Excess body fat increases the risk of depression

A new study from Aarhus University and Aarhus University Hospital, Denmark, shows that ten kilograms of extra body fat increases the risk of depression by seventeen percent.

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Carrying ten kilograms of excess body fat increases the risk of depression by seventeen per cent. The more fat, the greater the probability of developing depression. This is the main conclusion of a new study carried out by researchers from Aarhus University and Aarhus University Hospital, Denmark.

"Our study also indicated that the location of the fat on the body makes no difference to the risk of depression. This suggests that it is the psychological consequences of being overweight or obese which lead to the increased risk of depression, and not the direct biological effect of the fat. If the opposite was true we would have seen that fat located centrally on the body increased the risk the most, as it has the most damaging effect in biological terms," says the study's last author Dr. Søren Dinesen Østergaard. 

He is professor at the Department of Clinical Medicine at Aarhus University and affiliated with the Department of Affective Disorders at Aarhus University Hospital. 

Prior studies in the field have predominantly used Body Mass Index (BMI) to measure obesity. BMI is calculated solely on the basis of body weight and height and is therefore a fairly crude measure, that does not, for example, take build and muscle mass into account.

"BMI is an inaccurate way of measuring overweight and obesity. Many elite athletes with a large muscle mass and a low body fat mass will have a BMI above 25, which is classified as overweight according to the common definition. This obviously doesn't make much sense. Therefore, one of the strengths of our study is that we've been able to zoom in and look at the specific relationship between the amount of body fat and the risk of depression," explains Dr. Østergaard.

In the study, which has been published in the journal Translational Psychiatry, the researchers have analysed data from two large genetic data sets: the UK Biobank, which contains data on the correlation between genetic variants and physical measurements (including body fat mass distributed around parts of the body); and the Psychiatric Genomics Consortium, which contains information on the correlation between genetic variants and depression.

Dr. Østergaard also highlights his research group's choice of the 'Mendelian randomization' method as the main reason why the study was successful. He also emphasises that the findings are particularly significant in light of the fact that almost 40 per cent of the world's adult population is overweight. 

"In addition to the known physical consequences of obesity such as diabetes and cardiovascular disease, there is also a significant and now well-documented psychological component, which needs to be dealt with as well. This is yet another argument for resolving the obesity epidemic," he says, before emphasising that it is important to have a balanced approach to the issue: 

"As it appears to be the psychological consequences of obesity, such as a negative body image and low self-esteem that is the main driving force behind the increased risk of depression, society's efforts to combat obesity must not stigmatise, as this will probably increase the risk of depression even further. It is important to bear this in mind so we can avoid doing more harm than good in the effort to curb the obesity epidemic," says Dr. Østergaard. 

FACTS ABOUT MENDELIAN RANDOMIZATION:

Mendelian randomization (named after the Austrian monk Gregor Mendel, who was the father of modern genetics) is a method which in recent years has helped researchers to overcome a major challenge associated with observational studies - namely that of making causal inference. In observational studies researchers often find correlations between two conditions - e.g. between obesity and depression - where it is difficult, or rather impossible, to determine whether there is indeed a causal effect going from obesity to depression - or vice versa. Mendelian randomization may solve this challenge.

Mendelian randomization can be described as nature's version of the randomised controlled trials that are carried out when testing whether a new drug has the desired (causal) effect in the treatment of a disease. In the clinical trials of drugs, lots are drawn to determine whether individual participants will receive the active drug or a placebo, without them knowing which treatment they have been assigned to. Instead, Mendelian randomization takes advantage of the fact that a completely natural randomization takes place during the formation of the sex cells (egg cells and sperm cells), which represent the origin of all human beings. When sex cells are formed, the parents' genetic variants - including those that give rise to increased body fat- are randomly distributed. Therefore, some individuals will have received many of these variants and others less. In the study in question, the researchers have utilised this natural and random source of variation to determine whether people who have received many genetic variants for increased body fat have an increased risk of suffering depression.

THE RESEARCH RESULT - MORE INFORMATION

Genetic epidemiological study utilising data from the UK Biobank (with information on the association between genetic variants and fat mass based on a study of 330,000 people) and the Psychiatric Genomics Consortium (with information on the association between genetic variants and depression based on a study of 135,000 people with depression and 345,000 control subjects).

The research group comprises Maria S. Speed, Oskar H. Jefsen, Anders D. Børglum, Doug Speed and Søren D. Østergaard - all from Aarhus University.

Early childhood depression alters brain development

What do you think about this article by WASHINGTON UNIVERSITY SCHOOL OF MEDICINE?

