Intervention in 6-month-olds with autism eliminates symptoms, developmental delay

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'Infant Start' therapy removes disabling delay before most children are diagnosed "Treatment at the earliest age when symptoms of autism spectrum disorder (ASD) appear – sometimes in infants as young as 6 months old – significantly reduces symptoms so that, by age 3, most who received the therapy had neither ASD nor developmental delay, a UC Davis MIND Institute research study has found. The treatment, known as Infant Start, was administered over a six-month period to 6- to 15-month-old infants who exhibited marked autism symptoms, such as decreased eye contact, social interest or engagement, repetitive movement patterns, and a lack of intentional communication. It was delivered by the people who were most in tune with and spent the most time with the babies: their parents. “Autism treatment in the first year of life: A pilot study of Infant Start, a parent-implemented intervention for symptomatic infants,” is co-authored by UC Davis professors of Psychiatry and Behavioral Sciences Sally J. Rogers and Sally Ozonoff. It is published online today in the Journal of Autism and Developmental Disorders. "Most of the children in the study, six out of seven, caught up in all of their learning skills and their language by the time they were 2 to 3," said Rogers, the study's lead author and the developer of the Infant Start therapy. "Most children with ASD are barely even getting diagnosed by then." "For the children who are achieving typical developmental rates, we are essentially ameliorating their developmental delays," Rogers said. "We have speeded up their developmental rates and profiles, not for every child in our sample, but for six of the seven." Rogers credited the parents in the small, pilot study with making the difference. "It was the parents – not therapists – who did that," she said. "Parents are there every day with their babies. It's the little moments of diapering, feeding, playing on the floor, going for a walk, being on a swing, that are the critical learning moments for babies. Those moments are what parents can capitalize on in a way that nobody else really can." Early identification crucial Children diagnosed with autism typically receive early intervention beginning at 3 to 4 years, six to eight times later than the children who participated in the study. But the earliest symptoms of autism may be present before the child’s first birthday. Infancy is the time when children first learn social interaction and communication, so autism researchers and parents of children with the condition have been working to identify autism and begin intervention sooner. Effective autism treatment relies on early detection so that a child can begin therapy as soon as possible, to prevent or mitigate the full onset of symptoms and sometimes severe and lifelong disability. "We were very fortunate to have this treatment available for the affected infants identified through our study," said Ozonoff, who directs the MIND Institute's Infant Sibling Study, an early detection project that follows babies at risk for autism or ADHD from birth through age 3. "We want to make referrals for early intervention as soon as there are signs that a baby might be developing autism," Ozonoff said. "In most parts of the country and the world, services that address autism-specific developmental skills are just not available for infants this young." Of the seven babies in the study, four were part of the Infant Sibling Study. In addition to these four, the other three children were referred by community parents. The treatment group was compared with four other groups of children that included: High-risk children with older siblings with autism who did not develop autism Low-risk children who were the younger siblings of typically developing children Infants who developed autism by the age of 3 Children who also had early autism symptoms but chose to receive treatment at an older age Treatment based on Early Start Denver Model The treatment was based on the highly successful Early Start Denver Model (ESDM) intervention developed by Rogers and her colleague, Geraldine Dawson, professor of psychiatry, psychology and pediatrics at Duke University in North Carolina. ESDM is usually provided in the home by trained therapists and parents during natural play and daily routines. Parents were coached to concentrate their interactions on supporting their infants’ individualized developmental needs and interests, and embedded these practices into all of their play and caretaking, focusing on creating pleasurable social routines to increase their children’s opportunities for learning. Parents were encouraged to follow their infants’ interests and subtle cues and gauge activities in ways that optimized their child's attention and engagement. The intervention focused on increasing: Infant attention to parent faces and voices Parent-child interactions that attract infants' attention, bringing smiles and delight to both Parent imitation of infant sounds and intentional actions Parent use of toys to support, rather than compete with, the child's social attention The treatment sessions included: Greeting and parent progress sharing A warm-up period of parent play, followed by discussion of the activity and intervention goals Discussion of a new topic, using a parent manual Parents interacting in a typical daily routine with their child while fostering social engagement, communication and appropriate play, with coaching from therapists Parents practicing the approach with their child across one or two additional home routines with toys or caregiving activities Autism scores lowered by 18 to 36 months All of the participants who received treatment were between 6 and 15 months old, lived within a one-hour drive of the MIND Institute, and came from families where English was the primary language. They had normal vision and hearing and no significant medical conditions. All received assessments prior to their participation and at multiple points throughout the study. The treatment group of seven children received scores on the Autism Observation Scale for Infants (AOSI) and the Infant-Toddler Checklist that indicated they were highly symptomatic and at risk of developing ASD. Their symptoms also elicited clinical concern from professors Rogers and Ozonoff. The study measured the children’s and parents’ responses to the intervention. Treatment began immediately after enrollment and consisted of 12 one-hour sessions with infant and parent. It was followed by a six-week maintenance period with biweekly visits, and follow-up assessments at 24 and 36 months. The treatment sessions focused on parent–child interactions during typical daily life and provided parent coaching as needed to increase infant attention, communication, early language development, play and social engagement. The children who received the intervention had significantly more autism symptoms at 9 months, but significantly lower autism severity scores at 18- to 36-months of age, when compared with a small group of similarly symptomatic infants who did not receive the therapy. Overall, the children who received the intervention had less impairment in terms of autism diagnosis, and language and development delays than either of the other affected groups. Treating severe disability Given the preliminary nature of the findings, the study only suggests that treating these symptoms so early may lessen problems later. Larger, well controlled studies are needed to test the treatment for general use. However, the researchers said that this initial study is significant because of the very young ages of the infants, the number of symptoms and delays they exhibited early in life, the number of comparison groups involved, and because the intervention was low intensity and could be carried out by the parents in everyday routines. “I am not trying to change the strengths that people with ASD bring to this world," Rogers said when asked whether she is seeking to "cure" autism. "People with ASD contribute greatly to our culture," she said. "The diversity of human nature is what makes us a powerful and strong species. We are trying to reduce the disability associated with ASD." “My goal is for children and adults with autism symptoms to be able to participate successfully in everyday life and in all aspects of the community in which they want to participate: to have satisfying work, recreation, and relationships, education that meets their needs and goals, a circle of people they love, and to be generally happy with their lives.” ### Other study authors are Laurie Vismara of UC Davis and York University, Toronto; and A.L. Wagner, C. McCormick and Gregory Young, all of UC Davis. The study was funded by grants from the National Institute of Child Health and Human Development R21 HD 065275 to Sally Rogers and National Institute of Mental Health grant MH068398 to Ozonoff. At the UC Davis MIND Institute, world-renowned scientists engage in collaborative, interdisciplinary research to find the causes of and develop treatments and cures for autism, attention-deficit/hyperactivity disorder (ADHD), fragile X syndrome, 22q11.2 deletion syndrome, Down syndrome and other neurodevelopmental disorders. For more information, visit mindinstitute.ucdavis.edu." For more informationon this topic and other related subjects, please visit Counselor CEUs

