Ohio State; Pamela Cupp and Derek Lane of the University of Kentucky; and Rick Zimmerman of George Mason University.

The study was funded by a grant from the National Institute of Mental Health.

Widely Used Screening Tool Shown to Successfully Predict Suicide Attempts

2011-11-14T01:16:00.000-08:00

A widely used suicide screening tool can help determine who is most at risk for suicide by pinpointing the threshold at which a person’s suicidal thinking is severe enough to warrant professional intervention, according to a recent study published online ahead of print November 8, 2011, in the American Journal of Psychiatry.

Background
Developing effective suicide prevention strategies is a priority of the Action Alliance for Suicide Prevention, a public-private partnership developed to advance the national strategy for suicide prevention. One of its main goals is to more efficiently identify those at risk so as to better target intervention. Standardized, reliable screening tools are needed to achieve that.
The Columbia-Suicide Severity Rating Scale (C-SSRS) was developed by a team of researchers from Columbia University, the University of Pennsylvania and the University of Pittsburgh to be used as part of the NIMH-funded Treatment of Adolescent Suicide Attempters (TASA) study. It was developed to meet the need for tracking changes in a person’s suicidal thinking and behavior over time, and to determine who is most at risk. The scale addresses the full range of suicidal behavior and thinking, but includes only the most essential, evidence-based items required for thorough assessment. The scale is now widely used for assessing suicidal thinking and behavior across research and practice in both psychiatric and non-psychiatric settings. It is used domestically and internationally by numerous stakeholders such as first responders (e.g., police, EMTs, fire departments), the U.S. Army, National Guards, prisons, hospitals, schools, and judicial systems to better identify those in need and to direct limited resources.

In this current analysis, Kelly Posner Ph.D., of Columbia University, and colleagues compared the C-SSRS to other similar measures, all of which were administered in three separate studies that featured teens who had attempted suicide or adults presenting to emergency rooms with psychiatric problems. They aimed to determine the scale’s validity, reliability and internal consistency, compared to the other measures.

Results of the Study

The researchers found that compared to other measures, the C-SSRS could reliably predict a potential suicide attempt in those who had previously attempted suicide. It also was able to determine clinically meaningful points at which a person may be at risk for an impending suicide attempt, something that other scales have been unable to consistently determine. According to the researchers, this type of predictive information can more precisely identify who needs the most help and when, while saving time and money by not having to refer people for treatment who are not at imminent risk.

Significance

This was the first major study showing how well the C-SSRS works with regard to identifying those most at risk for suicidal behavior. It was able to show, for the first time, that behaviors beyond previous suicide attempts—such as self-injury or making preparations for an attempt—may be used as predictors of subsequent suicide attempts.

What’s Next

Because the studies used in this analysis were not widely representative, additional research is needed to replicate the findings among diverse community samples counselor ceus

Reference

Posner K, Brown GK, Stanley B, Brent DA, Yershova KV, Oquendo MA, Currier GW, Melvin GA, Greenhill L, Shen S, Mann JJ. The Columbia-Suicide Severity Rating Scale: Initial Validity and Internal Consistency Findings from Three Multisite Studies with Adolescents and Adults. American Journal of Psychiatry. Online ahead of print Nov 8,2011.

NIH-funded study shows pre-birth brain growth problems linked to autism

2011-11-10T10:17:00.000-08:00

Source: NIMH

Children with autism have more brain cells and heavier brains compared to typically developing children, according to researchers partly funded by the National Institutes of Health. Published in the Journal of the American Medical Association on Nov. 9, 2011, the small, preliminary study provides direct evidence for possible prenatal causes of autism.

"Earlier studies of head circumference and early brain overgrowth have pointed us in this direction, but there have been few quantitative neuroanatomical studies due to the lack of post-mortem tissue from children with autism," said Thomas R. Insel, M.D., director of the National Institute of Mental Health (NIMH), part of NIH. "These new results, along with an earlier study1 reporting altered wiring of the prefrontal cortex, focus our attention on this critical area of the brain in autism."

The prefrontal cortex is involved in various higher order functions such as language and communication, social behavior, mood, and attention. Children who have autism tend to show deficits in such functions.

Eric Courchesne, Ph.D., of the University of San Diego School of Medicine Autism Center of Excellence, and colleagues conducted direct counts of brain cells in specific regions of the prefrontal cortex in postmortem brains of seven boys who had autism and six typically developing males, ranging in age from 2-16 years. Most participants had died in accidents, but the researchers did not base their selection on causes of death.

To assist in this task, the researchers used a computerized tissue analysis system developed by co-investigator and NIMH grantee Peter Mouton, Ph.D., of the University of South Florida, Tampa, and colleagues.

The researchers found that children with autism had 67 percent more neurons in the prefrontal cortex and heavier brains for their age compared to typically developing children. Since these neurons are produced before birth, the study’s findings suggest that faulty prenatal cell birth or maintenance may be involved in the development of autism. Another possible factor that may contribute to the neuronal excess is a reduction in apoptosis, or programmed cell death, which normally occurs during the third trimester and early postnatal life.

Though small, this preliminary study examined all relevant postmortem tissue available at the time. The relative scarcity of tissue from very young children may limit future research as well, but efforts to include a larger number of samples are needed to confirm these findings and to identify patterns of age-related changes in autism.

This study was funded by Autism Speaks, Cure Autism Now, The Emch Foundation, the Simons Foundation, the Thursday Club Juniors, and the UCSD-NIH Autism Center of Excellence, which is supported by NIMH, the National Institute of Neurological Disorders and Stroke, and the Eunice Kennedy Shriver National Institute of Child Health and Human Development continuing education for counselors

Reference
Courchesne E, Mouton PR, Calhoun ME, Semendeferi K, Ahrens-Barbeau C, Hallet MJ, Barnes CC, Pierce K. Neuron Number and Size in Prefrontal Cortex of Children with Autism. JAMA. 2011 Nov 9;306(18).

1. Zikopoulos B, Barbas H. Changes in prefrontal axons may disrupt the network in autism. J Neurosci. 2010 Nov 3;30(44):14595-609. PubMed PMID: 21048117; PubMed Central PMCID: PMC3073590.

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The mission of the NIMH is to transform the understanding and treatment of mental illnesses through basic and clinical research, paving the way for prevention, recovery and cure. For more information, visit the NIMH website.

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit the NIH website.

Pitt team finds molecular evidence of brain changes in depressed females

2011-11-08T10:12:00.000-08:00

PITTSBURGH, Sept. 16 – Researchers at the University of Pittsburgh School of Medicine have discovered molecular-level changes in the brains of women with major depressive disorder that link two hypotheses of the biological mechanisms that lead to the illness. Their results, published online this week in Molecular Psychiatry, also allowed them to recreate the changes in a mouse model that could enhance future research on depression.

Although women are twice as likely as men to develop depression and have more severe and frequent symptoms, very little research has focused on them or been conducted in other female animals, noted senior author Etienne Sibille, Ph.D., associate professor of psychiatry, Pitt School of Medicine.

"It seemed to us that if there were molecular changes in the depressed brain, we might be able to better identify them in samples that come from females," he said. "Indeed, our findings give us a better understanding of the biology of this common and often debilitating psychiatric illness."

The researchers examined post-mortem brain tissue samples of 21 women with depression and 21 similar women without a history of depression. Compared to their counterparts, the depressed women had a pattern of reduced expression of certain genes, including the one for brain-derived neurotrophic factor (BDNF), and of genes that are typically present in particular subtypes of brain cells, or neurons, that express the neurotransmitter gamma-aminobutyric acid (GABA.) These findings were observed in the amygdala, which is a brain region that is involved in sensing and expressing emotion.

In the next part of the project, the researchers tested mice engineered to carry different mutations in the BDNF gene to see its impact on the GABA cells. They found two mutations that led to the same deficit in the GABA subtype and that also mirrored other changes seen in the human depressed brain.

Dr. Sibille noted that researchers have long suspected that low levels of BDNF play a role in the development of depression, and that there also is a hypothesis that reduced GABA function is a key factor.

"Our work ties these two concepts together because we first show that BDNF is indeed low in depression and second that low BDNF can influence specific GABA cells in a way that reproduces the biological profile we have observed in the depressed brain," he said.

The team is continuing to explore the molecular pathway between BDNF and GABA and others that could be important in depression LPC CEUs

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Co-authors include Gaelle Douillard-Guilloux, Ph.D., Rama Kota, Ph.D., Xingbin Wang, Ph.D., George C. Tseng, Ph.D., and David Lewis, M.D., all of the University of Pittsburgh; Jean-Philippe Guilloux, Ph.D, of Pitt and Universite Paris-Sud; Alain Gardier, Ph.D., of Universite Paris-Sud; and, Keri Martinowich, of the National Institute of Mental Health, part of the National Institutes of Health.

The study was funded by the National Institute of Mental Health.

About the University of Pittsburgh School of Medicine

As one of the nation's leading academic centers for biomedical research, the University of Pittsburgh School of Medicine integrates advanced technology with basic science across a broad range of disciplines in a continuous quest to harness the power of new knowledge and improve the human condition. Driven mainly by the School of Medicine and its affiliates, Pitt has ranked among the top 10 recipients of funding from the National Institutes of Health since 1997.

Likewise, the School of Medicine is equally committed to advancing the quality and strength of its medical and graduate education programs, for which it is recognized as an innovative leader, and to training highly skilled, compassionate clinicians and creative scientists well-equipped to engage in world-class research. The School of Medicine is the academic partner of UPMC, which has collaborated with the University to raise the standard of medical excellence in Pittsburgh and to position health care as a driving force behind the region's economy. For more information about the School of Medicine, see www.medschool.pitt.edu.

Young people say sex, paychecks come in second to self-esteem

2011-11-07T16:50:00.000-08:00

COLUMBUS, Ohio – Young people may crave boosts to their self-esteem a little too much, new research suggests.

Researchers found that college students valued boosts to their self-esteem more than any other pleasant activity they were asked about, including sex, favorite foods, drinking alcohol, seeing a best friend or receiving a paycheck.

"It is somewhat surprising how this desire to feel worthy and valuable trumps almost any other pleasant activity you can imagine," said Brad Bushman, lead author of the research and professor of communication and psychology at The Ohio State University.

Bushman conducted the research with Scott Moeller of Brookhaven National Laboratory and Jennifer Crocker, professor of psychology at Ohio State. The study appears online in the Journal of Personality and will be published in a future print edition.

In two separate studies, the researchers asked college students how much they wanted and liked various pleasant activities, such as their favorite food or seeing a best friend. They were asked to rate how much they wanted and liked each activity on a scale of 1 (not at all) to 5 (extremely).

One of the items they were asked about was self-esteem building experiences, such as receiving a good grade or receiving a compliment.

"We found that self-esteem trumped all other rewards in the minds of these college students," Bushman said.

Those students who indicated they highly valued self-esteem also showed it in the laboratory Continuing Education for Counselors

In one study, the participants took a test which purportedly measured their intellectual ability. Afterwards, the students were told if they waited another ten minutes, they could have their test re-scored using a new scoring algorithm that usually yields higher test results.

Students who highly valued self-esteem were more likely to stay to get the new scores.

"They were willing to spend their own precious time just to get a small boost in their self-esteem," Bushman said.

Bushman said there is nothing wrong with a healthy sense of self-esteem. But the results of this study suggest many young people may be a little too focused on pumping up their self-esteem.

Here's why: for all the pleasant activities examined in this study, participants were asked to rate both how much they liked the activity and how much they wanted it. Both questions were asked because addiction research suggests that addicts tend to report they "want" the object of their addiction (drugs, alcohol, gambling) more than they actually "like" it, Bushman said.

"The liking-wanting distinction has occupied an important place in addiction research for nearly two decades," Moeller said. "But we believe it has great potential to inform other areas of psychology as well."

In this study, participants liked all the pleasant activities more than they wanted them, which is healthy, Bushman said. But the difference between liking and wanting was smallest when it came to self-esteem.

"It wouldn't be correct to say that the study participants were addicted to self-esteem," Bushman said. "But they were closer to being addicted to self-esteem than they were to being addicted to any other activity we studied."

Findings showed that people with a strong sense of entitlement were the ones who were most likely to "want" the good things in life – including boosts to their self-esteem – even more than they actually "like" them.

Entitlement was measured as part of a narcissism scale which participants completed. In the scale, participants had to choose which of two statements they most agreed with. For example, people who scored high on entitlement were more likely to agree with "If I ruled the world, it would be a much better place" rather than "The thought of ruling the world frightens the hell out of me."

"Entitled people want all the good things in life, even if they don't particularly like them," Bushman said. "Of course, there's no problem with enjoying good things, but it is not healthy to want them more than you like them."

Bushman said he sees danger in this obsession with self-esteem. Research has shown that levels of self-esteem have been increasing, at least among college students in the United States, since the mid-1960s.

"American society seems to believe that self-esteem is the cure all for every social ill, from bad grades to teen pregnancies to violence," he said. "But there has been no evidence that boosting self-esteem actually helps with these problems. We may be too focused on increasing self-esteem."

Study co-author Crocker added, "The problem isn't with having high self-esteem; it's how much people are driven to boost their self-esteem. When people highly value self-esteem, they may avoid doing things such as acknowledging a wrong they did. Admitting you were wrong may be uncomfortable for self-esteem at the moment, but ultimately it could lead to better learning, relationships, growth, and even future self-esteem."

The study was partially supported by grants from the National Institute of Mental Health and the National Institute on Drug Abuse.

Psychologists Stress the Importance of Memory in Preventing Relapse after Therapy

2011-11-04T21:23:00.000-07:00

Addictions, phobias, post-traumatic stress disorder—such painful and harmful problems are recalcitrant to treatment. In the clinic, a person may suppress the association between the stimulus and the response—say, a bar with ashtrays and smoking—by learning to pair the stimulus with a new memory not involving smoking. But once out in the world, faced with bars and ashtrays aplenty, he relapses into the old behavior. Some treatment aims at helping the patient avoid locations and stimuli that trigger the harmful behavior LPC Continuing Education

A new article in Current Directions in Psychological Science, a journal published by the Association for Psychological Science, says this is not the most effective route. “The therapist really has little control over the context in which the patient finds himself,” says Ralph R. Miller, distinguished professor of psychology at the State University of New York at Binghamton, who wrote the article with SUNY colleague Mario A. Laborda. A more promising method, then, is: “Make the treatment memory stronger.”

Experimentalists like the authors use the term “extinction” for the process, as Miller puts it, of “teaching the subject new memories that oppose the old memories.” Clinicians call it “exposure therapy.”

The article reviews the psychological literature supporting four ways to make the extinction memory stronger and therefore more enduring: Give more therapy (or in the experimental context, more trials). Conduct the therapy in different locations and contexts—for instance, different rooms rather than always the same office. Space the extinction exercises—or in the lab, the experimental trials—over the therapeutic session. And finally, provide the treatment sessions separated by more time. These methods exploit established principles of learning: that increased practice enhances learning, and “spaced practice results in better memory than when the learning trials are massed,” says Miller.

Miller stresses the importance of animal laboratory research in finding new treatment methods. “We are developing excellent means in the animal lab to model human psychopathology, not just for screening drugs but for screening behavioral treatments. We additionally now have models of the treatment and the limitations of the treatments,” he says. Determining how to reduce those limitations using rats rather than humans is faster and requires fewer subjects, he says. Numerous clinical studies, moreover, “certify that our findings with rats also apply to humans.”

The research cited in Miller and Laborda’s paper is suggestive of a powerful theory: “It appears that memories are forever,” says Miller. It then ratifies those proven facts about learning. “We are providing alternate memories that compete with the deleterious memory”—say, a new, automatic mental image of having a drink and a conversation in a bar without picking up a cigarette, perhaps accompanied by a feeling of relaxation. “The trick is that the newer memory when it is retrieved will be stronger than the deleterious memory.”

Current Directions in Psychological Science, a journal of the Association for Psychological Science, publishes concise reviews on the latest advances in theory and research spanning all of scientific psychology and its applications. For a copy of "Preventing Recovery From Extinction and Relapse: A Product of Current Retrieval Cues and Memory Strengths"

Advice to divorcees: Go easy on yourself

2011-11-03T22:59:00.000-07:00

Divorce is tough, for just about everyone. But some people move through a breakup without overwhelming distress, even if they're sad or worried about money, while others get stuck in the bad feelings and can't seem to climb out. What accounts for the difference? LPC CEUs

Self-compassion, says an upcoming study in Psychological Science, a journal published by the Association for Psychological Science. Self-compassion—a combination of kindness toward oneself, recognition of common humanity, and the ability to let painful emotions pass—"can promote resilience and positive outcomes in the face of divorce," says psychologist David A. Sbarra, who conducted the study with University of Arizona colleagues Hillary L. Smith and Matthias R. Mehl. Independent of other personality traits, that one capacity predicts better adjustment shortly after divorce and up to nine months later.

The findings have implications for helping people learn to weather breakups in better health and better spirits.

"We're not interested in the basic statement, 'People who are coping better today do better nine months from now.' That doesn't help anybody," says Sbarra. "The surprising part here is that when we look at a bunch of positive characteristics"—such as self-esteem, resistance to depression, optimism, or ease with relationships—"this one characteristic—self-compassion— uniquely predicts good outcomes."

The study involved 105 people, 38 men and 67 women, whose mean age was about 40; they'd been married over 13 years and divorced an average of three to four months. On the first visit, participants were asked to think about their former partner for 30 seconds, then talk for four minutes about their feelings and thoughts related to the separation.

Four trained coders listened to the audio files and rated the participants' levels of self-compassion, using a standard measure of the construct. The participants also were assessed for other psychological traits, such as depression and their "relationship style." At the initial visit, three months later, and then after either six or nine months participants reported on their adjustment to the divorce, including the frequency with which they experienced intrusive thoughts and emotions about the separation and their ex-partner.

As expected, the people with high levels of self-compassion at the start both recovered faster and were doing better after a period of months.

How can these data help people going through divorce? Sbarra's friends, knowing what he studies, often ask for such advice.

"It's not easy to say, 'Be less anxious.' You can't change your personality so easily. We also know that women do better than men. But you can't change your sex. What you can change is your stance with respect to your experience." Understanding your loss as part of bigger human experience helps assuage feelings of isolation, he says. Mindfulness—noting jealousy or anger without judgment or rumination—lets you turn your mind to life in the present without getting stuck in the past.

Can all this be taught? The researchers are unsure but optimistic. Says Sbarra: "This study opens a window for how we can potentially cultivate self-compassion among recently separated adults" and help smooth the journey through one of life's most difficult experiences.

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For more information about this study, please contact: David A. Sbarra at sbarra@email.arizona.edu.

The APS journal Psychological Science is the highest ranked empirical journal in psychology. For a copy of the article "When Leaving Your Ex, Love Yourself: Observational Ratings of Self-compassion Predict the Course of Emotional Recovery Following Marital Separation" and access to other Psychological Science research findings, please contact Lucy Hyde at 202-293-9300 or lhyde@psychologicalscience.org.

Our brains are made of the same stuff, despite DNA differences

2011-10-31T14:54:00.000-07:00

Gene expression databases reveal “consistent molecular architecture”

Despite vast differences in the genetic code across individuals and ethnicities, the human brain shows a “consistent molecular architecture,” say researchers supported by the National Institutes of Health. The finding is from a pair of studies that have created databases revealing when and where genes turn on and off in multiple brain regions through development counselor ceus

“Our study shows how 650,000 common genetic variations that make each of us a unique person may influence the ebb and flow of 24,000 genes in the most distinctly human part of our brain as we grow and age,” explained Joel Kleinman, M.D., Ph.D., of the National Institute of Mental Health (NIMH) Clinical Brain Disorders Branch.

Kleinman and NIMH grantee Nenad Sestan, M.D., Ph.D. of Yale University, New Haven, Conn., led the sister studies in the Oct. 27, 2011 issue of the journal Nature.

“Having at our fingertips detailed information about when and where specific gene products are expressed in the brain brings new hope for understanding how this process can go awry in schizophrenia, autism and other brain disorders,” said NIMH Director Thomas R. Insel, M.D.

Both studies measured messenger RNAs or transcripts. These intermediate products carry the message from DNA, the genetic blueprint, to create proteins and differentiated brain tissue. Each gene can make several transcripts, which are expressed in patterns influenced by a subset of the approximately 1.5 million DNA variations unique to each of us. This unique set of transcripts is called our transcriptome – a molecular signature that is unique to every individual. The transcriptome is a measure of the diverse functional potential that exists in the brain.

Both studies found that rapid gene expression during fetal development abruptly switches to much slower rates after birth that gradually decline and eventually level off in middle age. These rates surge again as the brain ages in the last decades, mirroring rates seen in childhood and adolescence, according to one of the studies. The databases hold secrets to how the brain’s ever-changing messenger chemical systems, cells and development processes are related to gene expression patterns through development.

For example, if a particular version of a gene is implicated in a disorder, the new resources might reveal how that variation affects the gene’s expression over time and by brain region. By identifying even distant genes that may be turning on and off in-sync, the databases may help researchers discover whole modules of genes involved in the illness. They can also reveal how variation in one gene influences another’s expression.

Prefrontal cortex

Kleinman’s team focused on how genetic variations are linked to the expression of transcripts in the brain’s prefrontal cortex, the area that controls insight, planning and judgment, across the lifespan. They studied 269 postmortem, healthy human brains, ranging in age from two weeks after conception to 80 years old, using 49,000 genetic probes. The database on prefrontal cortex gene expression alone totals more than 1 trillion pieces of information, according to Kleinman.

Among key findings in the prefrontal cortex:
Individual genetic variations are profoundly linked to expression patterns. The most similarity across individuals is detected early in development and again as we approach the end of life.