"The brains of children who suffer clinical depression as preschoolers develop abnormally, compared with the brains of preschoolers unaffected by the disorder, according to new research at Washington University School of Medicine in St. Louis. Their gray matter -- tissue that connects brain cells and carries signals between those cells and is involved in seeing, hearing, memory, decision-making and emotion -- is lower in volume and thinner in the cortex, a part of the brain important in the processing of emotions. The new study is published Dec. 16 in JAMA Psychiatry. "What is noteworthy about these findings is that we are able to see how a life experience -- such as an episode of depression -- can change the brain's anatomy," said first author Joan L. Luby, MD, whose research established that children as young as 3 can experience depression. "Traditionally, we have thought about the brain as an organ that develops in a predetermined way, but our research is showing that actual experience -- including negative moods, exposure to poverty, and a lack of parental support and nurturing -- have a material impact on brain growth and development." The findings may help explain why children and others who are depressed have difficulty regulating their moods and emotions. The research builds on earlier work by Luby's group that detailed other differences in the brains of depressed children. Luby, the Samuel and Mae S. Ludwig Professor of Child Psychiatry, and her team studied 193 children, 90 of whom had been diagnosed with depression as preschoolers. They performed clinical evaluations on the children several times as they aged. The researchers also conducted MRI scans at three points in time as each child got older. The first scans were performed when the kids were ages 6 to 8, and the final scans were taken when they were ages 12 to 15. A total of 116 children in the study received all three brain scans. "If we had only scanned them at one age or stage, we wouldn't know whether these effects simply were present from birth or reflected an actual change in brain development," said co-investigator Deanna M. Barch, PhD, head of Washington University's Department of Psychological and Brain Sciences in Arts & Sciences. "By scanning them multiple times, we were able to see that the changes reflect an actual difference in brain maturation that emerges over the course of development." The gray matter is made up mainly of neurons, along with axons that extend from brain cells to carry signals. The gray matter processes information, and as children get older, they develop more of it. Beginning around puberty, the amount of gray matter begins to decline as communication between neurons gets more efficient and redundant processes are eliminated. "Gray matter development follows an inverted U-shaped curve," Luby said. "As children develop normally, they get more and more gray matter until puberty, but then a process called pruning begins, and unnecessary cells die off. But our study showed a much steeper drop-off, possibly due to pruning, in the kids who had been depressed than in healthy children." Further, the steepness of the drop-off in the volume and thickness of the brain tissue correlated with the severity of depression: The more depressed a child was, the more severe the loss in volume and thickness. The researchers determined that having depression was a key factor in gray matter development. In scans of children whose parents had suffered from depression -- meaning the kids would be at higher risk -- gray matter appeared normal unless the kids had suffered from depression, too. Interestingly, the differences in gray matter volume and thickness typically were more pronounced than differences in other parts of the brain linked to emotions. Luby explained that because gray matter is involved in emotion processing, it is possible some of the structures involved in emotion, such as the brain's amygdala, may function normally, but when the amygdala sends signals to the cortex -- where gray matter is thinner -- the cortex may be unable to regulate those signals properly. Luby and Barch are planning to conduct brain scans on even younger children to learn whether depression may cause pruning in the brain's gray matter to begin earlier than normal, changing the course of brain development as a child grows. "A next important step will involve determining whether early intervention might shift the trajectory of brain development for these kids so that they revert to more typical and healthy development," said Barch, also the Gregory B. Couch Professor of Psychiatry. Luby said that is the main challenge facing those who treat kids with depression. "The experience of early childhood depression is not only uncomfortable for the child during those early years," she said. "It also appears to have long-lasting effects on brain development and to make that child vulnerable to future problems. If we can intervene, however, the benefits might be just as long-lasting." ### Funding from the National Institute of Mental Health and the National Institutes of Health Blueprint of the National Institutes of Health (NIH), grant numbers R01 MH66031, R01 MH084840, R01 MH090786, R01 MH098454-S, U54 MH091657, 2R01 MH064769-06A1, PA-07-070 NIMH R01 5K01MH090515-04 and T32 MH100019. Luby JL, Belden AC, Jackson JL, Lessov-Schlaggar CN, Harms MP, Tillman R, Botteron K, Whalen D, Barch DM. Early childhood depression and alterations in the trajectory of gray matter maturation in middle childhood and early adolescence?. JAMA Psychiatry, published online Dec. 16, 2015. http://jamapsychiatry.com doi:10.1001/jamapsychiatry.2015.2356 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 sixth 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." For more information on depression and other mental health related topics,please visit Aspira Continuing Education Online Courses

Happy head, happy heart: Positive emotions may promote heart-healthy behaviors

What do you think of this article by NIMH? "People with heart disease may benefit from maintaining positive emotions, according to health researchers. Over the course of five years the researchers tracked more than 1,000 patients with coronary heart disease. Patients who reported higher positive psychological states were more likely to be physically active, sleep better and take their heart medications and were also less likely to smoke, compared to patients with lower levels of positive states. "Negative emotions and depression are known to have harmful effects on health, but it is less clear how positive emotions might be health-protective," said Nancy L. Sin, postdoctoral fellow in the Center for Healthy Aging and in the department of biobehavioral health at Penn State. "We found that positive emotions are associated with a range of long-term health habits, which are important for reducing the risk of future heart problems and death." The researchers assessed psychological well-being of participants at baseline and again at a five-year follow-up by asking the participants to rate the extent that they had felt 10 specified positive emotions, including "interested," "proud," "enthusiastic" and "inspired." Physical activity, sleep quality, medication adherence and alcohol and cigarette use were also measured at baseline and again five years later. The researchers report their findings in the today's (Oct. 2) issue of the journal Psychosomatic Medicine. "Higher levels of positive emotions were associated with less smoking, greater physical activity, better sleep quality and more adherence to medications" at baseline, said the researchers. They found no correlation between positive emotions and alcohol use. The results took into account patients' demographic factors, depressive symptoms and the severity of their heart conditions. Though positive emotions at baseline did not predict changes in health behaviors five years later, increases in positive emotions across the five-year period were associated with improvements in physical activity, sleep quality and medication adherence. There are a number of reasons why positive emotions are linked to optimal health habits, the researchers suggest. People with greater positive well-being may be more motivated and persistent in engaging in healthy behaviors. They might have more confidence in their abilities to maintain routines such as physical activity and sleep hygiene. Positive emotions may also enable people to better adjust their health goals and to proactively cope with stress and setbacks. "Efforts to sustain or enhance positive emotions may be promising for promoting better health behaviors," said the researchers. This research sets the stage for future work on interventions to improve health habits, Sin noted. Further research with other chronic disease populations and with electronic tracking of health behaviors should be conducted, she said. ### Judith Tedlie Moskowitz, professor, medical social sciences at the Feinberg School of Medicine, Northwestern University, and Mary A. Whooley, professor, medicine, epidemiology and biostatistics at the University of California San Francisco and physician at the San Francisco Veterans Affairs Medical Center, also worked on this research. The National Institute on Aging, the National Institute of Mental Health, the department of Veterans Affairs, the National Heart, Lung and Blood Institute, the Robert Wood Johnson Foundation and the American Federation for Aging Research supported this work. Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system." For more on this and other mental health subjects, please visit our course listing page Continuing Education Online Courses