Combined drugs and therapy most effective for severe nonchronic depression

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"The odds that a person who suffers from severe, nonchronic depression will recover are improved by as much as 30 percent if they are treated with a combination of cognitive therapy and antidepressant medicine rather than by antidepressants alone. However, a person with chronic or less severe depression does not receive the same additional benefit from combining the two. That is the result of a major new clinical trial published online by the journal JAMA Psychiatry on Aug. 20. In North America, about one in five women and one in 10 men suffer from major depression in her or his lifetime. "Our results indicate that combining cognitive therapy with antidepressant medicine can make a much bigger difference than we had thought to about one-third of patients suffering from major depressive disorder," said Steven Hollon, the Gertrude Conaway Professor of Psychology at Vanderbilt University, who directed the study. "On the other hand, it does not appear to provide any additional benefit for the other two-thirds." Previous studies have found that about two-thirds of all patients with major depressive disorder will improve on antidepressant medications and about one-third of patients will achieve full remission, but half then relapse before fully recovering. Cognitive therapy has proven to be about as effective as medication alone but its effects tend to be longer lasting. Combining the two has been estimated to improve recovery rates by 6 to 33 percent. "Now, we have to reconsider our general rule of thumb that combining the two treatments keeps the benefits of both," said Hollon. The new study was a randomized clinical trial involving 452 adult outpatients with chronic or recurrent major depressive disorder. Unlike previous studies that followed subjects for a set period of time, this study treated them for as long as it took first to remission (full normalization of symptoms) and then to recovery (six months without relapse), which in some cases took as long as three years. "This provided us with enough data so that we could drill down and see how the combined treatment was working for patients with different types and severity of depression: chronic, recurrent, severe and moderate," Hollon said. According to the psychologist, the results could have a major impact on how major depressive disorder is treated. The most immediate effect is likely to be in the United Kingdom, which, he said, is 10 years ahead of the United States in treatment of depression. The use of combined cognitive therapy and antidepressive medicine is standard for severe cases in the UK, and the English National Health Service is actively training its therapists in cognitive therapy and other empirically supported psychotherapies." ### Collaborators in the study were Robert DeRubeis and Jay Amsterdam from the University of Pennsylvania; Jan Fawcett from the University of New Mexico, Albuquerque; Richard Shelton from the University of Alabama, Birmingham; John Zajecka and Paula Young from Rush University; and Robert Gallop from West Chester University. The study was supported by grants MH60713, MH01697, MH60998 and MH060768 from the National Institute of Mental Health. For more information on mental health and counseling related topics, please visit Counselor CEUs

