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Autism Spectrum Disorder: Uncovering Clues to a Complicated Condition

Autism Spectrum Disorder Uncovering Clues to a Complicated Condition Autism is a complex brain disorder that first appears during early childhood. It affects how a person behaves and interacts with others. People with autism might not look you in the eye when talking. They may spend a lot of time lining up toys or other objects. Or they may say the same sentence over and over. The disorder is so variable—affecting each person in very different ways—that it can be difficult to diagnose and treat. This variability is why autism is called a “spectrum” disorder. It spans the spectrum from mild to severe and includes a wide range of symptoms. NIH-funded scientists have been working to uncover the secrets of autism. They’ve identified genes that may boost the risk for autism. They’ve developed therapies that can help many of those affected. And they’ve found that starting treatment as early as possible can lead to better outcomes. Still, there’s much more we need to learn about this complicated condition. About 1 in 88 children may have autism spectrum disorder, according to the U.S. Centers for Disease Control and Prevention. The number of affected children has been growing in recent years. Many researchers believe this increase is due to better diagnosis and awareness. Others suspect that yet-unknown factors may be partly to blame. Although the exact causes of autism are unclear, research suggests that both genes and the environment play important roles. Autism affects a child’s development in different ways, and so it’s known as a developmental disorder. Parents are often the first to suspect that something may not be quite right with their child’s development. They may notice their baby doesn’t make eye contact, becomes overly focused on certain objects or isn’t “babbling” like other children the same age. “A parent may first have concerns when a child is under 2 years of age,” says Dr. Connie Kasari, a child development expert at the University of California, Los Angeles. “A more certain diagnosis can usually be made by age 2, but some cases might not be clear until much later.” There are no direct tests, like blood tests or brain scans, that can identify autism. Instead, the condition is diagnosed by looking at a child’s behaviors and development. “All affected children have some sort of social impairment, but symptoms vary along a continuum,” Kasari says. “Impairment can range from kids who are in their ‘own world’ and seemingly unaware of others to high-functioning individuals who are just awkward and seem to miss the point of social interactions.” In May 2013, the American Psychiatric Association updated an important book that’s used to diagnose and classify mental disorders. The DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, 5th edition) includes an updated definition for autism spectrum disorder. The condition is now identified by looking for 2 broad categories of symptoms: problems with social communication and the presence of “stereotyped” behaviors, such as walking in certain patterns or insisting on specific or unusual routines. To be diagnosed with autism, these symptoms must arise during early childhood, even if they’re not noticed until later, when social demands increase. “The new DSM-5 definition moves all the disorders into a single spectrum, rather than the 4 separate autistic disorders described in the past,” says NIH pediatrician and neuroscientist Dr. Susan Swedo. She chaired the expert panel that updated the DSM-5 definition of autism spectrum disorders. “The new criteria are also more inclusive of minorities, adolescents and young adults with autism than the previous edition, which focused more on boys ages 4 to 9.” Getting diagnosed as early as possible is crucial. “Autism is treatable even though it’s not curable,” says Dr. David Mandell, an expert in autism and health services at the University of Pennsylvania. “If we intervene early enough with appropriate and intensive care, we can reduce a lot of impairments for many kids who have autism.” Research has shown that therapies focusing on behavior and communication can be helpful. Some drugs can also reduce certain related symptoms, but no medications have been approved by the U.S. Food and Drug Administration specifically for treating the main symptoms of autism. “Because autism is such a complicated disorder, no one therapy fits everyone,” Kasari explains. Kasari and her colleagues developed and tested several treatments that focus on improving social skills and communication. In one study, preschoolers with autism received intense training in basic skills such as playing and sharing attention. Five years later, these children tended to have stronger vocabularies and better communication skills than children who received standard therapy. “We’ve found that if we can improve these basic skills, we can also improve language learning for these kids,” Kasari says. “We’re now studying 2 potential therapies in at-risk babies, ages 12- to 21-months old, to see if we can push language development along faster for the children.” Scientists are also looking for ways to predict likely outcomes for children with autism. One NIH-funded team found that the brain waves of some 2-year-olds with autism can have a distinctive pattern when they listen to familiar words. The children with more severe social symptoms didn’t have a typical focused response in the brain region that processes language. Follow-up studies showed that these brain responses predicted the children’s developmental abilities 2 and 4 years later. “In the future, we’d like to be able to assess a child based on brain function or their genetic profile and then identify the intervention that might be best for that particular kid,” Mandell says. A growing number of studies are looking at autism in older age groups. “While we think about autism as a disorder of childhood, it actually continues through adolescence and into adulthood,” Mandell says. “Some adults with autism have been misdiagnosed, and they can find themselves being treated for other conditions. We’d like to develop better screening tools and ultimately provide these adults with skills and supports to help them become happy and productive citizens.” While research is ongoing, it’s clear that early diagnosis and treatment can improve outcomes for those with autism. If you’re concerned about your child’s social communication and behaviors, don’t wait. Talk with your child’s doctor. You may be referred to a specialist who can do a thorough evaluation. The earlier autism is diagnosed, the sooner specific therapy can begin Social Worker Continuing Education

PTSD raises risk for obesity in women

Women with PTSD gain weight more rapidly than women without disorder Women with post-traumatic stress disorder (PTSD) gain weight more rapidly and are more likely to be overweight or obese than women without the disorder, find researchers at Columbia University's Mailman School of Public Health and Harvard School of Public Health. It is the first study to look at the relationship between PTSD and obesity over time. Results appear online in JAMA Psychiatry. One in nine women will have PTSD at sometime over the course of their lifetime—twice as often as men. Women are also more likely to experience extreme traumatic events like rape that carry a high risk for the disorder. "PTSD is not just a mental health issue," says study senior author Karestan Koenen, PhD, Mailman School associate professor of Epidemiology. "Along with cardiovascular disease and diabetes, we can now add obesity to the list of known health risks of PTSD." PTSD - Clinical Practice Guideline for Management of Post Traumatic Stress CEU Course "The good news from the study is that it appears that when PTSD symptoms abate, risk of becoming overweight or obese is also significantly reduced," says first author Laura D. Kubzansky, PhD, Professor of Social and Behavioral Sciences at Harvard School of Public Health. However, despite the growing evidence of potential far-reaching problems associated with PTSD, it's estimated that only half of women in the United States with the disorder are ever treated. "Hopefully, wider recognition that PTSD can also influence physical health will improve this statistic, leading to better screening and treatments, including those to prevent obesity," says Dr. Kubzansky. While it's known that women with PTSD have high rates of obesity, it has been unclear whether PTSD was actually driving the weight gain. To explore the issue, the researchers analyzed data collected from 50,504 women, aged 22-44 years, taking part in the Nurses' Health Study II between 1989 and 2009. Participants were asked about the worst trauma they experienced and if they had related post-traumatic stress symptoms. The threshold for PTSD was the persistence of four or more symptoms over a month or longer. Common symptoms include re-experiencing the traumatic event, feeling under threat, social avoidance, and numbness. Normal-weight women who developed PTSD during the study period had 36% increased odds of becoming overweight or obese compared with women who experienced trauma but had no symptoms of PTSD. The higher risk was evident even for women with sub-threshold symptoms levels and remained after adjusting for depression, which has also been proposed as a major risk factor for obesity. In women with PTSD that began prior to the study period, body mass index increased at a more rapid pace than women without PTSD. The observed effect of PTSD on obesity is likely stronger in the general population of women than in nurses, notes Dr. Koenen. "Nurses are great for studies because they report health measures like BMI with a high degree of accuracy. But they are also more health conscious and probably less likely to become obese than most of us, which makes these results more conservative than they would otherwise be." Symptoms of PTSD rather than the trauma itself seemed to be behind the weight gain. "We looked at the women who developed PTSD and compared them to women who experienced trauma but did not develop PTSD. On the whole, before their symptoms emerged, the rate of change in BMI was the same as the women who never experienced trauma or did experience trauma but never developed symptoms," says Dr. Kubzansky. How exactly does PTSD lead to weight gain? The biological pathway is unknown, but scientists have a number of guesses. One is through the over-activation of stress hormones. PTSD may lead to disturbances in functioning of the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system, each of which are involved in regulating a broad range of body processes, including metabolism. Another is through unhealthy behavior patterns that may be used to cope with stress. Ongoing research is looking at whether PTSD increases women's preference for processed foods and decreases their likelihood of exercising Social Worker Continuing Education ### Co-authors include Pula Bordelois, MPH, and Andrea Roberts, PhD, at Harvard School of Public Health; Hee Jin Jun, DrPH, at the Channing Division of Network Medicine at Brigham and Women's Hospital; Noah Blustone, BA, at Harvard Medical School and Boston University; and Magdalena Cerda, DrPH, at Columbia's Mailman School. The study was supported by grants from the National Institute of Mental Health to Dr. Koenen (MH078928 and MH093612). The authors declare no conflict of interest.