Different types of related genes are expressed during prenatal development, infancy, and childhood, so that each of these stages shows a relatively distinct transcriptional identity. Three-fourths of genes reverse their direction of expression after birth, with most switching from on to off.

Expression of genes involved in cell division declines prenatally and in infancy, while expression of genes important for making synapses, or connections between brain cells, increases. In contrast, genes required for neuronal projections decline after birth – likely as unused connections are pruned.

By the time we reach our 50s, overall gene expression begins to increase, mirroring the sharp reversal of fetal expression changes that occur in infancy.

Genetic variation in the genome as a whole showed no effect on variation in the transcriptome as a whole, despite how genetically distant individuals might be. Hence, human cortexes have a consistent molecular architecture, despite our diversity.

In previous studies, Kleinman and colleagues have found that all genetic variations implicated to date in schizophrenia are associated with transcripts that are preferentially expressed in the fetal brain. This adds to evidence that the disorder originates in prenatal development. By contrast, he and his colleagues are examining evidence that genetic variation implicated in affective disorders may be associated with transcripts expressed later in life. They are also extending their database to include all transcripts of all the genes in the human genome, examining 1000 post-mortem brains, including many of people who had schizophrenia or other brain disorders.

Multiple brain regions

Sestan and colleagues characterized gene expression in 16 brain regions, including 11 areas of the neocortex, from both hemispheres of 57 human brains that spanned from 40 days post-conception to 82 years – analyzing the transcriptomes of 1,340 samples. Using 1.4 million probes, the researchers measured the expression of exons, which combine to form a gene’s protein product. This allowed them to pinpoint changes in these combinations that make up a protein, as well as to chart the gene’s overall expression.

Among key findings:
Over 90 percent of the genes expressed in the brain are differentially regulated across brain regions and/or over developmental time periods. There are also widespread differences across region and time periods in the combination of a gene’s exons that are expressed.

Timing and location are far more influential in regulating gene expression than gender, ethnicity or individual variation.

Among 29 modules of co-expressed genes identified, each had distinct expression patterns and represented different biological processes. Genetic variation in some of the most well-connected genes in these modules, called hub genes, has previously been linked to mental disorders, including schizophrenia and depression.

Telltale similarities in expression profiles with genes previously implicated in schizophrenia and autism are providing leads to discovery of other genes potentially involved in those disorders.

Sex differences in the risk for certain mental disorders may be traceable to transcriptional mechanisms. More than three-fourths of 159 genes expressed differentially between the sexes were male-biased, most prenatally. Some genes found to have such sex-biased expression had previously been associated with disorders that affect males more than females, such as schizophrenia, Williams syndrome, and autism.

The Sestan study was also funded by NIH’s National Institute on Child Health and Human Development, National Institute on Neurological Disorders and Stroke, and National Institute on Drug Abuse. Data for the Sestan study are posted at www.humanbraintranscriptome.org and at http://www.developinghumanbrain.org, as part of a larger ongoing study, BrainSpan, funded by NIMH under the American Recovery and Reinvestment Act to create an Atlas of Human Brain Development.

The Kleinman study data on genetic variability are accessible to qualified researchers at http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000417.v1.p1, while the gene expression data can be found at http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc5GSE30272. In addition, BrainCloud, a web browser application developed by NIMH to interrogate the Kleinman study data, can be downloaded at http://www.libd.org/braincloud.

Our brains are all made of the same stuff. Despite individual and ethnic genetic diversity, our prefrontal cortex shows a consistent molecular architecture. For example, overall differences in the genetic code (“genetic distance”) between African -Americans (AA) and caucasians (cauc) showed no effect on their overall difference in expressed transcripts (“transcriptional distance”). The vertical span of color-coded areas is about the same, indicating that our brains all share the same tissue at a molecular level, despite distinct DNA differences on the horizontal axis. Each dot represents a comparison between two individuals. The AA::AA comparisons (blue) generally show more genetic diversity than cauc::cauc comparisons (yellow), because caucasians are descended from a relatively small subset of ancestors who migrated from Africa, while African Americans are descended from a more diverse gene pool among the much larger population that remained in Africa. AA::cauc comparisons (green) differed most across their genomes as a whole, but this had no effect on their transcriptomes as a whole.
Source: Joel Kleinman, M.D., Ph.D., NIMH Clinical Brain Disorders Branch

Individual genetic variation likely affects the expression of genes. For example, across all ages and ethnicities studied, expression of a gene called ZSWIM7 stays low, medium or high in the prefrontal cortex, depending on which of three versions (A/A, A/G, G/G) is inherited. The versions are created by a tiny variation in the letters of the genetic code (DNA) at a location in the gene called rs1045599.
Source: Joel Kleinman, M.D., Ph.D., NIMH Clinical Brain Disorders Branch

Overall gene expression plummets 5-fold in infancy and 90-fold in childhood from its prenatal peak. The decline levels-off during the middle years, but expression surges again in the last decades of life, as the brain ages. Note: The fetal/infant graph at left is based on a different scale than the lifespan graph at right, so the two are not visually comparable.
Source: Joel Kleinman, M.D., Ph.D., NIMH Clinical Brain Disorders Branch

Males show more sex-biased gene expression. More genes differentially expressed (DEX) between the sexes were found in males than females, especially prenatally. Some genes found to have such sex-biased expression had previously been associated with disorders that affect males more than females, such as schizophrenia, Williams syndrome, and autism. Eleven of the brain areas shown are in the neocortex (NCX), or outer mantle.
Source: Nenad Sestan, M.D., Ph.D., Yale University Department of Neurobiology and Kavli Institute for Neuroscience

Profiling developmental processes. The expression data can be used to create trajectories for the expression of genes involved in particular processes, such as the development of synapses (structures that underlie communication between neurons). These expression trajectories can be compared for different regions, such as the NCX and cerebellar cortex (CBC).
Source: Nenad Sestan, M.D., Ph.D., Yale University Department of Neurobiology and Kavli Institute for Neuroscience

References

Colantuoni c, Lipska BK, Ye T, Hyde TM, Tao R, Leek JT, Colantuoni EA, Elkahloun AG, Herman MM, Weinberger DR, Kleinman JE. Temporal Dynamics and Genetic Control of Transcription in the human prefrontal cortex. Nature 2011. Oct 27

Kang HJ, Kawasawa1YI, Cheng F, Zhu Y, Xu X, Li M, Sousa1 AMM, Pletikos M, Meyer KA, Sedmak G, Guennel G, Shin Y, Johnson MB, Krsnik Z, Fertuzinhos MS, Umlauf S, Lisgo SN, Vortmeyer A, Weinberger DR, Mane S, Hyde TM, Huttner A, Reimers M, Kleinman JE, Šestan N. Spatiotemporal transcriptome of the human brain. Nature 2011. Oct 27.

***

The mission of the NIMH is to transform the understanding and treatment of mental illnesses through basic and clinical research, paving the way for prevention, recovery and cure. For more information, visit the NIMH website.

The National Institute on Drug Abuse is a component of the National Institutes of Health, U.S. Department of Health and Human Services. NIDA supports most of the world's research on the health aspects of drug abuse and addiction. The Institute carries out a large variety of programs to inform policy and improve practice. Fact sheets on the health effects of drugs of abuse and information on NIDA research and other activities can be found on the NIDA home page at www.drugabuse.gov. To order publications in English or Spanish, call NIDA's new DrugPubs research dissemination center at 1-877-NIDA-NIH or 240-645-0228 (TDD) or fax or email requests to 240-645-0227 or drugpubs@nida.nih.gov. Online ordering is available at http://drugpubs.drugabuse.gov. NIDA's new media guide can be found at http://drugabuse.gov/mediaguide/.

NINDS is the nation's leading funder of research on the brain and nervous system. The NINDS mission is to reduce the burden of neurological disease — a burden borne by every age group, by every segment of society, by people all over the world.

About the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): The NICHD sponsors research on development, before and after birth; maternal, child, and family health; reproductive biology and population issues; and medical rehabilitation. For more information, visit the Institute’s Web site at http://www.nichd.nih.gov/.

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit the NIH website.

The activities described in this release are funded in part through the American Recovery and Reinvestment Act. More information about NIH's Recovery Act grant funding opportunities can be found at http://grants.nih.gov/recovery/. To track the progress of HHS activities funded through the Recovery Act, visit www.hhs.gov/recovery. To track all federal funds provided through the Recovery Act, visit www.recovery.gov.

Perinatal antidepressant stunts brain development in rats

2011-10-25T23:17:00.000-07:00

Miswired brain circuitry traced to early exposure – NIH-funded study

Rats exposed to an antidepressant just before and after birth showed substantial brain abnormalities and behaviors, in a study funded by the National Institutes of Health.

After receiving citalopram, a serotonin-selective reuptake inhibitor (SSRI), during this critical period, long-distance connections between the two hemispheres of the brain showed stunted growth and degeneration. The animals also became excessively fearful when faced with new situations and failed to play normally with peers – behaviors reminiscent of novelty avoidance and social impairments seen in autism. The abnormalities were more pronounced in male than female rats, just as autism affects 3-4 times more boys than girls.

“Our findings underscore the importance of balanced serotonin levels – not too high or low -- for proper brain maturation,” explained Rick Lin, Ph.D., of the University of Mississippi Medical Center, Jackson, a Eureka Award grantee of the NIH’s National Institute of Mental Health.

Lin and colleagues report on their discovery online during the week of Oct. 24, 2011, in the Proceedings of the National Academy of Sciences.

Last July, a study reported an association between mothers taking antidepressants and increased autism risk in their children. It found that children of mothers who took SSRI’s during the year prior to giving birth ran twice the normal risk of developing autism – with treatment during the first trimester of pregnancy showing the strongest effect. A study published last month linked the duration of a pregnant mother’s exposure to SSRIs to modest lags in coordination of movement – but within the normal range – in their newborns counselor ceus

“While one must always be cautious extrapolating from medication effects in rats to medication effects in people, these new results suggest an opportunity to study the mechanisms by which antidepressants influence brain and behavioral development,” said NIMH Director Thomas R. Insel, M.D. “These studies will help to balance the mental health needs of pregnant mothers with possible increased risk to their offspring.”

Earlier studies had hinted that serotonin plays an important role in shaping the still-forming brain in the days just after a rat is born, which corresponds to the end of the third trimester of fetal development in humans. Experimental manipulations of the chemical messenger during this period interfered with formation of sensory-processing regions of the cortex, or outer mantle, and triggered aggressive and anxiety-related behaviors in rodents.

There is also recent evidence in humans that serotonin from the placenta helps shape development of the fetal brain early in pregnancy. Disrupted serotonin has been linked to mood and anxiety disorders. SSRIs, the mainstay medication treatment for these disorders, boost serotonin activity.

Lin and colleagues gave citalopram to male and female rat pups prenatally and postnatally and examined their brains and behavior as they grew up. Male, but not female, SSRI exposed rat pups abnormally froze when they heard an unfamiliar tone and balked at exploring their environment in the presence of unfamiliar objects or scents. These behaviors persisted into adulthood. The male pups especially also shunned normal juvenile play behavior – mimicking traits often seen in children with autism.

A key brain serotonin circuit, the raphe system, known to shape the developing brain during the critical period when the animals were exposed to the drug, showed dramatic reductions in density of neuronal fibers. Evidence of stunted development in the circuit coursed through much of the cortex and other regions important for thinking and emotion, such as the hippocampus.

The researchers also discovered miswiring in the structure responsible for communications between the brain’s left and right hemispheres, called the corpus collosum. Extensions of neurons, called axons, through which such long-distance communications are conducted, were deformed. A protective sheath, called myelin, that normally wraps and boosts axons’ efficiency-- like insulation on an electrical wire – was reduced by one-third in the treated animals. This damage was three times worse in male than in female pups and would likely result in abnormal communication between the two hemispheres, say the researchers.

Moreover, the perinatally exposed animals showed evidence of neurons firing out of sync and other electrophysiological abnormalities, suggesting faulty organization of neuronal networks in the cortex.

The research also was supported by the NIH’s National Center for Research Resources, National Institute of Neurological Disorders and Stroke and National Institute of Child Health and Human Development.

Cross-sections of the part of the rat brain that connects the left and right hemisphere (corpus collosum) show stunted development of neuronal wiring, called axons, in an animal that received an antidepressant (right) during a critical period around the time of birth. A protective sheath, called myelin (visible in normal animal at left), that normally wraps the axons and boosts their efficiency, failed to develop normally in the treated animal. The resultant inefficient neuronal communications could underlie the pattern of deficits seen in autism.
Source: Rick C.S. Lin, Ph.D., University of Mississippi Medical Center

Reference

Perinatal antidepressant exposure alters cortical network function in rodents. Simpson KL, Weaver KJ, de Villers-Sidani E, Lu JY-F, Cai Z, Pang Y, Rodriguez-Porcel F, Paul IA, Merzenich M, Lin RCS. 2011, Oct. 24, PNAS.

***

The mission of the NIMH is to transform the understanding and treatment of mental illnesses through basic and clinical research, paving the way for prevention, recovery and cure. For more information, visit the NIMH website.

The National Center for Research Resources (NCRR), a part of NIH, provides laboratory scientists and clinical researchers with the resources and training they need to understand, detect, treat and prevent a wide range of diseases. NCRR supports all aspects of translational and clinical research, connecting researchers, patients and communities across the nation. For more information, visit www.ncrr.nih.gov. NINDS is the nation's leading funder of research on the brain and nervous system. The NINDS mission is to reduce the burden of neurological disease — a burden borne by every age group, by every segment of society, by people all over the world.

About the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): The NICHD sponsors research on development, before and after birth; maternal, child, and family health; reproductive biology and population issues; and medical rehabilitation. For more information, visit the Institute’s Web site at http://www.nichd.nih.gov/.

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit the NIH website.

White House Names NIMH a “Champion of Change” for its Suicide Prevention Efforts

2011-10-22T10:08:00.000-07:00

Source: White House

The National Institute of Mental Health (NIMH) was named by the White House as a “Champion of Change” on August 25, 2011, for its efforts in supporting research on suicide prevention. Jane Pearson, Ph.D., and Kevin Quinn, Ph.D., of NIMH accepted the award at a ceremony and roundtable event at the White House, where they joined White House policy officials and others for a discussion of suicide prevention best practices. In addition to NIMH, the Suicide Prevention Resource Center (SPRC); Suicide Prevention Action Network; SAVE Foundation; the American Foundation for Suicide Prevention; National Suicide Prevention Lifeline; Blue Star Families; the Gay, Lesbian, and Straight Education Network (GLSEN); the Creative Coalition; and the Trevor Project, all of whom are dedicated to preventing suicide, were honored.

The White House Champions of Change initiative celebrates individuals and organizations from all walks of life who are making an impact in communities and helping the country rise to the challenges of the 21st century.

The roundtable discussion was moderated by Pamela J. Hyde, Administrator of the Substance Abuse and Mental Health Services Administration (SAMHSA); Andrea Palm, Senior Advisor for Health at the White House Domestic Policy Council; and Deborah Temkin, Research and Policy Coordinator for Bullying Prevention Initiatives at the Department of Education. The discussion focused on numerous issues important to suicide prevention including:
Media influences: how the media—including social media—has encouraged people to show their support of individuals in crisis ceus for counselors

Best practices: how the SPRC, which acts as a clearinghouse of evidence-based information related to suicide prevention, helps spread the word. The National Suicide Prevention Lifeline also continues to improve counseling services by using best practices.
Working Together: how each organization learns from the others. For instance, NIMH funds research associated with the National Suicide Prevention Lifeline, including research on the training of crisis counselors in an effort to improve counselors’ assessment and referral skills.
Prioritizing Next Steps: including identifying technological opportunities to help reduce suicide,(e.g., developing and testing phone apps for helping someone in crisis).
Early intervention: all agreed that for children, early intervention programs aimed at decreasing aggression and improving problem-solving skills are vital to ensuring children do not become bullies or reach a suicidal crisis.

NIMH is deeply honored to be identified as a Champion of Change. If you or someone you know is in crisis or considering suicide, call the National Suicide Prevention Lifeline at 1-800-273-TALK (8255), a free, 24-hour hotline that seamlessly connects anyone in suicidal crisis or emotional distress with their nearest crisis center.

National Survey Dispels Notion that Social Phobia is the Same as Shyness

2011-10-18T09:53:00.000-07:00

Source: NIMH

Normal human shyness is not being confused with the psychiatric anxiety disorder known as social phobia, according to an NIMH survey comparing the prevalence rates of the two among U.S. youth. The study was published online ahead of print October 17, 2011, in the journal Pediatrics.

Background

Social phobia is a disabling anxiety disorder characterized by overwhelming anxiety and excessive self-consciousness in everyday social or performance situations. Critics of the diagnosis have suggested that psychiatrists and pharmaceutical companies publicize social phobia, also known as social anxiety disorder, in order to increase sales of psychotropic medications, especially among youth. In addition, some have debated whether social phobia is just a “medicalization” of a normal variation in human temperament.

In response, Marcy Burstein, Ph.D., and colleagues at NIMH examined the rate of normal shyness among youth and its overlap with social phobia using data from the National Comorbidity Survey-Adolescent Supplement (NCS-A), a nationally representative, face-to-face survey of more than 10,000 teens aged 13-18 sponsored by NIMH. Social phobia was assessed using standard diagnostic criteria set by the American Psychiatric Association's Diagnostic and Statistical Manual (DSM-IV). To assess shyness, teens were asked to rate how shy they felt around peers that they did not know well.

Results of the Study

The authors found that while about half of youth identified themselves as shy, only 12 percent of shy youth also met criteria for social phobia in their lifetime. Moreover, among youth who did not identify themselves as shy, about 5 percent met criteria for social phobia, suggesting that social phobia and shyness are not necessarily directly related. Rather, the presence of social phobia may be independent of shyness in some instances.

In addition, those with social phobia were consistently more likely to also have another psychiatric disorder in their lifetime, like depression or a behavior or drug use disorder, compared to those who identified themselves as shy. Those with social phobia also showed higher levels of impairment in work or school, or among family or peers, though they were no more likely to be receiving professional treatment than those who were shy.

Finally, rates of prescribed medication use were low for all groups. Only about 2.3 percent of those with social phobia were taking the antidepressant paroxetine (commonly used to treat anxiety disorders), while 0.9 percent who described themselves as shy were taking it. In addition, those with social phobia were no more likely to be taking any prescribed psychiatric medication compared to the other groups.

Significance

The results suggest that social phobia is not simply shyness that has been inappropriately medicalized. Rather, social phobia affects a minority of youth and only a fraction of those who consider themselves to be shy. In addition, despite the greater disability that youth with social phobia experience and the greater likelihood that they will have another disorder, they are not more likely to be getting treatment compared to their peers, questioning the notion that these youth are being unnecessarily medicated continuing education for counselors

Citation

Burstein M, Ameli-Grillon L, Merikangas M. Shyness versus social phobia in U.S. youth. Pediatrics. Online ahead of print Oct 17, 2011.

Adding Psychotherapy to Medication Treatment Improves Outcomes in Pediatric OCD

2011-10-11T09:08:00.000-07:00

Source: NIMH

Youth with obsessive compulsive disorder (OCD) who are already taking antidepressant medication benefit by adding a type of psychotherapy called cognitive behavior therapy (CBT), according to an NIMH-funded study published September 21, 2011, in the Journal of the American Medical Association social worker continuing education

Background

Several studies have shown that, among adults with OCD, a form of CBT involving controlled exposure to feared situations plus training that helps the person refrain from compulsions is effective both alone and in combination with antidepressant medication. However, few studies of this type of combination therapy have been conducted among children. In addition, many children with OCD tend to respond only partially to antidepressant medication. Studies have found that among adults who only partially respond to antidepressant medication, adding CBT can be effective. However, until now, there have been no studies testing this same approach in youth.

Martin Franklin Ph.D., of the University of Pennsylvania, Jennifer Freeman Ph.D., of Brown University, John March M.D.,MPH, of Duke University, and colleagues set out to determine whether CBT can effectively augment antidepressant treatment in children who partially respond to the medication. Among 124 children ages 7-17, they compared three treatment options:
Medication management only (MM), prescribed and managed by a physician. All patients were taking a type of antidepressant known as a selective serotonin reuptake inhibitor (SSRI).
MM plus Instructional CBT (I-CBT), a shorter, less intensive version of CBT administered by the prescribing physician.
MM plus CBT provided by a trained CBT therapist. The CBT included a type of therapy called exposure plus response prevention (ERP), in which children are exposed to feared situations and taught how to respond to the resulting anxiety without engaging in compulsions.

Results

After 12 weeks of treatment, nearly 69 percent of those receiving MM+CBT had responded to treatment, compared to 34 percent receiving MM+I-CBT and 30 percent receiving MM. Those receiving MM+CBT showed more improvement in all respects, compared to those receiving MM and MM+I-CBT.

Significance

The findings are consistent with other studies demonstrating that ERP is an effective treatment strategy for OCD, both alone and in combination with SSRIs. The researchers conclude that the full version of CBT with ERP should be widely disseminated as opposed to a brief version that may not be effective.

What’s next

The researchers were unsure why there was so little difference in treatment response between the MM group and the MM+I-CBT group. They reasoned that the I-CBT was generally ineffective because it was brief and less intensive than the CBT. It also did not include key treatment components that are central to the full CBT protocol, such as exposure practices during the treatment sessions themselves. Future efforts should focus on making the full CBT with ERP more widely available in community settings, they concluded.