New evidence that chronic stress predisposes brain to mental illness

By Robert Sanders, Media Relations | February 11, 2014 BERKELEY — University of California, Berkeley, researchers have shown that chronic stress generates long-term changes in the brain that may explain why people suffering chronic stress are prone to mental problems such as anxiety and mood disorders later in life. myelin stained blue Myelin is stained blue in this cross section of a rat hippocampus. Myelin, which speeds electrical signals flowing through axons, is produced by oligodendrocytes, which increase in number as a result of chronic stress. New oligodendrocytes are shown in yellow. Image by Aaron Friedman and Daniela Kaufer. Their findings could lead to new therapies to reduce the risk of developing mental illness after stressful events. Doctors know that people with stress-related illnesses, such as post-traumatic stress disorder (PTSD), have abnormalities in the brain, including differences in the amount of gray matter versus white matter. Gray matter consists mostly of cells – neurons, which store and process information, and support cells called glia – while white matter is comprised of axons, which create a network of fibers that interconnect neurons. White matter gets its name from the white, fatty myelin sheath that surrounds the axons and speeds the flow of electrical signals from cell to cell. How chronic stress creates these long-lasting changes in brain structure is a mystery that researchers are only now beginning to unravel. In a series of experiments, Daniela Kaufer, UC Berkeley associate professor of integrative biology, and her colleagues, including graduate students Sundari Chetty and Aaron Freidman, discovered that chronic stress generates more myelin-producing cells and fewer neurons than normal. This results in an excess of myelin – and thus, white matter – in some areas of the brain, which disrupts the delicate balance and timing of communication within the brain. “We studied only one part of the brain, the hippocampus, but our findings could provide insight into how white matter is changing in conditions such as schizophrenia, autism, depression, suicide, ADHD and PTSD,” she said. The hippocampus regulates memory and emotions, and plays a role in various emotional disorders. Kaufer and her colleagues published their findings in the Feb. 11 issue of the journal Molecular Psychiatry. Does stress affect brain connectivity? Kaufer’s findings suggest a mechanism that may explain some changes in brain connectivity in people with PTSD, for example. One can imagine, she said, that PTSD patients could develop a stronger connectivity between the hippocampus and the amygdala – the seat of the brain’s fight or flight response – and lower than normal connectivity between the hippocampus and prefrontal cortex, which moderates our responses. “You can imagine that if your amygdala and hippocampus are better connected, that could mean that your fear responses are much quicker, which is something you see in stress survivors,” she said. “On the other hand, if your connections are not so good to the prefrontal cortex, your ability to shut down responses is impaired. So, when you are in a stressful situation, the inhibitory pathways from the prefrontal cortex telling you not to get stressed don’t work as well as the amygdala shouting to the hippocampus, ‘This is terrible!’ You have a much bigger response than you should.” white matter fibers in human brain White matter fiber architecture of the brain. Human Connectome Project. She is involved in a study to test this hypothesis in PTSD patients, and continues to study brain changes in rodents subjected to chronic stress or to adverse environments in early life. Stress tweaks stem cells Kaufer’s lab, which conducts research on the molecular and cellular effects of acute and chronic stress, focused in this study on neural stem cells in the hippocampus of the brains of adult rats. These stem cells were previously thought to mature only into neurons or a type of glial cell called an astrocyte. The researchers found, however, that chronic stress also made stem cells in the hippocampus mature into another type of glial cell called an oligodendrocyte, which produces the myelin that sheaths nerve cells. The finding, which they demonstrated in rats and cultured rat brain cells, suggests a key role for oligodendrocytes in long-term and perhaps permanent changes in the brain that could set the stage for later mental problems. Oligodendrocytes also help form synapses – sites where one cell talks to another – and help control the growth pathway of axons, which make those synapse connections. The fact that chronic stress also decreases the number of stem cells that mature into neurons could provide an explanation for how chronic stress also affects learning and memory, she said. Kaufer is now conducting experiments to determine how stress in infancy affects the brain’s white matter, and whether chronic early-life stress decreases resilience later in life. She also is looking at the effects of therapies, ranging from exercise to antidepressant drugs, that reduce the impact of stress and stress hormones. Kaufer’s coauthors include Chetty, formerly from UC Berkeley’s Helen Wills Neuroscience Institute and now at Harvard University; Friedman and K. Taravosh-Lahn at UC Berkeley’s Department of Integrative Biology; additional colleagues from UC Berkeley and others from Stanford University and UC Davis. The work was supported by a BRAINS (Biobehavioral Research Awards for Innovative New Scientists) award from the National Institute of Mental Health of the National Institutes of Health (R01 MH087495), a Berkeley Stem Cell Center Seed Grant, the Hellman Family Foundation and the National Alliance for Research on Schizophrenia and Depression. RELATED INFORMATION •Stress and glucocorticoids promote oligodendrogenesis in the adult hippocampus (2/11/14 Molecular Psychiatry) •Daniela Kaufer’s web site •Researchers find out why some stress is good for you (4/16/13 press release) For more information on this and other mental health topics, please visit Counselor CEUs