Regenstrief and IU study: Older adults with severe mental illness challenge healthcare system

INDIANAPOLIS – Although older adults with serious mental illness didn't have more recorded physical illness and had fewer outpatient visits to primary care physicians, they made more medical emergency department visits and had considerably longer medical hospitalizations than older adults without mental illness according to a study conducted by researchers from the Regenstrief Institute and the Indiana University Center for Aging Research. "Our comparison of health care utilization between seriously mentally ill patients and age-matched primary-care patients provides critical data for the physicians, health care systems and policy makers who will be caring for the growing number of older adults, many of whom have mental illness," said Regenstrief Institute investigator Hugh C. Hendrie, M.B., Ch.B., D.Sc., Indiana University Center for Aging Research center scientist and professor of psychiatry at the IU School of Medicine. Dr. Hendrie, who is a geriatric psychiatrist and health services researcher, is the first author of the study. The study, "Comorbidity Profile and Healthcare Utilization in Elderly Patients With Serious Mental Illnesses," is published in the December issue of The American Journal of Geriatric Psychiatry. A 2012 report from the Institute of Medicine estimated that as many of one in five older adults have one or more mental health conditions or problems stemming from substance misuse or abuse. The IOM report authors included Regenstrief Institute investigator Christopher Callahan, M.D., Cornelius and Yvonne Pettinga Professor of Medicine at the IU School of Medicine who is also a co-author of the new study. Dr. Callahan is founding director of the IU Center for Aging Research Social Worker Continuing Education The American Journal of Geriatric Psychiatry study notes, "The increased likelihood of falls together with the significantly greater number of emergency department visits and length of hospitalization also suggest that those with severe mental illness represent a vulnerable elderly population that deserve more intensive studies, leading hopefully to a better integrated model of medical and psychiatric care including consideration of psychosocial factors." Individuals with severe mental illness in the study were patients of Eskenazi Health Midtown Community Mental Health. The patients had severe chronic depression (48 percent), schizophrenia (39 percent) and bipolar disorder (14 percent). Others in the study were patients from Wishard-Eskenazi primary care sites. "This study highlights a major challenge faced by older adults with severe mental illnesses and the increased burden it places on our health care system," said Julie L. Szempruch, RN, CNS, associate vice president of Eskenazi Health Midtown Community Mental Health. ### Authors of "Comorbidity Profile and Healthcare Utilization in Elderly Patients With Serious Mental Illnesses," in addition to Drs. Hendrie and Callahan, are Donald Lindgren, LCSW, Donald P. Hay, M.D., Kathleen A. Lane, M.S., Sujuan Gao, Ph.D., Christianna Purnell, B.A., Stephanie Munger, M.P.H., Faye Smith, M.A., Jeanne Dickens, M.D., and Malaz A. Boustani, M.D., M.P.H. The study was supported by National Institute of Mental Health grant MH080827-01A1.

Ability to delay gratification may be linked to social trust, new CU-Boulder study finds

A person's ability to delay gratification—forgoing a smaller reward now for a larger reward in the future—may depend on how trustworthy the person perceives the reward-giver to be, according to a new study by researchers at the University of Colorado Boulder. A body of research that stretches back more than a half-century has shown that the ability to delay gratification is linked to a number of better life outcomes. On average, people who were able to delay gratification as children go on to have higher SAT scores, for example. They also tend to be more socially conscious as adolescents, less obese as adults, and less likely to abuse drugs or alcohol. But despite the long history of studying delayed gratification, little research has focused on the role of social trust in a person's ability to wait for a larger payoff in the future. "Most of the time, when people talk about delaying gratification, they talk about basic processes of evaluation and self-control," said Laura Michaelson, a CU-Boulder doctoral student in the Department of Psychology and Neuroscience and co-lead author of the new study appearing in the online journal Frontiers in Psychology. In general, people who choose not to delay gratification have often been characterized as irrational and as having poor impulse control. But if the role of social trust is considered, it introduces the possibility that the person who is choosing not to delay gratification may be acting rationally after all, the researchers said. "If you don't trust someone, it's rational not to wait for them to give you $20 in a month instead of $15 now," said study co-lead author Alejandro de la Vega, also a doctoral student in CU-Boulder's Department of Psychology and Neuroscience. To determine the role of social trust, the research team—which also included Christopher Chatham, a former CU-Boulder doctoral student now at Brown University, and psychology and neuroscience Professor Yuko Munakata—recruited participants using Amazon's Mechanical Turk, an online tool that can be used by scientists to quickly connect with a large number of people from a broad range of backgrounds. The researchers paid participants up to $1 to participate in an experiment in which they were asked to read the profiles of three fictional characters and then rate them on their trustworthiness. Participants were then asked whether they would opt to take a smaller amount of money offered immediately from each character or a larger amount of money that they would have to wait to collect. The results showed that the participants were less likely to delay gratification when they distrusted the person who was offering the reward. A second experiment—which relied on a larger group but asked each participant to read the profile of only one character—had similar results. The second study also paired one of three sketches of a face with each character. "This offers an alternative explanation for why certain populations might be notoriously bad at delaying gratification or notoriously impulsive, like criminals and addicts," Michaelson said. "It had been chalked up to a lack of self-control. But it may be the case that they are poor at delaying gratification because they have low social trust." The findings could have implications for determining the best intervention strategies to use with children who find it difficult to delay gratification. Creating environments in which children can develop social trust, for example, could be more effective than having those children work solely on self-control, Michaelson said. The findings also may be important for adults, especially in terms of economic decision-making, de la Vega said. Economists are interested in delayed gratification as it relates to making investments or building up savings instead of spending money immediately. The new CU-Boulder study suggests that how much a person trusts an investment banker or an economic adviser could affect the person's decisions about saving and spending Social Worker Continuing Education "These economic decisions are not being made in a complete vacuum," de la Vega said. "They might really be affected by how you perceive the person you're interacting with." The research team plans to follow up this study with research that involves participants interacting in person with the people who are offering the rewards. "There is a very real possibility the this relationship between social trust and delaying gratification might be even more strong and even more salient when you're in a real situation," Michaelson said. ### Read the full study online at http://www.frontiersin.org/Cognition/10.3389/fpsyg.2013.00355/abstract.