Citation

Franklin ME, Sapyta J, Freeman JB, Khanna M, Compton S, Almirall D, Moore P, Choate-Summers M, Garcia A, Edson AL, Foa EB, March JS. Cognitive behavior therapy augmentation of pharmacotherapy in pediatric obsessive compulsive disorder: the Pediatric OCD Treatment Study (POTS II) randomized controlled trial. Journal of the American Medical Association. 21 Sept 2011

Brain Chemical Linked to Joylessness Provides Insight Into Teen Depression

2011-10-06T22:23:00.000-07:00

Depressed teens with anhedonia, or the inability to experience pleasure, have lower levels of the neurotransmitter GABA in a key mood-regulating region of the brain, according to an NIMH-funded study published online October 3, in the Archives of General Psychiatry. The researchers note that focusing on specific symptoms and using different types of measures may offer new clues to the pathways and processes underlying depression and other mental disorders continuing education for social workers

Background

Symptoms of depression in teens can be highly varied and tend to overlap with signs of other disorders. Because of this, adolescent depression can be hard to study using conventional research tools and methods.

Guided by findings in adults, Vilma Gabbay, M.D., of New York University School of Medicine, and colleagues decided to focus on the neurotransmitter GABA. GABA has many important roles throughout the body and is involved in regulating communication between brain cells. Abnormalities in GABA production or function in the brain have been linked to several mental disorders, including schizophrenia and postpartum depression, and possibly learning disorders. GABA has also been linked to anhedonia, a symptom present in up to 59 percent of depressed teens.

The researchers used a type of specialized MRI to measure GABA levels in the brain region known as the anterior cingulate cortex (ACC) in 20 teens with depression, half of whom also had anhedonia. They were compared to 21 matched controls who did not have depression or anhedonia. Levels of anhedonia were scored numerically according to clinician- and self-rated assessments.

Results of the Study

Compared to controls, teens with depression and anhedonia had significantly lower ACC GABA levels. Lower ACC GABA levels were associated with more severe anhedonia symptoms among all participants.

Significance

The findings support a role for GABA in anhedonia and depression among teens. Also, by correlating GABA levels with numeric measures of anhedonia severity, the researchers were able to assess participants’ symptoms along a continuum. Compared to traditional measures that categorize symptoms only as being either present or absent, such continuous or “dimensional” measurements may provide greater specificity to disease evaluations in research.

What’s Next

Additional studies in larger populations are needed to confirm these findings. Advances in imaging techniques and technology may help to identify differing roles for other neurotransmitters associated with depression.

Reference

Gabbay V, Mao X, Klein RG, Ely BA, Babb JS, Panzer AM, Alonso CM, Shungu DC. Anterior Cingulate Cortex {gamma}-Aminobutyric Acid in Depressed Adolescents: Relationship to Anhedonia. Arch Gen Psychiatry. 2011 Oct 3. [Epub ahead of print] PubMed PMID: 21969419.

Prescribed stimulant use for ADHD continues to rise steadily

2011-09-28T09:55:00.000-07:00

NIH and AHRQ study finds pace of the rise has slowed in recent years

Source: NIMH

The prescribed use of stimulant medications to treat attention deficit hyperactivity disorder (ADHD) rose slowly but steadily from 1996 to 2008, according to a study conducted by the National Institutes of Health (NIH) and the Agency for Healthcare Research and Quality (AHRQ). The study was published online ahead of print September 28, 2011, in the American Journal of Psychiatry continuing education for Social Workers

ADHD is one of the most common childhood disorders, and can continue through adolescence and adulthood. Symptoms include difficulty staying focused and paying attention, difficulty controlling behavior, and hyperactivity (over-activity). The condition is frequently treated with stimulants such as methylphenidate (e.g., Ritalin), amphetamines (e.g., Adderall) or other types of medications. Behavioral therapies can also be effective.

During the 1990s, stimulant prescription use increased significantly, going from a prevalence rate among youth of 0.6 percent in 1987 to 2.7 percent in 1997, with the rate stabilizing around 2.9 percent in 2002. Recent reports, however, suggest that the prescribed use of these medications and the diagnosis of ADHD have continued to rise. Based on the Health Resources and Services Administration's National Survey of Children's Health, the percentage of children age 4-17 years diagnosed with ADHD increased from 7.8 percent in 2003 to 9.5 percent in 2007.

"Stimulant medications work well to control ADHD symptoms, but they are only one method of treatment for the condition. Experts estimate that about 60 percent of children with ADHD are treated with medication," said co-author Benedetto Vitiello, M.D., of NIH's National Institute of Mental Health (NIMH).

For this most recent survey, Dr. Vitiello and Samuel Zuvekas Ph.D., of AHRQ examined data from the AHRQ-sponsored Medical Expenditure Panel Survey, a nationally representative annual survey of U.S. households, to determine prescribed stimulant use among children under age 19 from 1996-2008. They found a slow but steady increase — from 2.4 percent in 1996 to 3.5 percent in 2008.The rate grew an average of 3.4 percent each year, which is substantially less than the growth rate between 1987 and 1996, which averaged about 17 percent per year.

Overall, prescription use among 6-12-year-olds was highest, going from 4.2 percent in 1996 to 5.1 percent in 2008. But the fastest growth of prescribed use occurred among 13-18-year-olds, going from 2.3 percent in 1996 to 4.9 percent in 2008. "This continuous increase among teens likely reflects a recent realization that ADHD often persists as children age. They do not always grow out of their symptoms," said Dr. Vitiello.

Prescription use among preschoolers remained very low at 0.1 percent from 2004 onward and decreased between 2002 and 2008, suggesting that stimulant use among very young children continues to be disfavored. Boys continued to be three times more likely to be prescribed a stimulant than girls, and use among white children continued to be higher than among black or Hispanic children (4.4 percent in 2008 among whites, compared to 2.9 percent in blacks and 2.1 percent in Hispanics). However, prescribed stimulant use is increasing among racial and ethnic minorities, likely suggesting more recognition of ADHD and acceptance of psychopharmacological treatment among these groups, according to the authors.

In addition, rates were substantially lower in Western states compared to other regions of the nation, with no increase in recent years, a finding consistent with other studies. In comparison, rates in the Northeast increased from 2.7 percent in 2002 to 4.6 percent in 2008.

"These persistent differences in prescribed stimulant use related to age, racial and ethnic background, and geographical location indicate substantial variability in how families and doctors approach ADHD treatment throughout the United States," said Dr. Zuvekas.

The researchers concluded that when comparing the rates of prescribed use with the estimated prevalence of ADHD diagnosis, it appears that many children with ADHD are not treated with stimulants. "The children with the most severe symptoms are more likely to be taking stimulants. Those with milder symptoms are more likely being treated with psychosocial treatments or other non-stimulant medications," they said.

Reference

Zuvekas S and Vitiello B. Stimulant medication use in children: a 12-year perspective. American Journal of Psychiatry. Online ahead of print September 28, 2011.

##

The Agency for Healthcare Research and Quality (http://www.ahrq.gov) is part of the U.S. Department of Health and Human Services. AHRQ's mission is to improve the quality, safety, efficiency and effectiveness of health care for all Americans. AHRQ's research helps people make more informed decisions and improve the quality of health care services.

The mission of the NIMH is to transform the understanding and treatment of mental illnesses through basic and clinical research, paving the way for prevention, recovery and cure. For more information, visit the NIMH website.

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit the NIH website.

Adding Psychotherapy to Medication Treatment Improves Outcomes in Pediatric OCD

2011-09-24T09:35:00.000-07:00

Source: NIMH

Youth with obsessive compulsive disorder (OCD) who are already taking antidepressant medication benefit by adding a type of psychotherapy called cognitive behavior therapy (CBT), according to an NIMH-funded study published September 21, 2011, in the Journal of the American Medical Association LCSW Continuing Education

Background

Several studies have shown that, among adults with OCD, a form of CBT involving controlled exposure to feared situations plus training that helps the person refrain from compulsions is effective both alone and in combination with antidepressant medication. However, few studies of this type of combination therapy have been conducted among children. In addition, many children with OCD tend to respond only partially to antidepressant medication. Studies have found that among adults who only partially respond to antidepressant medication, adding CBT can be effective. However, until now, there have been no studies testing this same approach in youth.

Martin Franklin Ph.D., of the University of Pennsylvania, Jennifer Freeman Ph.D., of Brown University, John March M.D.,MPH, of Duke University, and colleagues set out to determine whether CBT can effectively augment antidepressant treatment in children who partially respond to the medication. Among 124 children ages 7-17, they compared three treatment options:
Medication management only (MM), prescribed and managed by a physician. All patients were taking a type of antidepressant known as a selective serotonin reuptake inhibitor (SSRI).
MM plus Instructional CBT (I-CBT), a shorter, less intensive version of CBT administered by the prescribing physician.
MM plus CBT provided by a trained CBT therapist. The CBT included a type of therapy called exposure plus response prevention (ERP), in which children are exposed to feared situations and taught how to respond to the resulting anxiety without engaging in compulsions.

Results

After 12 weeks of treatment, nearly 69 percent of those receiving MM+CBT had responded to treatment, compared to 34 percent receiving MM+I-CBT and 30 percent receiving MM. Those receiving MM+CBT showed more improvement in all respects, compared to those receiving MM and MM+I-CBT.

Significance

The findings are consistent with other studies demonstrating that ERP is an effective treatment strategy for OCD, both alone and in combination with SSRIs. The researchers conclude that the full version of CBT with ERP should be widely disseminated as opposed to a brief version that may not be effective.

What’s next

The researchers were unsure why there was so little difference in treatment response between the MM group and the MM+I-CBT group. They reasoned that the I-CBT was generally ineffective because it was brief and less intensive than the CBT. It also did not include key treatment components that are central to the full CBT protocol, such as exposure practices during the treatment sessions themselves. Future efforts should focus on making the full CBT with ERP more widely available in community settings, they concluded.

Citation

Franklin ME, Sapyta J, Freeman JB, Khanna M, Compton S, Almirall D, Moore P, Choate-Summers M, Garcia A, Edson AL, Foa EB, March JS. Cognitive behavior therapy augmentation of pharmacotherapy in pediatric obsessive compulsive disorder: the Pediatric OCD Treatment Study (POTS II) randomized controlled trial. Journal of the American Medical Association. 21 Sept 2011.

Survey Assesses Trends in Psychiatric Hospitalization Rates

2011-09-20T15:31:00.000-07:00

Source: NIMH

Short-term inpatient psychiatric stays increased for youth but declined for older adults between 1996 and 2007, according to an analysis published online ahead of print August 1, 2011, in the Archives of General Psychiatry.

Background

Joseph C. Blader Ph.D., of Stony Brook University, evaluated data from 1996-2007 from the National Hospital Discharge Survey, an annual survey conducted by the National Center for Health Statistics. He aimed to determine the rates of short-term hospitalizations and length of stays among children, adolescents, adults, and older adults due to psychiatric diagnosis. This time period roughly corresponds to the decline in use of long-term inpatient services for psychiatric illnesses, decrease in number of psychiatric beds made available, and stricter criteria for insurance authorization of hospital admission. Social worker continuing education

Results of the Study

The data showed that hospitalization rates increased the most for children ages 5-12, going from 155 per 100,000 children in 1996 to 283 per 100,000 children in 2007. Among teens, the rate increased from 683 to 969 per 100,000. Among adults, the rate increased from 921 to 995 per 100,000. By contrast, the rate declined among the elderly, going from 977 to 807 per 100,000.

Hospital stays were consistently shorter among children and teens, especially those with private insurance. The proportion of inpatient days paid by private insurers declined among children (going from 36 percent to 21 percent), adolescents (going from 52 percent to 22 percent) and adults (going from 35 percent to 23 percent.)

Significance

The trends likely reflect an increase in clinical need rather than an overuse of hospital resources, especially when taking into account the decline in number of psychiatric beds available, according to Blader. Admission information and diagnostic trends over the same time period indicate that the impairments and problems of hospitalized patients appear to have grown more acute. He also notes that the trend corresponds with an increase in bipolar diagnosis, especially among youth. Blader suggests that as long-term care facilities decreased their capacity, short-term facilities may have had to compensate for the shortage. Surveys among state mental health officials during the same time period indicate they were worried about a shortage of beds for acute care as well.

What’s Next

More research is needed to determine how these trends are affecting quality of care and insurance issues and reimbursement.

Citation

Blader JC. Acute inpatient care for psychiatric disorders in the United States, 1996 through 2007. Archives of General Psychiatry. Online ahead of print Aug 1, 2011.

Thinking Globally to Improve Mental Health

2011-09-19T11:51:00.000-07:00

Source: NASA Jet Propulsion Laboratory (NASA-JPL)

Mental health experts are calling for a greater world focus on improving access to care and treatment for mental, neurological, and substance use (MNS) disorders, as well as increasing discoveries in research that will enable this goal to be met LPC Continuing Education

The Grand Challenges in Global Mental Health Initiative, led by the National Institutes of Health and the Global Alliance for Chronic Diseases, has identified the top 40 barriers to better mental health around the world. Similar to past grand challenges, which focused on infectious diseases and chronic, noncommunicable diseases, this initiative seeks to build a community of funders dedicated to supporting research that will significantly improve the lives of people living with MNS disorders within the next 10 years.

Twenty-five of the specific challenges and the process used to derive them are described in an article that will be published on July 7, 2011, in the journal Nature.

"Participating in global mental health research is an enormous opportunity, a means to accelerate advances in mental health care for the diverse U.S. population, as well as an extension of our vision of a world where mental illnesses are prevented and cured," said Thomas R. Insel, M.D., director of the National Institute of Mental Health (NIMH), the NIH institute heading this effort.

According to the paper's authors, the disorders targeted by the Grand Challenges in Global Mental Health—for example, schizophrenia, depression, epilepsy, dementia, and alcohol dependence—collectively account for more years of life lost to poor health, disability, or early death than either cardiovascular disease or cancer. Yet, compared to illnesses like cardiovascular disease and cancer, there are far fewer effective treatments or preventive methods. In addition, interventions are not widely available to those who need them most.

In recognizing the need to address this imbalance, Pamela Collins, M.D., M.P.H., of the NIMH Office for Research on Disparities and Global Mental Health, and colleagues assembled an international panel of experts to identify research priorities using the Delphi method, a widely accepted consensus-building tool. The panel consisted of 422 experts in fields such as neuroscience, basic behavioral science, mental health services, and epidemiology, and represented more than 60 countries.

Over the course of two months, NIMH staff pared the panel's initial list of 1,565 challenges down to 154, with input from a scientific advisory board. From this list, the expert panel selected the top 40, of which the top five challenges identified after the third and final round of ranking are:
Integrate screening and core packages of services into routine primary health care
Reduce the cost and improve the supply of effective medications
Improve children's access to evidence-based care by trained health providers in low- and middle-income countries
Provide effective and affordable community-based care and rehabilitation
Strengthen the mental health component in the training of all health care personnel.

These top five challenges were ranked according to the ability to reduce the burden of disease, ability to reduce inequalities in health and health care, length of time until results can be observed, and the ability for the topic to be researched effectively.

"Addressing these challenges could have far-reaching effects, including increasing access to services and ultimately, reducing the treatment gap associated with these disorders," said Dr. Collins.

The Grand Challenges in Global Mental Health Initiative is led by NIMH and the Global Alliance for Chronic Diseases, in partnership with the Wellcome Trust, the McLaughlin-Rotman Centre for Global Health, and the London School of Hygiene and Tropical Medicine. Other NIH components participating in the Grand Challenges in Global Mental Health include the Fogarty International Center; the National Heart, Lung, and Blood Institute; and the National Institute of Neurological Disorders and Stroke.

Reference

Collins PY, Patel V, Joestl SS, March D, Insel TR, Daar A, on behalf of the Grand Challenges in Global Mental Health Scientific Advisory Board and Executive Committee. Grand Challenges in Global Mental Health. Nature. 2011 July 7. 474(7354):pp.

###

The mission of the NIMH is to transform the understanding and treatment of mental illnesses through basic and clinical research, paving the way for prevention, recovery and cure. For more information, visit the NIMH website.

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit the NIH website.

Continued Use of Stimulants for ADHD Likely Does Not Increase Risk for Hypertension, but May Affect Heart Rate

2011-09-12T17:23:00.000-07:00

Source: NIMH

Chronic use of stimulant medication to treat attention deficit hyperactivity disorder (ADHD) in children does not appear to increase risk for high blood pressure over the long term, but it may have modest effects on heart rate, according to follow-up data from the NIMH-funded Multimodal Treatment Study of Children with ADHD (MTA). The study was published online ahead of print Sept 2, 2011, in the American Journal of Psychiatry continuing education for counselors

Background

The MTA was the first major multi-site trial comparing different treatments for ADHD in childhood. The initial results of the 14-month study, in which 579 children were randomly assigned to one of three intensive treatment groups (medication management alone, behavioral treatment alone, a combination of both) or to routine community care, were published in 1999. The researchers found that medication management alone or in combination with behavioral therapy produced better symptomatic relief for children with ADHD than just behavioral therapy or usual community care.

After the study ended, participants returned to community treatment and were free to pursue whatever treatment course they wished. MTA researchers gathered follow-up data from MTA study participants at 2, 3, 6, 8, and 10 years after study entry.

ADHD is often a chronic condition that continues into adolescence, so some children take stimulants for years. Because stimulants can affect the heart, doctors are concerned about the possible risks for rapid heart rate, hypertension (high blood pressure) or other cardiovascular effects after many years of use. But studies have been inconsistent about whether the effects are long-lasting.

For this most recent data analysis, Benedetto Vitiello, M.D., of NIMH, and MTA colleagues examined the MTA follow-up data to determine if there was an association between chronic use of stimulant medication and changes in blood pressure or heart rate over a 10-year period.

Results of the Study

At the end of the 14-month study, children who were randomized to stimulant treatment in the study had, on average, higher heart rates compared to the children who were randomized to non-medication or community care. Heart rates for the children who continued to take stimulants after the end of the study were slightly elevated at subsequent checks, but they did not have an abnormally elevated heart rate (e.g., tachycardia).

The researchers concluded that stimulant medication did not appear to increase the risk for abnormal elevations in blood pressure or heart rate over a 10-year period. However, because some epidemiological studies have indicated that even modest elevations in heart rate may increase a person’s lifetime risk for cardiovascular problems, the persistent effect of continuous stimulant treatment on heart rate should not be dismissed.

Significance

The results of this study indicate that the effect of stimulants on heart rate can be detected even after years of use, suggesting that the body does not get completely used to it. However, after 10 years of treatment, researchers found no increased risk for hypertension. In addition, none of the children reported any adverse cardiovascular events over the 10-year period.

The researchers do note that the effect on heart rate may be clinically significant for individuals who have underlying heart conditions. Therefore, children taking stimulants over the long-term should be monitored regularly for potential cardiovascular complications.

Citation

Vitiello B, Elliott GR, Swanson JM, Arnold E, Hechtman L, Abikoff H, Molina BSG, Wells K, Wigal T, Jensen PS, Greenhill LL, Kaltman JR, Severe JB, Odbert C, Hur K, Gibbons R. Blood pressure and heart rate in the multimodal treatment of attention deficit/hyperactivity disorder study over 10 years. American Journal of Psychiatry. Online ahead of print Sept 2, 2011.

Autism Risk in Younger Siblings May be Higher Than Previously Thought

2011-09-06T12:28:00.000-07:00

Autism Risk in Younger Siblings May be Higher Than Previously Thought

Parents of a child with autism spectrum disorder (ASD) face about a 19 percent chance that subsequent children will also develop ASD, according to a study partially funded by NIMH. This estimate is much higher than previous reports but may also be more accurate due to the study's size and design, according to the researchers. Their study was published August 15, 2011, online ahead of print in the journal Pediatrics ceus for social workers

Background

A few previous studies have explored the recurrence rate of ASD, or the likelihood of later-born siblings of children with ASD to also develop ASD. However, few studies addressed factors likely to influence risk estimates, such as:
Stoppage—the tendency for families to choose not to have more children after one child is diagnosed with ASD. Such families would not be included in research on ASD recurrence.
Overreporting—an error that can occur when researchers rely solely on parent reports or health records, which have been shown to inflate estimates.
Ascertainment bias—an example is overselection, which can occur when parents with one child who has ASD pay very close attention to a later child's development. They may be more likely to take part in ASD recurrence studies than other parents.

Taking a different approach, Sally Ozonoff, Ph.D., of the University of California-Davis, and colleagues evaluated data on 664 infants who were tested at 12 sites across the United States and Canada. All sites were members of the Baby Siblings Research Consortium (BSRC), an international network supported by the U.S. advocacy group Autism Speaks. All BSRC members contribute data to a centralized database that allows infant-sibling researchers to pool data across many sites and answer questions that require very large and geographically diverse samples to address.

The average age of the infant participants at the start of the study was 8 months, an age when signs of ASD are not usually present; two-thirds of the total study population were enrolled before age 6 months. All had at least one older sibling diagnosed with ASD, which was confirmed by a consortium doctor. The participants were themselves assessed for ASD multiple times in their first three years of life.

Results of the Study

Out of the total study sample, 18.7 percent of participants were diagnosed with ASD by age 3. Boys were nearly three times as likely as girls to be diagnosed with ASD. Participants who had more than one older sibling with ASD were about twice as likely to also be diagnosed with ASD, compared to participants who had only one older sibling with ASD.

Unlike some previous studies, the gender or IQ of the older sibling with ASD did not affect the later sibling's risk in the present study.

Significance

The findings indicate that ASD recurrence is 18 percent or higher, compared to 3-14 percent estimated in earlier studies. The researchers note that their study's size and design minimized the effects of stoppage, overreporting, and ascertainment bias.

Despite the strengths of their study, the researchers emphasize that recurrence estimates cannot provide information on an individual's risk. They highlight the need for careful and extensive counseling and thorough genetic work-ups for concerned parents, as well as close monitoring, especially of high-risk children, and prompt referrals for intervention by primary care providers.

What’s Next

According to the researchers, larger, population-based studies that include families of children with ASD who are not listed in the Baby Siblings Research Consortium may help to further refine recurrence estimates. Future studies will examine DNA collected from participants to examine genetic factors that may be associated with recurrence.