SHY hypothesis explains that sleep is the price we pay for learning

MADISON — Why do animals ranging from fruit flies to humans all need to sleep? After all, sleep disconnects them from their environment, puts them at risk and keeps them from seeking food or mates for large parts of the day. Two leading sleep scientists from the University of Wisconsin School of Medicine and Public Health say that their synaptic homeostasis hypothesis of sleep or "SHY" challenges the theory that sleep strengthens brain connections. The SHY hypothesis, which takes into account years of evidence from human and animal studies, says that sleep is important because it weakens the connections among brain cells to save energy, avoid cellular stress, and maintain the ability of neurons to respond selectively to stimuli. "Sleep is the price the brain must pay for learning and memory," says Dr. Giulio Tononi, of the UW Center for Sleep and Consciousness. "During wake, learning strengthens the synaptic connections throughout the brain, increasing the need for energy and saturating the brain with new information. Sleep allows the brain to reset, helping integrate, newly learned material with consolidated memories, so the brain can begin anew the next day. " Tononi and his co-author Dr. Chiara Cirelli, both professors of psychiatry, explain their hypothesis in a review article in today's issue of the journal Neuron. Their laboratory studies sleep and consciousness in animals ranging from fruit flies to humans; SHY takes into account evidence from molecular, electrophysiological and behavioral studies, as well as from computer simulations. "Synaptic homeostasis" refers to the brain's ability to maintain a balance in the strength of connections within its nerve cells. Why would the brain need to reset? Suppose someone spent the waking hours learning a new skill, such as riding a bike. The circuits involved in learning would be greatly strengthened, but the next day the brain will need to pay attention to learning a new task. Thus, those bike-riding circuits would need to be damped down so they don't interfere with the new day's learning. "Sleep helps the brain renormalize synaptic strength based on a comprehensive sampling of its overall knowledge of the environment," Tononi says, "rather than being biased by the particular inputs of a particular waking day." The reason we don't also forget how to ride a bike after a night's sleep is because those active circuits are damped down less than those that weren't actively involved in learning. Indeed, there is evidence that sleep enhances important features of memory, including acquisition, consolidation, gist extraction, integration and "smart forgetting," which allows the brain to rid itself of the inevitable accumulation of unimportant details. However, one common belief is that sleep helps memory by further strengthening the neural circuits during learning while awake. But Tononi and Cirelli believe that consolidation and integration of memories, as well as the restoration of the ability to learn, all come from the ability of sleep to decrease synaptic strength and enhance signal-to-noise ratios. While the review finds testable evidence for the SHY hypothesis, it also points to open issues. One question is whether the brain could achieve synaptic homeostasis during wake, by having only some circuits engaged, and the rest off-line and thus resetting themselves. Other areas for future research include the specific function of REM sleep (when most dreaming occurs) and the possibly crucial role of sleep during development, a time of intense learning and massive remodeling of brain Counselor CEUs

Autism early intervention found to normalize brain activity in children as young as 18 months