NIMH Grantee Receives 2013 Nobel Prize

Congratulations to current NIMH grantee Thomas C. Südhof, M.D., at Stanford University School of Medicine, for winning the Nobel Prize in Physiology or Medicine for his work on how the brain sends and receives chemical messages. Thomas C. Südhof, M.D. Thomas C. Südhof, M.D. Stanford University School of Medicine “We are extremely proud of Dr. Südhof,” said National Institute of Mental Health (NIMH) Director Thomas Insel, M.D. “NIMH has supported Dr. Südhof's ground-breaking research for more than two decades as part of our commitment to understanding the fundamental mechanisms of brain function." The human brain houses about 100 billion neurons—about half the number of stars in the Milky Way. Each of these neurons “converses” with, on average, thousands of other neurons, sending molecular messages in a matter of milliseconds, about the same timeframe as a camera flash. How these messages are sent in such a rapid and precise manner has long been a mystery to neuroscientists. When these messages go awry, mental disorders such as schizophrenia, autism, and depression may arise. Specifically, Dr. Südhof parsed the proteins that are used in a synapse—the gap between neurons where one neuron reaches out to talk to another via chemical messengers known as neurotransmitters. These specialized spaces are comprised of three components: the messenger or presynaptic neuron, the recipient or postsynaptic neuron, and the cleft or space between these two neurons. Dr. Südhof’s work identified key molecules involved in the rapid release of neurotransmitters from the terminals of presynaptic neurons and revealed how electrical signals in the form of calcium ions instruct a protein called synaptotagmin. Once calcium binds to synaptotagmin, the protein serves as a switch for neurotransmitter-carrying cellular shuttles called vesicles to fuse with the outer surface of the presynaptic neuron and release these chemical messengers into the synaptic cleft. Upon release, the neurotransmitters cross the synaptic cleft and bind to docking sites or receptors on the postsynaptic neuron, triggering an electrical signal to pulse through it. Südhof’s work revealed that synaptotagmins also act as universal calcium sensors in non-neuronal cells, functioning, for example, in the release of hormones such as insulin from pancreatic beta cells. Dr. Südhof shares the world’s most prestigious science award with James E. Rothman, Ph.D., at Yale University, and Randy W. Schekman, Ph.D., at the University of California, Berkeley. Dr. Rothman unraveled protein machinery that allows vesicles to fuse with their targets to permit transfer of cargo. Dr. Schekman discovered a set of genes that were required for vesicle traffic. The researchers will share a prize that totals roughly $1.2 million USD. Previously, Dr. Südhof and Richard H. Scheller, Ph.D., at Genentech, collected the 2013 Albert Lasker Basic Medical Research Award for their work. Known as “America’s Nobels,” the Lasker Awards often predict future Nobel Prize recipients. The National Institutes of Health (NIH) has supported Dr. Südhof’s research over the past 22 years. In turn, Dr. Südhof has served on several study sections at the NIH Center for Scientific Review, in addition to the Molecular, Cellular, and Developmental Neuroscience study section at NIMH. Over the years, Dr. Südhof’s work on the neurotransmitter release machinery has been supported with research program grants as well as center grants from NIMH. He is also the recipient of an NIMH MERIT (Method to Extend Research in Time) award, which along with an additional NIMH grant and funding from the Howard Hughes Medical Institute helped support his Nobel work. MERIT awards provide up to 10 years of stable research support for highly productive outstanding investigators working on projects well aligned with the mission of NIMH Social Worker Continuing Education Dr. Südof also holds an NIH TR01 award for work to facilitate the creation of neurons from non-neuronal cells (skin fibroblasts of human patients). This work is anticipated to provide a novel way for scientists to study the biological effects of gene mutations associated with neuropsychiatric diseases

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

Brain Imaging Predicts Psychotherapy Success in Patients with Social Anxiety Disorder

Treatment for social anxiety disorder or social phobia has entered the personalized medicine arena—brain imaging can provide neuromarkers to predict whether traditional options such as cognitive behavioral therapy will work for a particular patient, reported a National Institute of Mental Health (NIMH)-funded study that was published in the January 2013 issue of JAMA Psychiatry. Background Social anxiety disorder (SAD)— the fear of being judged by others and humiliated— is the third most prevalent psychiatric disorder in Americans, after depression and alcohol dependence, according to the National Comorbidity Survey, a U.S. poll on mental health. This fear can be so strong that it interferes with daily life activities like going to work or school. If left untreated, some sufferers use alcohol, food, or drugs to reduce the fear at social events, which often leads to other disorders such as alcoholism, eating disorders, and depression. The NIMH claims that 6.8 percent of U.S. adults and 5.5 percent of 13- to 15-year-olds, the age of onset for this chronic disorder, are annually afflicted Social Worker Continuing Education Although psychotherapy and drugs, such as antidepressants and benzodiazepines, exist as treatments for SAD, current behavioral measures poorly predict which would work better for individual patients. “Half of social anxiety disorder patients have satisfactory response to treatment. There is little evidence about which patient would benefit from a particular form of treatment,” said John D. Gabrieli, Ph.D., lead author of the study. “Currently, there is no rational basis for prescribing one treatment over the other. Which treatment a patient gets depends on whom they see.” Enter personalized medicine, the use of genetic or other biological markers to tailor treatments to those who would actually benefit from them, thus sparing the expense and side effects for those who would not. Brain imaging could identify neuromarkers or targeted areas of the brain that could one day optimize treatment for individual patients. Neuromarkers are being used in other areas of mental illness, for instance, to predict the onset of psychosis in schizophrenia and the likelihood of relapse in drug addiction. In this study, Gabrieli, at the Massachusetts Institute of Technology in Cambridge, and his colleagues, used functional magnetic resonance imaging (fMRI) in 39 SAD patients before a 12-week course of cognitive behavioral therapy. The patients viewed angry versus neutral faces and scenes while undergoing fMRI examination (see first slide). Compared to neutral faces, angry faces convey disapproval and are likely to prompt excessive fear responses and negative connotations in SAD patients; cognitive behavioral therapy teaches these patients ways to downregulate their responses. The patients’ brain images were then compared to their scores on a conventional clinical measure, the Liebowitz Social Anxiety Scale (LSAS), a questionnaire which they took before and after therapy completion. Results of the Study SAD patients responded more to the images of faces and not scenes, which is characteristic for the social basis of this disorder. Patients whose brains reacted strongly to the facial images before treatment benefitted more from the therapy than those who reacted to these the least (see second slide). Specifically, changes in two occipitotemporal brain regions—areas involved in early processing of visual cues such as faces—correlated with positive cognitive behavioral therapy outcome. These neuromarkers predicted treatment outcome better than the currently used LSAS. Significance This study is the first of its kind to use neuroimaging to predict treatment response in SAD patients. Neuromarkers may become a practical clinical tool to guide the selection of optimal treatments for individual patients. Integration of neuromarkers with genetic, behavioral, and other biomarkers is likely to further refine the prediction. What’s Next A larger study comparing people with SAD with normal participants is needed to verify the results. fMRI studies using other facial expressions (disgust or fear) might be better predictors. Studies that look at other treatment options, such as drugs, are also needed to confirm which treatment is optimal. Researchers asked patients with social phobia to undergo functional magnetic resonance imaging (fMRI) while viewing images of neutral versus angry faces and scenes. The patients’ brains showed more activity when they viewed the faces. Source: Gabrieli Lab, MIT Patients with social phobia whose brains “lit” up the most, particularly in two regions towards the back of the brain that process what we see, responded the best to psychotherapy. Source: Gabrieli Lab, MIT Reference Doehrmann O, Ghosh SS, Polli FE, Reynolds GO, Horn F, Keshavan A, Triantafyllou C, Saygin ZM, Whitfield-Gabrieli S, Hofmann SG, Pollack M, Gabrieli JD. Predicting Treatment Response in Social Anxiety Disorder from Functional Magnetic Resonance Imaging. JAMA Psychiatry. January 2013. 70(1):87–97.

