New Data Reveal Extent of Genetic Overlap Between Major Mental Disorders

Schizophrenia, Bipolar Disorder Share the Most Common Genetic Variation Press Release • August 12, 2013 The largest genome-wide study of its kind has determined how much five major mental illnesses are traceable to the same common inherited genetic variations. Researchers funded in part by the National Institutes of Health found that the overlap was highest between schizophrenia and bipolar disorder; moderate for bipolar disorder and depression and for ADHD and depression; and low between schizophrenia and autism. Overall, common genetic variation accounted for 17-28 percent of risk for the illnesses. “Since our study only looked at common gene variants, the total genetic overlap between the disorders is likely higher,” explained Naomi Wray, Ph.D., University of Queensland, Brisbane, Australia, who co-led the multi-site study by the Cross Disorders Group of the Psychiatric Genomics Consortium (PGC), which is supported by the NIH’s National Institute of Mental Health (NIMH). “Shared variants with smaller effects, rare variants, mutations, duplications, deletions, and gene-environment interactions also contribute to these illnesses.” Dr. Wray, Kenneth Kendler, M.D., of Virginia Commonwealth University, Richmond, Jordan Smoller, M.D., of Massachusetts General Hospital, Boston, and other members of the PGC group report on their findings August 11, 2013, in the journal Nature Genetics. “Such evidence quantifying shared genetic risk factors among traditional psychiatric diagnoses will help us move toward classification that will be more faithful to nature,” said Bruce Cuthbert, Ph.D., director of the NIMH Division of Adult Translational Research and Treatment Development and coordinator of the Institute’s Research Domain Criteria (RDoC) project, which is developing a mental disorders classification system for research based more on underlying causes. Earlier this year, PGC researchers – more than 300 scientists at 80 research centers in 20 countries – reported the first evidence of overlap between all five disorders. People with the disorders were more likely to have suspect variation at the same four chromosomal sites. But the extent of the overlap remained unclear. In the new study, they used the same genome-wide information and the largest data sets currently available to estimate the risk for the illnesses attributable to any of hundreds of thousands of sites of common variability in the genetic code across chromosomes. They looked for similarities in such genetic variation among several thousand people with each illness and compared them to controls – calculating the extent to which pairs of disorders are linked to the same genetic variants. The overlap in heritability attributable to common genetic variation was about 15 percent between schizophrenia and bipolar disorder, about 10 percent between bipolar disorder and depression, about 9 percent between schizophrenia and depression, and about 3 percent between schizophrenia and autism. The newfound molecular genetic evidence linking schizophrenia and depression, if replicated, could have important implications for diagnostics and research, say the researchers. They expected to see more overlap between ADHD and autism, but the modest schizophrenia-autism connection is consistent with other emerging evidence. The study results also attach numbers to molecular evidence documenting the importance of heritability traceable to common genetic variation in causing these five major mental illnesses. Yet this still leaves much of the likely inherited genetic contribution to the disorders unexplained – not to mention non-inherited genetic factors. For example, common genetic variation accounted for 23 percent of schizophrenia, but evidence from twin and family studies estimate its total heritability at 81 percent. Similarly, the gaps are 25 percent vs. 75 percent for bipolar disorder, 28 percent vs. 75 percent for ADHD, 14 percent vs. 80 percent for autism, and 21 percent vs. 37 percent for depression. Among other types of genetic inheritance known to affect risk and not detected in this study are contributions from rare variants not associated with common sites of genetic variation. However, the researchers say that their results show clearly that more illness-linked common variants with small effects will be discovered with the greater statistical power that comes with larger sample sizes. “It is encouraging that the estimates of genetic contributions to mental disorders trace those from more traditional family and twin studies. The study points to a future of active gene discovery for mental disorders” said Thomas Lehner, Ph.D., chief of the NIMH Genomics Research Branch, which funds the project.