An intensive early intervention therapy that is effective for improving cognition and language skills among very young children with autism also normalizes their brain activity, decreases their autism symptoms and improves their social skills, a nationwide study has found. The researchers said the study is the first to demonstrate that an autism early intervention program can normalize brain activity. "We know that infant brains are quite malleable and previously demonstrated that this therapy capitalizes on the potential of learning that an infant brain has in order to limit autism's deleterious effects," said study author Sally Rogers, professor of psychiatry and behavioral sciences and a researcher with the UC Davis MIND Institute. "The findings on improved behavioral outcomes and the ability to normalize brain activity associated with social activities signify that there is tremendous potential for the brains of children with autism to develop and grow more normally," Rogers said. Published online today in the Journal of the American Academy of Child & Adolescent Psychiatry, the randomized, case-controlled, multi-centered study titled "Early behavioral intervention is associated with normalized brain activity in young children with autism," found that the children who received the intervention exhibited greater brain activation when viewing faces rather than objects, a response that was typical of the normal children in the study, and the opposite of the children with autism who received other intervention counselor ceus The U.S. Centers for Disease Control and Prevention estimates that 1 in 88 children born today will be diagnosed with autism spectrum disorder. Hallmarks of the neurodevelopmental condition include persistent deficits in social communication and relatedness, and repetitive or restrictive patterns of interest that appear in early childhood and impair everyday functioning. Named the Early Start Denver Model (ESDM), the intervention method was developed by Rogers and Geraldine Dawson, chief science officer of the research and advocacy organization Autism Speaks. The therapy fuses a play-based, developmental, relationship-based approach and the teaching methods of applied behavioral analysis. "This may be the first demonstration that a behavioral intervention for autism is associated with changes in brain function as well as positive changes in behavior," said Thomas R. Insel, director of the National Institute of Mental Health, which funded the study. "By studying changes in the neural response to faces, Dawson and her colleagues have identified a new target and a potential biomarker that can guide treatment development." For the present study, the researchers recruited 48 diverse male and female children diagnosed with autism between 18 and 30 months in Sacramento, Calif., and in Seattle, as well as typically developing case controls. The ratio of male-to-female participants was more than 3-to-1. Autism is five times more common among boys than girls. Approximately half of the children with autism were randomly assigned to receive the ESDM intervention for over two years. The participants received ESDM therapy for 20 hours each week, and their parents also were trained to deliver the treatment, a core feature of the intervention. The other participants with autism received similar amounts of various community-based interventions as well as evaluations, referrals, resource manuals and other reading materials. At the study's conclusion, the participants' brain activity was assessed using electroencephalograms (EEGs) that measured brain activation while viewing social stimuli -- faces -- and non-social stimuli -- toys. Earlier studies have found that typical infants and young children show increased brain activity when viewing social stimuli rather than objects, while children with autism show the opposite pattern. Twice as many of the children who received the ESDM intervention showed greater brain activation when viewing faces rather than when viewing objects -- a demonstration of normalized brain activity. Eleven of the 15 children who received the ESDM intervention, 73 percent, showed more brain activation when viewing faces than toys. Similarly, 12 of the 17 typically developing children, or 71 percent, showed the same pattern. But the majority -- 64 percent -- of the recipients of the community intervention showed the opposite, "autistic" pattern, i.e., greater response to toys than faces. Only 5 percent showed the brain activation of typical children. Further, the children receiving ESDM who had greater brain activity while viewing faces also had fewer social-pragmatic problems and improved social communication, including the ability to initiate interactions, make eye contact and imitate others, said MIND Institute researcher Rogers. Use of the ESDM intervention has been shown to improve cognition, language and daily living skills. A study published in 2009 found that ESDM recipients showed more than three times as much gain in IQ and language than the recipients of community interventions. "This is the first case-controlled study of an intensive early intervention that demonstrates both improvement of social skills and normalized brain activity resulting from intensive early intervention therapy," said Dawson, the study's lead author and professor of psychiatry at the University of North Carolina, Chapel Hill. "Given that the American Academy of Pediatrics recommends that all 18- and 24-month-old children be screened for autism, it is vital that we have effective therapies available for young children as soon as they are diagnosed." "For the first time," Dawson continued, "parents and practitioners have evidence that early intervention can alter the course of brain and behavioral development in young children. It is crucial that all children with autism have access to early intervention which can promote the most positive long-term outcomes." Rogers, Dawson and Laurie J. Vismara, also a researcher with the MIND Institute, have authored two books on the intervention. One for professionals is titled "Early Start Denver Model for Young Children with Autism: Promoting Language, Learning, and Engagement" and one for parents titled "An Early Start for Your Child with Autism: Using Everyday Activities to Help Kids Connect, Communicate, and Learn." The ESDM intervention is available in Sacramento through the MIND Institute clinic and in a number of locations throughout the U.S. and other nations. Training in delivering the ESDM method is provided through the MIND Institute and the University of Washington. ### Other study authors include Emily J.H. Jones, Kaitlin Venema, Rachel Lowy, Susan Faja, Dana Kamara, Michale Murias, Jessica Greenson, Jamie Winter, Milani Smith and Sara J. Webb, all of the University of Washington, and Kristen Merkle of Vanderbilt University. The study was funded by a grant from the National Institute of Mental Health and by a postdoctoral fellowship to Jones from Autism Speaks. Autism Speaks is the world's leading autism science and advocacy organization. It is dedicated to funding research into the causes, prevention, treatments and a cure for autism; increasing awareness of autism spectrum disorders; and advocating for the needs of individuals with autism and their families. At the UC Davis MIND Institute, world-renowned scientists engage in collaborative, interdisciplinary research to find the causes of and develop treatments and cures for autism, attention-deficit/hyperactivity disorder (ADHD), fragile X syndrome, 22q11.2 deletion syndrome, Down syndrome and other neurodevelopmental disorders. For more information, visit mindinstitute.ucdavis.edu