Switching Off a Specific Brain Region Can Alter Ingrained Habits in Rats

Ingrained habits in rats can be quickly broken—and reestablished—by targeting and switching off a specific site in the brain’s prefrontal cortex using a technique known as optogenetics, according to an NIMH-funded study published November 13, 2012, in the Proceedings of the National Academy of Sciences (PNAS). Background Studies have established that the prefrontal region of the brain is associated with habit formation and expression. It is also linked to emotion regulation and to regions in the brain that are associated with behavioral flexibility, which counteracts habit. Kyle Smith Ph.D., Ann Graybiel Ph.D., of the Massachusetts Institute of Technology, and colleagues, trained rats to run a T-shaped maze. At the decision point, the rats were cued to turn to either one side, where chocolate milk awaited them as a reward, or to the other side, where the reward was sugar water. Eventually, running the maze and responding to each cue correctly became a habit, and the rats continued to do so even after the rewards were removed. The researchers then returned the rewards but paired the chocolate milk with exposure to lithium chloride, which causes nausea. Once the rats realized the milk made them ill, they declined to drink it. However, they continued to run the maze and turn toward the chocolate milk side of the maze when cued, indicating that running in that direction when prompted had become a nearly automatic behavior. Results of the Study To determine whether the habit could be broken, the researchers then applied a technique known as optogenetics—in which a laser light is delivered to brain cells through optical fibers—to see if they could manipulate a specific region of the rats’ prefrontal cortex known as the infralimbic (IL) cortex. When the laser was turned on and the IL cortex was disrupted, the rats nearly instantaneously stopped running habitually toward the chocolate milk reward. Instead, they appeared to act more thoughtfully, running toward the other side, where the untainted sugar water awaited. Once the rats were broken of the habit of running automatically to the chocolate milk side, they began to develop a habit of always running to the other side, even when they were cued to run toward the chocolate milk, and even after the untainted chocolate milk was returned. But when the IL region was again disrupted optogenetically, the rats returned to their original habit of running to the chocolate milk side when cued to do so. Significance Control of a small part of the prefrontal cortex can change whether or not habits are expressed. An old habit can be blocked abruptly, and a new habit can override it. But if the new habit is then blocked, the old habit returns, thus lending credence to the notion that old habits die hard Social Worker Continuing Education In addition, the fact that habitual behavior can be altered if IL activity is disturbed suggests that the circuitry in this region of the brain is coordinating on some level with other brain regions that directly access circuits involved in behavioral flexibility, as well as addictive behaviors. What’s Next Although the optogenetic technique is too invasive to use in humans, it does have implications for potentially disrupting destructive habits. Targeting this specific region of the brain could lead to better ways of controlling addiction disorders or mental disorders in which habitual behaviors are out of balance, such as obsessive compulsive disorder. Reference Smith K, Virkud A, Deisseroth K, Graybiel A. Reversible online control of habitual behavior by optogenetic perturbation of media prefrontal cortex. PNAS. Nov 13, 2012. 109(46):18932-18937.

Rate of Bipolar Symptoms Among Teens Approaches That of Adults

The rate of bipolar symptoms among U.S. teens is nearly as high as the rate found among adults, according to NIMH-funded research published online ahead of print on May 7, 2012, in the Archives of General Psychiatry. Background Nationally representative data indicate that about 3.9 percent of adults meet criteria for bipolar disorder in their lifetime, and 2.6 percent meet criteria in a given year.1 However, limited data exist on the rates of bipolar disorder among adolescents, despite strong evidence indicating that bipolar disorder tends to emerge in adolescence or early adulthood. Kathleen Merikangas, Ph.D., of NIMH, and colleagues analyzed data from the NIMH-funded National Comorbidity Survey-Adolescent Supplement (NCS-A), a nationally representative, face-to-face survey of more than 10,000 teens ages 13 to 18. Using criteria established by the American Psychiatric Association’s Diagnostic and Statistical Manual (DSM-IV), the researchers assessed teens for the hallmark symptoms of bipolar disorder—mania and depression. They also examined the rates of teens who showed evidence of mania alone. Results of the Study The researchers found that 2.5 percent of youth met criteria for bipolar disorder in their lifetime, and 2.2 percent met criteria within a given year. About 1.7 percent reported having mania alone within their lifetime, and 1.3 percent reporting having mania alone within a given year. Rates increased with age—about 2 percent of younger teens reported bipolar disorder symptoms, whereas 3.1 percent of older teens did. Significance The findings reveal that the prevalence of bipolar disorder in adolescents approaches that of adults, underscoring the widely held belief that the disorder first appears in youth. In addition, the presence of mania alone suggests that mania without depression should receive greater attention when evaluating mood disorders in teens, especially since it may precede or be associated with behavioral problems such as substance use disorders and attention deficit hyperactivity disorder, according to the researchers. What’s Next The researchers highlighted the need to follow up with these youth, to see if they continue to manifest bipolar symptoms as they age. More research is needed on the overlap of mania with other emotional and behavioral disorders, as well as the core features and risk factors for the development of mania in adolescents social worker continuing education Citation 1 Merikangas K, Cui L, Kattan G, Carlson G, Youngstrom E, Angst J. Mania with and without depression in a community sample of U.S. adolescents. Archives of General Psychiatry. Online ahead of print May 7, 2012.