Common inherited genetic variation (single nucleotide polymorphisms, or SNPs) accounted for up to about 28 percent of the risk for some disorders, such as ADHD (dark green). Among pairs of disorders (light green), schizophrenia and bipolar disorder (SCZ-BPD) shared about 16 percent of the same common genetic variation (coheritabilities). Source: Cross-Disorder Group of the Psychiatric Genomics Consortium Professional Counselor Continuing Education Reference Cross-Disorder Group of the Psychiatric Genomics Consortium. Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs. Nature Genetics, August 11, 2013 Grants R01MH065562, R01MH43518, R01MH065554, R01MH65707, R01MH065571, R01MH65588, R01MH65578, R01MH65558 ### 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. Press Contact(s) Jules Asher NIMH Press Office 301-443-4536 NIMHPress@nih.gov More Science News about: Attention Deficit Hyperactivity Disorder (ADHD) Autism Bipolar Disorder Depression Schizophrenia Contact the Press Office Phone: 301-443-4536 Email: NIMHpress@mail.nih.gov Press Resources Mental Health Information Statistics on Mental Disorders Summaries of Scientific Meetings Information about NIMH RePORTER: Research Portfolio Online Reporting Tool Expenditures and Results PubMed Central: An Archive of Life Sciences Journals Recommendations for Reporting on Suicide News from the Field News from the Field NIMH-Funded Science on EurekAlert Teen Eating Disorders Increase Suicide Risk The Love Hormone is 2-Faced Fear Factor: Missing Brain Enzyme Leads to Abnormal Levels of Fear in Mice, Reveals New Research More news from the field... Bookmark & Share Newsletters RSS Feeds Facebook

Community-based Treatments Offset Depression Disparities

Depression can affect anyone, but it hits ethnic groups more heavily partly because of reduced access to quality mental health care. To offset this imbalance, researchers from the RAND Corporation and UCLA, and community partners from more than two dozen community agencies, compared whether evidence-based quality improvement programs, which include psychotherapies such as cognitive behavioral therapy and antidepressant medications, are better implemented through involvement of the entire community or through clinic-based programs. The researchers polled 1,018 depressed patients in 90 randomized community- and clinic-based programs. The community-based approaches--in such places as churches, senior centers, and barber shops--worked best at improving mental-health quality of life, increasing physical activity, reducing homelessness risk factors, and getting more people to seek hospital and primary physician care. Project officer and Associate Director of Dissemination and Implementation Research David Chambers, Ph.D., discusses in a video the significance of these findings. For further details, see RAND Corporation’s press release, “Incorporating Community Groups Into Depression Care Can Improve Coping Among Low-Income Patients, Study Finds.” Aspira Continuing Education Online Courses