Reference

Ozonoff S, Young GS, Carter A, Messinger D, Yirmiya N, Zwaigenbaum L, Bryson S, Carver LJ, Constantino JN, Dobkins K, Hutman T, Iverson JM, Landa R, Rogers SJ, Sigman M, Stone WL. Recurrence Risk for Autism Spectrum Disorders: A Baby Siblings Research Consortium Study. Pediatrics. 2011 Aug 15. [Epub ahead of print] PubMed PMID: 21844053.

Biology, Not Just Society, May Increase Risk of Binge Eating During Puberty

2011-08-28T21:03:00.000-07:00

Source: Kelly Klump, Ph.D., Michigan State University

Biological changes associated with puberty may influence the development of binge eating and related eating disorders, according to a recent study on female rats conducted by NIMH-funded researchers. After puberty, the rats showed binge eating patterns that resemble those in humans, supporting the role of biological factors, since rats do not experience pressures to be thin or other psychosocial risk factors commonly associated with human eating disorders. The study was published online ahead of print on May 16, 2011, in the Journal of Abnormal Psychology.

Background
Among girls, symptoms of binge eating or bulimia nervosa often arise around puberty. Past research has largely focused on psychosocial roots for this association, but biological changes that occur during and after puberty are likely to have an effect as well.

Kelly Klump, Ph.D., of Michigan State University, and colleagues tested this theory in an animal model since animals do not experience psychological risk factors during puberty. They used a rat model that can distinguish between rats that are resistant to binge eating (BER) from those prone to binge eating (BEP), based on their individual eating habits.

For this study, the researchers studied binge eating risk from pre-puberty to adulthood in 66 female rats. In addition to their standard food, the rats were provided intermittent access to cake frosting, a highly enjoyable but nutritionally empty and high fat food.

Results
Over the course of development, all rats ate more frosting as they matured. However, a difference in frosting intake between BER and BEP rats emerged during puberty—no differences in frosting intake were observed in pre-puberty, but large differences were observed in puberty and adulthood (see Figure 1)

The researchers noted that rats in the BER and BEP groups ate similar amounts of the standard food and were similar in body weight. This suggests that the BEP rats were not overeaters generally, but were instead, prone to binge eat on high-fat foods only.

Significance
The findings reveal dramatic increases in binge eating proneness during puberty, suggesting that increases in binge eating and similar eating disorders during and after puberty in girls may be partially due to biological factors ceus for counselors

Similar to binge eating in humans, BEP rats ate much more of the high-fat food but did not increase their consumption of the standard food. Also, all rats preferred the high-fat food, regardless of developmental stage, which is similar to behaviors seen in girls; for example, girls tend to prefer candy over healthier treats at all ages. In both rats and humans, this behavior begins to diverge during puberty, with some consuming much more of the high-fat food than others.

Unlike humans, however, the percentage of binge eating rats (30 percent) was much higher than estimates in humans (3.5–19 percent). According to the researchers, this difference may indicate that binge eating in rats is a “pure” form of binge eating that is unmodified by psychosocial factors—such as social disapproval or guilt—that tends to decrease binge eating rates in humans.

What’s Next
More research is needed to develop and validate animal models of the cognitive and behavioral symptoms of eating disorders. Studies exploring the mechanisms underlying developmental changes that occur during puberty, for example the action of ovarian hormones, may also inform research on eating disorders.

Reference
Klump KL, Suisman JL, Culbert KM, Kashy DA, Sisk CL. Binge eating proneness emerges during puberty in female rats: A longitudinal study. J Abnorm Psychol. 2011 May 16. [Epub ahead of print] PubMed PMID: 21574664.

Source: Kelly Klump, Ph.D., Michigan State University

Adapted with permission from APA

For Minor Depression, Study Shows No Benefit Over Placebo from St. John’s Wort, Citalopram

2011-08-09T08:56:00.000-07:00

An extract of the herb St. John's Wort and a standard antidepressant medication both failed to outdo a placebo in relieving symptoms of minor depression in a clinical trial comparing the three. The results of this study, consistent with earlier research, do not support the use of medications for mild depression counselor ceus

Background
St. John's Wort is a plant whose yellow flowers have been the source of extracts used medicinally for centuries. It is widely used to treat depression, as a nutritional supplement in the United States, and as a prescription medication in Europe. Evidence from clinical trials of St. John's Wort has failed to show effectiveness for treatment of major depression; but research has raised the question as to whether the herb might offer benefit for people with less severe depression.

This Study
This study, focusing specifically on minor depression, was conducted by Mark Hyman Rapaport and colleagues at the Cedars-Sinai Medical Center and David Geffen School of Medicine in Los Angeles; the Massachusetts General Hospital, in Boston; and the University of Pittsburgh. Participants in the study had minor depression, defined as the presence of two to four symptoms used to diagnose major depression, with at least one symptom being depressed mood or anhedonia, a lack of pleasure in activities usually found enjoyable. Symptoms had to have been present for six months to two years. Subjects were randomly assigned to receive St. John's Wort, the antidepressant medication citalopram, or a placebo. Neither participants, nor the staff treating them, knew what treatment they took. Seventy-three subjects completed the trial.

Results from the trial showed that no treatment relieved depression more than any other; patients in all three of the treatment groups showed improvements in symptoms over the course of the study, and in measures of quality of life and psychological well-being.

Patients in all three treatment groups—including placebo—also frequently reported side effects. In addition, before treatment began in this study, more than half of participants responded positively when they were asked if they had any of a broad list of physical or psychological complaints. This finding suggests that it's important to assess both physical and psychological symptoms even before treatment begins; otherwise, many of these symptoms might be interpreted as medication-related.

Significance
While minor depression is by definition a milder condition than major depression, research suggests it has consequences for health and well-being that go beyond the symptoms themselves, including lost work days, social difficulties, and possibly a higher risk of developing future major depression.

The authors are careful to point out that the reason that there was no difference in benefit between St. John's Wort, citalopram, and placebo was not because the study was too small to detect a difference, but because participants taking placebo experienced substantial improvement in measures of depression and well-being—participation in the study had positive effects. In addition, participants taking all three treatments—even those on placebo—experienced side-effects. Fewer of the subjects taking St. John's Wort reported that side effects were distressing (40 vs. 60 percent); but St. John's Wort recipients reported more gastrointestinal and sleep problems than those receiving placebo.

Identifying effective and safe ways to treat minor depression remains an important goal; further research on non-pharmacologic treatment is needed to identify the optimal psychotherapies for minor depression.

This study was funded by the National Institute of Mental Health and the National Center for Complementary and Alternative Medicine, National Institutes of Health.

Reference
Rapaport, M.H., Nierenberg, A.A., Howland, R., Dording, C., Schettler, P.J., and Mischoulon, D. The treatment of minor depression with St. John's Wort or citalopram: Failure to show benefit over placebo. Journal of Psychiatric Research 45:931-941, 2011.

Thinking Globally to Improve Mental Health

2011-07-13T00:22:00.000-07:00

Source: NASA Jet Propulsion Laboratory (NASA-JPL)
Mental health experts are calling for a greater world focus on improving access to care and treatment for mental, neurological, and substance use (MNS) disorders, as well as increasing discoveries in research that will enable this goal to be met.

The Grand Challenges in Global Mental Health Initiative, led by the National Institutes of Health and the Global Alliance for Chronic Diseases, has identified the top 40 barriers to better mental health around the world. Similar to past grand challenges, which focused on infectious diseases and chronic, noncommunicable diseases, this initiative seeks to build a community of funders dedicated to supporting research that will significantly improve the lives of people living with MNS disorders within the next 10 years.

Twenty-five of the specific challenges and the process used to derive them are described in an article that will be published on July 7, 2011, in the journal Nature.

"Participating in global mental health research is an enormous opportunity, a means to accelerate advances in mental health care for the diverse U.S. population, as well as an extension of our vision of a world where mental illnesses are prevented and cured," said Thomas R. Insel, M.D., director of the National Institute of Mental Health (NIMH), the NIH institute heading this effort.

According to the paper's authors, the disorders targeted by the Grand Challenges in Global Mental Health—for example, schizophrenia, depression, epilepsy, dementia, and alcohol dependence—collectively account for more years of life lost to poor health, disability, or early death than either cardiovascular disease or cancer. Yet, compared to illnesses like cardiovascular disease and cancer, there are far fewer effective treatments or preventive methods. In addition, interventions are not widely available to those who need them most.

In recognizing the need to address this imbalance, Pamela Collins, M.D., M.P.H., of the NIMH Office for Research on Disparities and Global Mental Health, and colleagues assembled an international panel of experts to identify research priorities using the Delphi method, a widely accepted consensus-building tool. The panel consisted of 422 experts in fields such as neuroscience, basic behavioral science, mental health services, and epidemiology, and represented more than 60 countries social worker ceus

Over the course of two months, NIMH staff pared the panel's initial list of 1,565 challenges down to 154, with input from a scientific advisory board. From this list, the expert panel selected the top 40, of which the top five challenges identified after the third and final round of ranking are:

Integrate screening and core packages of services into routine primary health care
Reduce the cost and improve the supply of effective medications
Improve children's access to evidence-based care by trained health providers in low- and middle-income countries
Provide effective and affordable community-based care and rehabilitation
Strengthen the mental health component in the training of all health care personnel.
These top five challenges were ranked according to the ability to reduce the burden of disease, ability to reduce inequalities in health and health care, length of time until results can be observed, and the ability for the topic to be researched effectively.

"Addressing these challenges could have far-reaching effects, including increasing access to services and ultimately, reducing the treatment gap associated with these disorders," said Dr. Collins.

The Grand Challenges in Global Mental Health Initiative is led by NIMH and the Global Alliance for Chronic Diseases, in partnership with the Wellcome Trust, the McLaughlin-Rotman Centre for Global Health, and the London School of Hygiene and Tropical Medicine. Other NIH components participating in the Grand Challenges in Global Mental Health include the Fogarty International Center; the National Heart, Lung, and Blood Institute; and the National Institute of Neurological Disorders and Stroke.

Reference
Collins PY, Patel V, Joestl SS, March D, Insel TR, Daar A, on behalf of the Grand Challenges in Global Mental Health Scientific Advisory Board and Executive Committee. Grand Challenges in Global Mental Health. Nature. 2011 July 7. 474(7354):pp.

The mission of the NIMH is to transform the understanding and treatment of mental illnesses through basic and clinical research, paving the way for prevention, recovery and cure. For more information, visit the NIMH website.

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases.

Support Program Can Help Caregivers Cope with Relative’s Mental Illness

2011-06-29T10:58:00.000-07:00

A free, nationally available program can significantly improve a family's ability to cope with an ill relative's mental disorder, according to an NIMH-funded study published June 2011 in Psychiatric Services, a journal of the American Psychiatric Association.

Background
The Family-to-Family (FTF) education and support program is a free, 12-week course offered by the National Alliance on Mental Illness (NAMI). FTF is offered throughout the United States, in two Canadian provinces and in three regions in Mexico. With more than 3,500 volunteer teachers, it is supported by local donations or municipal funds. Since 1991, 250,000 family members have participated in the program. It is the most widely available education and support program for family members of individuals with mental illnesses.

Two previous studies suggested that FTF reduces caregivers' stress and helps them gain a sense of empowerment over their situation. For this most recent evaluation of the program, Lisa Dixon, M.D., M.P.H., of the University of Maryland, and colleagues aimed to determine its effectiveness using a randomized controlled trial. Half of the 318 participants were assigned to the program immediately after enrolling in the study, while the other half were waitlisted for the program for at least three months (control condition). Those who were waitlisted were free to seek assistance from other sources.

Participants were interviewed at the beginning of the three-month program and again three months later. They were asked about their problem-solving and coping skills, their overall distress level and worries about their ill relative's situation. They were also asked about their sense of empowerment to manage challenges within the family, the mental health system, and the community. They were also tested regarding their factual knowledge about mental illness.

Results of the Study
Compared to the waitlisted control group, FTF participants showed significantly greater improvements in coping with their ill relative's condition by learning more about the illness and gaining a sense of empowerment in the family, service system and community. FTF participants also showed increased acceptance of their family member's illness as well as improved problem-solving skills, compared to those who were waitlisted. Results also suggested that FTF participants' overall sense of emotional distress eased.

Significance
The researchers concluded that FTF effectively enhances coping skills among families of people with mental illness. These results echo those found in the previous qualitative studies. The researchers suggest the program can positively influence how family members solve problems and "navigate emotional difficulties" surrounding their loved one's illness.

What's Next
Additional research is needed to conclusively determine if the positive effects of FTF can improve the outcomes of the individuals with mental illness for whom the family members were taking the class.

Citation
Dixon LB, Lucksted A, Medoff DR, Burland J, Stewart B, Lehman AF, Fang LJ, Sturm V, Brown C, Murray-Swank A. Outcomes of a randomized study of a peer-taught family-to-family education program for mental illness. Psychiatric Services. 2011 June. 62(6):591-597.

CEUs for Social Workers

Drug Boosts Growth Factor to Jumpstart Rapid Antidepressant Response

2011-06-20T15:54:00.000-07:00

Little-known Enzyme Pivotal, Mouse Study Reveals
A study in mice has pinpointed a pivotal new player in triggering the rapid antidepressant response produced by ketamine. By deactivating a little-known enzyme, the drug takes the brakes off rapid synthesis of a key growth factor thought to lift depression, say NIMH-funded researchers LPCC Continuing Education

"Other agents that work through this pathway and block the enzyme may also similarly induce anti-depressant-like effects and hold promise for development of new treatments," said Lisa Monteggia, Ph.D., of the University of Texas Southwestern Medical Center, Dallas.

Monteggia, Ege Kavalali, Ph.D., and colleagues reported their findings online June 15, 2011 in the journal Nature.

Unlike currently available antidepressants that take weeks to work, ketamine can lift mood within hours. Yet adverse side effects preclude it from becoming a practical treatment. So, researchers have been studying its mechanism of action, in hopes of developing safer alternatives that work the same way.

Earlier studies had shown that the growth factor, called brain-derived neurotrophic factor (BDNF), produces antidepressant-like effects. To find out if BDNF is involved in ketamine's action, the researchers gave the drug to mice genetically engineered to lack BDNF. Unlike in control mice, ketamine failed to produce a fast-acting antidepressant-like response in such BDNF knockout mice exposed to experimental situations that trigger depression-like behaviors. This and other tests confirmed that ketamine's rapid antidepressant effects depend on rapid synthesis of BDNF in the brain's memory center, or hippocampus.

The researchers determined that this happens so quickly — within 30 minutes — because it only requires the translation of BDNF mRNA into protein, rather than transcription, which involves new gene expression and takes much longer.

Ketamine achieves this boost in BDNF levels by first blocking a protein on neurons (brain cells) called the NMDA receptor. The Texas team discovered that this blockade, in turn, deactivates an enzyme called eukaryotic elongation factor 2 (eEF2) kinase, that restrains BDNF synthesis. So, ketamine (and presumably other agents that similarly turn off the enzyme) effectively takes the brakes off of this antidepressant mechanism.

"Selectively inhibiting the eEF2 kinase was sufficient to trigger a rapidly acting antidepressant response in control mice but not in mice lacking BDNF," explained Monteggia.

The researchers discovered that the boost in BDNF occurs while neurons are in their default mode — not doing anything in particular. But the cells continue communicating via a low level of background chatter, spontaneously releasing chemical messengers that bind to receptors. So, when ketamine blocks NMDA receptors, it prevents their naturally-occurring messenger chemical, glutamate, from binding to them.

"Interference with such spontaneous neurotransmission to trigger production of a protein represents a novel mode of drug action," Monteggia noted. "It may also hold clues to what goes awry in the brain in disorders like depression."

Although BDNF levels fall off sharply following the transient increase triggered by ketamine, she says evidence may also support a role for BDNF in the drug's longer-term antidepressant effects. The exact role of another enzyme implicated in ketamine's antidepressant action remains to be determined, in light of the new findings. Yale researchers reported last Fall that the drug triggered increased connections between neurons via effects on the enzyme, called mTOR.

"This discovery of a novel pathway involved in mediating fast-acting antidepressant action holds hope for development of new rapid-acting medications," said Monteggia.

When in their default state, neurons that mediate ketamine's action engage in the brain's equivalent of background chatter. They spontaneously spray out (orange) the chemical messenger glutamate (green circles), which binds to NMDA receptors (black ovals) on adjoining neurons. This activates the enzyme eEF2 kinase, which suppresses synthesis of BDNF, a growth factor that has antidepressant effects. Treatment with ketamine blocks the binding of the neurotransmitter to the receptors (blue dots on black ovals), which inactivates the enzyme, taking the brakes off translation of BDNF into protein. This jumpstarts a fast-acting antidepressant effect.

Source: Lisa Monteggia, Ph.D., University of Texas Southwestern Medical Center

Reference
NMDA receptor blockade at rest triggers rapid behavioural antidepressant responses. Autry AE, Adachi M, Nosyreva E, Na ES, Los MF, Cheng PF, Kavalali ET, Monteggia LM. Nature. 2011 Jun 15. doi: 10.1038/nature10130. [Epub ahead of print] PMID:21677641

Focusing on School Attendance Reduces HIV Risk Among Orphaned Teens

2011-06-13T14:11:00.000-07:00

Source: iStock
A comprehensive school support program effectively reduced risk factors associated with infection with HIV among teens who had lost one or both parents, according to early results from a pilot study funded by NIMH. The paper was published online ahead of print on February 17, 2011, in the Journal of Adolescent Health LPCC Continuing Education

Background
Current statistics estimate there are more than 11 million children living in sub-Saharan Africa who have lost one or both parents to HIV/AIDS. These children are at increased risk of dropping out of school, which in turn increases their risk for unprotected sexual behavior. Some research suggests that interventions that aim to change a person's living conditions, such as methods designed to help them stay in school, may be effective in reducing or preventing HIV infection among these at-risk children.

To further explore this idea, Hyunsan Cho, Ph.D., of the Pacific Institute for Research and Evaluation in Chapel Hill, N.C., and colleagues recruited 105 students, ages 12-14, from a rural area in Kenya with high HIV prevalence who had lost one or both parents to any cause. All participants received supportive household supplies (e.g., mosquito nets, blankets, food supplements) every two weeks. Participants randomly assigned to the test group also received school uniforms and money to pay school fees. A local woman, designated as a "community visitor," was assigned for every 10 teens in the test group to visit their homes at least monthly. She also visited the teens' schools weekly to monitor their school attendance and address problems that may lead to absenteeism.

Results
After one year, teens in the test group were less likely to have:

Dropped out of school (4 percent vs 12 percent of the control group)
Begun having sex (19 percent vs 33 percent control)
Reported attitudes supporting initiation of sexual relationships at a young age
Teens in the test group were also more likely to perceive that adults in the family liked or cared about them, and were generally less likely to endorse attitudes accepting of husbands beating their wives.

Significance
According to the researchers, these findings support previous research suggesting that comprehensive, community-based school support can help reduce multiple HIV risk factors among orphaned teens. The researchers also found evidence that school support enhances social bonding and positive attitudes toward gender equity.

What's Next
Given that these findings resulted from an experimental pilot study, the researchers emphasized that future studies should include more participants and focus on methods for generalizing this approach to broader populations.

Reference
Cho H, Hallfors DD, Mbai II, Itindi J, Milimo BW, Halpern CT, Iritani BJ. Keeping Adolescent Orphans in School to Prevent Human Immunodeficiency Virus Infection : Evidence From a Randomized Controlled Trial in Kenya. J Adolesc Health. 2011 Feb 17. [online ahead of print]

Stress-Defeating Effects of Exercise Traced to Emotional Brain Circuit

2011-06-12T15:41:00.000-07:00

Evidence in both humans and animals points to emotional benefits from exercise, both physical and mental. Now, in recent experiments with mice, scientists have traced the stress-buffering effect of activity to a brain circuit known to be involved in emotional regulation as well as mood disorders and medication effects. The finding is a clue to understanding the neurological roots of resilience, key to developing new means of prevention and treatment for stress-related illness ceus for counselors

Background
In ongoing research, NIMH scientists have used a mouse model that mirrors particularly well the impact of social stress on mood in humans. Male mice are intensely aggressive when housed together; if these mice are placed in conditions that result in defeat by another mouse, they will behave in a way that mimics depression, much like a human might. Previous research demonstrated that mice housed in an environment with plenty of opportunities for exercise and exploration are relatively unfazed by bullying; they are resilient compared to mice housed in more spartan surroundings. The benefits from activity and stimulation depend on the growth of new neurons in the brain in mice (Novel Model of Depression from Social Defeat Shows Restorative Power of Exercise). A next step was to pinpoint where in the brain changes were taking place in response to exercise that resulted in stress resilience.

This Study
Before any mice were exposed to social defeat, all the mice in the study were housed for three weeks in either impoverished housing, with nothing but wood chip bedding; standard housing with a cardboard tube and place for a nest; or "enriched housing," with running wheels and tubes of various shapes and sizes to explore. After three weeks, half of the mice in each type of housing were then placed for two more weeks in close quarters with another mouse, but prevented from fighting by a barrier to prevent injury.

Mice that had been housed in the impoverished or standard housing, and that had been subject to social defeat, reacted to standard behavioral tests in a way that suggests depression; they were measurably passive and cautious, for example, avoiding light-filled spaces and preferring the safety of darkness. Bullied mice that had been housed in enriched environments behaved just like mice that had not experienced social defeat. As in earlier studies, the enriched environment seemed to protect them from the effects of social stress.