Many Youths with Autism Not Employed or In College 2 Years After High School

Young adults with autism spectrum disorder (ASD) are less likely to have a job or be enrolled in any type of postsecondary education when compared to peers with a speech/learning impairment or learning disability, according to a study partially funded by NIMH. Published in the June issue of Pediatrics, the findings emphasize the need to improve transition planning for students with ASD before they leave high school. Background Past studies on post-high school activities of youths with ASD were limited by having relatively few participants, lacking adequate diversity in the study population, or studying a narrow set of outcomes. As a result, it was unclear if those studies gave accurate descriptions of the ASD youth population as a whole, and if so, how broadly any findings could be applied. Using nationally representative data from the National Longitudinal Transition Study-2, Paul Shattuck, Ph.D., of Washington University, and colleagues assessed the activities of about 1,900 youths identified as having autism, speech/language impairment, learning disability, or mental retardation between the years 2007-2008. Data were provided by the youths’ parents or guardians or from the youths themselves if they were able to understand and answer the survey questions. All participants had previously received special education services and were no longer in high school. Results of the Study Compared to youths in other disability categories, those with ASD were less likely to have a job after high school. Youths with ASD were also less likely to be enrolled in any type of schooling than youths with speech/learning impairment or learning disability, but more likely than youths with mental retardation. In the first 2 years after leaving high school, youths with ASD were at significant risk of being completely disengaged, meaning to not be employed or in any postsecondary education. The participation rates, with rounded percentages, are summarized in the table below: *Additional data on youths’ participation in vocational or technical education showed a similar distribution social worker continuing education Youths from low-income families were much more likely to become disengaged, regardless of the severity of their disability. More impaired youths were also at greater risk of disengagement. Significance The results indicate that young adults with ASD experience unique challenges in finding work or enrolling in appropriate educational opportunities after leaving high school. In a related paper, also partially supported by NIMH funding, Dr. Shattuck noted that “the evidence base on services for adults with ASD is inadequate for informing policy and program decisions to meet the needs of this growing population.” In this context, the researchers emphasized the need to improve transition planning for youths with ASD or other special education needs as they prepare to leave high school. What’s Next According to the researchers, as more and more children are diagnosed with ASD, the demand for specialized adult services, jobs, and education will also continue to grow. Supporting targeted initiatives such as JobTIPS and further research on how to reduce or prevent disengagement will help inform efforts to better serve this population. References Shattuck PT, Narendorf SC, Cooper B, Sterzing PR, Wagner M, Taylor JL. Postsecondary Education and Employment Among Youth With an Autism Spectrum Disorder. Pediatrics. 2012 Jun;129(6):1042-9. Epub 2012 May 14. PubMed PMID: 22585766; PubMed Central PMCID: PMC3362908. Shattuck PT, Roux AM, Hudson LE, Taylor JL, Maenner MJ, Trani JF. Services for adults with an autism spectrum disorder. Can J Psychiatry. 2012 May;57(5):284-91. PubMed PMID: 22546060. Related funding: R01-MH086489

Exposure to violence has long-term stress effects among adolescents

UNIVERSITY PARK, Pa. -- Children who are exposed to community violence continue to exhibit a physical stress response up to a year after the exposure, suggesting that exposure to violence may have long-term negative health consequences, according researchers at Penn State and University College London. "We know that exposure to violence is linked with aggression, depression, post-traumatic stress symptoms and academic and cognitive difficulties in the short term, but little is known about the long-term effects of such exposure," said Elizabeth Susman, Jean Phillips Shibley Professor of Biobehavioral Health, Penn State. "Our data show that the stress reaction to violence exposure is not just immediate. There's an effect that endures." The scientists recruited 124 adolescents, ranging in age from 8 to 13 and living in small city and rural communities, to participate in the study social worker continuing education "Most studies of the effects of exposure to violence look at children who live in inner cities and urban communities," said Melissa Peckins, biobehavioral health graduate student, Penn State. "Our study is unique because we focused on children who live in small towns, so they are not children you would normally expect to be exposed to a lot of violence. Also, these were healthy children without a history of reported maltreatment." The researchers gave each of the adolescents a questionnaire, which identified their lifetime exposure to violence and exposure within the past 12 months. They then gave the adolescents the beginning of a story and asked them to complete it in front of two mock judges, whom they were told were evaluating their responses and performances for later comparison to those of other children the same age. Following the story-completion task, adolescents were also given a serial subtraction task. "The story completion task and mental arithmetic task are commonly used to elicit a stress response in laboratory settings," Peckins said. "Our hypothesis was that children who have been exposed to more violent events in the past year will have an attenuated response to the laboratory stressor -- even 12 months after the incidence -- compared with children who experienced fewer violent events." The team measured the children's stress responses by comparing the cortisol levels present in samples of their saliva collected before and after the stress test was administered. "In males, we found that as exposure to violence increased, cortisol reactivity decreased, so cortisol reactivity was attenuated; it was a habituation effect," Peckins said. The finding was not present in females. The results were published online in a recent issue of the Journal of Adolescent Health. "In enduring stressful conditions, we may have adapted evolutionarily to suppress our cortisol levels because higher and more prolonged levels of cortisol in the bloodstream can lead to negative health consequences, such as autoimmune disorders, lowered immunity, arthritis and atypical depression. This may explain why cortisol reactivity was lower for males," Susman said. "However, there is a theory that females may react to stressful situations by talking about it, which may be their way of reducing the negative effects of cortisol in the bloodstream. If parents and other adults are available to discuss episodes of violence with children, it might help the children, especially females, to reduce their cortisol levels." In the future, the team hopes to examine the role of duration of exposure to violence and time elapsed after exposure to violence on cortisol reactivity. ### Other researchers on this project were Samantha Dockray, research fellow, University College London, and Jacey Eckenrode, graduate student in biobehavioral health and Jodi Heaton, administrative assistant, biobehavioral health, both at Penn State. The National Institute of Mental Health, the General Clinical Research Center of the National Institutes of Health and Penn State supported this work.