Bullying Exerts Psychiatric Effects into Adulthood

Once considered a childhood rite of passage, bullying lingers well into adulthood. Bullies and victims alike are at risk for psychiatric problems such as anxiety, depression, substance abuse, and suicide when they become adults, reported a study partially funded by the National Institute of Mental Health (NIMH) that was published in the April issue of JAMA Psychiatry. Background Bullying is a repetitive, aggressive act done to abuse or intimidate others. It can take on various forms—primarily verbal, emotional, and physical, although cyberbullying is also on the rise. Typically these scenes occur inside school or on the playground, but they can also happen at home or at work. A power imbalance usually is involved in which one child or a group of children torments another child who is considered “weaker.” Methods employed by bullies include threats, rumor-spreading, and exclusion. Most of what experts know about the effects of bullying comes from short-term observational studies. These studies reflect general society’s view that most people overcome these events by the time they become adults. “Initially I too was skeptical about these long-term effects,” says study author William Copeland, Ph.D., at Duke University, who as an epidemiologist knew of other traumatic events that do not linger psychologically, such as maltreatment and physical abuse. “Yet this is something that stays with people. A large number of people express lasting effects decades after their childhood experiences.” Copeland and his colleagues tapped into a local population sample of 1,420 children from 11 Western North Carolina counties. Starting at the ages of 9, 11, and 13, the kids, along with their parents, were interviewed annually until the age of 16, fielding questions about peer relations and home and community settings. The participating children were again interviewed at 19, 21, and 24 to 26 years of age. Four groups emerged from this longitudinal study: people who were never involved in bullying, people who were victims, people who were bullies, and people who were both. Results of the Study More than half of the study’s youth reported being neither a bully nor a victim. Around a quarter of the study group claimed that they were victimized. About 7 percent confessed to being a bully. A similar percentage said that they were both, a group the researchers labeled as “bully-victims.” Compared to those who went through childhood unscathed, victims had four times the prevalence of agoraphobia, generalized anxiety, and panic disorder when they became adults. Overall, bullies had four times the risk of developing antisocial personality disorder. These disorders still stood even after other factors were taken into account, such as preexisting psychiatric problems or family hardships. Bully-victims fared the worst. Also known as “loners,” these individuals start out with less developed social skills and are seen as more impulsive and aggressive. When picked on, they respond by picking on others. Their numbers, compared to those never involved in bullying, tell the story: 14 times the risk of panic disorder, 5 times the risk of depressive disorders, and 10 times the risk of suicidal thoughts and behavior. “Victims report the greatest anxiety problems. They might become successful people later on, but they still think about the event and hold onto it. Bullies are socially adept and may find ways in adulthood to use these skills in a pro-social manner. Folks really underestimate who are the bully-victims. These are the ones who end up having the most significant emotional problems including suicidality,” explained Copeland, who is also a father of two Social Worker Continuing Education Significance All these disorders impart a great emotional and financial cost to society. Lowering and/or preventing bullying could possibly reduce human suffering and long-term health costs—not to mention creating a safer environment for children to grow up in. Research into resilience or why some are able to bounce back in adulthood is ongoing. Some key molecules and brain circuit pathways have been identified in animals. Other research areas under exploration include physiology, genetics, epigenetics, and cognitive therapies. What’s Next Studies looking into which interventions work best for bullying are underway. Once these interventions are identified, research is needed to see at what stages in life they should they be administered. Lastly, other factors that play a role in bullying and victimization, such as sexual orientation, need exploration. “This study suggests that we should pay attention to what’s going on between peers,” said Copeland, adding that kids spend more time each day with their peers, including school and online, than with their parents. “What happens to kids when they’re with their peers is as important, or may be more important, than what happens at home,” said Copeland. Reference Copeland WE, Wolke D, Angold A, Costello EJ. Adult Psychiatric Outcomes of Bullying and Being Bullied by Peers in Childhood and Adolescence. JAMA Psychiatry, published April 2013. Grant number: K23 MH080230

Out of sync with the world: Body clocks of depressed people are altered at cell level

