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July 08, 2013
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
June 19, 2013
Bullying Exerts Psychiatric Effects into Adulthood
Once considered a childhood rite of passage, bullying lingers well into adulthood. Bullies and victims alike are at risk for psychiatric problems such as anxiety, depression, substance abuse, and suicide when they become adults, reported a study partially funded by the National Institute of Mental Health (NIMH) that was published in the April issue of JAMA Psychiatry.
Background
Bullying is a repetitive, aggressive act done to abuse or intimidate others. It can take on various forms—primarily verbal, emotional, and physical, although cyberbullying is also on the rise. Typically these scenes occur inside school or on the playground, but they can also happen at home or at work. A power imbalance usually is involved in which one child or a group of children torments another child who is considered “weaker.” Methods employed by bullies include threats, rumor-spreading, and exclusion.
Most of what experts know about the effects of bullying comes from short-term observational studies. These studies reflect general society’s view that most people overcome these events by the time they become adults.
“Initially I too was skeptical about these long-term effects,” says study author William Copeland, Ph.D., at Duke University, who as an epidemiologist knew of other traumatic events that do not linger psychologically, such as maltreatment and physical abuse. “Yet this is something that stays with people. A large number of people express lasting effects decades after their childhood experiences.”
Copeland and his colleagues tapped into a local population sample of 1,420 children from 11 Western North Carolina counties. Starting at the ages of 9, 11, and 13, the kids, along with their parents, were interviewed annually until the age of 16, fielding questions about peer relations and home and community settings. The participating children were again interviewed at 19, 21, and 24 to 26 years of age. Four groups emerged from this longitudinal study: people who were never involved in bullying, people who were victims, people who were bullies, and people who were both.
Results of the Study
More than half of the study’s youth reported being neither a bully nor a victim. Around a quarter of the study group claimed that they were victimized. About 7 percent confessed to being a bully. A similar percentage said that they were both, a group the researchers labeled as “bully-victims.”
Compared to those who went through childhood unscathed, victims had four times the prevalence of agoraphobia, generalized anxiety, and panic disorder when they became adults. Overall, bullies had four times the risk of developing antisocial personality disorder. These disorders still stood even after other factors were taken into account, such as preexisting psychiatric problems or family hardships.
Bully-victims fared the worst. Also known as “loners,” these individuals start out with less developed social skills and are seen as more impulsive and aggressive. When picked on, they respond by picking on others. Their numbers, compared to those never involved in bullying, tell the story: 14 times the risk of panic disorder, 5 times the risk of depressive disorders, and 10 times the risk of suicidal thoughts and behavior.
“Victims report the greatest anxiety problems. They might become successful people later on, but they still think about the event and hold onto it. Bullies are socially adept and may find ways in adulthood to use these skills in a pro-social manner. Folks really underestimate who are the bully-victims. These are the ones who end up having the most significant emotional problems including suicidality,” explained Copeland, who is also a father of two Social Worker Continuing Education
Significance
All these disorders impart a great emotional and financial cost to society. Lowering and/or preventing bullying could possibly reduce human suffering and long-term health costs—not to mention creating a safer environment for children to grow up in.
Research into resilience or why some are able to bounce back in adulthood is ongoing. Some key molecules and brain circuit pathways have been identified in animals. Other research areas under exploration include physiology, genetics, epigenetics, and cognitive therapies.
What’s Next
Studies looking into which interventions work best for bullying are underway. Once these interventions are identified, research is needed to see at what stages in life they should they be administered. Lastly, other factors that play a role in bullying and victimization, such as sexual orientation, need exploration.
“This study suggests that we should pay attention to what’s going on between peers,” said Copeland, adding that kids spend more time each day with their peers, including school and online, than with their parents. “What happens to kids when they’re with their peers is as important, or may be more important, than what happens at home,” said Copeland.
Reference
Copeland WE, Wolke D, Angold A, Costello EJ. Adult Psychiatric Outcomes of Bullying and Being Bullied by Peers in Childhood and Adolescence. JAMA Psychiatry, published April 2013.
Grant number: K23 MH080230
June 10, 2013
Out of sync with the world: Body clocks of depressed people are altered at cell level
June 01, 2013
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.
May 06, 2013
Nearly 20 percent of suicidal youths have guns in their home
Researchers say emergency department doctors should screen all pediatric patients for suicide risk
WASHINGTON, DC – Nearly one in five children and teens found to be at risk for suicide report that there are guns in their homes, and 15 percent of those at risk for suicide with guns in the home know how to access both the guns and the bullets, according to a study to be presented Monday, May 6, at the Pediatric Academic Societies (PAS) annual meeting in Washington, DC.
Suicide is the second leading cause of death among young people ages 10 to 24 years in the United States, according to Centers for Disease Control and Prevention data. Nearly half of youths who die by suicide use a firearm.