Therapists phone it in and keep more patients

Telephone therapy retains more patients than face-to-face sessions and improves depression CHICAGO --- Phoning it in is more effective than the therapist's couch when it comes to keeping patients in psychotherapy. New Northwestern Medicine research shows patients who had therapy sessions provided over the phone were more likely to complete 18 weeks of treatment than those who had face-to-face sessions. The study, published in the June 6 issue of the Journal of the American Medical Association, is the first large trial to compare the benefits of face-to-face and telephone therapy. Phone therapy is a rapidly growing trend among therapists. About 85 percent of psychologists now deliver some of their services over the phone because competing demands, transportation time and other problems make it difficult for many patients to get to their offices social worker continuing education "Now therapists can make house calls," said David Mohr, the lead author and a professor of preventive medicine at Northwestern University Feinberg School of Medicine. "Our study found psychotherapy conveniently provided by telephone to patients wherever they are is effective and reduces dropout. This suggests these services now should be covered by insurance." While telephone therapy was as effective as face-to-face sessions in reducing depression during treatment, the improvement ebbed slightly six months after treatment ended compared to face-to-face therapy. The randomized control trial included 325 primary care patients with major depressive disorder. The results showed 20.9 percent of patients who had cognitive behavioral therapy over the phone dropped out compared to 32.7 percent for face-to-face therapy. Patients in both therapies showed equally good improvement in their depression when treatment ended. Six months after treatment ended, all patients remained much improved. However, patients who had the telephone therapy scored three points higher on a depression scale than those who had face-to-face sessions. "The three point difference is of questionable clinical significance but it raises the question whether some individuals are at risk of worsening after treatment with telephone therapy compared to face-to-face," Mohr said. It may be that the slight worsening seen in the telephone therapy after the end of treatment was because patients who had more mental health difficulties and who would have dropped out of face-to-face sessions were retained in telephone therapy, Mohr noted. Thus, this may not be a real finding. "But we can't rule out the possibility that it may be true and there is something about face-to-face treatment that creates better results for some people," Mohr said. "The physical presence of the therapist may be therapeutic in a way that helps some patients maintain their improvement in mood. There may be a unique quality about the human contact that increases resilience and maintains the skills learned to manage depression after treatment has ended." Mohr said he hopes the study results will encourage insurance providers including Medicare to reimburse telephone therapy sessions, which many companies currently don't cover. "There is good reason to reimburse these sessions," Mohr said. "Many people can't get to a therapist's office, but they want to talk to someone. Telephone therapy is highly effective and offers a solution to people with depression who otherwise would be left out." This is particularly true for disabled people or those who live where care is unavailable, such as in rural areas, he noted. Research shows people prefer talk therapy to antidepressant medication, but many quickly drop out of treatment or don't follow up on a referral from their primary care physicians, likely the result of obstacles that prevent them from getting to the therapist's office. ### Other Northwestern authors include: Joyce Ho, Jenna Duffecy, Michelle Nicole Burns, Ling Jin and Juned Siddique. This study was funded by the National Institute of Mental Health of the National Institutes of Health research grant NIMH R01-MH059708.

Most Children with ASD Diagnosed After Age 5, Use Multiple Services and Medications

Fewer than one out of five school-aged children with special health care needs were diagnosed with autism spectrum disorder (ASD) by age 2, according to new data from an NIMH-funded study. These diagnoses were made by a variety of health care providers, and most children in the study used multiple health care services (such as speech or language therapy) and multiple medications social worker continuing education Background Identifying ASD at an early age allows children to start treatment sooner, which can improve their later development and learning, and may also reduce a child’s need for specialized services or treatments later in life. To determine the experiences of school-aged children with special health care needs, Lisa Colpe, Ph.D., M.P.H., and Bev Pringle, Ph.D., of the NIMH Division of Services and Intervention Research, collaborated with colleagues who conducted more than 4,000 telephone interviews with parents or guardians of a child between the ages of 6-17 who had a confirmed diagnosis of ASD, intellectual disability, and/or developmental delay. These survey interviews were a part of the Pathways to Diagnosis and Services Study, sponsored by NIMH using funds available from the American Recovery and Reinvestment Act of 2009 (Recovery Act). Additional collaborators on this project include the National Center for Health Statistics at the Centers for Disease Control and Prevention (CDC) and the Maternal and Child Health Bureau at the Health Resources and Services Administration (HRSA). Results of the Study Key findings include: The median age when school aged children with special health care needs and ASD were first identified as having ASD was 5 years. Those identified as having ASD at younger than 5 years were diagnosed most often by generalists (such as pediatricians, family physicians, and nurse practitioners) and psychologists. Those identified later than 5 years were diagnosed primarily by psychologists and psychiatrists. Nine out of ten school-aged children with special health care needs and ASD used at least one health care service, such as behavioral intervention or modification services, sensory integration therapy, cognitive based therapy, occupational therapy, physical therapy, social skills training, or speech or language therapy. Social skills training and speech or language therapy were the most commonly used service, each used by almost 60 percent, or three out of five, of these children. More than half of school-aged children with special health care needs and ASD used at least one psychotropic medication. “Psychotropic medication” refers to any medication used to treat a mental disorder. Almost 33 percent of these children used stimulant medications 25 percent used anti-anxiety or mood-stabilizing medications 20 percent used antidepressants. Further findings are available in the NCHS Data Brief and Frequently Asked Questions. Significance The new data detail the experiences of young children with ASD, describing when they are first identified as having ASD, who is making those identifications, and the services and medications the children use to meet their developmental needs. What’s Next NIMH encourages researchers to access and analyze the new dataset to produce more studies on the early life experiences and the diagnostic, service, and treatment issues relevant to children with ASD and special health care needs. The Pathways to Diagnosis and Services Study dataset can be accessed at http://www.cdc.gov/nchs/slaits/spds.htm. Reference Pringle BA, Colpe LJ, Blumberg SJ, Avila RM, Kogan MD. Diagnostic History and Treatment of School-Aged Children with Autism Spectrum Disorder and Special Health Care Needs. NCHS data brief, no 97. Hyattsville, MD: National Center for Health Statistics. 2012.