Finding of disrupted brain gene orchestration gives first direct evidence of circadian rhythm changes in depressed brains, opens door to better treatment ANN ARBOR, Mich. — Every cell in our bodies runs on a 24-hour clock, tuned to the night-day, light-dark cycles that have ruled us since the dawn of humanity. The brain acts as timekeeper, keeping the cellular clock in sync with the outside world so that it can govern our appetites, sleep, moods and much more. But new research shows that the clock may be broken in the brains of people with depression -- even at the level of the gene activity inside their brain cells. It's the first direct evidence of altered circadian rhythms in the brain of people with depression, and shows that they operate out of sync with the usual ingrained daily cycle. The findings, in the Proceedings of the National Academy of Sciences, come from scientists from the University of Michigan Medical School and other institutions. The discovery was made by sifting through massive amounts of data gleaned from donated brains of depressed and non-depressed people. With further research, the findings could lead to more precise diagnosis and treatment for a condition that affects more than 350 million people worldwide. What's more, the research also reveals a previously unknown daily rhythm to the activity of many genes across many areas of the brain – expanding the sense of how crucial our master clock is professional counselor continuing education In a normal brain, the pattern of gene activity at a given time of the day is so distinctive that the authors could use it to accurately estimate the hour of death of the brain donor, suggesting that studying this "stopped clock" could conceivably be useful in forensics. By contrast, in severely depressed patients, the circadian clock was so disrupted that a patient's "day" pattern of gene activity could look like a "night" pattern -- and vice versa. The work was funded in large part by the Pritzker Neuropsychiatric Disorders Research Fund, and involved researchers from the University of Michigan, University of California's Irvine and Davis campuses, Weill Cornell Medical College, the Hudson Alpha Institute for Biotechnology, and Stanford University. The team uses material from donated brains obtained shortly after death, along with extensive clinical information about the individual. Numerous regions of each brain are dissected by hand or even with lasers that can capture more specialized cell types, then analyzed to measure gene activity. The resulting flood of information is picked apart with advanced data-mining tools. Lead author Jun Li, Ph.D., an assistant professor in the U-M Department of Human Genetics, describes how this approach allowed the team to accurately back-predict the hour of the day when each non-depressed individual died – literally plotting them out on a 24-hour clock by noting which genes were active at the time they died. They looked at 12,000 gene transcripts isolated from six regions of 55 brains from people who did not have depression. This provided a detailed understanding of how gene activity varied throughout the day in the brain regions studied. But when the team tried to do the same in the brains of 34 depressed individuals, the gene activity was off by hours. The cells looked as if it were an entirely different time of day. "There really was a moment of discovery," says Li, who led the analysis of the massive amount of data generated by the rest of the team and is a research assistant professor in U-M's Department of Computational Medicine at Bioinformatics. "It was when we realized that many of the genes that show 24-hour cycles in the normal individuals were well-known circadian rhythm genes – and when we saw that the people with depression were not synchronized to the usual solar day in terms of this gene activity. It's as if they were living in a different time zone than the one they died in." Huda Akil, Ph.D., the co-director of the U-M Molecular & Behavioral Neuroscience Institute and co-director of the U-M site of the Pritzker Neuropsychiatric Disorders Research Consortium, notes that the findings go beyond previous research on circadian rhythms, using animals or human skin cells, which were more easily accessible than human brain tissues. "Hundreds of new genes that are very sensitive to circadian rhythms emerged from this research -- not just the primary clock genes that have been studied in animals or cell cultures, but other genes whose activity rises and falls throughout the day," she says. "We were truly able to watch the daily rhythm play out in a symphony of biological activity, by studying where the clock had stopped at the time of death. And then, in depressed people, we could see how this was disrupted." Now, she adds, scientists must use this information to help find new ways to predict depression, fine-tune treatment for each depressed patient, and even find new medications or other types of treatment to develop and test. One possibility, she notes, could be to identify biomarkers for depression – telltale molecules that can be detected in blood, skin or hair. And, the challenge of determining why the circadian clock is altered in depression still remains. "We can only glimpse the possibility that the disruption seen in depression may have more than one cause. We need to learn more about whether something in the nature of the clock itself is affected, because if you could fix the clock you might be able to help people get better," Akil notes. The team continues to mine their data for new findings, and to probe additional brains as they are donated and dissected. The high quality of the brains, and the data gathered about how their donors lived and died, is essential to the project, Akil says. Even the pH level of the tissue, which can be affected by the dying process and the time between death and freezing tissue for research, can affect the results. The team also will have access to blood and hair samples from new donors. ### The researchers note that the Pritzker funding in combination with federal research funding made it possible for the scientists to study this issue in an exploratory way. The research was historically funded by a Conte Center grant from the National Institute of Mental Health, and partly funded by the William Lion Penzner Foundation, the Della Martin Foundation, the Office of Naval Research (N00014-09-1-059 and N00014-12-1-0366), the National Alliance for Research on Schizophrenia and Depression's Abramson Family Foundation Investigator Award, and an International Mental Health Research Organization – Johnson & Johnson Rising Star Translational Research Award. In addition to Li and Akil, the study's authors are Blynn G. Bunney, Fan Meng, Megan H. Hagenauer, David M. Walsh, Marquis P. Vawter, Simon J. Evans, Prabakhara V. Choudary, Preston Cartagena, Jack D. Barchas, Alan F. Schatzberg, the late Edward G. Jones, Richard M. Myers, U-M MBNI co-director Stanley J. Watson, Jr., and William E. Bunney. Reference: PNAS Early Edition, http://www.pnas.org/cgi/doi/10.1073/pnas.1305814110