Study identifies factors related to violence in veterans

CHAPEL HILL, N.C. – A national survey identifies which U.S. military veterans may be at most risk of aggression after deployment and what strategies could potentially help reduce likelihood of violence when service members return home counselor ceus The study examined protective factors that are important in preventing violence, including employment, meeting basic needs, living stability, social support, spiritual faith, ability to care for oneself, perceived self-determination, and resilience (ability to adapt to stress). Veterans with these factors in place were 92 percent less likely to report severe violence than veterans who did not endorse these factors. The majority of veterans (over three-quarters of those studied) did endorse most of these protective factors and thus posed a low threat of violence. These findings are reported in an article published June 25, 2012 in the Journal of Clinical Psychiatry of a National Institute of Mental Health-funded study led by Eric B. Elbogen, PhD, Research Director of the Forensic Psychiatry Program in the University of North Carolina School of Medicine and Psychologist in the U.S. Department of Veterans Affairs. "When you hear about veterans committing acts of violence, many people assume that post-traumatic stress disorder (PTSD) or combat exposure are to blame," Elbogen said. "But our study shows that is not necessarily true." The national survey revealed that other factors are just as important to understanding violence in veterans, including alcohol misuse, criminal background, as well as veterans' living, work, social, and financial circumstances. In fact, the survey found that veterans who didn't have enough money to cover basic needs were more likely to report aggressive behavior than veterans with PTSD. "Our study suggests the incidence of violence could be reduced by helping veterans develop and maintain protective factors in their lives back home," Elbogen said. The survey was conducted between July 2009 and April 2010. Responses were collected from 1,388 veterans who served in the Iraq and Afghanistan War era and theater after Sept. 11, 2001. The sample included veterans from all branches of the U.S. military and all 50 states. One-third of survey respondents self-identified committing an act of aggression towards others in the past year, most of which involved relatively minor aggressive behavior. Eleven percent of the sample reported more severe violence. Elbogen noted, "Although the majority of study participants did not report aggression, the potential for violence does remain a significant concern among a subset of returning veterans." Dr. Sally Johnson, co-author and Professor in the UNC Forensic Psychiatry Program, points out "Some veterans do not cope well with the loss of the structure, social, and financial support available in the military environment. Attention to helping veterans establish psychosocial stability in the civilian environment can help reduce post-deployment adjustment problems including aggression." ### The other co-authors H. Ryan Wagner, PhD, Virginia M. Newton, PhD Christine Timko, PhD, Jennifer J. Vasterling, PhD, and Jean C. Beckham, PhD are affiliated with the Department of Veterans Affairs.

Antipsychotic drug may be helpful treatment for anorexia nervosa

Mouse model of anorexia offers opportunity to study drugs effective for disorder

Low doses of a commonly used atypical antipsychotic drug improved survival in a mouse model of anorexia nervosa, University of Chicago researchers report this month. The result offers promise for a common and occasionally fatal eating disorder that currently lacks approved drugs for treatment.

Mice treated with small doses of the drug olanzapine were more likely to maintain their weight when given an exercise wheel and restricted food access, conditions that produce activity-based anorexia (ABA) in animals. The antidepressant fluoxetine, commonly prescribed off-label for anorexic patients, did not improve survival in the experiment.

"We found over and over again that olanzapine was effective in harsher conditions, less harsh conditions, adolescents, adults — it consistently worked," said the paper's first author Stephanie Klenotich, graduate student in the Committee on Neurobiology at the University of Chicago Biological Sciences.

The study, published in Neuropsychopharmacology, was the product of a rare collaboration between laboratory scientists and clinicians seeking new treatment options for anorexia nervosa. As many as one percent of American women will suffer from anorexia nervosa during their lifetime, but only one-third of those people will receive treatment.

Patients with anorexia are often prescribed off-label use of drugs designed for other psychiatric conditions, but few studies have tested the drugs' effectiveness in animal models.