The NIMH investigators carrying out this study, Michael Lehmann and Miles Herkenham, then looked within the brain to see what exercise was changing to protect against stress. They focused on a functional circuit of brain centers known to be involved in emotional processing. In mice that had been housed in an enriched environment, levels of a protein that signals the activity level of neurons were increased in cells in the infralimbic cortex (ILC), a part of this circuit. Parts of the brain closely wired to and "downstream" from the ILC, that is, receiving activating signals from it, showed similar elevated activity. If the ILC was inactivated at the beginning of the experiment, environmental enrichment failed to have a positive effect. But if it was inactivated after the first three weeks of housing, environmental enrichment worked; the parts of the brain that receive signals from the ILC remained activated and the mice were stress resilient. The ILC was, in effect, a gateway for the positive activity in these "downstream" parts of the brain. Once these centers were activated by the ILC, it didn't matter if the ILC was still online.

Enrichment had the opposite effect on a part of the brain that is an important trigger for the body's stress response system. So enrichment seemed to enhance positive behavior, while at the same time, dampened activity in an area linked with an increased stress response.

Significance
A central target of research is understanding how stress contributes to mood disorders and why some animals and people seem resilient to the same stresses that can make others ill. Much recent research is aimed at investigating mental processes and disorders in terms of neural circuits. Abnormalities in how the brain deals with fear memories, for example, are thought to play a role in both anxiety disorders and depression. In rats that have been conditioned to fear a particular sound, stimulation of the ILC can dampen the fear reaction. In the study reported here, experience in the environment had the effect of inoculating the mice against a stressor, through changes in this same circuit in the brain.

The areas of the brain examined in this study are analogous to brain regions with altered function in people with disorders like depression and post traumatic stress disorder. Knowledge of the physiological basis of emotional resilience is crucial to developing strategies to help prevent mood disorders; it can also offer targets for the development of new medications for which there remains a pressing need.

Reference
Lehmann, M.I., and Herkenham, M. Environmental enrichment confers stress resiliency to social defeat through an infralimbic cortex-dependent neuroanatomical pathway. Journal of Neuroscience 31:6159-6173, 2011.

Autism Blurs Distinctions Between Brain Regions

2011-06-07T10:57:00.000-07:00

Erodes Molecular Identities in Cortex – NIH-funded Study
Autism blurs the molecular differences that normally distinguish different brain regions, a new study suggests. Among more than 500 genes that are normally expressed at significantly different levels in the front versus the lower middle part of the brain's outer mantle, or cortex, only 8 showed such differences in brains of people with autism, say researchers funded in part by the National Institutes of Health continuing education for social workers

"Such blurring of normally differentiated brain tissue suggests strikingly less specialization across these brain areas in people with autism," explained Daniel Geschwind, M.D., Ph.D., of the University of California, Los Angeles, a grantee of the NIH's National Institute of Mental Health. "It likely reflects a defect in the pattern of early brain development."

He and his colleagues published their study online May 26, 2011 in the journal Nature. The research was based on post mortem comparisons of brains of people with the disorder and healthy controls.

In fetal development, different mixes of genes turn on in different parts of the brain to create distinct tissues that perform specialized functions. The new study suggests that the pattern regulating this gene expression goes awry in the cortex in autism, impairing key brain functions.

"This study provides the first evidence of a common signature for the seemingly disparate molecular abnormalities seen in autism," said NIMH director Thomas R. Insel, M.D. "It also points to a pathway-based framework for understanding causes of other brain disorders stemming from similar molecular roots, such as schizophrenia and ADHD."

In an earlier study, the researchers showed that genes that turn on and off together at the same time hold clues to the brain's molecular instructions. These modules of co-expressed genes can reveal genetic co-conspirators in human illness, through what Geschwind and colleagues call "guilt by association." A gene is suspect if its expression waxes and wanes in sync with others in an illness-linked module.

Using this strategy, the researchers first looked for gene expression abnormalities in brain areas implicated in autism — genes expressed at levels different than in brains of healthy people. They found 444 such differently expressed genes in the cortexes of postmortem brains of people with autism.

Most of the same genes turned out to be abnormally expressed in the frontal cortex as in the temporal cortex (lower middle) of autistic brains. Of these, genes involved in synapses, the connections between neurons, tended to be under-expressed when compared with healthy brains. Genes involved in immune and inflammatory responses tended to be over-expressed. Significantly, the same pattern held in a separate sample of autistic and control brains examined as part of the study.

Autistic and healthy control brains were similarly organized –– modules of co-expressed genes correlated with specific cell types and biological functions.

Yet normal differences in gene expression levels between the frontal and temporal cortex were missing in the modules of autistic brains. This suggests that the normal molecular distinctions — the tissue differences — between these regions are nearly erased in autism, likely affecting how the brain works. Strikingly, among 174 genes expressed at different levels between the two regions in two healthy control brains, none were expressed at different levels in brains of people with autism.

An analysis of gene networks revealed two key modules of co-expressed genes highly correlated with autism.

One module was made up of genes in a brain pathway involved in neuron and synapse development, which were under-expressed in autism. Many of these genes were also implicated in autism in previous, genome-wide studies. So, several different lines of evidence now converge, pointing to genes in this M12 module (see picture below) as genetic causes of autism.

A second module of co-expressed genes, involved in development of other types of brain cells, was over-expressed in autism. These were determined not to be genetic causes of the illness, but likely gene expression changes related to secondary inflammatory, immune, or possible environmental factors involved in autism.

This newfound ability to see genes in the context of their positions in these modules, or pathways, provides hints about how they might work to produce illness, according to Geschwind and colleagues. For example, from its prominent position in the M12 module, the researchers traced a potential role in creating defective synapses to a gene previously implicated in autism.

Follow-up studies should explore whether the observed abnormalities in the patterning of gene expression might also extend to other parts of the brain in autism, say the researchers.

Earthquakes and Mental Health

2011-05-31T12:56:00.000-07:00

Impact on Children and Families

Because earthquakes are unexpected and can be very destructive, being in one can be terrifying. People fear they will be injured or killed. They may be separated from family, with hours passing before knowing if their loved ones are safe. They may see collapsed buildings or other destruction and experience the horror of seeing severely injured people or even dead bodies. As they assess the damage, people may find that a relative or close friend has been killed or that their home has been destroyed. Earthquakes are particularly difficult physically and emotionally for people who are disabled or have special needs ceus for social workers

In the aftermath, people may continue to encounter sights, sounds, smells, sensations, and inner feelings that remind them-even years after-of the earthquake. These traumatic reminders can bring on distressing mental images, thoughts, and emotional/physical reactions. Common reminders include aftershocks, cracks in the wall, rumbling noises, destroyed buildings, smells of fire and smoke, the place where they experienced the earthquake, seeing people with disabilities, funerals, anniversaries of the date, and television or radio news about earthquakes.

An earthquake may serve as a reminder of prior trauma and loss, making the current reactions even worse. Post-earthquake problems with living conditions, food, water, electricity, transportation, school, work, and daily routines may make living very difficult for weeks or even months. Efforts to contend with these adversities may significantly reduce a person's coping and emotional resources, and in turn interfere with their ability to recover

Post-earthquake studies of children and adults from around the world have found that:
•Those with the most severe earthquake-related experiences and losses have the most severe and persistent posttraumatic stress and grief reactions.
•There can be widespread separation-anxiety in children and adolescents following the event.
•Depression, associated with posttraumatic stress reactions and disruption to living circumstances, often occurs after major earthquakes.
•Ongoing problems may include: marital discord; substance abuse; delinquent, aggressive or withdrawn behavior; and complaints about physical health, including headaches, stomachaches, rapid heartbeat, tightness in the chest, and appetite and digestive problems.
•Children and adolescents lose trust in the safety and security of the world, and in the ability of adults to protect them.
•Specialized trauma- or grief-focused mental health services can help children and adolescents recover from the psychological consequences of an earthquake.

Recovery: After an Earthquake

Most families will recover over time, particularly with the support of family, friends, and organizations. The length of recovery will depend, in part, upon how frightening the earthquake was, whether evacuation from home was necessary, and the extent of the damage and loss. Some families will be able to return to their normal routines rather quickly, while others will have to contend with repairing damage to their home and possessions, finding medical care, and facing financial hardship. Some families will have lost a loved one or a pet. Others will need to deal with school closings or changes in school schedules.

Children's functioning and recovery will be influenced by how their parents and caregivers cope during and after the earthquake. Children often turn to adults for information, comfort, and help. Children do best when parents and teachers remain (or at least appear) calm, answer children's questions honestly, and respond as best they can to requests.

What You Should Know About Tornadoes

2011-05-26T10:32:00.000-07:00

A tornado is a rapidly rotating column of air that extends from the cloud base to the ground. Tornadoes generally travel from west/southwest to east/northeast, but they can travel in any direction and can change their course suddenly. Sometimes tornadoes are preceded by heavy rain, wind, and hail; other times they seem to arise out of relatively clear conditions. Sometimes people hear a loud roar or trainlike sound when a tornado approaches. While tornadoes have occurred in all fifty states, the Midwestern and Southern states have the greatest number. The most violent tornadoes tend to be in the spring, but they can occur any time of the year.

Advances in weather prediction have resulted in fewer tornado-related injuries and fatalities. Unfortunately, these advances have led to a false sense of security. If a tornado watch (when atmospheric conditions are favorable for forming a tornado) should become a tornado warning (when a tornado has formed), families should seek shelter quickly. The National Oceanographic and Atmospheric Administration's Storm Prediction Center has a Tornado FAQ with more information about tornadoes.

Impact on Children and Families

A tornado threatens the usual assumptions of safety. The winds and flying debris can disrupt telephone lines and other utilities, breaking down communication. A powerful storm can blow off the roofs of houses, break windows, blow open doors, split trees in two, and destroy entire homes. Leaving shelter is dangerous, as windblown items such as shards of glass, parts of houses, and uprooted trees can cause sudden injury or death.

Tornadoes are unusual storms, as their path is often erratic. In the same neighborhood, some houses may be leveled completely while others sustain little damage. While scattered destruction can be easier on the community than that of a flood or a hurricane—in that not all community resources may be used up—the inconsistent pattern of damage can cause feelings of guilt in those spared or unfairness in those recovering. Children may develop unusual ideas or myths about why a tornado did or did not hit their home.

Children may see anxiety and fear in parents and caregivers who are usually confident. They may lose their homes and cherished pets, memorabilia, and toys. They may see collapsed or damaged buildings—including their schools or familiar community landmarks. They may encounter rubble, debris, or other wreckage, and experience the horror of seeing severely injured people or dead bodies.

As with other natural disasters, there may be a spectrum of psychological casualties. Individuals with preexisting emotional and behavioral problems may get worse if their support systems fail, they run out of medications, and/or their routine destabilizes. Others may develop chronic emotional and behavioral problems following exposure to pervasive stresses, such as the loss of community infrastructure, home or employment, or family or friends. In addition, emotional and physical exhaustion may affect individuals or families' ability to recover counselor ceus

Children and adults frequently experience traumatic reminders, during which they suddenly relive and reexperience the emotions, fears, thoughts, and perceptions, they experienced at the time of the tornado. Typical traumatic reminders include tornado watches and warnings, thunderstorms, dark clouds, high winds, and hail.

Common emotional reactions of children and family members exposed to a tornado include:
•Feelings of insecurity, unfairness, anxiety, fear, anger, sadness, despair, and worries about the future
•Fear that another tornado will occur
•Believing myths or folklore as to the cause of the tornado
•Disruptive behaviors, irritability, temper tantrums, agitation, or hyperactivity
•Clinging/dependent behaviors or avoidant and phobic symptoms
•Physical symptoms, such as stomachaches, headaches, loss of appetite, nightmares, or sleep problems
•Increased concerns regarding the safety of family members, friends, and loved ones
•School-based problems, with decreased motivation and school performance

Adolescents may differ from younger children in how they respond to a tornado or other natural disaster. Some believe they will not live long and may exhibit:

•Socially withdrawn, angry, or irritable
•Risky behavior
•Conflict with authority

Many School-aged Children with ASD in South Korea Go Undiagnosed

2011-05-24T10:43:00.000-07:00

Total population study points to possible higher rates of ASDs when screening the general population and the growing worldwide concern for screening, diagnosis, and services

Source: Getty
The prevalence of autism spectrum disorder (ASD) among children in South Korea appears to be much higher than the range of estimates previously reported in other countries, according to a study partly funded by NIMH. The researchers found that two-thirds of ASD cases occurred in children attending mainstream schools; these children had not been previously diagnosed and had never received treatment for the disorder. The study was published online ahead of print on May 9, 2011, in the American Journal of Psychiatry CEUs for counselors

Background
Recent reports of increased prevalence of ASD have raised concerns among parents, researchers, and policymakers. However, it is still unclear whether these estimates reflect a true rise in ASD occurrence or improved rates of detection and diagnosis. And because different studies use different designs and methods, they may not be truly comparable. There are also limited data on the prevalence of ASD in countries outside of North America and Europe.

To address these issues, Young Shin Kim, M.D., Ph.D., of Yale School of Medicine, and colleagues targeted all children ages 7-12 in a South Korean community representative of the country's general population. The researchers asked parents and teachers about the children's social interactions, and whether they had communication problems or restricted and repetitive behaviors.

The researchers then evaluated 286 children suspected as having ASD based on the answers given. Of these children, 114 attended special education schools, had a history of mental health service use, or were listed in the local disability registry. For study purposes, the researchers considered these children to have a high probability of having ASD. The other 172 children attended regular schools, had never received special education or mental health services, and were not listed in the disability registry.

The study incorporated multiple measures to address potential cultural issues. For example, board-certified Korean child psychiatrists trained in both Korea and the United States conducted the diagnostic assessments using screening and diagnostic tools validated for Korean children. An anthropologist on the research team also organized focus groups with local parents and teachers to identify beliefs that may influence symptom reporting and to address stigma related to ASD.

Results of the Study
Based on diagnostic assessments, the prevalence of ASD among the total study population was 2.64 percent. Among the children attending regular schools, the prevalence was 1.89 percent and boys were 2.5 times more likely to have ASD than girls. Among the high-probability group the prevalence of ASD was 0.75 percent and boys were 5 times more likely to have ASD than girls.

Of the 2.64 percent of all ASD cases, 0.94 percent met diagnostic criteria for autism and 1.7 percent met criteria for other types of ASD, including Asperger's disorder and pervasive developmental disorder not otherwise specified.

Significance
Unlike previous studies that analyzed health records and registries, the researchers attempted to look at each child in every school in a particular community, even children who did not have a record of any special education need. According to the researchers, this method unmasked cases that could have gone unnoticed if they had relied solely on health records. As a result, this study's estimate of ASD prevalence is higher than previously reported estimates, which range from 0.6 percent to 1.8 percent.

However, according to the researchers, the prevalence in the high probability group is similar to reports in other studies that have focused on the same target populations. The major difference in this study was that two-thirds of ASD cases were identified in the general population among children who never had contact with care systems. This particular finding highlights the importance of screening mainstream school populations as well as clinical populations in future studies. The researchers also suggest that the highly structured educational system in South Korea may allow children with less severe ASD symptoms to manage in general education settings, despite their impairments.

What's Next
More research is needed to find out whether these results can be repeated in other populations in Korea and other countries. The researchers note that more rigorous ASD screening may provide a more accurate estimate of the number of people with ASD, and that this number may exceed previous prevalence estimates. Additionally, this study only addressed ASD prevalence, or the current number of people with the disorder. Incidence studies—those that focus on the numbers of new cases—are essential to examine possible environmental and other potential causes of the rising ASD prevalence.

Reference
Kim YS, Leventhal BL, Koh YJ, Fombonne E, Laska E, Lim EC, Cheon KA, Kim SJ, Kim YK, Lee HK, Song DH, Grinker RR. Prevalence of Autism Spectrum Disorders in a Total Population Sample. Am J Psychiatr.

Depressed Teens with History of Abuse Less Likely to Respond to Combination Treatment

2011-05-22T18:49:00.000-07:00

Adolescents with treatment-resistant depression who have a history of abuse—especially physical abuse—are less likely to respond to combination treatment than to medication alone, according to data from the NIMH-funded Treatment of Resistant Depression in Adolescents (TORDIA) study. The new study was published in the March 2011 issue of the Journal of the American Academy of Child and Adolescent Psychiatry.

Background
Although the relationship between childhood abuse and risk for depression or other mental disorder is well-established, few studies have examined whether a history of abuse may affect response to treatment, especially among adolescents. Some studies have suggested that a history of abuse is associated with a lower response to cognitive behavioral therapy (CBT), a type of psychotherapy that emphasizes problem-solving and behavior change social worker ceus

In the Treatment of Resistant Depression in Adolescents (TORDIA) study, teens whose depression had not improved after an initial course of selective serotonin reuptake inhibitor (SSRI) antidepressant treatment were randomly assigned to one of four interventions for 12 weeks:

Switch to another SSRI—paroxetine (Paxil), citalopram (Celexa) or fluoxetine (Prozac)
Switch to a different SSRI plus CBT
Switch to venlafaxine (Effexor), a different type of antidepressant called a serotonin and norepinephrine reuptake inhibitor (SNRI)
Switch to venlafaxine plus CBT
As reported in May 2010, about 40 percent of those who completed 24 weeks of treatment achieved remission, regardless of the treatment to which they had initially been assigned. The risk for relapse remained high, however.

About 13 percent of TORDIA participants had a history of physical abuse, 17 percent had a history of sexual abuse, and 5 percent had a history of both. In this most recent study, Wael Shamseddeen, M.D., MPH, of Rosalind Franklin University of Medicine and Sciences in North Chicago, and colleagues examined the association between having a history of physical or sexual abuse and response to combination treatment among TORDIA participants.

Results of the Study
The researchers found that teens without a history of abuse had a higher response rate to combination therapy compared to medication-only therapy (63 percent vs. 37.6 percent). Those with a history of sexual abuse responded similarly to combination and medication-only therapy (48 percent vs. 42 percent). However, those with a history of physical abuse had a much lower response rate to combination therapy (18.4 percent) compared to medication-only (52.4 percent).

Significance
The researchers were unable to identify the specific mechanism that might affect response to combination therapy among teens with a history of physical abuse. They suggest that because abuse can affect a child's brain development, abused youth may need psychotherapeutic approaches that target trauma before engaging in traditional CBT designed to treat depression. The researchers also suggest that abused youth may have a tendency to avoid unpleasant emotions, and therefore may have been averse to CBT. It is possible that therapeutic approaches that focus more on behavior and do not rely heavily on the processing of negative thoughts and emotions may be more acceptable and effective for these youth.

What's Next
The researchers concluded that more research is needed into the ways in which abuse history can confer treatment resistance among teens with hard-to-treat depression, and in developing alternative treatment approaches that are more effective.

Reference
Shamseddeen W, Asarnow JR, Clarke G, Vitiello B, Wagner KD, Birmaher B, Keller MB, Emslie G, Iyengar S, Ryan ND, McCracken JT, Porta G, Mayes T, Brent D. Impact of physical and sexual abuse on treatment response in the Treatment of Resistant Depression in Adolescents Study (TORDIA). Journal of the American Academy of Child and Adolescent Psychiatry. 2011 March. 50(3):293-301.

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5-minute Screen Identifies Subtle Signs Of Autism in 1-year Olds

2011-05-21T17:58:00.000-07:00

NIH-funded Study Demonstrates Feasibility and Effectiveness of Conducting Systematic Screening During Well-Baby Check-Ups

A five-minute checklist that parents can fill out in pediatrician waiting rooms may someday help in the early diagnosis of autism spectrum disorder (ASD) , according to a study funded by the National Institutes of Health. Published today in the Journal of Pediatrics, the study's design also provides a model for developing a network of pediatricians to adopt such a change to their practice. Continuing education for counselors

"Beyond this exciting proof of concept, such a screening program would answer parents' concerns about their child's possible ASD symptoms earlier and with more confidence than has ever been done before," noted Thomas R. Insel, M.D., director of the National Institute of Mental Health (NIMH), part of NIH.

Identifying autism at an early age allows children to start treatment sooner, which can greatly improve their later development and learning. However, many studies show a significant delay between the time parents first report concerns about their child's behavior and the eventual ASD diagnosis, with some children not receiving a diagnosis until well after they've started school.

Recognizing the need to improve early ASD screening, Karen Pierce, Ph.D., of the University of California, San Diego, and colleagues established a network of 137 pediatricians across San Diego County. Following an hour-long educational seminar, the pediatricians screened all infants at their 1-year, well-baby check-up using the Communication and Symbolic Behavior Scales Developmental Profile Infant-Toddler Checklist, a brief questionnaire that detects ASD, language delay, and developmental delay. The questionnaire asks caregivers about a child's use of eye gaze, sounds, words, gestures, objects and other forms of age-appropriate communication. Any child who failed the screen was referred for further testing and was re-evaluated every six months until age 3.

Out of 10,479 infants screened, 32 were identified as having ASD. After excluding for late onset and regression cases, this is consistent with current rates that would be expected at 12 months, according to the researchers. When including those identified as having language delay, developmental delay, or some other form of delay, the brief screen provided an accurate diagnosis 75 percent of the time.

Following the screen, all toddlers diagnosed with ASD or developmental delay and 89 percent of those with language delay were referred for behavioral therapy. On average, these children were referred for treatment around age 17 months. For comparison, a 2009 study using data from the Centers for Disease Control and Prevention found that, on average, children currently receive an ASD diagnosis around 5.7 years (68.4 months) of age, with treatment beginning sometime later.

In addition to tracking infant outcomes, the researchers also surveyed the participating pediatricians. Prior to the study, few of the doctors had been screening infants systematically for ASD. After the study, 96 percent of the pediatricians rated the program positively, and 100 percent of the practices have continued using the screening tool.

"In the context of a virtual lack of universal screening at 12 months, this program is one that could be adopted by any pediatric office, at virtually no cost, and can aid in the identification of children with true developmental delays," said Dr. Pierce.