Ketamine Cousin Rapidly Lifts Depression Without Side Effects

Neurons in a subsection of the adult rat hippocampus are stained with a monoclonal antibody (yellow) that enhances learning and memory. A portion of this antibody is where GLYX-13 came from. Source: Dr. Joseph Moskal, Ph.D., Northwestern University GLYX-13, a molecular cousin to ketamine, induces similar antidepressant results without the street drug side effects, reported a study funded by the National Institute of Mental Health (NIMH) that was published last month in Neuropsychopharmacology. Background Major depression affects about 10 percent of the adult population and is the second leading cause of disability in U.S. adults, according to the World Health Organization. Despite the availability of several different classes of antidepressant drugs such as selective serotonin reuptake inhibitors (SSRIs), 30 to 40 percent of adults are unresponsive to these medications. Moreover, SSRIs typically take weeks to work, which increases the risk for suicide. Enter NMDA (N-methyl-D-aspartate) receptor modulators. In the 1970s, researchers linked the receptors to learning and memory. Biotech and pharmaceutical companies in the 1980s attempted to apply chemical blockers to these receptors as a means to prevent stroke. But blocking these receptors led to the opposite effect—--the rise of cardiovascular disease. Research in the field dampened until a glutamate receptor antagonist already approved for anesthesia, and known on the streets as “Special K”, ketamine, made headlines in the early 2000s. Human clinical studies demonstrated that ketamine can ward off major and bipolar depressive symptoms within 2 hours of administration and last for several days. Ketamine is fraught with serious side effects including excessive sleepiness, hallucinations, and substance abuse behavior. “Ketamine lit the field back up,“ said Joseph Moskal, Ph.D., a molecular neurobiologist at Northwestern University and senior study author. “Our drug, GLYX-13, is very different. It does not block the receptor ion channel, which may account for why it doesn’t have the same side effects.” Moskal’s journey with GLYX-13 came about from his earlier days as a Senior Staff Fellow in NIMH’s Intramural Research Program. While at NIMH, he created specific molecules, monoclonal antibodies, to use as new probes to understand pathways of learning and memory. Some of the antibodies he created were for NMDA receptors. When he moved to Northwestern University, Moskal converted the antibodies to small protein molecules. Comprised of only four amino acids, GLYX-13 is one of these molecules. Previous electrophysiological and conditioning studies had suggested that GLYX-13, unlike ketamine, enhanced memory and learning in rats, particularly in the brain’s memory hub or hippocampus. GLYX-13 also produced analgesic effects. Using several rat behavioral and molecular experiments, Moskal’s research team tested four compounds: GLYX-13, an inactive, “scrambled” version of GLYX-13 that had its amino acids rearranged, ketamine, and the SSRI fluoxetine. Results of the Study GLYX-13 and ketamine produced rapid acting (1 hour) and long-lasting (24 hour) antidepressant-like effects in the rats. Fluoxetine, an SSRI that typically takes from 2–4 weeks to show efficacy in humans, did not produce a rapid antidepressant effect in this study. As expected, the scrambled GLYX-13 showed no antidepressant-like effects at all. The researchers observed none of the aforementioned side effects of ketamine in the GLYX-13–treated rats. Protein studies indicated an increase in the hippocampus of the NMDA receptor NR2B and a receptor for the chemical messenger glutamate called AMPA. Electrophysiology studies in this brain region showed that GLYX-13 and ketamine promoted long-lasting signal transmission in neurons, known as long-term potentiation/synaptic plasticity. This phenomenon is essential in learning and memory. The researchers propose how GLYX-13 works: GLYX-13 triggers NR2B receptor activation that leads to intracellular calcium influx and the expression of AMPA, which then is responsible for increased communication between neurons. These results are consistent with data from a recent Phase 2 clinical trial, in which a single administration of GLYX-13 produced statistically significant reductions in depression scores in patients who had failed treatment with current antidepressants. The reductions were evident within 24 hours and persisted for an average of 7 days. After a single dose of GLYX-13, the drug’s antidepressant efficacy nearly doubled that seen with most conventional antidepressants after 4–6 weeks of dosing. GLYX-13 was well tolerated and it did not produce any of the schizophrenia-like effects associated with other NMDA receptor modulating agents. Significance NMDA receptors need a molecule each of the amino acid chemical messengers glutamate and glycine to become activated. Moskal speculates that GLYX-13 either directly binds to the glycine site on the NMDA receptor or indirectly modulates how glycine works with the receptor. Resulting activation of more NMDA and AMPA receptors leads to an increase in memory, learning—and antidepressant effects. By contrast, ketamine only blocks the NMDA receptor, but also increases the activity of the AMPA receptor. Knowledge of these mechanisms could lead to the development of more effective antidepressants. What’s Next GLYX-13 is now being tested in a Phase 2 repeated dose antidepressant trial, where Moskal and his colleagues at Naurex, Inc., a biotechnology company he founded, hope to find in humans the optimal dosing for the drug. They also want to see if this molecule, and others like it, regulate other NMDA receptor subtypes—there are over 20 of them—and whether it will work on other disorders, such as schizophrenia, attention-deficit hyperactivity disorder, and autism. “One could call NMDA modulators such as GLYX-13 ‘comeback kids,’” said Moskal. “A toolkit that I developed in 1983 is now setting the stage in 2013 for the development of possible new therapeutics that may provide individuals suffering from depression with a valuable new treatment option.” Alcoholism and Drug Abuse Counselors Continuing Education Reference Burgdorf J, Zhang X-l, Nicholson KL, Balster RL, Leander JD, Stanton PK, Gross AL, Kroes RA, Moskal JR. GLYX-13, a NMDA Receptor Glycine-Site Functional Partial Agonist, Induces Antidepressant-Like Effects Without Ketamine-Like Side Effects. Neuropsychopharmacology, April 2013. 38:729–742.