Teenage Girls Are Exposed to More Stressors that Increase Depression Risk

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"Adolescence is often a turbulent time, and it is marked by substantially increased rates of depressive symptoms, especially among girls. New research indicates that this gender difference may be the result of girls’ greater exposure to stressful interpersonal events, making them more likely to ruminate, and contributing to their risk of depression. The findings are published in Clinical Psychological Science, a journal of the Association for Psychological Science. This is a photo of a pensive looking girl sitting on steps.“These findings draw our focus to the important role of stress as a potential causal factor in the development of vulnerabilities to depression, particularly among girls, and could change the way that we target risk for adolescent depression,” says psychology researcher and lead author on the study, Jessica Hamilton of Temple University. “Although there is a range of other vulnerabilities that contribute to the emergence of girls’ higher rates of depression during adolescence, our study highlights an important malleable pathway that explains girls’ greater risk of depression.” Research has shown that cognitive vulnerabilities associated with depression, such as negative cognitive style and rumination, emerge during adolescence. Teens who tend to interpret events in negative ways (negative cognitive style) and who tend to focus on their depressed mood following such events (rumination) are at greater risk of depression. Hamilton, a doctoral student in the Mood and Cognition Laboratory of Lauren Alloy at Temple University, hypothesized that life stressors, especially those related to adolescents’ interpersonal relationships and that adolescents themselves contribute to (such as a fight with a family member or friend), would facilitate these vulnerabilities and, ultimately, increase teens’ risk of depression. The researchers examined data from 382 Caucasian and African American adolescents participating in an ongoing longitudinal study. The adolescents completed self-report measures evaluating cognitive vulnerabilities and depressive symptoms at an initial assessment, and then completed three follow-up assessments, each spaced about 7 months apart. As expected, teens who reported higher levels of interpersonal dependent stress showed higher levels of negative cognitive style and rumination at later assessments, even after the researchers took initial levels of the cognitive vulnerabilities, depressive symptoms, and sex into account. Girls tended to show more depressive symptoms at follow-up assessments than did boys — while boys’ symptoms seemed to decline from the initial assessment to follow-up, girls’ symptoms did not. Girls also were exposed to a greater number of interpersonal dependent stressors during that time, and analyses suggest that it is this exposure to stressors that maintained girls’ higher levels of rumination and, thus, their risk for depression over time. The researchers emphasize that the link is not driven by reactivity to stress — girls were not any more reactive to the stressors that they experienced than were boys. “Simply put, if boys and girls had been exposed to the same number of stressors, both would have been likely to develop rumination and negative cognitive styles,” Hamilton explains. Importantly, other types of stress — including interpersonal stress that is not dependent on the teen (such as a death in the family) and achievement-related stress — were not associated with later levels of rumination or negative cognitive style. “Parents, educators, and clinicians should understand that girls’ greater exposure to interpersonal stressors places them at risk for vulnerability to depression and ultimately, depression itself,” says Hamilton. “Thus, finding ways to reduce exposure to these stressors or developing more effective ways of responding to these stressors may be beneficial for adolescents, especially girls.” According to Hamilton, the next step will be to figure out why girls are exposed to more interpersonal stressors: “Is it something specific to adolescent female relationships? Is it the societal expectations for young adolescent girls or the way in which young girls are socialized that places them at risk for interpersonal stressors? These are questions to which we need to find answers!” Co-authors on the study include Jonathan P. Stange and Lauren B. Alloy of Temple University and Lyn Y. Abramson of the University of Wisconsin-Madison. This work was supported by NIMH Grants MH79369 and MH101168 to Lauren B. Alloy. Jonathan P. Stange was supported by National Research Service Award F31MH099761 from NIMH." For more information on mental health topics, please visit CEUs for MFTs

Combined drugs and therapy most effective for severe nonchronic depression

What do you think of this article released by NIMH?

"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

Anxiety linked to higher long-term risk of stroke

American Heart Association Rapid Access Journal Report The greater your anxiety level, the higher your risk of having a stroke, according to new research published in the American Heart Association journal Stroke. The study is the first in which researchers linked anxiety and stroke independent of other factors such as depression. Anxiety disorders are one of the most prevalent mental health problems. Symptoms include feeling unusually worried, stressed, nervous or tense. Over a 22 year period, researchers studied a nationally representative group of 6,019 people 25-74 years old in the first National Health and Nutrition Examination Survey (NHANES I). Participants underwent an interview and took blood tests, medical examinations and completed psychological questionnaires to gauge anxiety and depression levels. Researchers tracked strokes through hospital or nursing home reports and death certificates. After accounting for other factors, they found that even modest increases in anxiety were associated with greater stroke risk. People in the highest third of anxiety symptoms had a 33 percent higher stroke risk than those with the lowest levels. "Everyone has some anxiety now and then. But when it's elevated and/or chronic, it may have an effect on your vasculature years down the road," said Maya Lambiase, Ph.D., study author and cardiovascular behavioral medicine researcher in the Department of Psychiatry at the University of Pittsburgh School of Medicine, in Pittsburgh, Penn. People with high anxiety levels are more likely to smoke and be physically inactive, possibly explaining part of the anxiety-stroke link. Higher stress hormone levels, heart rate or blood pressure could also be factors, Lambiase said. In earlier work, researchers found that depression was linked to greater risk of stroke. In contrast to anxiety, depression is a persistent feeling of hopelessness, dejection, and lack of energy, among other symptoms. Stroke is the No. 4 killer and a leading cause of disability in the United States Continuing Education for MFTs ### Co-authors are Laura Kubzansky, Ph.D. and Rebecca Thurston, Ph.D. Author disclosures are on the manuscript. The National Heart, Lung, and Blood Institute and the National Institute of Mental Health funded the study. For the latest heart and stroke news, follow us on Twitter: @HeartNews. For stroke science, follow the Stroke journal at @StrokeAHA_ASA. Statements and conclusions of study authors published in American Heart Association scientific journals are solely those of the study authors and do not necessarily reflect the association's policy or position. The association makes no representation or guarantee as to their accuracy or reliability. The association receives funding primarily from individuals; foundations and corporations (including pharmaceutical, device manufacturers and other companies) also make donations and fund specific association programs and events. The association has strict policies to prevent these relationships from influencing the science content. Revenues from pharmaceutical and device corporations are available at http://www.heart.org/corporatefunding.