Zebrafish study isolates gene related to autism, schizophrenia and obesity

What can a fish tell us about human brain development? Researchers at Duke University Medical Center transplanted a set of human genes into a zebrafish and then used it to identify genes responsible for head size at birth. Researchers at Duke University Medical Center transplanted a set of human genes into a zebrafish and then used it to identify genes responsible for head size at birth. Head size in human babies is a feature that is related to autism, a condition that recent figures have shown to be more common than previously reported, 1 in 88 children in a March 2012 study. Head size is also a feature of other major neurological disorders, such as schizophrenia. "In medical research, we need to dissect events in biology so we can understand the precise mechanisms that give rise to neurodevelopmental traits," said senior author Nicholas Katsanis, Ph.D., Jean and George Brumley Jr., MD, Professor of Developmental Biology, and Professor of Pediatrics and Cell Biology. "We need expert scientists to work side by side with clinicians who see such anatomic and other problems in patients, if we are to effectively solve many of our medical problems." The study was published online in Nature journal on May 16. Katsanis knew that a region on chromosome 16 was one of the largest genetic contributors to autism and schizophrenia, but a conversation at a European medical meeting pointed him to information that changes within that same region of the genome also were related to changes in a newborn's head size. The problem was difficult to address because the region had large deletions and duplications in DNA, which are the most common mutational mechanisms in humans. "Interpretation is harrowingly hard," said Katsanis, who is also director of the Duke Center for Human Disease Modeling. The reason is that a duplication of DNA or missing DNA usually involves several genes. "It is very difficult to go from 'here is a region with many genes, sometimes over 50' to 'these are the genes that are driving this pathology,'" Katsanis said. "There was a light bulb moment," Katsanis said. "The area of the genome we were exploring gave rise to reciprocal (opposite) defects in terms of brain cell growth, so we realized that overexpressing a gene in question might give one phenotype – a smaller head, while shutting down the same gene might yield the other, a larger head." The researchers transplanted a common duplication area of human chromosome 16 known to contain 29 genes into zebrafish embryos and then systematically turned up the activity of each transplanted human gene to find which might cause a small head (microcephaly) in the fish. They then suppressed the same gene set and asked whether any of them caused the reciprocal defect: larger heads (macrocephaly). The researchers knew that deletion of the region that contained these 29 genes occurred in 1.7% of children with autism. It took the team a few months to dissect such a "copy number variant" – an alteration of the genome that results in an abnormal number of one or more sections of chromosomal DNA. "Now we can go from a genetic finding that is dosage-sensitive and start asking reasonable questions about this gene as it pertains to neurocognitive traits, which is a big leap," Katsanis said. Neurocognitive refers to the ability to think, concentrate, reason, remember, process information, learn, understand and speak. Many human conditions have anatomical features that are also related to genetics, he said. "There are major limitations in studying autistic or schizophrenic behavior in zebrafish, but we can measure head size, jaw size, or facial abnormalities." The single gene in question, KCTD13, is responsible for driving head size in zebrafish by regulating the creation and destruction of new neurons (brain cells). This discovery let the team focus on the analogous gene in humans. "This gene contributes to autism cases, and probably is associated with schizophrenia and also childhood obesity," Katsanis said. Once the gene has been uncovered, researchers can examine the protein it produces. "Once you have the protein, you can start asking valuable functional questions and learning what the gene does in the animal or human," Katsanis said. Copy number variants, such as the ones this team found on chromosome 16, are now thought to be one of the most common sources of genetic mutations. Hundreds, if not thousands, of such chromosomal deletions and duplications have been found in patients with a broad range of clinical problems, particularly neurodevelopmental disorders. "Now we may have an efficient tool for dissecting them, which gives us the ability to improve both diagnosis and understanding of disease mechanisms," Katsanis said. The current study suggests that KCTD13 is a major contributor to some cases of autism, but also points to the synergistic action of this gene with two other genes in the region, named MVP and MAPK3, Katsanis said. Other authors include lead author Christelle Golzio, Jason Willer and Edwin Oh of the Duke Center for Human Disease Modeling and Department of Cell Biology; Mike Talkowski, Mei Sun and Jim Guzella from the Molecular Neurogenetics Unit, Center for Human Genetic Research, Massachusetts General Hospital in Boston; Sebastien Jacquemont, Alexandre Reymond and Jacques Beckmann from the Service de Génétique Médicale, Centre Hospitalier Universitaire Vaudois, in Lausanne, Switzerland; and Yu Taniguchi, Akira Sawa and Atsushi Kamiya from the Department of Psychiatry, Johns Hopkins University School of Medicine in Baltimore. Funding is from a Silvio O. Conte Center grant from the National Institute of Mental Health (NIMH), National Institutes of Health grants, the Simons Foundation, the Autism Consortium of Boston, the Leenaards Foundation Prize, the Swiss National Science Foundation, a National Science Foundation Sinergia grant, an NIMH National Research Service Award, and an academic study award from the University of Lausanne. NIH-related grants: Silvio O. Conte center grant from the National Institute of Mental Health, NIH MH-084018 (AS, AK, and NK), grant MH-091230 (AK), grant HD06286 (JFG) and an NIMH National Research Service Award (F32MH087123) social worker continuing education

LA BioMed researchers remain at the forefront of mental health initiatives

The month of May recognized as Mental Health Awareness Month LOS ANGELES (April 30, 2012) – With the month of May recognized nationally as Mental Health Awareness Month, the physician-researchers at the Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center (LA BioMed) continue to be at the forefront of mental health initiatives, engaging in clinical trials to help find therapies and treatments for individuals who suffer from mood and anxiety disorders. According to the National Institute of Mental Health (NIMH), mental health concerns affect 1 in 10 Americans today, but fewer than 25 percent of people with a diagnosable mental disorder seek treatment. Ira Lesser, M.D., is a principal investigator at LA BioMed and Chair, Department of Psychiatry, at Harbor-UCLA. At LA BioMed, he has led a number of clinical trials on mood and anxiety disorders, including the largest ever conducted on depression – Sequenced Treatment Alternatives to Relieve Depression (STAR*D) – a study funded by the NIMH. LA BioMed was one of 41 clinical sites participating, enrolling the greatest number of individuals and was the highest primary care enrolling site in the country. "With a growing number of individuals being diagnosed with a mental health disorder, it's imperative that we educate these individuals as to the options available to them, and also encourage them to seek treatment," said Dr. Lesser. "At LA BioMed, we are working to develop treatments and therapies that will not only help to cure but also help individuals cope with their existing conditions in the long term." In addition to STAR*D, Dr. Lesser and his staff (Karl Burgoyne, M.D., Benjamin Furst, M.D., Deborah Flores, M.D.) are working on other clinical trials including Biomarkers for Rapid Identification of Treatment Effectiveness in Major Depression (BRITE) and Biomarkers for Outcomes in Late-Life Depression (BOLD). Working alongside Dr. Lesser is LA BioMed investigator Michele Berk, Ph.D., who is directing a multi-site, randomized clinical trial that tests the effects of dialectical behavior therapy (DBT) on teenagers who have attempted suicide or engaged in self-harm behaviors, such as cutting. Suicide now ranks as the third leading cause of death in the U.S. among youth ages 10-19. DBT has been shown to be effective in reducing suicidal behavior in adults with depression and personality disorders. Sponsored by the NIMH, this study is the first such clinical trial in the U.S. to test the effectiveness of DBT in adolescents. John W. Tsuang, M.D., in conjunction with Steven J. Shoptaw, Ph.D., from the UCLA Department of Family Medicine, is spearheading a Phase I clinical safety trial that for the first time examines the effects of Ibudilast when administered with metamphetamine (MA), an addictive stimulant that is closely related to amphetamine. Funded by the National Institutes of Health National Institute on Drug Abuse (NIDA), this study will help to determine the effects of Ibudilast - combined with relevant doses of MA - on heart rate and blood pressure, and whether or not Ibudilast alters the way in which the body absorbs, distributes, and metabolizes MA. The development of one or more medications to reduce MA abuse, when implemented with evidence-based behavioral and counseling interventions, would have obvious public health significance. Dr. Tsuang is hoping that following the initial safety trial, physicians will be able to utilize Ibudilast in treating patients with MA dependence to help them improve memory and reduce the damage done to their central nervous system due to MA abuse social worker continuing education About LA BioMed Founded in 1952, LA BioMed is one of the country's leading nonprofit independent biomedical research institutes. It has approximately 100 principal researchers conducting studies into improved treatments and cures for cancer, inherited diseases, infectious diseases, illnesses caused by environmental factors and more. It also educates young scientists and provides community services, including prenatal counseling and childhood nutrition programs. LA BioMed is academically affiliated with the David Geffen School of Medicine at UCLA and located on the campus of Harbor-UCLA Medical Center. For more information, please visit www.LABioMed.org