"Anorexia nervosa is the most deadly psychiatric disorder, and yet no approved pharmacological treatments exist," said Stephanie Dulawa, PhD, assistant professor of Psychiatry & Behavioral Neuroscience at the University of Chicago Medicine and senior author of the study. "One wonders why there isn't more basic science work being done to better understand the mechanisms and to identify novel pharmacological treatments."

One challenge is finding a medication that patients with anorexia nervosa will agree to take regularly, said co-author Daniel Le Grange, PhD, professor of Psychiatry & Behavioral Neuroscience and director of the Eating Disorders Clinic at the University of Chicago Medicine. Drugs that directly cause weight gain or carry strong sedative side effects are often rejected by patients.

"Patients are almost uniformly very skeptical and very reluctant to take any medication that could lower their resolve to refrain from eating," Le Grange said. "There are long-standing resistances, and I think researchers and clinicians have been very reluctant to embark on that course, since it's just littered with obstacles."

Both fluoxetine and olanzapine have been tried clinically to supplement interventions such as family-based treatment and cognitive-behavioral therapy. But their direct effect on anorexia nervosa behavior — in humans or animals — is lacking in sufficient data.

To test the effectiveness of these drugs in laboratory mice, Klenotich adapted the ABA protocol from previously published rat studies: Mice given 24-hour access to a running wheel but only six hours a day of food access become hyperactive, eat less and rapidly lose weight, with a 25 percent reduction from baseline considered to be the "drop-out" survival point.

In Klenotich's study, mice were pretreated with fluoxetine, olanzapine or saline before starting the ABA protocol, and treatment continued throughout the ABA period. Researchers then measured how many mice in each group reached the drop-out point for weight loss over 14 days of food restriction and exercise wheel access. Treatment with the antipsychotic olanzapine significantly increased survival over the control group, while fluoxetine treatment produced no significant effects on survival.

Importantly, a low dose of olanzapine did not decrease overall running activity in the mice, indicating that sedative effects of the drug were minimal. In future experiments, the researchers hope to use different drugs and genetic methods to determine exactly how olanzapine is effective against symptoms of anorexia nervosa, perhaps pointing toward a better drug without the negative image or side effects of an antipsychotic.

"We can dissect the effect of olanzapine and hopefully identify the mechanisms of action, and identify what receptor systems we want to target," Klenotich said. "Hopefully, we can develop a newer drug that we can aim towards the eating disorders clinic as an anorexic-specific drug that might be a little more acceptable to patients."

The study offers support for the clinical use of olanzapine, for which clinical trials are already under way to test in patients. Le Grange said the development of a pharmacological variant that more selectively treats anorexia nervosa could be a helpful way to avoid the "stigma" of taking an antipsychotic while giving clinicians an additional tool for helping patients.

"I think the clinical field is certainly very ready for something that is going to make a difference," Le Grange said. "I'm not saying there's a 'magic pill' for anorexia nervosa, but we have been lacking any pharmacological agent that clearly contributes to the recovery of our patients. Many parents and many clinicians are looking for that, because it would make our job so much easier if there was something that could turn symptoms around and speed up recovery."

Additionally, the study demonstrated the innovative experimental design and translational results that can come from a collaboration of laboratory and clinical experts.

"We don't talk to one another often enough in basic science and clinical science," Le Grange said. "More of that would be helpful for clinicians to understand the neurobiology of this disease. I'm very excited about the way this project is going, and I think it's going to be clinically very informative."


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The paper, "Olanzapine, but not fluoxetine, treatment increases survival in activity-based anorexia in mice," was published online March 7 by Neuropsychopharmacology (doi: 10.1038/npp.2012.7). In addition to Klenotich, Dulawa and Le Grange, authors include Mariel Seiglie and Priya Dugad of the University of Chicago and Matthew S. McMurray and Jamie Roitman of the University of Illinois at Chicago. Funding for the research was provided by the National Institute of Mental Health.

For more news from the University of Chicago Medical Center, follow us on Twitter at @UChicagoMed, or visit our Facebook page at facebook.com/UChicagoMed, our research blog at sciencelife.uchospitals.edu, or our newsroom at uchospitals.edu/news. counselor ceus

Computer-Based Treatment Eases Anxiety Symptoms in Children

Small Clinical Trial Supports Larger Scale Testing

A computer-based training method that teaches a person with anxiety to shift attention away from threatening images reduced symptoms of anxiety in a small clinical trial in children with the condition. The results of this first randomized clinical trial of the therapy in children with anxiety suggest that the approach warrants more extensive testing as a promising therapy.