OHSU Vollum Institute research gives new insight into how antidepressants work in the brain

Vollum Institute scientist publishes two papers on neurotransmission in today’s edition of Nature Research from Oregon Health & Science University's Vollum Institute, published in the current issue of Nature, is giving scientists a never-before-seen view of how nerve cells communicate with each other. That new view can give scientists a better understanding of how antidepressants work in the human brain — and could lead to the development of better antidepressants with few or no side effects. The article in today’s edition of Nature came from the lab of Eric Gouaux, Ph.D., a senior scientist at OHSU's Vollum Institute and a Howard Hughes Medical Institute Investigator. The article describes research that gives a better view of the structural biology of a protein that controls communication between nerve cells. The view is obtained through special structural and biochemical methods Gouaux uses to investigate these neural proteins. The Nature article focuses on the structure of the dopamine transporter, which helps regulate dopamine levels in the brain. Dopamine is an essential neurotransmitter for the human body's central nervous system; abnormal levels of dopamine are present in a range of neurological disorders, including Parkinson's disease, drug addiction, depression and schizophrenia. Along with dopamine, the neurotransmitters noradrenaline and serotonin are transported by related transporters, which can be studied with greater accuracy based on the dopamine transporter structure. The Gouaux lab's more detailed view of the dopamine transporter structure better reveals how antidepressants act on the transporters and thus do their work Alcoholism and Drug Abuse Counselors Continuing Education The more detailed view could help scientists and pharmaceutical companies develop drugs that do a much better job of targeting what they're trying to target — and not create side effects caused by a broader blast at the brain proteins. "By learning as much as possible about the structure of the transporter and its complexes with antidepressants, we have laid the foundation for the design of new molecules with better therapeutic profiles and, hopefully, with fewer deleterious side effects," said Gouaux. Gouaux's latest dopamine transporter research is also important because it was done using the molecule from fruit flies, a dopamine transporter that is much more similar to those in humans than the bacteria models that previous studies had used. The dopamine transporter article was one of two articles Gouaux had published in today’s edition of Nature. The other article also dealt with a modified amino acid transporter that mimics the mammalian neurotransmitter transporter proteins targeted by antidepressants. It gives new insights into the pharmacology of four different classes of widely used antidepressants that act on certain transporter proteins, including transporters for dopamine, serotonin and noradrenaline. The second paper in part was validated by findings of the first paper — in how an antidepressant bound itself to a specific transporter. "What we ended up finding with this research was complementary and mutually reinforcing with the other work — so that was really important," Gouaux said. "And it told us a great deal about how these transporters work and how they interact with the antidepressant molecules." Gouaux's discoveries over the years in neurotransmission have established him as one of the top investigators in his field. His research has important implications for understanding the mechanisms of not just antidepressants, but also drugs used for the treatment of a wide range of psychiatric and neurological diseases. Gouaux's co-authors on the dopamine transporter paper were both members of his lab; Aravind Penmatsa, Ph.D., and Kevin Wang, Ph.D. Gouaux's co-authors on the second Nature paper were also members or former members of his lab: Hui Wang, Ph.D.; April Goehring, Ph.D.; Kevin Wang, Aravind Penmatsa and Ryan Ressler, Ph.D. Both papers were funded by the American Heart Association, the National Institute of Mental Health, (1F32MH093120 and 5R37MH070039) and the Howard Hughes Medical Institute. About the OHSU Vollum Institute The Vollum Institute is a privately endowed research institute at OHSU and is dedicated to basic research that will lead to new treatments for neurological and psychiatric diseases. Vollum scientists have transformed the field of neuroscience and, in particular, have been pioneers in the study of cellular signaling, neuronal development, gene regulation and the neurobiology of disease. About OHSU Oregon Health & Science University is a nationally prominent research university and Oregon’s only public academic health center. It serves patients throughout the region with a Level 1 trauma center and nationally recognized Doernbecher Children’s Hospital. OHSU operates dental, medical, nursing and pharmacy schools that rank high both in research funding and in meeting the university’s social mission. OHSU’s Knight Cancer Institute helped pioneer personalized medicine through a discovery that identified how to shut down cells that enable cancer to grow without harming healthy ones. OHSU Brain Institute scientists are nationally recognized for discoveries that have led to a better understanding of Alzheimer’s disease and new treatments for Parkinson’s disease, multiple sclerosis and stroke. OHSU’s Casey Eye Institute is a global leader in ophthalmic imaging, and in clinical trials related to eye disease.