The biology behind alcohol-induced blackouts

A person who drinks too much alcohol may be able to perform complicated tasks, such as dancing, carrying on a conversation or even driving a car, but later have no memory of those escapades. These periods of amnesia, commonly known as "blackouts," can last from a few minutes to several hours. Now, at Washington University School of Medicine in St. Louis, neuroscientists have identified the brain cells involved in blackouts and the molecular mechanism that appears to underlie them. They report July 6, 2011, in The Journal of Neuroscience, that exposure to large amounts of alcohol does not necessarily kill brain cells as once was thought. Rather, alcohol interferes with key receptors in the brain, which in turn manufacture steroids that inhibit long-term potentiation (LTP), a process that strengthens the connections between neurons and is crucial to learning and memory. Better understanding of what occurs when memory formation is inhibited by alcohol exposure could lead to strategies to improve memory. "The mechanism involves NMDA receptors that transmit glutamate, which carries signals between neurons," says Yukitoshi Izumi, MD, PhD, research professor of psychiatry at Washington University School of Medicine in St. Louis. "An NMDA receptor is like a double-edged sword because too much activity and too little can be toxic. We've found that exposure to alcohol inhibits some receptors and later activates others, causing neurons to manufacture steroids that inhibit LTP and memory formation." social worker continuing education Izumi says the various receptors involved in the cascade interfere with synaptic plasticity in the brain's hippocampus, which is known to be important in cognitive function. Just as plastic bends and can be molded into different shapes, synaptic plasticity is a term scientists use to describe the changeable properties of synapses, the sites where nerve cells connect and communicate. LTP is the synaptic mechanism that underlies memory formation. The brain cells affected by alcohol are found in the hippocampus and other brain structures involved in advanced cognitive functions. Izumi and first author Kazuhiro Tokuda, MD, research instructor of psychiatry, studied slices of the hippocampus from the rat brain. When they treated hippocampal cells with moderate amounts of alcohol, LTP was unaffected, but exposing the cells to large amounts of alcohol inhibited the memory formation mechanism.

IMAGE:When exposed to large amounts of alcohol, neurons in the hippocampus produce steroids (shown in bright green, at left), which inhibit the formation of memory. "It takes a lot of alcohol to block LTP and memory," says senior investigator Charles F. Zorumski, MD, the Samuel B. Guze Professor and head of the Department of Psychiatry. "But the mechanism isn't straightforward. The alcohol triggers these receptors to behave in seemingly contradictory ways, and that's what actually blocks the neural signals that create memories. It also may explain why individuals who get highly intoxicated don't remember what they did the night before." But not all NMDA receptors are blocked by alcohol. Instead, their activity is cut roughly in half. "The exposure to alcohol blocks some NMDA receptors and activates others, which then trigger the neuron to manufacture these steroids," Zorumski says. The scientists point out that alcohol isn't causing blackouts by killing neurons. Instead, the steroids interfere with synaptic plasticity to impair LTP and memory formation. "Alcohol isn't damaging the cells in any way that we can detect," Zorumski says. "As a matter of fact, even at the high levels we used here, we don't see any changes in how the brain cells communicate. You still process information. You're not anesthetized. You haven't passed out. But you're not forming new memories." Stress on the hippocampal cells also can block memory formation. So can consumption of other drugs. When combined, alcohol and certain other drugs are much more likely to cause blackouts than either substance alone. The researchers found that if they could block the manufacture of steroids by neurons, they also could preserve LTP in the rat hippocampus. And they did that with drugs called 5-alpha-reductase inhibitors. These include finasteride and dutasteride, which are commonly prescribed to reduce a man's enlarged prostate gland. In the brain, however, those substances seem to preserve memory. "We would expect there may be some differences in the effects of alcohol on patients taking these drugs," Izumi says. "Perhaps men taking the drugs would be less likely to experience intoxication blackouts." The researchers plan to study 5-alpha-reductase inhibitors to see how easily they get into the brain and to determine whether those drugs, or similar substances, might someday play a role in preserving memory. Tokuda K, Izumi Y, Zorumski CF. Ethanol enhances neurosteroidogenesis in hippocampal pyramidal neurons by paradoxical NMDA receptor activation, The Journal of Neuroscience, vol. 31(27), pp. 9905-9909. July 6, 2011. This work was supported by grants from the National Institute of Mental Health, the National Institute of General Medical Sciences, and the National Institute on Alcohol Abuse and Alcoholism of the National Institutes of Health (NIH), and by the Bantley Foundation. Washington University School of Medicine's 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children's hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked fourth in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children's hospitals, the School of Medicine is linked to BJC HealthCare.

Excessive worrying may have co-evolved with intelligence

What is usually seen as pathology may aid survival of the species

Worrying may have evolved along with intelligence as a beneficial trait, according to a recent study by scientists at SUNY Downstate Medical Center and other institutions. Jeremy Coplan, MD, professor of psychiatry at SUNY Downstate, and colleagues found that high intelligence and worry both correlate with brain activity measured by the depletion of the nutrient choline in the subcortical white matter of the brain. According to the researchers, this suggests that intelligence may have co-evolved with worry in humans.

"While excessive worry is generally seen as a negative trait and high intelligence as a positive one, worry may cause our species to avoid dangerous situations, regardless of how remote a possibility they may be," said Dr. Coplan. "In essence, worry may make people 'take no chances,' and such people may have higher survival rates. Thus, like intelligence, worry may confer a benefit upon the species."

In this study of anxiety and intelligence, patients with generalized anxiety disorder (GAD) were compared with healthy volunteers to assess the relationship among intelligence quotient (IQ), worry, and subcortical white matter metabolism of choline. In a control group of normal volunteers, high IQ was associated with a lower degree of worry, but in those diagnosed with GAD, high IQ was associated with a greater degree of worry. The correlation between IQ and worry was significant in both the GAD group and the healthy control group. However, in the former, the correlation was positive and in the latter, the correlation was negative. Eighteen healthy volunteers (eight males and 10 females) and 26 patients with GAD (12 males and 14 females) served as subjects.

Previous studies have indicated that excessive worry tends to exist both in people with higher intelligence and lower intelligence, and less so in people of moderate intelligence. It has been hypothesized that people with lower intelligence suffer more anxiety because they achieve less success in life.

The results of their study, "The Relationship between Intelligence and Anxiety: An Association with Subcortical White Matter Metabolism," was published in a recent edition of Frontiers in Evolutionary Neuroscience, and can be read at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3269637/pdf/fnevo-03-00008.pdf.

The study was selected and evaluated by a member of the Faculty of 1000 (F1000), placing it in their library of the top 2% of published articles in biology and medicine.

SUNY Downstate Medical Center, founded in 1860, was the first medical school in the United States to bring teaching out of the lecture hall and to the patient's bedside. A center of innovation and excellence in research and clinical service delivery, SUNY Downstate Medical Center comprises a College of Medicine, Colleges of Nursing and Health Related Professions, a School of Graduate Studies, a School of Public Health, University Hospital of Brooklyn, and an Advanced Biotechnology Park and Biotechnology Incubator.

SUNY Downstate ranks eighth nationally in the number of alumni who are on the faculty of American medical schools. More physicians practicing in New York City have graduated from SUNY Downstate than from any other medical school social worker continuing education

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.

Adding Psychotherapy to Medication Treatment Improves Outcomes in Pediatric OCD

Source: NIMH

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

Background

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

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

Results

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

Significance

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

What’s next

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

Citation

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