Background

As many as a quarter of 13- to 18-year-olds have met the criteria for an anxiety disorder at some point. Currently available treatments—including cognitive behavioral therapy and medication—relieve symptoms of anxiety in about 70 percent of children treated. Most children with clinical anxiety do not receive treatment, partly because of difficulties in access to care, including distance and financial resources. Scientists are searching for additional approaches, including therapies that do not involve medication with its associated side effects counselor ceus

A treatment called attention bias modification (ABM) has emerged from the observation that people with anxiety unconsciously pay more attention than others to anything that seems threatening. One way of detecting such a bias is a dot probe test. In the test, people view a computer screen on which angry and neutral faces are flashed briefly, adjacent to each other. After the faces disappear, a test image of dots appears where either one or the other face was, and the person has to respond by pushing a button. People with anxiety consistently respond more quickly to dots that appear where the angry face was located.

ABM presents patients with an exercise similar to the dot probe test, but the dots always appear where the neutral face was, and thus consistently draw the attention of the participant to this non-threatening image. A recent meta-analyses of ABM in adults by some of the same investigators who carried out this work suggested its potential as a treatment.

This Study

Researchers at Tel Aviv University (TAU) in Israel carried out a clinical trial on ABM as an outcome of a three-year collaboration with scientists at the National Institute of Mental Health and the University of Maryland, College Park, Maryland. Yair Bar-Haim of TAU led the study, which appears in the American Journal of Psychiatry. The study enrolled 40 children, 8 to 14 years old, who had sought help for anxiety. For children receiving ABM, after faces appeared on a screen, two dots appeared on the screen; children had to determine whether the dots were side by side, or one above the other. In every case, dots appeared only where the neutral face had been. There were also two control groups: in the first, dots appeared equally frequently where angry and neutral faces appeared; in the second, the only faces that appeared throughout were neutral, so the dots always appeared in the location of a neutral face. The object of the second control group was to help confirm that any therapeutic effect was from the ABM training, and not from desensitizing the children to threatening faces. Children in the study were randomly assigned to receive treatment, or to be in one of two control groups. All children had four training sessions over 4 weeks, with 480 dot-probe trials per session.

Although the trial was small, there was a “reasonably robust” decrease in the severity of anxiety, according to the authors. Following ABM, both the number and severity of symptoms were reduced.

Significance

An important feature of ABM, says NIMH author Daniel Pine, is that it addresses the fundamental neurological function underlying anxiety: attention. Changes in attention happen very quickly—in milliseconds. “We know from neuroscience that if you want to change behaviors that happen very quickly, you have to practice. You can’t just tell someone how to drive, or throw a ball. You have to practice,” says Pine.

Longitudinal studies that follow children into adulthood suggest that most chronic mood and anxiety disorders in adults begin as high levels of anxiety in children. In fact, childhood anxiety is as important in predicting adult depression as it is for adult anxiety. The ability to influence attention biases early in development might provide a powerful means of prevention for both of these disorders later in life. The approach requires no medication and in practical terms, the computer-based nature of ABM lends itself to large-scale dissemination, in a medium children are comfortable with. Larger-scale trials will be able to provide more information on the efficacy of the treatment in children and how it works to reduce symptoms of anxiety.

# # #

Reference

Eldar, S., Apter, A., Lotan, D., Perez-Edgar, K., Naim, R, Fox, N.A., Pine, D.S., and Bar-Haim, Y. American Journal of Psychiatry. 2012 Feb 1;169(2):213-30.

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

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

Background

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

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

Results of the Study

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

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

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

Significance

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

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

What’s Next

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

Reference

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

Training Peers Improves Social Outcomes for Some Kids with ASD

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

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

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

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

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

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

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

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

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

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

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

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

Reference

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

Clinical Trials Number: NCT00095420

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

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

FOCUS ON TESTING HURTS STUDENTS IN HIGH SCHOOL HEALTH CLASSES

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

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

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


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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

The results are clear, Anderman said.

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

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

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

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

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

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

Widely Used Screening Tool Shown to Successfully Predict Suicide Attempts

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

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

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

Results of the Study

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

Significance

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

What’s Next

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

Reference

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Gene expression databases reveal “consistent molecular architecture”

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

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

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

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

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

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

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

Prefrontal cortex

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

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

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

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

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

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


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

Multiple brain regions

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

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

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

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

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

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


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

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


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


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


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


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


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

References

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

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

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

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

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

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

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

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

Perinatal antidepressant stunts brain development in rats

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

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

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

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

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

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

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

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

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

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

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

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

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

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


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

Reference

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

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

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

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

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