The researchers note that future studies should seek to further validate and refine this screening tool, track children until a much older age, and assess barriers to treatment follow up.

This study was also supported by an NIMH Autism Center of Excellence grant as well as Autism Speaks and the Organization for Autism Research.

Reference
Pierce K, Carter C, Weinfeld M, Desmond J, Hazin R, Bjork R, Gallagher N. Catching, Studying, and Treating Autism Early: The 1-Yr Well-Baby Check-Up Approach. J Pediatr. 2011 Apr. [Epub ahead of print]

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The mission of the NIMH is to transform the understanding and treatment of mental illnesses through basic and clinical research, paving the way for prevention, recovery and cure. For more information, visit the NIMH website.

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit the NIH website.

Light Switches Brain Pathway On-and-Off to Dissect How Anxiety Works

2011-05-20T20:54:00.000-07:00

Turns Cowering Mice into Instant Adventurers
Scientists, for the first time, have switched anxiety on-and-off in active animals by shining light at a brain pathway. Instinctively reclusive mice suddenly began exploring normally forbidding open spaces when a blue laser activated the pathway – and retreated into a protected area when it dimmed. By contrast, anxiety-like behaviors increased when an amber laser inhibited the same pathway. Researchers, supported in part by NIMH, used a virus, genetic engineering and fiber-optics to control the pathway in the brain's fear center with millisecond precision. CEUs for Social Workers

"Our findings reveal how balanced antagonistic brain pathways are continuously regulating anxiety," explained Karl Deisseroth, M.D., Ph.D., of Stanford University, a practicing psychiatrist as well as a neuroscientist. "We have pinpointed an anxiety-quelling pathway and demonstrated a way to control it that may hold promise for new types of anti-anxiety treatments."

NIMH grantees Deisseroth, Kay M. Tye, Ph.D., and colleagues, report on their findings March 17, 2011 in the journal Nature.

Optogenetic alchemy
Anxiety disorders are the most common type of psychiatric illness, affecting more than 1 in 4 people at some time during their lives. To understand the neural basis of these disorders, researchers are studying the workings of circuitry in the fear center, called the amygdala, in rodents.

Deisseroth's team has pioneered a method, called optogenetics, of experimentally activating brain activity with light. They incorporate a protein borrowed from light-reactive organisms to make brain tissue similarly light-responsive. Previously, they used this tool to activate particular types of neurons. The new study is the first to use it to reversibly manipulate a specific projection of a neuron (see picture below). It's also the first time the technique has been used to study anxiety as opposed to fear – a generalized state versus a transient reaction to an immediate threat.

The researchers borrowed a gene that codes for a light-sensitive protein from algae and delivered it to the amygdala pathway via a virus. In the algae, the protein's function is to activate a pathway that causes the organism to swim toward blue spectrum light. Hence a blue light now activated the amygdala pathway. When they wanted to inhibit the pathway in response to light, they similarly borrowed a gene from a light-responsive bacterium that codes for a protein that inhibits a pathway in response to a particular spectrum of light — in this case amber — and infected the amygdala pathway with that gene.

When the researchers optogenetically activated whole neuronal cell bodies in the amygdala, it increased anxiety-like behavior: mice hunkered down in a protected corner of a maze and wouldn't venture into more exposed areas. These and related findings led the researchers to hypothesize that they would get the same effect if they narrowed the focus of the activation to just a specific neuronal projection (see picture below).

A post-doc's eureka! moment
But it turned out that the opposite was true.

When they activated the projection with the blue laser, the engineered mice suddenly seemed to summon the courage to explore the more exposed parts of the maze that they would normally avoid (see video below).

"I was quite surprised. We did not see aversion. We did not see fear. We did not see any of these things I expected to see," said Tye, whose post-doctoral study is supported by a NIMH-funded training grant. "I suddenly got this huge, dramatic effect of reduction in anxiety-related behaviors and I had to follow it up. So I pretty much dropped my original ideas of what I was going to study during my fellowship and started pursuing this."

When the researchers blocked activity in the projection with the amber laser, the animals showed even more anxiety-like behavior than they usually do. The experiments hint at how the brain is able to regulate anxiety levels — on a millisecond timescale — by dialing activity up and down in such antagonistic amygdala pathways.

Futuristic anxiety treatment?
Tye said she and Deisseroth plan to follow up with further dissection of anxiety pathways. She also hopes to examine whether such optogenetic manipulations, sustained over hours or days, might induce long-lasting adaptations — perhaps for weeks –– in the set-points of anxiety pathways.

A future anxiety disorder treatment that might similarly target such specific pathways could, theoretically, quell anxiety instantly without producing unwanted side effects, such as drowsiness, often experienced with current anti-anxiety medications. For patients with severely debilitating anxiety, a treatment something like deep brain stimulation for depression, but more precisely targeted at a specific pathway, might someday be feasible, she suggested."Everything else in your brain should be unperturbed, because the manipulation would be so specific," explained Tye.

Video shows a mouse under "optogenetic" control while in an anxiety-producing situation. Being in elevated, open spaces makes mice anxious. So, in this "elevated-plus maze," the mouse normally stays in the arms with high walls; it normally won't venture into arms with low walls. However, this mouse has been genetically engineered to have an anxiety-quelling pathway in its fear hub activate when a blue laser shines on it via the fiber-optic cable. At those times (when the blue text appears), the animal gains courage and ventures into the normally scary places. Video speeds up a 15 minute session 10-fold.

Researchers were surprised to discover that activating the whole cell body of an amygdala neuron increased anxiety in mice, while activating just one of its projections had the opposite effect. So unraveling the secrets of how anxiety works might require dissecting the action of each such pathway individually, say the researchers.

Reference
Amygdala circuitry mediating reversible and bidirectional control of anxiety. Tye KM, Prakash R, Kim SY, Fenno LE, Grosenick L, Zarabi H, Thompson KR, Gradinaru V, Ramakrishnan C, Deisseroth K. Nature. 2011 Mar 17;471(7338):358-62. Epub 2011 Mar 9. PMID: 21389985

Tired Neurons Caught Nodding Off in Sleep-deprived Rats

2011-05-18T12:02:00.000-07:00

Performance Decline Belies Seeming Wakefulness – NIH-funded Study
A new study in rats is shedding light on how sleep-deprived lifestyles might impair functioning without people realizing it. The more rats are sleep-deprived, the more some of their neurons take catnaps — with consequent declines in task performance. Even though the animals are awake and active, brainwave measures reveal that scattered groups of neurons in the thinking part of their brain, or cortex, are briefly falling asleep, scientists funded by the National Institutes of Health have discovered CEUs for counselors

"Such tired neurons in an awake brain may be responsible for the attention lapses, poor judgment, mistake-proneness and irritability that we experience when we haven't had enough sleep, yet don't feel particularly sleepy," explained Giulio Tononi, M.D., Ph.D., of the University of Wisconsin-Madison. "Strikingly, in the sleep-deprived brain, subsets of neurons go offline in one cortex area but not in another — or even in one part of an area and not in another."

Tononi and colleagues report their findings online in the April 28, 2011 issue of the journal Nature. Their study was funded in part by the NIH's National Institute of Mental health and a NIH Director's Pioneer Award, supported through the Common Fund, and administered by NIMH and the National Institute on Neurological Disorders and Stroke.

Previous studies had hinted at such local snoozing with prolonged wakefulness. Yet little was known about how underlying neuronal activity might be changing.

To learn more, the researchers tracked electrical activity at multiple sites in the cortex as they kept rats awake for several hours. They put novel objects into their cages — colorful balls, boxes, tubes and odorous nesting material from other rats. The sleepier the rats got, more subsets of cortex neurons switched off, seemingly randomly, in various localities. These tired neurons' electrical profiles resembled those of neurons throughout the cortex during NREM or slow wave sleep. Yet, the rats' overall EEG, a measure of brain electrical activity at the scalp, confirmed that they were awake, as did their behavior. So neuronal tiredness differs from more overt "microsleep" — 3-15-second lapses with eyes closing and sleep-like EEG - that is sometimes experienced with prolonged wakefulness. It is more analogous to local lapses seen in some forms of epilepsy, suggest the researchers.

However subtle, having tired neurons did interfere with task performance. If neurons switched off in the motor cortex within a split second before a rat tried to reach for a sugar pellet, it decreased its likelihood of success by 37.5 percent. And the overall number of such misses increased significantly with prolonged wakefulness. This suggests that tired neurons, and accompanying increases in slow wave activity, might help to account for the impaired performance of sleep-deprived people who may seem behaviorally and subjectively awake.

Subsets of neurons going offline with longer wakefulness is, in many ways, the mirror image of progressive changes that occur during recovery sleep following a period of sleep deprivation. Tononi suggests that both serve to maintain equilibrium — part of the compensatory mechanisms that regulate sleep need. Just as sleep deprivation produces a brain-wide state of instability, it may also trigger local instability in the cortex, possibly by depleting levels of brain chemical messengers. So, tired neurons might nod off as part of an energy-saving or restorative process for overloaded neuronal connections.

"Research suggests that sleep deprivation during adolescence may have adverse emotional and cognitive consequences that could affect brain development," noted NIMH Director Thomas R. Insel, M.D. "The broader line of studies to which this belongs, are, in part, considering changes in sleep patterns of the developing brain as a potential index to the health of neural connections that can begin to go awry during the critical transition from childhood to the teen years."

Source: Giulio Tononi, M.D., Ph.D., University of Wisconsin-Madison

Reference
Local sleep in awake rats. Vyazovskiy VV, Olcese U, Hanlon EC, Nir Y, Cirelli C, Tononi G. Nature. 2011 April 28.

Novel Model of Depression from Social Defeat Shows Restorative Power of Exercise

2011-05-17T14:03:00.000-07:00

New Neurons Pinpointed as Central to Exercise Benefit

In a study in a mouse model that mimics the contribution of social stress to human depression, an environment that promotes exercise and exploration alleviated depressive behavior in the mice. The beneficial effect of activity depended on the growth of new neurons in the adult brain Continuing Education for Counselors

Background
In the 1990s scientists established that new neurons grow in the adult as well as the immature brain. The functions of neurogenesis, or new neuronal growth, are still being explored, but it is known that stress slows this growth in the hippocampus―a brain center involved in the formation of new memories―and that antidepressant treatment promotes it.

Previous research in animal models has also demonstrated that environmental enrichment―the addition of features in an animal's cage that provide opportunities for exercise and investigation―fosters resilience to stress and can alleviate the depression-like behavior that results from uncontrollable stress. Environmental enrichment has also been shown to promote hippocampal neurogenesis in animals.

This Study
This work, by Michael Lehmann and Robert Schloesser and colleagues in NIMH's intramural research program, focused on the ability of environmental enrichment to reverse depressive behaviors caused by social defeat, a situation paralleling the social stresses that can trigger human depression. Past work in animal models has often used physical stressors such as electric shock, restraint, or forced exercise to create depressive behaviors. In addition, the scientists inserted a gene in mice that made it possible to selectively interrupt the growth of new neurons at a specific time and in a specific population of cells in the hippocampus, avoiding any spillover effects to other tissues.

More on Mouse Behavior
Although "dominant and aggressive" may not sound like descriptors that apply to mice, male mice in the wild live apart from other males and they are intensely aggressive if housed together. In this study, male mice were allowed to interact directly for no more than five minutes at a time and were supervised to make sure one mouse did not injure or kill the other.
Mice naturally cover territory in the wild; if furnished with running wheels in a cage, they will, on their own, run the equivalent of as much as 6 to 10 kilometers in one day.
Stress―in this case social defeat stress―has unmistakable effects on the behavior of mice. Researchers use a variety of tests to describe changes in behavioral tendencies, including observing how boldly the mice explore an unfamiliar cage; how much time they will choose to spend in a dark (safe) vs. light (risky) compartment; and the extent to which they'll indulge their taste for something pleasant like sweetened water. Mice who have been the losers of repeated social defeats are visibly cautious and subdued, even in the judgment of observers who do not know whether they were winners or losers in a conflict.
Test mice in this study were housed across a partition in the home cage of a dominant, aggressor mouse. For 5 minutes per day, the partition was removed, allowing the "intruder" and dominant mouse to interact directly. After 2 weeks, the test mice consistently behaved submissively. The test mice were then divided and placed in either a spare environment, or one enriched with running wheels, and tubes of various shapes and sizes. Some of the mice assigned to either environment were a standard laboratory strain. Others had an inserted gene targeted to a population of hippocampal cells that give rise to new neurons; in mice with this transgene, the antibiotic valganciclovir is toxic to dividing cells so neurogenesis is prevented when the drug was added to the animals' feed.

The nontransgenic test mice in the enriched environment, but not those in the more spartan cages, recovered from the submissive behavior seen after social defeat. The transgenic mice, in which neurogenesis was stopped, remained submissive, resembling the mice housed in the impoverished environment.

In tests to probe affect, or mood, the transgenic mice housed in the enriched environment also resembled mice housed in the impoverished environment in that they showed the same reduced inclination to explore, greater anxiety, and a less than normal interest in sweet solutions which mice usually prefer. Interruption of neurogenesis had no effects on the baseline health and behavior of the animals, so the lack of new neurons did not cause depression, but interfered with recovery.

Significance
This study demonstrates that psychosocial stress in mice can cause behavior resembling human depression, which environmental enrichment can ameliorate as long as neurogenesis is intact.

Key elements of this study included its use of a social stressor, more analogous to the social experiences that can contribute to human depression than the physical stressors often used in research. In addition, the use of the transgene in test animals enabled the scientists to control the interruption of neurogenesis with precision with respect to both timing and location and with no effects on neighboring cells.

According to author Michael Lehmann, "There are multiple avenues through which environmental enrichment can have a positive impact on depression. In this model we use a natural psychosocial stressor with relevance to social stress in humans, to induce depressive-like behaviors. We show that environmental enrichment can facilitate the recovery from social stress, and that adult neurogenesis is a requirement for the rehabilitating effects of enrichment."

The authors suggest that neurogenesis may be central to the ability of an animal to update emotional information upon exposure to a novel environment. With neurogenesis impaired, they may be unable to integrate information on the features of a new, changed environment. The resulting cognitive distortions may trigger symptoms of major depression.

Research suggests that one important consequence of environmental enrichment is its impact on the function of the body's stress response system. Animals in these enriched environments show positive effects on the physiology of stress resilience. In humans, successful antidepressant treatment is reflected in similar beneficial changes. Prior research has also linked neurogenesis with positive changes in the stress response system.

The authors also point out that in humans, physical exercise and positive psychosocial activity have beneficial effects on depression and stress resilience. Forms of entertainment that encourage mental activity, according to Lehmann, such as reading, video games, exercise and outdoor recreation could have longer lasting changes for many suffering from mild depressive symptoms than pharmacologic treatment, without the accompanying side effects.

Reference
Schloesser, R.J., Lehmann, M., Martinowich, K., Manji, H.K., and Herkenham, M. Environmental enrichment requires adult neurogenesis to facilitate recovery from psychosocial stress. Molecular Psychiatry 2010 Dec;15(12):1152-1163. Epub 2010 March 23.

Combination Antidepressant Therapy May Not Improve Odds of Remission Among Chronically Depressed

2011-05-16T13:06:00.000-07:00

A combination of two antidepressants may not be any more effective in treating chronic major depression than a single antidepressant, according to an NIMH-funded study published online ahead of print May 2, 2011, in the American Journal of Psychiatry CEUs for Counselora

Background
When treating depression, doctors sometimes prescribe a second antidepressant medication if a patient does not improve after several weeks. Because some antidepressants work for some people and not others, the hope is that adding another one will increase the odds of remission. However, treatment guidelines generally do not recommend adding another medication until it is evident the first one is not working.

Madhukar H. Trivedi, M.D., at the University of Texas Southwestern, and colleagues aimed to determine if combination antidepressant therapy as a first treatment step might produce a higher remission rate among people with chronic major depression. In the Combining Medications to Enhance Depression Outcomes (CO-MED) trial, 665 adult participants from several sites around the country were randomly assigned to one of three antidepressant combinations:

Escitalopram plus placebo
Bupropion sustained release plus escitalopram
Venlafaxine plus mirtazapine
Although participants did not know which treatments they were receiving, clinicians were aware of their patients' treatment assignments so that they could adjust doses as necessary to manage symptoms and side effects. The measurement of primary outcome was based on a self-reporting scale called the Quick Inventory of Depressive Symptoms.

Results of the Study
After three months, remission rates among the three groups all were around 38 percent. After seven months, remission rates continued to be similar among the three treatment groups and averaged around 45 percent. However, the venlafaxine plus mirtazapine combination was associated with a higher risk for side effects and serious adverse events compared to the other treatment options.

Significance
Despite other research suggesting combination antidepressant treatment may work better than a single medication, neither of the combination therapies in this trial appeared to be more effective than the single medication plus placebo. The researchers suggest that the chronic nature of participants' major depression may be associated with lower remission rates. They also noted that dosage differences may account for the difference in outcomes compared to other studies.

What's Next
Further evaluation is needed to determine if other drug combinations may affect remission rates differently. Results also highlight the need to evaluate biological markers as a means of personalizing treatment and possibly improving remission rates in major depression.

Reference
Rush AJ, Trivedi MH, Stewart JW, Nierenberg AA, Fava M, Kurian BT, Warden D, Morris DW, Luther JF, Husain MM, Cook IA, Shelton RC, Lesser IM, Kornstein SG, Wisniewski SR. Combining medications to enhance depression outcomes (CO-MED): Acute and long-term outcomes: a single-blind randomized study. Journal of American Psychiatry. online ahead of print May 2, 2011.

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Study Reveals New Clues to How Depression May Develop

2011-05-07T17:15:00.000-07:00

Activating neurons in a brain structure linked to disappointment increased depression-like behaviors in rats, while suppressing the neurons' activity reduced the behaviors, according to an NIMH-funded study. The findings help to explain previous research linking this brain structure to depression in humans and highlight a cellular process that hadn't been previously explored in mood disorders research. The study was published in the February 24, 2011, issue of Nature.

Background
Depression is one of the most studied mental disorders, with research honing in on brain structures, circuits, and biochemical processes critical to the development of the disorder. Yet many questions remain about how changes in the brain result in the observable symptoms and behaviors associated with depression. Counselor continuing education
To advance the science in this area, Bo Li, Ph.D., of Cold Spring Harbor Laboratory in New York, and colleagues, explored the role and connectivity of neurons in the lateral habenula (LHb) in rats that showed learned helplessness, a set of behaviors similar to symptoms of depression in people. The LHb is associated with how humans and animals experience disappointment or anticipate negative outcomes.

Results of the Study
The researchers found that LHb neurons receive input from many different brain regions involved in responding to stress. LHb neurons also connect out to many brain regions, such as the ventral tegmental area (VTA). The VTA helps to control reward-seeking behavior and may have a role in depression and other mood disorders.

LHb neurons in helpless rats were more responsive, such that communication signals to the VTA were more likely to be transmitted in the helpless rats than in control rats. In an attempt to moderate this phenomenon, the researchers tested the effects of deep brain stimulation (DBS), a surgical procedure currently being tested in humans for treatment-resistant depression. Applying continuous electrical stimulation directly to the LHb resulted in greatly reduced transmission to the VTA and a marked reduction in helpless behavior. The effects on transmission lasted only as long as the stimulation lasted. More intense stimulation resulted in stronger behavioral effects.

Significance
Although LHb activity was previously unstudied in the context of mood disorders, these findings suggest that this brain structure may actually play a central role in the development of depression.

What's Next
Further studies focusing on the molecular processes and signals underlying LHb activity in depression may reveal new targets for treatment development, according to the researchers. Such new treatments also may be able to reverse some forms of depressive disorders.

This study was supported in part by a Biobehavioral Research Award for Innovative New Scientists (BRAINS) from NIMH. Dr. Li was one of 12 researchers to receive this award in 2010.

Manic Phase of Bipolar Disorder Benefits from Breast Cancer Medication

2011-03-17T21:54:00.000-07:00

The medication tamoxifen, best known as a treatment for breast cancer, dramatically reduces symptoms of the manic phase of bipolar disorder more quickly than many standard medications for the mental illness, a new study shows. Researchers at the National Institutes of Health's National Institute of Mental Health (NIMH) who conducted the study also explained how: Tamoxifen blocks an enzyme called protein kinase C (PKC) that regulates activities in brain cells. The enzyme is thought to be over-active during the manic phase of bipolar disorder. Professional Counselor Continuing Education.

By pointing to PKC as a target for new medications, the study raises the possibility of developing faster-acting treatments for the manic phase of the illness. Current medications for the manic phase generally take more than a week to begin working, and not everyone responds to them. Tamoxifen itself might not become a treatment of choice, though, because it also blocks estrogen — the property that makes it useful as a treatment for breast cancer — and because it may cause endometrial cancer if taken over long periods of time. Currently, tamoxifen is approved by the Food and Drug Administration for treatment of some kinds of cancer and infertility, for example. It was used experimentally in this study because it both blocks PKC and is able to enter the brain.

Results of the study were published online in the September issue of Bipolar Disorders by Husseini K. Manji, MD, Carlos A. Zarate Jr., MD, and colleagues.

Almost 6 million American adults have bipolar disorder, whose symptoms can be disabling. They include profound mood swings, from depression to vastly overblown excitement, energy, and elation, often accompanied by severe irritability. Children also can develop the illness.

During the manic phase of bipolar disorder, patients are in "overdrive" and may throw themselves intensely into harmful behaviors they might not otherwise engage in. They might indulge in risky pleasure-seeking behaviors with potentially serious health consequences, for example, or lavish spending sprees they can't afford. The symptoms sometimes are severe enough to require hospitalization.