Depression Therapy Effective for Poor, Minority Moms

Faced with the dual demands of motherhood and poverty, as many as one fourth of low-income minority mothers struggle with major depression. But the stigma associated with mental illness coupled with limited access to quality treatment prevent the majority of these struggling women from receiving help. Now a new study shows that screening for the disorder and providing short-term, relationship-focused therapy through weekly home visits can relieve depression among minority mothers, even in the face of poverty and personal histories of abuse or violence. Such help can have far reaching benefits not only for mothers, but also for their children, say the authors. "It's amazing, really," says psychologist Sheree Toth, lead author and executive director of the University of Rochester's Mt. Hope Family Center. "This research tracked a 14-week intervention for mothers who are terribly overwhelmed, surrounded by high-crime neighborhoods, lacking social support, and often traumatized—my fear was, 'this is never going to work.'" But to the surprise of Toth and her Rochester team, the series of convenient, one-hour therapy sessions relieved depression in participants much better than standard clinic-based care. The study participants also continued to improve eight-months after the treatment ended, regaining a sense of hope and control over their lives and reporting feeling more connected to and supported by others. For example, on the Beck Depression Inventory (BDI), a widely used questionnaire in which a score of 19 or above indicates major depression, women in the study group saw their depressive symptoms decline from an average of 27 at the beginning of therapy to 9.6 eight months after the program concluded. By contrast, women who received community care remained clinically depressed, with an average BDI score of 21 at the follow-up.

Women who received home-based interpersonal therapy saw their depression subside by the end of treatment and continue to improve eight months later. Women who received standard care experienced much less relief. The results, says Toth, point to the need for screening high-risk populations. None of these women were seeking treatment, but were identified instead through a questionnaire and an interview at physicians' offices and clinics for the Women, Infants, and Children (WIC) subsidized nutrition program. Says Toth: "When I go to the doctor, they ask me if I use my seatbelt. Why would we not be asking questions about depression when we know the chances of being hit by a car are way less than the chances of being hit by depression? People are suffering needlessly." Published online November 8 in Development and Psychopathology, the findings are good news for mothers and their children alike. "Extensive research has shown that young children whose primary caregivers are depressed often begin life on the wrong foot," explains Toth. "They may fail to develop secure attachments, setting them up for a cascade of difficulties, from behavior problems during childhood and failure in school to involvement in the juvenile justice system and major psychiatric problems down the road." Despite the widespread prevalence of depression among minority mothers, researchers have largely overlooked this vulnerable population. "In fact, studies that formed the empirical base for the American Psychiatric Association guidelines for depression treatment included 3,860 participants, with only 27 identified as African American and none as being of Latina descent," the authors write. To address the imbalance, the researchers tracked 128 low-income mothers of one-year-olds, 60 percent of whom were Black, 20 percent Hispanic, and 20 percent Caucasian. In addition to poverty, the vast majority of these mothers faced extensive life challenges. All but 6 percent had been depressed for more than a year, 87 percent reported histories of child abuse, 30 percent had been raped or sexually assaulted by a relative, and 27 percent suffered from posttraumatic stress disorder. The study tested the effectiveness of interpersonal psychotherapy, a short-term depression treatment that has worked with more advantaged populations. "A big part of this approach is instilling hope," says Robin Sturm, a co-author and one of the family therapists who worked on the study. She and other therapists first help clients recognize that feelings, such as a lack of energy or motivation, are symptoms of depression not signs of laziness or other character flaws. "If they can separate themselves from the symptoms, it helps them see that they can get better," says Sturm. The bulk of the intervention then focuses on identifying and easing one or two key relationship problems in clients' lives. This could be overcoming the loss of a loved one, reconnecting with a family member, or learning how to resolve conflicts with a partner. Using a variety of tools, from role-playing to analyzing arguments, participants practice more effective ways to interact. "The aha moment is when these women realize, 'I have a sense of control,'" says Sturm. "Perhaps there is domestic violence. They can't control what the other person does, but they can control what they do. That stuck feeling is the hallmark of depression." A critical element of the study model was to offer therapy in clients' homes, an option chosen by 85 percent of participants. "It sends a powerful message that I am willing to come to you," explains Sturm, who, if needed, also met with clients in her car or drove them to the clinic for their appointment. "When people are depressed, it may be too hard to have the energy to make it to appointments," she says. The program's flexibility also reduced the need for childcare and transportation, resulting in a compliance rate of 100 percent, the authors report. Therapists were also sensitive to the stigma of mental illness in minority communities. If clients appeared uncomfortable with a diagnosis like depression, therapists used terms like overwhelmed or moody instead and stressed that such feelings were common for parents faced with the demands of childrearing. Instead of therapy, they sometimes describe their appointments as "spending some time talking about how you are feeling." The program involved no anti-depressants or other medication, further distancing the intervention from psychiatric care, says Sturm. To assess the effectiveness of this flexible, problem-solving approach, the study randomly assigned a second group of mothers to standard community care, matched by race, education, age, and other factors. The control group received clinic-based counseling or cognitive behavior therapy, a common short-term treatment for depression, along with a variety of other interventions, including medication, support groups, and marital and family counseling. The comparison was clear: home-based, interpersonal psychotherapy lifted depression much more effectively than standard care. The findings underscore the importance of actively screening and offering culturally sensitive, convenient care for our most vulnerable populations, says co-author Fred Rogosch, associate professor of psychology at the University of Rochester and director of research for Mt. Hope Family Center. In one clinical trial, 83 percent of low-income young minority women referred for treatment for depression did not attend even one session. "Most of these women don't even like to talk about depression. Most of these women would never have asked for treatment," says Rogosch. "When I go to the doctor, they ask me if I use my seatbelt," says Sheree Toth. "Why would we not be asking questions about depression when we know the chances of being hit by a car are way less than the chances of being hit by depression? People are suffering needlessly." "We also are concerned about the children of mothers who feel isolated, helpless, and angry. That is not the ideal emotional environment for infants and toddlers to grow up in. Reaching out to these mothers is critical for their children," says Rogosch. Even with the creative accommodations offered in this study, Rogosch notes that 40 percent of mothers identified as depressed declined all care. The authors suggest that future research should explore ways to make the interview process even more welcoming. Assaf Oshri and Julie Gravener from the University of Rochester and Antonio Alexander Morgan-López from the University of North Carolina at Chapel Hill also contributed to the paper. The research was supported by the National Institutes of Mental Health, grant MH091070 LPC Continuing Education About the University of Rochester The University of Rochester (www.rochester.edu) is one of the nation's leading private universities. Located in Rochester, N.Y., the University gives students exceptional opportunities for interdisciplinary study and close collaboration with faculty through its unique cluster-based curriculum. Its College, School of Arts and Sciences, and Hajim School of Engineering and Applied Sciences are complemented by its Eastman School of Music, Simon School of Business, Warner School of Education, Laboratory for Laser Energetics, School of Medicine and Dentistry, School of Nursing, Eastman Institute for Oral Health, and the Memorial Art Gallery.

