Genetic manipulation boosts growth of brain cells linked to learning, enhances antidepressants

DALLAS -- UT Southwestern Medical Center investigators have identified a genetic manipulation that increases the development of neurons in the brain during aging and enhances the effect of antidepressant drugs.

The research finds that deleting the Nf1 gene in mice results in long-lasting improvements in neurogenesis, which in turn makes those in the test group more sensitive to the effects of antidepressants.

"The significant implication of this work is that enhancing neurogenesis sensitizes mice to antidepressants – meaning they needed lower doses of the drugs to affect 'mood' – and also appears to have anti-depressive and anti-anxiety effects of its own that continue over time," said Dr. Luis Parada, director of the Kent Waldrep Center for Basic Research on Nerve Growth and Regeneration and senior author of the study published in the Journal of Neuroscience.

Just as in people, mice produce new neurons throughout adulthood, although the rate declines with age and stress, said Dr. Parada, chairman of developmental biology at UT Southwestern. Studies have shown that learning, exercise, electroconvulsive therapy and some antidepressants can increase neurogenesis. The steps in the process are well known but the cellular mechanisms behind those steps are not.

"In neurogenesis, stem cells in the brain's hippocampus give rise to neuronal precursor cells that eventually become young neurons, which continue on to become full-fledged neurons that integrate into the brain's synapses," said Dr. Parada, an elected member of the prestigious National Academy of Sciences, its Institute of Medicine, and the American Academy of Arts and Sciences.

The researchers used a sophisticated process to delete the gene that codes for the Nf1 protein only in the brains of mice, while production in other tissues continued normally. After showing that mice lacking Nf1 protein in the brain had greater neurogenesis than controls, the researchers administered behavioral tests designed to mimic situations that would spark a subdued mood or anxiety, such as observing grooming behavior in response to a small splash of sugar water.

The researchers found that the test group mice formed more neurons over time compared to controls, and that young mice lacking the Nf1 protein required much lower amounts of anti-depressants to counteract the effects of stress. Behavioral differences between the groups persisted at three months, six months and nine months. "Older mice lacking the protein responded as if they had been taking antidepressants all their lives," said Dr. Parada.

"In summary, this work suggests that activating neural precursor cells could directly improve depression- and anxiety-like behaviors, and it provides a proof-of-principle regarding the feasibility of regulating behavior via direct manipulation of adult neurogenesis," Dr. Parada said.

Dr. Parada's laboratory has published a series of studies that link the Nf1 gene – best known for mutations that cause tumors to grow around nerves – to wide-ranging effects in several major tissues. For instance, in one study researchers identified ways that the body's immune system promotes the growth of tumors, and in another study, they described how loss of the Nf1 protein in the circulatory system leads to hypertension and congenital heart disease social worker ceus

The current study's lead author is former graduate student Dr. Yun Li, now a postdoctoral researcher at the Massachusetts Institute of Technology. Other co-authors include Yanjiao Li, a research associate of developmental biology, Dr. Renée McKay, assistant professor of developmental biology, both of UT Southwestern, and Dr. Dieter Riethmacher of the University of Southampton in the United Kingdom.

The study was supported by the National Institutes of Health's National Institute of Neurological Disorders and Stroke, and National Institute of Mental Health. Dr. Parada is an American Cancer Society Research Professor.

This news release is available on our World Wide Web home page at www.utsouthwestern.edu/home/news/index.html

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Thinking Globally to Improve Mental Health

Source: NASA Jet Propulsion Laboratory (NASA-JPL)
Mental health experts are calling for a greater world focus on improving access to care and treatment for mental, neurological, and substance use (MNS) disorders, as well as increasing discoveries in research that will enable this goal to be met.

The Grand Challenges in Global Mental Health Initiative, led by the National Institutes of Health and the Global Alliance for Chronic Diseases, has identified the top 40 barriers to better mental health around the world. Similar to past grand challenges, which focused on infectious diseases and chronic, noncommunicable diseases, this initiative seeks to build a community of funders dedicated to supporting research that will significantly improve the lives of people living with MNS disorders within the next 10 years.

Twenty-five of the specific challenges and the process used to derive them are described in an article that will be published on July 7, 2011, in the journal Nature.

"Participating in global mental health research is an enormous opportunity, a means to accelerate advances in mental health care for the diverse U.S. population, as well as an extension of our vision of a world where mental illnesses are prevented and cured," said Thomas R. Insel, M.D., director of the National Institute of Mental Health (NIMH), the NIH institute heading this effort.