"People think of the depressive phase of this brain disorder as the time of risk, but the manic phase has its own dangers," said NIMH Director Thomas R. Insel, MD. "Being able to treat the manic phase more quickly would be a great asset to patients, not just for restoring balance in mood, but also because it could help stop harmful behaviors before they start or get out of control."

The three-week study included eight patients who were given tamoxifen and eight who were given a placebo (a sugar pill); all were adults and all were having a manic episode at the time of the study. Neither the patients nor the researchers knew which of the substances the patients were getting.

By the end of the study, 63 percent of the patients taking tamoxifen had reduced manic symptoms, compared with only 13 percent of those taking a placebo. Patients taking tamoxifen responded by the fifth day — which corresponds with the amount of time needed to build up enough tamoxifen in the brain to dampen PKC activity.

The researchers decided to test tamoxifen's effects on the manic phase of bipolar disorder because standard medications used to treat this phase, specifically, are known to lower PKC activity — but they do it through a roundabout biochemical route that takes time. Tamoxifen is known instead to block PKC directly. As the researchers suspected would happen, tamoxifen's direct actions on PKC resulted in much faster relief of manic symptoms, compared with some of the standard medications available today.

"We now have proof of principle. Our results show that targeting PKC directly, rather than through the trickle-down mechanisms of current medications, is a feasible strategy for developing faster-acting medications for mania," said Manji. "This is a major step toward developing new kinds of medications."

Findings from another recent NIMH study strengthen the results. This previous study showed that the risk of developing bipolar disorder is influenced by a variation in a gene called DGKH. The gene makes a PKC-regulating protein known to be active in the biochemical pathway through which standard medications for bipolar disorder exert their effects - another sign that PKC is a promising direct target at which to aim new medications for the illness.

"Mania isn't just your average mood swing, where any of us might feel upbeat in response to something that happens. It's part of a brain disorder whose behavioral manifestations can severely undermine people's jobs, relationships, and health," said Zarate. "The sooner we can help patients get back on an even keel, the more we can help them avoid major disruptions to their lives and the lives of people around them."

Reference
Zarate Jr. CA, Singh JB, Carlson PJ, Quiroz J, Jolkovsky L, Luckenbaugh DA, Manji HK. Efficiency of a Protein Kinase C Inhibitor (Tamoxifen) in the Treatment of Acute Mania: A Pilot Study. Bipolar Disorders, online ahead of print, September 2007.
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The mission of the NIMH is to transform the understanding and treatment of mental illnesses through basic and clinical research, paving the way for prevention, recovery and cure. For more information, visit the NIMH website.

The National Institutes of Health (NIH) — The Nation’s Medical Research Agency — includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit the NIH website.

International Impact of Bipolar Disorder Highlights Need for Recognition and Better Treatment Availability

2011-03-09T18:40:00.000-08:00

The severity and impact of bipolar disorder and bipolar-like symptoms are similar across international boundaries, according to a study partially funded by NIMH. The results were published in the March 2011 issue of the Archives of General Psychiatry. Marriage and Family Therapist Continuing Education

Background
Although several studies report prevalence rates of mental disorders on an international level, the numbers have varied because each study tends to use different methodology and definitions. To remedy this, the World Health Organization’s World Mental Health (WMH) survey initiative used consistent data collection methods in 11 countries in the Americas, Europe, Asia, the Middle East and New Zealand. The survey also applied common diagnostic definitions for mental disorders found in the Diagnostic and Statistical Manual for Mental Disorders (DSM-IV).

NIMH researcher Kathleen Merikangas, Ph.D., and colleagues used WMH data to track prevalence rates of three subtypes of bipolar spectrum disorder—bipolar I, bipolar II and bipolar disorder not otherwise specified (BD-NOS). Bipolar I disorder is considered the classic form of the illness, in which a person experiences recurrent episodes of mania and depression. People with bipolar II disorder experience a milder form of mania called hypomania that alternates with depressive episodes. People with BD-NOS, sometimes called subthreshold bipolar disorder, have manic and depressive symptoms as well, but they do not meet strict criteria for any specific type of bipolar disorder noted in the DSM-IV. Yet, BD-NOS can significantly impair those who have it.

Results of the Study
The prevalence rates of bipolar I, bipolar II and BD-NOS were 0.6 percent, 0.4 percent, and 1.4 percent, respectively, with an overall bipolar spectrum rate of 2.4 percent. The United States had the highest prevalence rate of bipolar spectrum (4.4 percent), while India had the lowest rate (0.1 percent). More than half of those with bipolar disorder in adulthood note that their illness began in their adolescent years.

Across all countries studied, 75 percent of those who had bipolar symptoms met criteria for having at least one other disorder. Anxiety disorders, especially panic disorder, were the most common coexisting disorders, followed by behavior disorders and substance use disorders. Patterns of coexisting conditions were similar across countries.

Less than half of those with bipolar symptoms received mental health treatment. In low income countries, only 25 percent reported having contact with a mental health professional.

Significance
This study provides the first international prevalence data on bipolar disorder using reliable, standardized methodology. It highlights the international impact of bipolar disorder and the need for better recognition and treatment availability. The findings also support the notion that, given its multi-dimensional nature, bipolar disorder may be better characterized as a spectrum disorder.

In addition, because so many people note that their illness began in adolescence — a critical time of life for educational, occupational and social development — early detection, intervention, and possibly prevention of subsequent coexisting disorders and complications should be emphasized.

What’s Next
More research is needed to better define the thresholds and boundaries of bipolar symptoms. In addition, further research is needed to better understand why and how the disorder tends to originate in adolescence and persist into adulthood, and how it intersects with coexisting mental disorders.

Reference
Merikangas KR, Jin R, He J, Kessler RC, Lee S, Sampson NA, Viana MC, Andrade LH, Hu C, Karam EG, Mora MEM, Browne MO, Ono Y, Posada-Villa J, Sagar R, Zarkov Z. Prevalence and correlates of bipolar spectrum disorder in the World Mental Health Survey Initiative. Archives of General Psychiatry. March 2011. 68(3):241-251.

Most Teens with Eating Disorders Go Without Treatment

2011-03-08T11:39:00.000-08:00

About 3 percent of U.S. adolescents are affected by an eating disorder, but most do not receive treatment for their specific eating condition, according to an NIMH-funded study published online ahead of print March 7, 2011, in the Archives of General Psychiatry. Social Worker Continuing Education
Background
Kathleen Merikangas, Ph.D., of NIMH and colleagues analyzed data from the National Comorbidity Study-Adolescent Supplement (NCS-A), a nationally representative, face-to-face survey of more than 10,000 teens ages 13 to 18. Previously published results found that about 20 percent of youth are affected by a severe mental disorder, and a substantial proportion of these youth do not receive mental health care.

In this new study, the authors tracked the prevalence of eating disorders and the proportion of those youth who received treatment for these disorders.

Results of the Study
According to the data, 0.3 percent of youth have been affected by anorexia, 0.9 percent by bulimia, and 1.6 percent by binge-eating disorder. The researchers also tracked the rate of some forms of eating disorders not otherwise specified (ED-NOS), a catch-all category of symptoms that do not meet full criteria for specific disorders but still impact a person’s life. ED-NOS is the most common eating disorder diagnosis. Overall, another 0.8 percent had subthreshold anorexia, and another 2.5 percent had symptoms of subthreshold binge-eating disorder.

In addition,

Hispanics reported the highest rates of bulimia, while Whites reported the highest rates of anorexia.
The majority who had an eating disorder also met criteria for at least one other psychiatric disorder such as depression.
Each eating disorder was associated with higher levels of suicidal thinking compared to those without an eating disorder.
Significance
The prevalence of these disorders and their association with coexisting disorders, role impairment, and suicidal thinking suggest that eating disorders represent a major public health concern. In addition, the significant rates of subthreshold eating conditions support the notion that eating disorders tend to exist along a spectrum and may be better recognized by doctors if they included a broader range of symptoms. In addition, the findings clearly underscore the need for better access to treatment specifically for eating disorders.

Reference
Swanson SA, Crow SJ, LeGrange D, Swendsen J, Merikangas KR. Prevalence and correlates of eating disorders in adolescents: results from the National Comorbidity Survey Replication Adolescent Supplement. Archives of General Psychiatry. Online ahead of print March 7, 2011.

New study shows that most substance abuse treatment programs accept private health insurance

2011-03-02T11:57:00.000-08:00

Study indicates that most will be ready to adapt to greater health care coverage provided by the Affordable Care Act and Mental Health Parity and Addiction Equity Act
A new nationwide survey of substance abuse treatment facilities reveals that in 2008 nearly two thirds (65 percent) accepted some private health insurance payment. The survey conducted by the Substance Abuse and Mental Health Services Administration (SAMHSA) also indicated that there were significant differences in the level of private insurance payment acceptance among different types of substance abuse treatment facilities. Professional Counselor Continuing Education
For example, private insurance payment was accepted by 85 percent of facilities with a primary focus on mental health services, 82 percent of facilities offering general health care, and 78 percent of facilities offering a mix of mental health and substance abuse treatment services. On the other hand, private insurance payment was accepted by only 56 percent of facilities primarily focused on substance abuse treatment services and 37 percent of facilities focused on other services (e.g., providing shelter for people experiencing homelessness).

"The ability to bill third party payers including private insurers and Medicaid is critical to the survival of treatment facilities," said SAMHSA Administrator Pamela S. Hyde, J.D. "The dramatic increase in numbers of people covered with health insurance that includes coverage for mental and substance use disorders will revolutionize the behavioral health field. Treatment facilities need to be preparing now and SAMHSA has technical assistance resources available to help."

The study noted that substance abuse treatment facilities that accepted private insurance payments were far more likely than those that did not to accept payment from other sources such as Medicaid (68 percent versus 31 percent), state-financed health insurance (53 percent versus 14 percent) and Medicare (48 percent versus 12 percent).

This capacity of substance abuse programs to bill Medicaid may become more critical as Medicaid’s coverage of substance abuse services becomes more comparable to its coverage of mental health services.

Other significant differences between treatment programs that accepted private insurance payment and those that did not include the use of cognitive-behavioral therapy services at their facilities (70 percent versus 58 percent). Facilities accepting private insurance were more likely than others to accept adolescents into their programs (58 percent versus 33 percent).

The study also showed that treatment facilities located in more central large urban areas were less likely than rurally situated facilities to accept private insurance payment (54 percent versus 78 percent). In general the further away facilities were from central city areas, the more likely they were to accept private insurance payment.

The study, Acceptance of Private Health Insurance in Substance Abuse Treatment Facilities is based on data from SAMHSA’s Treatment Episode Data Set (TEDS) -- a reporting system involving treatment facilities from across the country. The study was developed as part of SAMHSA’s strategic initiative on data, outcomes, and quality -- an effort to inform policy makers and service providers on the nature and scope of behavioral health issues

Same Genes Suspected in Both Depression and Bipolar Illness

2011-02-22T10:03:00.000-08:00

Increased Risk May Stem From Variation in Gene On/Off Switch
Source: UCSC Genome BrowserResearchers, for the first time, have pinpointed a genetic hotspot that confers risk for both bipolar disorder and depression. People with either of these mood disorders were significantly more likely to have risk versions of genes at this site than healthy controls. One of the genes, which codes for part of a cell's machinery that tells genes when to turn on and off, was also found to be over-expressed in the executive hub of bipolar patients' brains, making it a prime suspect. The results add to mounting evidence that major mental disorders overlap at the molecular level. LPCC Continuing Education
"People who carry the risk versions may differ in some dimension of brain development that may increase risk for mood disorders later in life," explained Francis McMahon, M.D., of the NIMH Mood and Anxiety Disorders Program, who led the study.

McMahon and an international team of investigators, supported, in part by NIMH, report on the findings of their genome-wide meta-analysis online January 17, 2010 in the journal Nature Genetics.

Background
Major mood disorders affect 20 percent of the population and are among the leading causes of disability worldwide. It's long been known that bipolar disorder and unipolar depression often run together in the same families, hinting at some shared lineage. Yet, until now, no common genes or chromosomal locations had been identified.

McMahon and colleagues analyzed data from five different genome-wide association studies (GWAS) totaling more than 13,600 people, and confirmed their results in 3 additional independent samples totaling 4,677 people.

Findings of This Study
Genetic variations on Chromosome 3 were significantly associated with both mood disorders. The suspect gene, called PBRM1, codes for a protein critical for chromatin remodeling, a key process in regulating gene expression. A neighboring gene is involved in the proliferation of brain stem cells.

The researchers pinpointed a "protective" version of the PBRM1 gene that is carried by 41 percent of healthy controls, but only 38 percent of people with bipolar and unipolar depression. The risk version was found in 62 percent of mood disorder cases and 59 percent of controls. The researchers also showed that PBRM1 is expressed more in the prefrontal cortex of people with bipolar disorder than in controls.

Significance
Since mood disorders likely involve altered gene expression during brain development and in response to stress, PBRM1's profile makes it a good potential candidate gene. This first genetic evidence of unipolar/bipolar overlap is also the first significant genome-wide association with any psychiatric illness in the Chromosome 3p region.

However, the findings underscore limitations of the GWAS approach, which looks for connections to gene versions that are common in the population. Having one copy of this risk variant increases vulnerability for developing a mood disorder by a modest 15 percent. Why do some people with this variant — and presumably other, yet to be discovered, shared risk genes — develop bipolar disorder while others develop unipolar depression or remain healthy? Environmental influences and epigenetic factors may be involved, suggest the researchers, who note that "genetic association findings so far seem to account for little of the inherited risk for mood disorders."

"Our results support the growing view that there aren't common genes with large effects that confer increased risk for mood disorders," said McMahon. "If there were, in this largest sample to date, we would have found them. The disorders likely involve many genes with small effects — and different genes in different families — complicating the search. Rarer genes with large effects may also exist."

What's Next?
Ultimately, findings such as these may lead to identification of common biological pathways that may play a role in both unipolar and bipolar illness and suggest strategies for better treatment, said McMahon. The results add to other evidence of overlap that is spurring a new NIMH initiative to make sense of research findings that don't fit neatly into current diagnostic categories. See: Genes and Circuitry, Not Just Clinical Observation, to Guide Classification for Research.

Bipolar disorder and unipolar depression often run in the same families, as this pedigree diagram illustrates. The new study is the first to trace both illnesses to a shared chromosomal hotspot.

Source: NIMH Genetics Initiative Bipolar Disorder Consortium

Reference
Meta-analysis of genome-wide association data identifies a risk locus for major mood disorders on 3p21.1.the Bipolar Disorder Genome Study (BiGS) Consortium, McMahon FJ, Akula N, Schulze TG, Muglia P, Tozzi F, Detera-Wadleigh SD, Steele CJ, Breuer R, Strohmaier J, Wendland JR, Mattheisen M, Mühleisen TW, Maier W, Nöthen MM, Cichon S, Farmer A, Vincent JB, Holsboer F, Preisig M, Rietschel M. Nat Genet. 2010 Jan 17. [Epub ahead of print]PMID: 20081856

Samples included in the meta-analysis:
dbGaP National Institute of Mental Health bipolar disorder
Genetic Association Information Network MDD
Wellcome Trust Case Control Consortium
German sample
Systematic Treatment Enhancement Program for Bipolar Disorder

Preference for Moving Shapes vs. People Linked to Autism in Babies

2011-02-21T11:08:00.000-08:00

A 1-minute video showing computer screensavers next to videos of dancing children may prove to be a simple, inexpensive screening tool for autism spectrum disorders (ASD) in toddlers. According to an NIMH-funded study, infants as young as 14 months old who had autism spent more time looking at the moving shapes than social images, in contrast to typically developing children and those who had delays but not autism. The study was published online, September 6, 2010, in the Archives of General Psychiatry. Alcoholism and Drug Abuse Counselors Continuing Education

Background
Among the hallmark signs of ASD are repetitive behaviors, which may include persistent and intense preoccupation with objects. For example, a child with ASD may fixate on moving objects or parts of objects, like the moving blade of a fan or spinning tires on a car. Whether this behavior could predict or identify ASD in very young children had not previously been studied.

About the study
To study this phenomenon, Karen Pierce, Ph.D., at the University of California San Diego School of Medicine, and colleagues enrolled 110 toddlers, ages 14-42 months. Of this group, 37 had ASD, 22 were developmentally delayed (DD) but did not have ASD, and 51 had typical development (TD).

The toddlers viewed a 1-minute video showing geometric patterns on one side—basically a computer screensaver—and children exercising, dancing, or otherwise in action on the other side. Using eye tracking technology, the researchers measured how long the toddlers looked at each type of movement and how many times they switched from looking at one type or part of an image to another.

Results
In this study, 40 percent of toddlers with ASD spent significantly more time fixating on moving geometric patterns compared with 9.9 percent in the DD group and 1.9 percent of TD children. The other 60 percent of toddlers with ASD performed similarly to their DD and TD peers, showing a preference for social movement. If a toddler spent more than 69 percent of the time fixating on geometric patterns, ASD could be predicted 100 percent of the time.

While viewing the video, DD and TD children tended to let their eyes wander, changing their focus from one part of an image to another. Among toddlers with ASD, however, those who preferred geometric patterns showed significantly less eye movement when viewing geometric patterns, gazing at only a few parts of an image for extended periods of time. These children also showed significantly more frequent eye movement than DD or TD toddlers when viewing social movement.

A subsample of 41 toddlers were re-tested an average of 8 months later. The researchers found that the toddlers' preferences generally stayed the same between the original study and the follow-up.

Significance
The results suggest that assessing infants' visual preference for geometric vs. social movement, including the amount of time they spend staring at moving geometric patterns, is an inexpensive and easy-to-conduct screening method for ASD.

"What an infant prefers to look at when given a choice between two images may turn out to be a more clearly observable indicator of autism risk than how he or she looks at a single image," Pierce said.

That most of the toddlers with ASD in this study responded in the same way as DD and TD children came as a surprise to the researchers. They suggest that differing patterns of brain activity may underlie toddlers' preference for geometric or social movement. Brain imaging studies would help to confirm whether subgroups of ASD can be distinguished by brain activity patterns.

What's Next
According to the researchers, this screening tool may also be useful in identifying babies who would benefit from further developmental evaluation or even early treatment. The findings also provide new lines of inquiry regarding the role of various brain regions involved in processing social cues and shifting attention in the development of ASD.

Sample "social" image (left) and "geometric" image (right) from Pierce's eye tracking study. Forty percent of babies later diagnosed as having autism preferred to look at the moving geometric images, in contrast to just 2 percent of typically developing babies.

Source: Karen Pierce, Ph.D., UC San Diego

Reference
Pierce K, Conant D, Hazin R, Stoner R, Desmond J. A Preference for Geometric Patterns Early in Life is a Risk Factor for Autism. Arch Gen Psychiatry. 2010 Sep 6. [Epub ahead of print]

Social Phobia Patients Have Heightened Reactions to Negative Comments

2011-02-20T09:28:00.000-08:00

In a study using functional brain imaging, NIMH scientists found that when people with generalized social phobia were presented with a variety of verbal comments about themselves and others ("you are ugly," or "he's a genius," for example) they had heightened brain responses only to negative comments about themselves. Knowledge of the social cues that trigger anxiety and what parts of the brain are engaged when this happens can help scientists understand and better treat this anxiety disorder. LPC Continuing Education
Background

Generalized social phobia (GSP) is the most common of all anxiety disorders. It is marked by overwhelming anxiety and self-consciousness in social situations. One approach to understanding anxiety disorders is to use functional brain imaging (fMRI) to explore how the brain responds to different types of social signals. fMRI can provide information on the relative activity—and thus the engagement—of different parts of the brain by tracking the local demands made for oxygen delivered by circulating blood. Scientists using this technology have reported, for example, that people with GSP have heightened responses to a variety of positive, negative, and neutral facial expressions, not just expressions that others perceive as threatening.

Results of this Study

People with GSP had heightened responses to negative comments (relative to a comparison group without the disorder) in two brain areas: the first, the medial prefrontal cortex (MPFC), is involved in the sense and evaluation of self; the second, the amygdala, is central to emotional processing. The responses revealed by scanning paralleled the participants' self-report of how they felt after seeing the various positive, negative, and neutral comments presented.

Significance

This work, conducted by NIMH intramural investigators Karina Blair, Ph.D., Daniel Pine, M.D., and colleagues, provided information on the specific social cues that trigger anxiety in people with GSP. It adds to previous evidence that the amygdala is involved and, in implicating the MPFC, gives clues for further research to explore on how people with GSP interpret social cues. Functional brain scanning can thus help to define patterns of brain functioning that underlie anxiety disorders, providing information that can inform treatment.

What's Next?

A previous study by these investigators found that the reaction of the brain to facial expressions was different in people with GSP than in those with general anxiety disorder (GAD). This suggests that the two disorders do not represent mild and severe forms in a single spectrum of anxiety disorders, but two neurologically different disorders.

Continuing research will reexamine these differences to see if they occur across different tasks, providing confirmation for understanding them as different disorders, which could lead to more targeted and effective forms of treatment for each disorder. Future studies will also explore more deeply the nature of the thought process underlying the reaction of people with GSP to negative comments about themselves and the interaction of the amygdala and MPFC. Finally, brain scanning offers a means to study the effects of treatment; scanning can, for example, provide information on the effects of medications in these parts of the brain.

Left amygdala (left) and medial prefrontal cortex (circled in yellow, right) activated strongly in people with social phobia (in comparison to those without GSP) in response to criticism of themselves.

References
Blair, K. et al. American Journal of Psychiatry. 2008 Sep;165(9):1193-202. Epub 2008 May 15. PMID: 18483136

Blair, K. et al. Archives of General Psychiatry. 2008 Oct;65(10):1176-1184.