Nearly 20 percent of suicidal youths have guns in their home

Researchers say emergency department doctors should screen all pediatric patients for suicide risk WASHINGTON, DC – Nearly one in five children and teens found to be at risk for suicide report that there are guns in their homes, and 15 percent of those at risk for suicide with guns in the home know how to access both the guns and the bullets, according to a study to be presented Monday, May 6, at the Pediatric Academic Societies (PAS) annual meeting in Washington, DC. Suicide is the second leading cause of death among young people ages 10 to 24 years in the United States, according to Centers for Disease Control and Prevention data. Nearly half of youths who die by suicide use a firearm. Researchers conducted a study to create a suicide risk screening tool that health care professionals in emergency departments (EDs) could use to figure out which youths need further mental health evaluation to keep them from harming themselves. As part of that study, researchers asked youths about access to guns in or around their home and about gun/bullet storage. "For more than 1.5 million adolescents, the ED is their primary point of contact with the health care system, which makes the ED an important place for identifying youth at risk for suicide," said Stephen J. Teach, MD, MPH, FAAP, associate chief in the Division of Emergency Medicine at Children's National Medical Center in Washington, DC, and co-author who will be presenting the study at the PAS meeting. Many clinicians and parents do not know how to ask youth about suicide, so they require screening tools to assist in detection, added study senior author Lisa M. Horowitz, PhD, MPH, staff scientist/pediatric psychologist at the National Institute of Mental Health, National Institutes of Health, Bethesda, Md. "According to our data, when asked their opinion, nearly all of the kids in our study were in favor of suicide screening in the ED. Our study shows that if you ask kids directly about suicide, they will tell you what they are thinking." Study participants included 524 patients ages 10 to 21 who were seen for medical/surgical or psychiatric complaints at one of three pediatric EDs. They were asked to fill out a 17-item questionnaire that the researchers used to develop the Ask Suicide-Screening Questions (ASQ), a four-question screening tool that can be used for all pediatric patients visiting the ED. The ASQ has been validated against a longer more in-depth suicide assessment tool. "While many youths who kill themselves have mental health disorders, up to 40 percent of youths who kill themselves have no known mental illness," said co-author and youth suicide expert Jeffrey A. Bridge, PhD, principal investigator at The Research Institute at Nationwide Children's Hospital and associate professor of pediatrics at The Ohio State University. "Therefore, it is important to screen all children and adolescents for suicide, regardless of the reason they are visiting the ED." Of the patients who completed the screening tools, 151 (29 percent) were found to be at risk for suicide, and 17 percent of them reported guns in or around the home. Of those at risk for suicide and reporting guns in the home, 31 percent knew how to access the guns, 31 percent knew how to access the bullets, and 15 percent knew how to access both the guns and the bullets. "This study highlights the importance of parents understanding the risks of having guns in their homes," said Dr. Bridge. "Being at risk for suicide and having access to firearms is a volatile mix. These conversations need to take place in the ED with families of children at risk for suicide." Suicide Prevention CE Course ### To view the abstract, "Access to Firearms among Patients Screening Positive for Suicide Risk in Pediatric Emergency Departments," go to http://www.pas-meeting.org/2013DC/Abstracts/LB%20Pub%20All%202013.pdf The research was supported by the Intramural Research Program of the National Institute of Mental Health, the National Institutes of Health (Drs. Horowitz & Pao); institutional research funds from the Research Institute at Nationwide Children's Hospital and grant K01 MH-69948 from the National Institute of Mental Health (Dr. Bridge); institutional research funds from the Program for Patient Safety and Quality at Boston Children's Hospital Boston (Dr. Wharff). The Pediatric Academic Societies (PAS) are four individual pediatric organizations that co-sponsor the PAS Annual Meeting – the American Pediatric Society, the Society for Pediatric Research, the Academic Pediatric Association, and the American Academy of Pediatrics. Members of these organizations are pediatricians and other health care providers who are practicing in the research, academic and clinical arenas. The four sponsoring organizations are leaders in the advancement of pediatric research and child advocacy within pediatrics, and all share a common mission of fostering the health and well-being of children worldwide. For more information, visit http://www.pas-meeting.org. Follow news of the PAS meeting on Twitter at http://twitter.com/PedAcadSoc.