According to the paper's authors, the disorders targeted by the Grand Challenges in Global Mental Health—for example, schizophrenia, depression, epilepsy, dementia, and alcohol dependence—collectively account for more years of life lost to poor health, disability, or early death than either cardiovascular disease or cancer. Yet, compared to illnesses like cardiovascular disease and cancer, there are far fewer effective treatments or preventive methods. In addition, interventions are not widely available to those who need them most.

In recognizing the need to address this imbalance, Pamela Collins, M.D., M.P.H., of the NIMH Office for Research on Disparities and Global Mental Health, and colleagues assembled an international panel of experts to identify research priorities using the Delphi method, a widely accepted consensus-building tool. The panel consisted of 422 experts in fields such as neuroscience, basic behavioral science, mental health services, and epidemiology, and represented more than 60 countries social worker ceus

Over the course of two months, NIMH staff pared the panel's initial list of 1,565 challenges down to 154, with input from a scientific advisory board. From this list, the expert panel selected the top 40, of which the top five challenges identified after the third and final round of ranking are:

Integrate screening and core packages of services into routine primary health care
Reduce the cost and improve the supply of effective medications
Improve children's access to evidence-based care by trained health providers in low- and middle-income countries
Provide effective and affordable community-based care and rehabilitation
Strengthen the mental health component in the training of all health care personnel.
These top five challenges were ranked according to the ability to reduce the burden of disease, ability to reduce inequalities in health and health care, length of time until results can be observed, and the ability for the topic to be researched effectively.

"Addressing these challenges could have far-reaching effects, including increasing access to services and ultimately, reducing the treatment gap associated with these disorders," said Dr. Collins.

The Grand Challenges in Global Mental Health Initiative is led by NIMH and the Global Alliance for Chronic Diseases, in partnership with the Wellcome Trust, the McLaughlin-Rotman Centre for Global Health, and the London School of Hygiene and Tropical Medicine. Other NIH components participating in the Grand Challenges in Global Mental Health include the Fogarty International Center; the National Heart, Lung, and Blood Institute; and the National Institute of Neurological Disorders and Stroke.

Reference
Collins PY, Patel V, Joestl SS, March D, Insel TR, Daar A, on behalf of the Grand Challenges in Global Mental Health Scientific Advisory Board and Executive Committee. Grand Challenges in Global Mental Health. Nature. 2011 July 7. 474(7354):pp.

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

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

Depressed Teens with History of Abuse Less Likely to Respond to Combination Treatment

Adolescents with treatment-resistant depression who have a history of abuse—especially physical abuse—are less likely to respond to combination treatment than to medication alone, according to data from the NIMH-funded Treatment of Resistant Depression in Adolescents (TORDIA) study. The new study was published in the March 2011 issue of the Journal of the American Academy of Child and Adolescent Psychiatry.

Background
Although the relationship between childhood abuse and risk for depression or other mental disorder is well-established, few studies have examined whether a history of abuse may affect response to treatment, especially among adolescents. Some studies have suggested that a history of abuse is associated with a lower response to cognitive behavioral therapy (CBT), a type of psychotherapy that emphasizes problem-solving and behavior change social worker ceus

In the Treatment of Resistant Depression in Adolescents (TORDIA) study, teens whose depression had not improved after an initial course of selective serotonin reuptake inhibitor (SSRI) antidepressant treatment were randomly assigned to one of four interventions for 12 weeks:

Switch to another SSRI—paroxetine (Paxil), citalopram (Celexa) or fluoxetine (Prozac)
Switch to a different SSRI plus CBT
Switch to venlafaxine (Effexor), a different type of antidepressant called a serotonin and norepinephrine reuptake inhibitor (SNRI)
Switch to venlafaxine plus CBT
As reported in May 2010, about 40 percent of those who completed 24 weeks of treatment achieved remission, regardless of the treatment to which they had initially been assigned. The risk for relapse remained high, however.

About 13 percent of TORDIA participants had a history of physical abuse, 17 percent had a history of sexual abuse, and 5 percent had a history of both. In this most recent study, Wael Shamseddeen, M.D., MPH, of Rosalind Franklin University of Medicine and Sciences in North Chicago, and colleagues examined the association between having a history of physical or sexual abuse and response to combination treatment among TORDIA participants.