Interactive computer program helps patients talk with their physician about depression

(SACRAMENTO, Calif.) – Patients who used an interactive computer program about depression while waiting to see their primary-care doctor were nearly twice as likely to ask about the condition and significantly more likely to receive a recommendation for antidepressant drugs or a mental-health referral from their physician, according to a new study by researchers at UC Davis. The study, published online today in the Journal of the American Medical Association, was conducted to evaluate the effectiveness of a waiting-room intervention that encourages primary- care patients to discuss depression symptoms and care with their physician. While patients who received treatment or a referral for depression did not report improved mental health 12 weeks later, the study did show that providing information to patients about depression is an effective way to start the conversation in a primary-care setting about mental health. "We have developed an easy-to-use tool to help people with depression identify the symptoms, feel more comfortable discussing it with a primary-care provider and accept treatment if it is needed," said Anthony Jerant, professor of family and community medicine at UC Davis and senior author of the study. "This brief and relatively inexpensive intervention could be easily and widely implemented in a variety of health-care settings." Depression is an underrecognized and undertreated condition that can easily be overlooked during a typical primary-care visit. While calculating the number of people suffering from untreated depression is difficult, the Centers for Disease Control estimates that nationally 1-in-10 adults has reported symptoms of depression. The National Institute of Mental Health has said that major depressive disorders affect approximately 14.8 million American adults, or about 6.7 percent of the U.S. population age 18 and older in a given year. When left untreated, depression poses high costs to society, jeopardizing relationships and employment, decreasing quality of life, prompting alcohol and drug abuse and, in some cases, leading to the higher risk of suicide Core Elements in Responding to Mental Health Crises CE Course Three waiting-room interventions tested The new study involved nearly 900 patients and 135 primary-care clinicians at seven Northern California health-care sites. Prior to their medical appointments, patients were screened for depression. All patients were then randomized to view one of three interventions: •A video – similar to a public-service announcement – focused on recognizing depression and talking with doctors about symptoms •An interactive multimedia computer program that provided patients with instant feedback and information tailored to different levels of depressive symptoms and treatment preferences •A non-depression-related video on healthy sleep The clinicians did not know which intervention their patients viewed. Immediately after the patients' appointments, the researchers determined if the patients discussed depression with their clinicians and whether they left with prescriptions for medications to treat depression and if they received a referral for mental-health services. Help for the most depressed The results showed that patients with baseline depression who either watched the informational video or used the computer program were nearly twice as likely as control subjects to request information about depression during their appointment. Those who used the interactive computer program were significantly more likely to receive a prescription or referral for depression (26 percent) than were those who viewed either the depression video (17.5 percent) or the video on sleep (16.3 percent). The computer program had the greatest impact on patients who were most depressed, according to the baseline screening. The investigators also studied the effects of the interventions on people who were not likely to be depressed according to the baseline screening. Among these patients, rates of prescribing and referral were low (about 5 percent) and did not differ by intervention group. According to Richard Kravitz, UC Davis professor of internal medicine and lead author of the study, it is important for public-health interventions to avoid inadvertently expanding unnecessary treatments that can do more harm than good and waste health-care resources. "We were concerned that the interventions could lead to treatment for depression for those who do not actually have it," said Kravitz. "Our interactive computer program, however, increased help for those who needed it the most without increasing treatment for those who didn't." According to Jerant, this study is the largest to compare "targeted" versus "tailored" interventions for stimulating people with depression to seek and accept treatment. Targeted interventions, such as the informational video used in the study, use terms and images most likely to resonate with the target audience, based on specific demographic factors. Four different versions were used in this study, targeted toward gender and income levels. The video took about three minutes to watch. Tailored interventions, such as the study's interactive computer program, integrate patient-specific answers to deliver information and guidance. The program used in the study, developed by the study investigators, prompted users to answer questions about symptoms of depression, informed users as to whether or not they were likely to be depressed, and provided guidance depending on the users' specific needs and interests. Patients assigned to the computer program spent about two to 15 minutes on it, with a median of five minutes. Kravitz speculated that the informational video did not work as well because, like a television commercial advertising a medication, it may require multiple repetitions to be effective. In contrast, the interactive computer program quickly provided a high level of personalization, which may account for its higher degree of effectiveness with a single use. The UC Davis investigators intend to further refine and study the interactive computer model to identify patients who need to receive more extensive treatment for their depression Professional Counselor Continuing Education ### Other UC Davis investigators on the study were Peter Franks, Daniel Tancredi, Christina Slee, Robert Bell, Debora Paterniti, Camille Cipri, Ana-Maria Iosif, Andrew Hudnut, Simon Dvorak and Charles Turner. Additional authors were Maga Jackson-Triche of the Northern California VA Health Care System, Steven Kelly-Reif of Kaiser Permanente Medical Group in Sacramento, Mitchell Feldman and Sarah Olson of UC San Francisco, and Ronald Epstein and Paul Duberstein of University of Rochester in New York. The study, titled "Patient Engagement Programs for Recognition and Initial Treatment of Depression in Primary Care," was supported by grants from the National Institute of Mental Health (1R01MH079387, K24MH072756 and K24MH02712).

