January 31, 2012

Ethnic Disparities Persist in Depression Diagnosis and Treatment Among Older Americans



Older racial and ethnic minorities living in the community are less likely to be diagnosed with depression than their white counterparts, but are also less likely to get treated, according to a recent NIMH-funded analysis published online ahead of print December 15, 2011, in the American Journal of Public Health.


Source: iStock Photo

Background

Depression is a significant health concern for older adults, regardless of ethnic or racial status. Previous studies have found racial and ethnic differences in the diagnosis and treatment of depression among the general population.

Using 2001-2005 data from the nationally representative Medicare Current Beneficiary Survey (MCBS), Ayse Akincigil Ph.D., of Rutgers University and colleagues examined rates of depression diagnosis and treatment among older adults living in the community. The survey asked questions about health care use and costs, insurance coverage beyond Medicare, access to care, and use of services.

Results

The survey found that about 6.4 percent of whites, 4.2 percent of African Americans, and 7.2 percent of Hispanics were diagnosed with depression. Among those diagnosed, 73 percent of whites received treatment (either with antidepressants, psychotherapy or both), while 60 percent of African Americans received treatment and 63.4 percent of Hispanics received treatment. These kinds of diagnosis and treatment differences are consistent with previous studies, the researchers noted. They also noted pronounced differences in socioeconomic status and quality of insurance coverage across ethnicities. Fewer whites reported having low incomes than ethnic minorities. However, these differences did not appear to account for the disparities in diagnosis or treatment rates.

Significance

The findings are consistent with the notion that depression continues to be under-recognized and undertreated among older minorities. According to the researchers, future research should investigate cultural factors such as help-seeking patterns, stigma, and patient attitudes and knowledge about depression as potential factors contributing to the disparities. For instance, ethnic minorities may be less likely to seek help for a mood disorder, and those with lower incomes may have more difficulty gaining access to specialized health care. In addition, they may be more likely to seek help from nonmedical providers, such as pastors or lay counselors, according to the researchers. Other research has suggested that minorities tend to cite stigma or shame associated with having a mental disorder as a reason for not seeking help for depression.

Differences in diagnosis rates may also reflect the notion that African Americans tend to have a greater sense of distrust of doctors in general compared to white patients, said the researchers. In addition, minority patients also may be more likely to present with more physical aspects of depression such as sleep problems or pain, rather than mood or cognitive symptoms, which can complicate detection and diagnosis of depression.

What’s Next

The researchers suggest possible ways to minimize the disparities in depression diagnosis and treatment among older minorities. For instance, psychiatrists and other health care workers could be offered public financial incentives for practicing in poorer communities where depressed older people may go untreated. In addition, adding cross-cultural education into professional training opportunities for health care workers could further reduce disparities. In the meantime, promising approaches such as universal depression screening programs could be implemented, the researchers concluded Nursing CEUs

Citation

Akincigil A, Olfson M, Siegel M, Zurlo K, Walkup J, Crystal S. Racial and ethnic disparities in depression care in community-dwelling elderly in the United States. American Journal of Public Health. Online ahead of print Dec. 15, 2011.

January 18, 2012

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



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

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

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

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

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

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

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

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

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

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

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


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

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

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

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

January 17, 2012

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


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

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

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


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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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






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

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

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

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

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

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

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

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

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

January 12, 2012

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




Finding Shows Therapeutic Potential of Small-Molecule Targeting Strategy

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

Background

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

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

This Study

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

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

Significance

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

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

Reference

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


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

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

January 11, 2012

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

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

Background



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

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

Results of the Study

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

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

Significance

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

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

What’s Next

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

Reference

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

January 03, 2012

School absenteeism, mental health problems linked


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

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

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

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

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

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

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


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