Researchers conducted a study to create a suicide risk screening tool that health care professionals in emergency departments (EDs) could use to figure out which youths need further mental health evaluation to keep them from harming themselves. As part of that study, researchers asked youths about access to guns in or around their home and about gun/bullet storage.
"For more than 1.5 million adolescents, the ED is their primary point of contact with the health care system, which makes the ED an important place for identifying youth at risk for suicide," said Stephen J. Teach, MD, MPH, FAAP, associate chief in the Division of Emergency Medicine at Children's National Medical Center in Washington, DC, and co-author who will be presenting the study at the PAS meeting.
Many clinicians and parents do not know how to ask youth about suicide, so they require screening tools to assist in detection, added study senior author Lisa M. Horowitz, PhD, MPH, staff scientist/pediatric psychologist at the National Institute of Mental Health, National Institutes of Health, Bethesda, Md. "According to our data, when asked their opinion, nearly all of the kids in our study were in favor of suicide screening in the ED. Our study shows that if you ask kids directly about suicide, they will tell you what they are thinking."
Study participants included 524 patients ages 10 to 21 who were seen for medical/surgical or psychiatric complaints at one of three pediatric EDs. They were asked to fill out a 17-item questionnaire that the researchers used to develop the Ask Suicide-Screening Questions (ASQ), a four-question screening tool that can be used for all pediatric patients visiting the ED. The ASQ has been validated against a longer more in-depth suicide assessment tool.
"While many youths who kill themselves have mental health disorders, up to 40 percent of youths who kill themselves have no known mental illness," said co-author and youth suicide expert Jeffrey A. Bridge, PhD, principal investigator at The Research Institute at Nationwide Children's Hospital and associate professor of pediatrics at The Ohio State University. "Therefore, it is important to screen all children and adolescents for suicide, regardless of the reason they are visiting the ED."
Of the patients who completed the screening tools, 151 (29 percent) were found to be at risk for suicide, and 17 percent of them reported guns in or around the home. Of those at risk for suicide and reporting guns in the home, 31 percent knew how to access the guns, 31 percent knew how to access the bullets, and 15 percent knew how to access both the guns and the bullets.
"This study highlights the importance of parents understanding the risks of having guns in their homes," said Dr. Bridge. "Being at risk for suicide and having access to firearms is a volatile mix. These conversations need to take place in the ED with families of children at risk for suicide." Suicide Prevention CE Course
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To view the abstract, "Access to Firearms among Patients Screening Positive for Suicide Risk in Pediatric Emergency Departments," go to http://www.pas-meeting.org/2013DC/Abstracts/LB%20Pub%20All%202013.pdf
The research was supported by the Intramural Research Program of the National Institute of Mental Health, the National Institutes of Health (Drs. Horowitz & Pao); institutional research funds from the Research Institute at Nationwide Children's Hospital and grant K01 MH-69948 from the National Institute of Mental Health (Dr. Bridge); institutional research funds from the Program for Patient Safety and Quality at Boston Children's Hospital Boston (Dr. Wharff).
The Pediatric Academic Societies (PAS) are four individual pediatric organizations that co-sponsor the PAS Annual Meeting – the American Pediatric Society, the Society for Pediatric Research, the Academic Pediatric Association, and the American Academy of Pediatrics. Members of these organizations are pediatricians and other health care providers who are practicing in the research, academic and clinical arenas. The four sponsoring organizations are leaders in the advancement of pediatric research and child advocacy within pediatrics, and all share a common mission of fostering the health and well-being of children worldwide. For more information, visit http://www.pas-meeting.org. Follow news of the PAS meeting on Twitter at http://twitter.com/PedAcadSoc.
April 29, 2013
Forced exercise may still protect against anxiety and stress, says CU-Boulder study
Being forced to exercise may still help reduce anxiety and depression just as exercising voluntarily does, according to a new study by researchers at the University of Colorado Boulder.
Past studies have shown that people who exercise are more protected against stress-related disorders. And scientists know that the perception of control can benefit a person's mental health. But it has been an open question whether a person who feels forced to exercise, eliminating the perception of control, would still reap the anxiety-fighting benefits of the exercise.
People who may feel forced to exercise could include high school, college and professional athletes, members of the military or those who have been prescribed an exercise regimen by their doctors, said Benjamin Greenwood, an assistant research professor in CU-Boulder's Department of Integrative Physiology.
"If exercise is forced, will it still produce mental health benefits?" Greenwood asked. "It's obvious that forced exercise will still produce peripheral physiological benefits. But will it produce benefits to anxiety and depression?"
To seek an answer to the question Greenwood and his colleagues, including Monika Fleshner, a professor in the same department, designed a lab experiment using rats. During a six-week period, some rats remained sedentary, while others exercised by running on a wheel.