Forced exercise may still protect against anxiety and stress, says CU-Boulder study

Being forced to exercise may still help reduce anxiety and depression just as exercising voluntarily does, according to a new study by researchers at the University of Colorado Boulder. Past studies have shown that people who exercise are more protected against stress-related disorders. And scientists know that the perception of control can benefit a person's mental health. But it has been an open question whether a person who feels forced to exercise, eliminating the perception of control, would still reap the anxiety-fighting benefits of the exercise. People who may feel forced to exercise could include high school, college and professional athletes, members of the military or those who have been prescribed an exercise regimen by their doctors, said Benjamin Greenwood, an assistant research professor in CU-Boulder's Department of Integrative Physiology. "If exercise is forced, will it still produce mental health benefits?" Greenwood asked. "It's obvious that forced exercise will still produce peripheral physiological benefits. But will it produce benefits to anxiety and depression?" To seek an answer to the question Greenwood and his colleagues, including Monika Fleshner, a professor in the same department, designed a lab experiment using rats. During a six-week period, some rats remained sedentary, while others exercised by running on a wheel. The rats that exercised were divided into two groups that ran a roughly equal amount of time. One group ran whenever it chose to, while the other group ran on mechanized wheels that rotated according to a predetermined schedule. For the study, the motorized wheels turned on at speeds and for periods of time that mimicked the average pattern of exercise chosen by the rats that voluntarily exercised. After six weeks, the rats were exposed to a laboratory stressor before testing their anxiety levels the following day. The anxiety was quantified by measuring how long the rats froze, a phenomenon similar to a deer in the headlights, when they were put in an environment they had been conditioned to fear. The longer the freezing time, the greater the residual anxiety from being stressed the previous day. For comparison, some rats were also tested for anxiety without being stressed the day before. "Regardless of whether the rats chose to run or were forced to run they were protected against stress and anxiety," said Greenwood, lead author of the study appearing in the European Journal of Neuroscience in February. The sedentary rats froze for longer periods of time than any of the active rats. "The implications are that humans who perceive exercise as being forced — perhaps including those who feel like they have to exercise for health reasons — are maybe still going to get the benefits in terms of reducing anxiety and depression," he said. Anxiety Disorders CE Course ### Other CU-Boulder authors include Katie Spence, Danielle Crevling, Peter Clark and Wendy Craig. All the authors are members of Monika Fleshner's Stress Physiology Laboratory in the Department of Integrative Physiology. The research was funded by the National Institutes of Mental Health and the Defense Advanced Research Projects Agency.