National Institute of Mental Health (NIMH) Grantees To Receive 2013 Lasker Award

A current and a former National Institute of Mental Health (NIMH) grantee recently collected the prestigious 2013 Albert Lasker Basic Medical Research Award for their meticulous mapping of the molecular mechanisms involved in neurotransmitter release, the process by which the brain sends and receives chemical messages. Richard H. Scheller, Ph.D. Richard H. Scheller, Ph.D Genentech Thomas C. Südhof, M.D., at Stanford University School of Medicine, and Richard H. Scheller, Ph.D., at Genentech, parsed the proteins that enable one neuron to speak to another. This communication occurs across the synapse, a gap that separates the two neurons. Collectively called the “SNARE complex,” these proteins include vesicle-associated membrane protein (VAMP/synaptobrevin), synaptogamin, syntaxin, and SNAP-25. The complex allows for the preparation and release of the neurotransmitters into the synapse. Defects in this process contribute to mental disorders such as schizophrenia, depression, bipolar disorder, epilepsy, and many other pathological conditions. Thomas C. Südhof, M.D. Thomas C. Südhof, M.D. Stanford University School of Medicine Dr. Südhof is a current NIMH grantee and 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. Dr. Scheller received research support from NIMH, and served on both the NIMH Molecular, Cellular, and Developmental Neuroscience study section, and the National Advisory Mental Health Council. Both have received the NIMH MERIT Award. Known as “America’s Nobels” because many recipients go on to win the Nobel Prize, the Lasker Awards are among the most respected science prizes in the world. Congratulations, Drs. Südof and Scheller Aspira Continuing Education Online Courses

Community-based Treatments Offset Depression Disparities

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

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

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

Ketamine Cousin Rapidly Lifts Depression Without Side Effects

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

Surprising Rate of Women Have Depression After Childbirth

One in every seven women have significant depressive symptoms March 13, 2013 | by Marla Paul CHICAGO --- A surprisingly high number of women have postpartum depressive symptoms, according to a new, large-scale study by a Northwestern Medicine® researcher. This is the largest scale depression screening of postpartum women and the first time a full psychiatric assessment has been done in a study of postpartum women who screened positive for depression Depressive Disorders CE Course The study, which included a depression screening of 10,000 women who had recently delivered infants at single obstetrical hospital, revealed a large percentage of women who suffered recurrent episodes of major depression. The study underscored the importance of prenatal as well as postpartum screening. Mothers’ and infants’ health and lives hang in the balance. The lives of several women who were suicidal when staff members called them for the screening were saved likely as a result of the study’s screening and immediate intervention. “In the U.S., the vast majority of postpartum women with depression are not identified or treated even though they are at higher risk for psychiatric disorders,” said Northwestern Medicine lead study author Katherine L. Wisner, M.D. “It’s a huge public health problem. A woman’s mental health has a profound effect on fetal development as well as her child’s physical and emotional development.” Wisner is director of Northwestern’s Asher Center for the Study and Treatment of Depressive Disorders and the Norman and Helen Asher Professor of Psychiatry and Behavioral Sciences and professor of obstetrics and gynecology at Northwestern University Feinberg School of Medicine. She’s also a physician at Northwestern Memorial Hospital. “A lot of women do not understand what is happening to them,” Wisner said. “They think they’re just stressed or they believe it is how having a baby is supposed to feel.” The paper was be published in JAMA Psychiatry March 13. Wisner conducted the research when she was at the University of Pittsburgh. In the study, 14 percent of the women screened positive for depression. Of that group, 826 received full psychiatric assessments during at-home visits. Some of the key findings from those assessments: - In women who screened positive for depression, 19.3 percent thought of harming themselves. “Most of these women would not have been screened and therefore would not have been identified as seriously at risk,” Wisner said. “We believe screening will save lives.” Suicide accounts for about 20 percent of postpartum deaths and is the second most common cause of mortality in postpartum women. - Many women who screened positive for major depression postpartum had already experienced at least one episode of depression previously and, in addition, had an anxiety disorder. The study found 30 percent of women had depression onset prior to pregnancy, 40 percent postpartum and 30 percent during pregnancy. More than two-thirds of these women also had an anxiety disorder. “Clinicians need to know that the most common clinical presentation in the post-birth period is more complex than a single episode of depression,” Wisner said. “The depression is recurrent and superimposed on an anxiety disorder.“ - Of the women who screened positive for major depression, 22 percent had bipolar disorder, the majority of whom had not been diagnosed by their physicians. There is often a delay in correctly diagnosing bipolar disorder, which depends on identifying not only the depressed phase but the manic or hypomanic phase as well. But postpartum is the highest risk period for new episodes of mania in a woman’s life. “That’s a very high rate of bipolar disorder that has never been reported in a population screened for postpartum depression before,” said Wisner. “It is significant because antidepressant drug treatment alone can worsen the course of bipolar disorder.” In addition, women who have been pregnant in the past year are less likely to seek treatment for depression than women who have not been pregnant, previous research has shown. Maximizing a woman’s overall mental and physical health in pregnancy and after childbirth is critically important. “Depression during pregnancy increases the risk to a woman and her fetus,” Wisner said. “Depression is a physiological dysregulation disorder of the entire body.” Maternal prenatal stress and depression is linked to preterm birth and low infant birth weight, which increases the risk of cardiovascular disease. Depression also affects a woman’s appetite, nutrition and prenatal care and is associated with increased alcohol and drug use. Women with untreated depression have a higher body mass index preconception, which carries additional risks. When a new mother is depressed, her emotional state can interfere with child development and increases the rate of insecure attachment and poor cognitive performance of her child, Wisner said. Screening prenatal and postpartum are essential (Illinois requires mandatory screening for perinatal mental health disorders), but the health care field must develop cost effective and accessible treatment, Wisner emphasized. “If we identify patients we must have treatment to offer them,” Wisner said. The study was funded by grant RO1 MH 071825 from the National Institute of Mental Health of the National Institutes of Health.