Brain Activity Patterns in Anxiety-Prone People Suggest Deficits in Handling Fear

2011-02-15T16:59:00.000-08:00

Anxiety as a personality trait appears to be linked to the functioning of two key brain regions involved in fear and its suppression, according to an NIMH-funded study. Differences in how these two regions function and interact may help explain the wide range of symptoms seen in people who have anxiety disorders. The study was published February 10, 2011 in the journal, Neuron. Social Worker Continuing Education
Background
Anxiety disorders are characterized by an excessive, irrational dread of everyday situations. Some people may experience general, chronic anxiety, while others become anxious in response to one or more specific triggers. Many studies have implicated two brain regions in anxiety—the amygdala in fear responses and the ventral prefrontal cortex (vPFC) in suppressing or regulating fear. Questions remain, however, about how trait anxiety—a person's typical anxiety level on any given day—affects amygdala and vPFC functioning.

To explore these questions, Sonia Bishop, Ph.D., of the University of California Berkeley (at the University of Cambridge (UK) at the time of data collection), and colleagues designed a series of experiments to determine how the amygdala and vPFC responded in three types of situations:

Cued fear—a neutral signal or cue is followed by an aversive event. In this study, the cue was an actor in a video placing his hands over his ears and the aversive event was a loud scream. The cue provided a reliable prediction of the aversive event. Cued fear can be compared to the situation-specific type of anxiety experienced by those with a specific phobia, such as a fear of heights.
Contextual fear—a neutral cue and an aversive event occur independently of each other. The cue did not provide a reliable prediction of the aversive event. Contextual fear may be similar to the non-specific anxiety that affects people with generalized anxiety disorder.
Safety—a neutral signal or cue occurs alone without an aversive event. The safety situation served as a comparison for the other two situations.
The researchers assessed the level of trait anxiety of 23 healthy study participants, ages 18 to 41. Each participant underwent a training session that exposed them to the above conditions. Two days after the training session, participants had their brain activity recorded through functional magenetic resonance imaging (fMRI), a noninvasive imaging method, while re-exposed to the cued fear, contextual fear, and safety conditions in the scanner.

Results from the Study
Participants with high trait anxiety showed greater amygdala response to cued fear situations compared to those with low trait anxiety. According to the researchers, this finding suggests that individual differences in amygdala response may contribute to differences in vulnerability to cue-specific anxiety disorders, such as specific phobia.

Participants with low trait anxiety showed increased vPFC activity in response to cued fear and more strongly sustained vPFC activity during contextual fear situations, compared to those with high trait anxiety. Notably, vPFC activity in participants with low trait anxiety occurred before the aversive event had ceased. The researchers suggest that this process—engaging brain areas that help to suppress fear even when the source of fear is still present—may help to protect against chronic anxiety disorders even when stressful life events are ongoing.

Significance
The study's findings support a potential role of the amygdala in vulnerability to anxiety disorders and a potential role of the vPFC in protection against them.

"Individual differences in the functioning of one or both of these brain regions may help account for the variability in symptoms across different anxiety disorders," said Bishop. "A better understanding of these processes may help inform treatment choice and predict treatment response."

This study was supported in part by a Biobehavioral Research Award for Innovative New Scientists (BRAINS) from NIMH. Dr. Bishop was one of 12 researchers to receive this award in 2010.

Reference
Indovina I, Robbins TW, Núñez-Elizalde AO, Dunn BD, Bishop SJ. Fear-Conditioning Mechanisms Associated with Trait Vulnerability to Anxiety in Humans. Neuron. 2011 Feb 10;69(3):563-71.

Family-Focused Therapy Effective in Treating Depressive Episodes of Bipolar Youth

2011-02-08T22:44:00.000-08:00

Adolescents with bipolar disorder who received a nine-month course of family-focused therapy (FFT) recovered more quickly from depressive episodes and stayed free of depression for longer periods than a control group, according to an NIMH-funded study published September 2008 in the Archives of General Psychiatry. MFT Continuing Education
In FFT, the patient and his or her family are heavily involved in psychosocial treatment sessions. They learn to identify the symptoms of bipolar disorder, its course, and how to spot impending episodes or relapses. Patients and families also learn communication and problem-solving skills, and illness management strategies. For this trial, David Miklowitz, Ph.D., of the University of Colorado, and colleagues adapted the therapy to the needs of adolescents and their families.

The 58 participants, ages 12 to 17, were recruited from the University of Colorado and the University of Pittsburgh, and randomly assigned to either 21 50-minute sessions of FFT or to a control intervention called enhanced care (EC). EC included three 50-minute sessions with patients and their families that focused on relapse prevention planning, taking medication as directed, and dealing with conflict at home. All participants took mood-stabilizing medication such as lithium as well. Participants were evaluated every three months during the first year of the two-year study and every six months in the second year.

Although the rate of recovery was high for all participants—91.4 percent—participants in the FFT group recovered faster from depressive symptoms than the EC group. This was especially pronounced in youths who were in the midst of a major depressive episode at the beginning of the study. In the FFT group, the average time to recovery from major depression was 10 weeks, compared to 14 weeks for the EC group. The FFT group also spent less time depressed—about three weeks compared to the EC group’s five weeks—and had less severe depressive symptoms over the two years than the EC group.

The results are similar to those of the NIMH-funded Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD), which found that adult participants who received up to 30 sessions of FFT, cognitive behavioral therapy, or interpersonal therapy plus mood stabilizing medications recovered more rapidly from depressive episodes than the participants who received only three psychoeducational sessions in addition to medication.

The adolescent participants in the new study eventually recovered from manic symptoms as well, but neither of the treatments showed a statistically significant advantage in treating mania, a finding also consistent with STEP-BD results. The researchers conclude that for full recovery from adolescent bipolar disorder, FFT may need to be augmented with psychoeducational interventions that are effective against mania symptoms.

Reference
Miklowitz DJ, Axelson DA, Birmaher B, George EL, Taylor DO, Schneck CD, Beresford CA, Dickinson M, Craighead WE, Brent DA. Family-focused treatment for adolescents with bipolar disorder. Archives of General Psychiatry. 2008 Sept; 65(9).

Key Molecule in Inflammation-Related Depression Confirmed

2011-02-04T20:28:00.000-08:00

Scientists have confirmed the role of an immune-activated enzyme in causing inflammation-related depression-like symptoms in mice. The work clarifies how the immune system can trigger depression and, more broadly, demonstrates the potential of this animal model for exploring the relationship between chronic inflammation—a common feature of diseases such as heart disease, cancer, and diabetes—and depression. LPC Continuing Education
Background

When an individual is infected with viruses or bacteria, cells of the immune system respond by secreting proteins called cytokines. These cytokines not only trigger inflammation and orchestrate the body's immune response against the infection, but they also cause changes in behavior, such as fatigue and withdrawal. Beyond these commonly experienced behavioral signs of illness, previous research has shown that cytokines can also cause depression in people with physical illnesses but who have no prior history of mental illness. For instance, around one-third of patients receiving the cytokine interferon-α for treatment of cancer or hepatitis C develop major depression. Clinical evidence has suggested that an enzyme (IDO) activated by these same cytokines might be a key player.

This Study

In this work, scientists used a weakened form of the tuberculosis relative, bacille Calmette-Guérin (BCG), to model chronic inflammation. This strain of bacteria is used outside the U.S. as a vaccine for tuberculosis. Infection of mice with high doses of BCG persistently activates the immune system; as a consequence, the mice develop depressive-like behavior after initial signs of illness have subsided. This study demonstrated that mice in which the gene for IDO is knocked out, or in which IDO is chemically blocked, do not exhibit depressive-like effects. The authors conclude that IDO is a necessary step in the development of this immunity-related depression.

Significance

The compound used in this work to block IDO may have potential as a treatment for depression in instances when immunotherapy such as interferon-α is used. In addition, chronic, low-grade inflammation is a feature not only of infectious diseases, but conditions like cancer, diabetes, obesity, and heart disease. Depression co-occurs frequently with these common diseases and is associated with poorer prospects for future health. Work in this animal model has the potential to provide insight into the role of chronic inflammation in precipitating depression that is often associated with these chronic conditions.

Scientists at the University of Illinois, Urbana-Champaign, led by Jason O'Connor, Robert Dantzer, and Keith Kelley, conducted this work with collaborators at the Centre National de la Recherche Scientifique, Bordeaux, France, and Miles Herkenham at the National Institute of Mental Health. The National Institute of Mental Health and the National Institute on Aging funded this research.

What's Next

The use of BCG in this mouse model offers a means to explore the molecular cascade induced by IDO that leads to inflammation-associated depression. The exact mechanism by which IDO causes these depressive behaviors is not yet clear; exploration of the downstream effects of IDO may provide additional avenues for developing approaches to blocking the development of immune-related depression.

Reference
O'Connor, J.C., Lawson, M.A., Andre, C., Briley, E.M., Szegedi, S.S., Lestage, J., Castanon, N., Herkenham, M., Dantzer, R., and Kelley, K.W. Induction of IDO by Bacille Calmette-Guerin Is Responsible for Development of Murine Depressive-Like Behavior. Journal of Immunology 2009 Mar 1;182(5):3202-12. PMID: 19234218

Combination Treatment for Psychotic Depression Holds Promise

2011-02-03T15:40:00.000-08:00

A combination of an atypical antipsychotic medication and an antidepressant known as a selective serotonin reuptake inhibitor (SSRI) may be more effective in treating psychotic depression than an atypical antipsychotic alone, according to results from an NIMH-funded clinical study. Social Worker Continuing Education
Background
Psychotic depression is characterized by major depression accompanied by symptoms such as hallucinations, delusions, and breaks with reality. A person with psychotic depression may be unwilling or unable to care for him or herself and often is admitted to the hospital. Typically, psychotic depression is treated with electroconvulsive therapy (ECT), known to be effective but not always acceptable to patients and their families. It is less commonly treated with an antipsychotic or an antipsychotic plus an antidepressant.

Results of the Study
In a 12-week trial, all 259 participants were required to have psychotic depression with at least one delusion or irrational belief, although not all had hallucinations. Participants were randomly assigned to one of two treatments—the atypical antipsychotic olanzapine (Zyprexa) plus the SSRI sertraline (Zoloft) (combination therapy), or to olanzapine plus a placebo, or inactive, pill (monotherapy). Barnett S. Meyers, M.D., of Cornell University, and colleagues compared rates of remission and side effects among the participants. They also compared the responses of the 117 patients younger than 60 with the responses of the 142 patients older than 60 to determine if the two age groups responded differently.

The researchers conducted assessments at the beginning of the trial, weekly for the first six weeks, and then every other week until week 12. They found that 42 percent of those on combination therapy remitted compared to 24 percent of those on the monotherapy, with no significant differences in remission rates between age groups. Combination therapy's superiority became most evident between weeks eight and 12 of the trial.

Overall, the two age groups experienced comparable side effects. Both groups experienced significant increases in cholesterol and triglyceride levels, and both gained weight. However, the younger age group gained twice as much on average—about 14 pounds—compared to the older group, which gained an average of 7 pounds. This finding is consistent with other reports that have found older adults tend to gain less weight with atypical antipsychotics, specifically olanzapine, the researchers said. However, older participants also tended to be on lower doses of the antipsychotic than the younger adults, which may partially explain the disparity in weight gain, according to the researchers.

Unexpectedly, older participants had no more difficulty tolerating the medications than younger participants, nor were they any more likely to experience falls, sedation or have greater movement disorder symptoms than younger participants.

Overall, about 45 percent of participants dropped out of the study, although the drop-out rate was lower in the combination treatment group (37 percent) compared to the monotherapy group (53 percent).

Significance
Because the drop-out rate was relatively high and no follow-up data on those who discontinued were collected, the authors caution against applying the study's results to clinical practice prematurely. Still, the authors suggest that combination therapy holds promise as an alternative therapy to ECT. "Psychotic depression is difficult to treat," said NIMH Director Thomas R. Insel, M.D. "This study provides insight into one approach to treatment that may be a valid alternative for many patients who cannot or will not undergo ECT."

What's Next
Longer-term studies are needed to evaluate side effects. "Future research must weigh the benefits of continuing atypical antipsychotic medication beyond 12 weeks against the risks of associated metabolic side effects," lead author Meyers concluded.

Reference
Meyers BS, Flint AJ, Rothschild AJ, Mulsant BH, Whyte EM, Peasley-Miklus C, Papademetriou E, Leon AC, Heo M for the STOP-PD study group. A double-blind randomized controlled trial of olanzapine plus sertraline versus olanzapine plus placebo for psychotic depression—The Study of Pharmacotherapy of Psychotic Depression (STOP-PD). Archives of General Psychiatry. 2009;66(3):838-847.

Air Force Suicide Prevention Program Reduces Suicide Rate

2011-02-02T10:46:00.000-08:00

U.S. Air Force Photo/ Staff Sgt. Angelita M. LawrenceA U.S. Air Force suicide prevention program is associated with reduced suicide rates among Air Force personnel during times in which the program was rigorously implemented and monitored, according to an NIMH-funded study published online ahead of print May 13, 2010, in the American Journal of Public Health. LCSW CEUs
Background
The Air Force Suicide Prevention Program (AFSPP) was implemented in 1997. Based on the premise that individuals at risk for suicide exhibit early warning signs, AFSPP emphasizes leadership and community involvement in reducing suicide by encouraging Air Force leaders to actively support and get involved with suicide prevention efforts. It trains commanders in how and when to seek out mental health services for their troops, provides training to all military and civilian personnel in suicide prevention, and incorporates other community-based components.

Kerry Knox, Ph.D., of the University of Rochester Medical Center, and colleagues studied the impact of AFSPP in reducing suicide among Air Force personnel from 1997 until 2008. They examined suicide rates from 1981 to 2008 to provide historical context during three military conflicts, and a downsizing of the Air Force that occurred in the 1990s.

Results of the Study
The researchers found that suicide rates were significantly lower after the program was launched than before—an average of two suicides per 100,000 per quarter occurred during the intervention period compared to three suicides per 100,000 per quarter prior to the intervention rollout. During the third quarter of 2004, however, suicide rates increased. Knox and colleagues suggest that the upward spike may have been the result of a diminished implementation of ASFPP due to increased demands from the two ongoing wars in Iraq and Afghanistan. In response, Air Force leadership took steps to strengthen implementation of the program and ensure compliance of its components, according to the authors.

Significance
The results suggest that the program is effective but its success is contingent on continuous implementation efforts and ongoing monitoring. The program cannot be maintained by "inherent momentum," the authors concluded.

What's Next
The authors suggest that the program, if maintained and monitored for compliance, can continue to keep suicide rates low in the Air Force. They also suggest that the program could be implemented in other communities and organizations to prevent suicide and reduce the stigma associated with the mental and psychosocial problems that often precipitate suicide attempts.

Reference
Knox K, Pflanz S, Talcott GW, Campise RL, Lavigne JE, Bajorska A, Tu X, Caine ED. The US Air Force Suicide Prevention Program: Implications for Public Health Policy. American Journal of Public Health. Online ahead of print May 13, 2010.

Study Identifies Three Effective Treatments for Childhood Anxiety Disorders

2011-02-01T09:53:00.000-08:00

Treatment that combines a certain type of psychotherapy with an antidepressant medication is most likely to help children with anxiety disorders, but each of the treatments alone is also effective, according to a new study funded by the National Institutes of Health’s National Institute of Mental Health (NIMH). The study was published online Oct. 30, 2008, in the New England Journal of Medicine. MFT Continuing Education

“Anxiety disorders are among the most common mental disorders affecting children and adolescents. Untreated anxiety can undermine a child’s success in school, jeopardize his or her relationships with family, and inhibit social functioning,” said NIMH Director Thomas R. Insel, M.D. “This study provides strong evidence and reassurance to parents that a well-designed, two-pronged treatment approach is the gold standard, while a single line of treatment is still effective.”

The Child/Adolescent Anxiety Multimodal Study (CAMS) randomly assigned 488 children ages 7 years to 17 years to one of four treatment options for a 12-week period:

Cognitive behavioral therapy (CBT), a specific type of therapy that, for this study, taught children about anxiety and helped them face and master their fears by guiding them through structured tasks;
The antidepressant sertraline (Zoloft), a selective serotonin reuptake inhibitor (SSRI);
CBT combined with sertraline;
pill placebo (sugar pill).
The children, recruited from six regionally dispersed sites throughout the United States, all had moderate to severe separation anxiety disorder, generalized anxiety disorder or social phobia. Many also had coexisting disorders, including other anxiety disorders, attention deficit hyperactivity disorder, and behavior problems.

John Walkup, M.D., of Johns Hopkins Medical Institutions, and colleagues found that among those in combination treatment, 81 percent improved. Sixty percent in the CBT-only group improved, and 55 percent in the sertraline-only group improved. Among those on placebo, 24 percent improved. A second phase of the study will monitor the children for an additional six months.

“CAMS clearly showed that combination treatment is the most effective for these children. But sertraline alone or CBT alone showed a good response rate as well. This suggests that clinicians and families have three good options to consider for young people with anxiety disorders, depending on treatment availability and costs,” said Walkup.

Results also showed that the treatments were safe. Children taking sertraline alone showed no more side effects than the children taking the placebo and few children discontinued the trial due to side effects. In addition, no child attempted suicide, a rare side effect sometimes associated with antidepressant medications in children.

CAMS findings echo previous studies in which sertraline and other SSRIs were found to be effective in treating childhood anxiety disorder. The study’s results also add more evidence that high-quality CBT, with or without medication, can effectively treat anxiety disorders in children, according to the researchers.

“Further analyses of the CAMS data may help us predict who is most likely to respond to which treatment, and develop more personalized treatment approaches for children with anxiety disorders,” concluded Philip C. Kendall, Ph.D., of Temple University, a senior investigator of the study. “But in the meantime, we can be assured that we already have good treatments at our disposal.”

The six CAMS sites were Duke University; New York State Psychiatric Institute/Columbia University Medical Center; Johns Hopkins University; Temple University/University of Pennsylvania; University of California, Los Angeles; and the Western Psychiatric Institute and Clinic/University of Pittsburgh Medical Center.

Reference
Walkup JT, Albano AM, Piacentini J, Birmaher B, Compton SN, Sherrill J, Ginsburg GS, Rynn MA, McCracken J, Waslick B, Iyengar S, March JS, Kendall PC. Cognitive-behavioral therapy, sertraline and their combination for children and adolescents with anxiety disorders: acute phase efficacy and safety. New England Journal of Medicine. Online ahead of print 30 Oct 2008.

The mission of the NIMH is to transform the understanding and treatment of mental illnesses through basic and clinical research, paving the way for prevention, recovery and cure. For more information, visit the NIMH website.

The National Institutes of Health (NIH) — The Nation’s Medical Research Agency — includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit the NIH website.

Caffeine No Substitute for a Nap to Enhance Memory: Equivalent of 2-3 Cups of Coffee Worsens Motor Learning and Word Recall

2011-01-31T11:40:00.000-08:00

Hoping to improve your tennis serve? It's probably better to catch a few winks than load up on java after a lesson, results of a NIMH-supported study suggest. Caffeine impaired such motor learning and verbal memory, while an afternoon nap benefited all three types of learning tested by Sara Mednick, Ph.D., and colleagues at the University of California, San Diego. The researchers report on their findings in the November issue of Behavioural Brain Research. CEUs for MFTs
Background

Ninety percent of Americans use caffeine daily, some substituting it for sleep. While the stimulant enhances alertness and concentration, it's been unclear whether it also helps learning and memory. By contrast, daytime naps, like nighttime sleep, benefit both alertness and memory, Mednick and colleagues have shown in a series of studies.

In this first head-to-head day-time comparison, 61 participants trained in the morning on verbal memory, motor, and perceptual learning tasks. After lunch, one group napped (60-90 min), while two other groups listened to a book on tape and received a pill containing either the caffeine equivalent of a little less than a Tall Starbucks brewed coffee (200mg) or a placebo. Later in the afternoon, the three groups were tested to see how well they had learned the tasks.

Findings of This Study

The nap group performed significantly better on a finger tapping motor task and in recalling words, than the caffeine group. The nap group also trumped the other groups on a texture discrimination task of perceptual learning. The placebo group performed better than the caffeine group on all three tasks. Curiously, just thinking that the pill might contain caffeine — the placebo effect — helped as much as a nap on the motor task.

Significance

Evidence suggests that caffeine interferes with tasks that require processing explicit, as opposed to implicit, information - like recalling a specific word, versus remembering how to type or ride a bike. Studies show that consolidation of such explicit verbal memory during sleep depends on lowered levels of the chemical messenger acetylcholine in the brain's memory hub. Yet, by blocking activity of a natural sedative chemical, caffeine boosts acetylcholine in this hub.

"This increase in acetylcholine by caffeine may impair the consolidation process by blocking replay of new memories," proposes Mednick. "Consistent with this, we found that the greater the explicit component of each task, the worse the caffeine group performed."

What's Next?

"Such an impairment of performance runs counter to society's assumption that caffeine typically benefits cognitive performance," she notes. "Apparent improvements with caffeine might actually reflect a relief from withdrawal symptoms. Just as no medicinal alternative to a good night's rest has been discovered, so too caffeine, the most common pharmacological intervention for sleepiness, may not be an adequate substitute for the memory enhancements of daytime sleep, either."

Mednick and colleagues are using new pharmacological agents found to selectively enhance particular stages of nighttime sleep to see if they can enhance memory consolidation during daytime naps. Brain imaging will pinpoint effects on neural circuits. These studies of pharmacologically enhanced naps could lead to improved treatments for memory impairment in mental disorders, based on manipulations of sleep, say the researchers.

Reference
Mednick SC, Cai DJ, Kanady J, Drummond SP. Comparing the benefits of caffeine, naps and placebo on verbal, motor and perceptual memory. Behav Brain Res. 2008 Nov 3;193(1):79-86. Epub 2008 May 8. PMID: 18554731