Results of the Study
The researchers found that teens without a history of abuse had a higher response rate to combination therapy compared to medication-only therapy (63 percent vs. 37.6 percent). Those with a history of sexual abuse responded similarly to combination and medication-only therapy (48 percent vs. 42 percent). However, those with a history of physical abuse had a much lower response rate to combination therapy (18.4 percent) compared to medication-only (52.4 percent).

Significance
The researchers were unable to identify the specific mechanism that might affect response to combination therapy among teens with a history of physical abuse. They suggest that because abuse can affect a child's brain development, abused youth may need psychotherapeutic approaches that target trauma before engaging in traditional CBT designed to treat depression. The researchers also suggest that abused youth may have a tendency to avoid unpleasant emotions, and therefore may have been averse to CBT. It is possible that therapeutic approaches that focus more on behavior and do not rely heavily on the processing of negative thoughts and emotions may be more acceptable and effective for these youth.

What's Next
The researchers concluded that more research is needed into the ways in which abuse history can confer treatment resistance among teens with hard-to-treat depression, and in developing alternative treatment approaches that are more effective.

Reference
Shamseddeen W, Asarnow JR, Clarke G, Vitiello B, Wagner KD, Birmaher B, Keller MB, Emslie G, Iyengar S, Ryan ND, McCracken JT, Porta G, Mayes T, Brent D. Impact of physical and sexual abuse on treatment response in the Treatment of Resistant Depression in Adolescents Study (TORDIA). Journal of the American Academy of Child and Adolescent Psychiatry. 2011 March. 50(3):293-301.

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Most Teens with Eating Disorders Go Without Treatment

About 3 percent of U.S. adolescents are affected by an eating disorder, but most do not receive treatment for their specific eating condition, according to an NIMH-funded study published online ahead of print March 7, 2011, in the Archives of General Psychiatry. Social Worker Continuing Education
Background
Kathleen Merikangas, Ph.D., of NIMH and colleagues analyzed data from the National Comorbidity Study-Adolescent Supplement (NCS-A), a nationally representative, face-to-face survey of more than 10,000 teens ages 13 to 18. Previously published results found that about 20 percent of youth are affected by a severe mental disorder, and a substantial proportion of these youth do not receive mental health care.

In this new study, the authors tracked the prevalence of eating disorders and the proportion of those youth who received treatment for these disorders.

Results of the Study
According to the data, 0.3 percent of youth have been affected by anorexia, 0.9 percent by bulimia, and 1.6 percent by binge-eating disorder. The researchers also tracked the rate of some forms of eating disorders not otherwise specified (ED-NOS), a catch-all category of symptoms that do not meet full criteria for specific disorders but still impact a person’s life. ED-NOS is the most common eating disorder diagnosis. Overall, another 0.8 percent had subthreshold anorexia, and another 2.5 percent had symptoms of subthreshold binge-eating disorder.

In addition,

Hispanics reported the highest rates of bulimia, while Whites reported the highest rates of anorexia.
The majority who had an eating disorder also met criteria for at least one other psychiatric disorder such as depression.
Each eating disorder was associated with higher levels of suicidal thinking compared to those without an eating disorder.
Significance
The prevalence of these disorders and their association with coexisting disorders, role impairment, and suicidal thinking suggest that eating disorders represent a major public health concern. In addition, the significant rates of subthreshold eating conditions support the notion that eating disorders tend to exist along a spectrum and may be better recognized by doctors if they included a broader range of symptoms. In addition, the findings clearly underscore the need for better access to treatment specifically for eating disorders.

Reference
Swanson SA, Crow SJ, LeGrange D, Swendsen J, Merikangas KR. Prevalence and correlates of eating disorders in adolescents: results from the National Comorbidity Survey Replication Adolescent Supplement. Archives of General Psychiatry. Online ahead of print March 7, 2011.

Social Worker Continuing Education CEU CEUs

Online Social Worker Continuing Education CEU CEUs

Course Listing:

Domestic Violence/Spousal and Partner Abuse
Substance Abuse and Dependence
Law and Ethics (Califonia only)
HIV and Aids
Aging and Long Term Care
Child Abuse
Crisis Counseling
Cross Cultural Counseling
Managed Care
PTSD
Anxiety Disorders
Depressive Disorder
Medical Necessity
Cognitive Behavioral Therapy
Pychopharmacology
BipolarDisorder
Conflict Resolution
Anger Management
Assessment and Diagnosis
Elder Abuse
Family Therapy
Group Therapy
Human Sexuality