December 15, 2011

NDAR Federation Creates Largest Source of Autism Research Data to Date

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.


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.

December 06, 2011

Suspect Gene Variants Boost PTSD Risk after Mass Shooting

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.


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]

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.

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



December 01, 2011

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

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.


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.


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.


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

November 28, 2011

Training Peers Improves Social Outcomes for Some Kids with ASD

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).


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


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.

November 27, 2011

Psychologists chase down sleep demons

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.

November 25, 2011

Diagnoses of autism spectrum disorders vary widely across clinics

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.


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

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

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

November 23, 2011

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

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."


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

November 19, 2011

Intervention Shows Promise in Treating Depression Among Preschoolers

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.


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.


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.


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.

November 16, 2011


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.

November 14, 2011

Widely Used Screening Tool Shown to Successfully Predict Suicide Attempts

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.

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.


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


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.

November 10, 2011

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

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

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.


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.

November 08, 2011

Pitt team finds molecular evidence of brain changes in depressed females

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


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

November 07, 2011

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

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.

November 04, 2011

Psychologists Stress the Importance of Memory in Preventing Relapse after Therapy

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"

November 03, 2011

Advice to divorcees: Go easy on yourself

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.


For more information about this study, please contact: David A. Sbarra at

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

October 31, 2011

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

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 and at, 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, while the gene expression data can be found at In addition, BrainCloud, a web browser application developed by NIMH to interrogate the Kleinman study data, can be downloaded at

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


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, Ε estan 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 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 Online ordering is available at NIDA's new media guide can be found at

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

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 To track the progress of HHS activities funded through the Recovery Act, visit To track all federal funds provided through the Recovery Act, visit