Astrocytes identified as target for new depression therapy

Tufts neuroscientists find that starry brain cells can be used to mimic sleep deprivation BOSTON (January 23, 2013) — Neuroscience researchers from Tufts University have found that our star-shaped brain cells, called astrocytes, may be responsible for the rapid improvement in mood in depressed patients after acute sleep deprivation. This in vivo study, published in the current issue of Translational Psychiatry, identified how astrocytes regulate a neurotransmitter involved in sleep. The researchers report that the findings may help lead to the development of effective and fast-acting drugs to treat depression, particularly in psychiatric emergencies. Drugs are widely used to treat depression, but often take weeks to work effectively. Sleep deprivation, however, has been shown to be effective immediately in approximately 60% of patients with major depressive disorders. Although widely-recognized as helpful, it is not always ideal because it can be uncomfortable for patients, and the effects are not long-lasting Marriage and Family Therapist Continuing Education During the 1970s, research verified the effectiveness of acute sleep deprivation for treating depression, particularly deprivation of rapid eye movement sleep, but the underlying brain mechanisms were not known. Most of what we understand of the brain has come from research on neurons, but another type of largely-ignored cell, called glia, are their partners. Although historically thought of as a support cell for neurons, the Phil Haydon group at Tufts University School of Medicine has shown in animal models that a type of glia, called astrocytes, affect behavior. Haydon's team had established previously that astrocytes regulate responses to sleep deprivation by releasing neurotransmitters that regulate neurons. This regulation of neuronal activity affects the sleep-wake cycle. Specifically, astrocytes act on adenosine receptors on neurons. Adenosine is a chemical known to have sleep-inducing effects. During our waking hours, adenosine accumulates and increases the urge to sleep, known as sleep pressure. Chemicals, such as caffeine, are adenosine receptor antagonists and promote wakefulness. In contrast, an adenosine receptor agonist creates sleepiness. "In this study, we administered three doses of an adenosine receptor agonist to mice over the course of a night that caused the equivalent of sleep deprivation. The mice slept as normal, but the sleep did not reduce adenosine levels sufficiently, mimicking the effects of sleep deprivation. After only 12 hours, we observed that mice had decreased depressive-like symptoms and increased levels of adenosine in the brain, and these results were sustained for 48 hours," said first author Dustin Hines, Ph.D., a post-doctoral fellow in the department of neuroscience at Tufts University School of Medicine (TUSM). "By manipulating astrocytes we were able to mimic the effects of sleep deprivation on depressive-like symptoms, causing a rapid and sustained improvement in behavior," continued Hines. "Further understanding of astrocytic signaling and the role of adenosine is important for research and development of anti-depressant drugs. Potentially, new drugs that target this mechanism may provide rapid relief for psychiatric emergencies, as well as long-term alleviation of chronic depressive symptoms," said Naomi Rosenberg, Ph.D., dean of the Sackler School of Graduate Biomedical Sciences and vice dean for research at Tufts University School of Medicine. "The team's next step is to further understand the other receptors in this system and see if they, too, can be affected." ### Senior author, Phillip G. Haydon, Ph.D., is the Annetta and Gustav Grisard professor and chair of the department of neuroscience at Tufts University School of Medicine (TUSM). Haydon is also a member of the neuroscience program faculty at the Sackler School of Graduate Biomedical Sciences at Tufts. Additional authors are Luke I. Schmitt, B.S., a Ph.D. candidate in neuroscience at the Sackler School; Rochelle M. Hines, Ph.D., a post-doctoral fellow in the department of neuroscience at TUSM; and Stephen J. Moss, Ph.D., a professor of neuroscience at Tufts University School of Medicine and a member of the neuroscience program faculty at the Sackler School. Hines DJ, Schmitt LI, Hines RM, Moss SJ, Haydon PG. Translational Psychiatry. "Antidepressant effects of sleep deprivation require astrocyte-dependent adenosine mediated signaling." (2013) 3, e212; doi:10.1038/tp.2012.136. Published online 15 January 2013. This research was supported by award number R01MH095385 from the National Institute of Mental Health, part of the National Institutes of Health, as well as by award number R01NS037585 from the National Institute of Neurological Disorders and Stroke, both of the National Institutes of Health. Dustin Hines was partially funded by the Heart and Stroke Foundation of Canada. Haydon is co-founder and president of GliaCure Inc., which has licensed a pending patent application filed by Tufts University claiming compounds that modulate the signaling cascades, and related methods of use, described in this paper. About Tufts University School of Medicine and the Sackler School of Graduate Biomedical Sciences Tufts University School of Medicine and the Sackler School of Graduate Biomedical Sciences at Tufts University are international leaders in innovative medical education and advanced research. The School of Medicine and the Sackler School are renowned for excellence in education in general medicine, biomedical sciences, special combined degree programs in business, health management, public health, bioengineering and international relations, as well as basic and clinical research at the cellular and molecular level. Ranked among the top in the nation, the School of Medicine is affiliated with six major teaching hospitals and more than 30 health care facilities. Tufts University School of Medicine and the Sackler School undertake research that is consistently rated among the highest in the nation for its effect on the advancement of medical science. If you are a member of the media interested in learning more about this topic, or speaking with a faculty member at the Tufts University School of Medicine or another Tufts health sciences researcher, please contact Siobhan Gallagher.