The rats that exercised were divided into two groups that ran a roughly equal amount of time. One group ran whenever it chose to, while the other group ran on mechanized wheels that rotated according to a predetermined schedule. For the study, the motorized wheels turned on at speeds and for periods of time that mimicked the average pattern of exercise chosen by the rats that voluntarily exercised.
After six weeks, the rats were exposed to a laboratory stressor before testing their anxiety levels the following day. The anxiety was quantified by measuring how long the rats froze, a phenomenon similar to a deer in the headlights, when they were put in an environment they had been conditioned to fear. The longer the freezing time, the greater the residual anxiety from being stressed the previous day. For comparison, some rats were also tested for anxiety without being stressed the day before.
"Regardless of whether the rats chose to run or were forced to run they were protected against stress and anxiety," said Greenwood, lead author of the study appearing in the European Journal of Neuroscience in February. The sedentary rats froze for longer periods of time than any of the active rats.
"The implications are that humans who perceive exercise as being forced — perhaps including those who feel like they have to exercise for health reasons — are maybe still going to get the benefits in terms of reducing anxiety and depression," he said.
Anxiety Disorders CE Course
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Other CU-Boulder authors include Katie Spence, Danielle Crevling, Peter Clark and Wendy Craig. All the authors are members of Monika Fleshner's Stress Physiology Laboratory in the Department of Integrative Physiology.
The research was funded by the National Institutes of Mental Health and the Defense Advanced Research Projects Agency.
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April 21, 2013
Brain scans might predict future criminal behavior
Low anterior cingulate activity linked to repeat offenses
ALBUQUERQUE, NM and DURHAM, NC--A new study conducted by The Mind Research Network in Albuquerque, N.M., shows that neuroimaging data can predict the likelihood of whether a criminal will reoffend following release from prison.
The paper, which is to be published in the Proceedings of the National Academy of Sciences, studied impulsive and antisocial behavior and centered on the anterior cingulate cortex (ACC), a portion of the brain that deals with regulating behavior and impulsivity.
You can view the paper by clicking here: http://www.pnas.org/cgi/doi/10.1073/pnas.1219302110.
The study demonstrated that inmates with relatively low anterior cingulate activity were twice as likely to reoffend than inmates with high-brain activity in this region.
"These findings have incredibly significant ramifications for the future of how our society deals with criminal justice and offenders," said Dr. Kent A. Kiehl, who was senior author on the study and is director of mobile imaging at MRN and an associate professor of psychology at the University of New Mexico. "Not only does this study give us a tool to predict which criminals may reoffend and which ones will not reoffend, it also provides a path forward for steering offenders into more effective targeted therapies to reduce the risk of future criminal activity."
The study looked at 96 adult male criminal offenders aged 20-52 who volunteered to participate in research studies. This study population was followed over a period of up to four years after inmates were released from prison.
"These results point the way toward a promising method of neuroprediction with great practical potential in the legal system," said Dr. Walter Sinnott-Armstrong, Stillman Professor of Practical Ethics in the Philosophy Department and the Kenan Institute for Ethics at Duke University, who collaborated on the study. "Much more work needs to be done, but this line of research could help to make our criminal justice system more effective."
The study used the Mind Research Network's Mobile Magnetic Resonance Imaging (MRI) System to collect neuroimaging data as the inmate volunteers completed a series of mental tests.
"People who reoffended were much more likely to have lower activity in the anterior cingulate cortices than those who had higher functioning ACCs," Kiehl said. "This means we can see on an MRI a part of the brain that might not be working correctly -- giving us a look into who is more likely to demonstrate impulsive and anti-social behavior that leads to re-arrest."
The anterior cingulate cortex of the brain is "associated with error processing, conflict monitoring, response selection, and avoidance learning," according to the paper. People who have this area of the brain damaged have been "shown to produce changes in disinhibition, apathy, and aggressiveness. Indeed, ACC-damaged patients have been classed in the 'acquired psychopathic personality' genre."
Kiehl says he is working on developing treatments that increase activity within the ACC to attempt to treat the high-risk offenders.
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The four-year study was supported by grants from the National Institute on Drug Abuse (NIDA), the National Institute of Mental Health (NIMH), and pilot funds by the John D. and Catherine T. MacArthur Foundation Law and Neuroscience Project. The study was conducted in collaboration with the New Mexico Corrections Department.
ABOUT THE MIND RESEARCH NETWORK
The Mind Research Network (MRN), headquartered in Albuquerque, N.M., is committed to advancing the diagnosis and treatment of mental illness and other brain disorders. MRN is a 501(c)3 non-profit organization consisting of an interdisciplinary association of scientists located at universities, national laboratories and research centers around the world and is focused on imaging technology and its emergence as an integral element of neuroscience investigation.
The Mind Research Network is a part of the Lovelace Respiratory Research Institute family of companies Professional Counselor Continuing Education
Learn more at http://www.mrn.org
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