The Mental Health Social Worker

A gene called DISC1, (for “disrupted in schizophrenia”) has been a leading contender among possible genetic causes since it was implicated in schizophrenia in a large Scottish clan two decades ago. The DISC1 gene codes for a protein important for brain development, as well as for mood and memory – functions that are disturbed in schizophrenia. However, until now there have been few clues as to how DISC1 might increase risk for the chronic mental disorder.

A new study suggests how impaired expression of DISC1 might wreak havoc during early critical periods as the developing brain gets wired up. NIMH researchers have discovered that previously unknown shortened forms of the gene were expressed 2.5 times more in the fetal brain than after birth. By contrast, other forms were expressed more evenly across development. The shortened forms were also over-expressed in brains of adults who had schizophrenia.

“These shortened forms may result in a functionally aberrant and truncated protein that is more highly expressed in the brains of people with schizophrenia” explained NIMH’s Dr. Joel Kleinman, who led the research.

Drs. Kleinman, Barbara Lipska, Kenji Nakata, Daniel Weinberger and colleagues, report on their discoveries in postmortem brain tissue online, during the week of August 24, 2009 in the Proceedings of the National Academy of Science (PNAS).

Background

The new findings may help explain the molecular roots of the illness in the Scottish clan, in which more than half of the members developed schizophrenia or other serious mental disorders. Previous studies had traced their disease, in part, to a different aberration, a mismatch called a translocation, in which a chunk of genetic material from one chromosome gets attached to another chromosome. But this has never been seen in other families. A translocation, like the shorter messenger RNA forms, would result in shortened forms of DISC1 protein. So other affected families and the Scottish clan could in fact share a similar illness process, say the researchers.

Results of This Study

The researchers linked several illness-implicated variations in the DISC1 gene to the shorter forms of DISC1 products, called messenger RNAs, that transform the gene into protein. The results suggest that variations in the DISC1 gene boost risk for schizophrenia by producing shortened messenger RNAs that are predominantly expressed during the formative period when the fetal brain is taking shape.

Significance

“Our results cast a new light on apparent failures to replicate findings that have long plagued psychiatric genetics” said Kleinman. “We discovered that different genetic variations can result in the same or similar messenger RNAs and protein. That means that different studies could turn up different variations and still be pointing to the same underlying disease process. So some findings thought to be non-replications may ultimately prove to be replications.”

Since at least a half-dozen genes implicated in schizophrenia by the NIMH group interact with DISC1, the downstream adverse effects of impaired DISC1 on brain systems are likely considerable, said Kleinman.

What’s Next

One of the suspect gene variants associated with a shortened messenger RNAs is detectable in white blood cells, raising the possibility that it could someday be used as a genetic marker for the illness.

NIMH’s Dr. Joel Kleinman explained how the DISC1 gene may increase risk for schizophrenia at a recent NIMH seminar.

Reference

Nakata K, Lipska BL, Hyde TM, Ye T, Fink E, Morita Y, Vakkalanka R, Bareboim M, Sei Y, Weinberger DR, Kleinman JE. DISC1 splice variants are upregulated in schizophrenia and associated with risk polymorphisms. Aug 24, 2009 PNAS.

Washington, DC – Pregnant women with depression face complicated treatment decisions
because of the risks associated with both untreated depression and the use of antidepressants. A new report from The American College of Obstetricians and Gynecologists (ACOG) and the American Psychiatric Association (APA) attempts to help doctors and patients weigh the risks and benefits of various treatment options.

Based on an extensive review of existing research, ACOG and APA offer recommendations for the treatment of women with depression during pregnancy. The report, “The Management of Depression During Pregnancy: A Report from the American Psychiatric Association and The American College of Obstetricians and Gynecologists,” is published in Obstetrics & Gynecology (September 2009) and General Hospital Psychiatry (September/October 2009).

Depression is common during pregnancy—between 14 percent and 23 percent of pregnant women will experience depressive symptoms while pregnant. In 2003, approximately 13 percent of women took an antidepressant at some time during their pregnancy.

“Depression in pregnant women often goes unrecognized and untreated in part because of concerns about the safety of treating women during pregnancy,” said lead author Kimberly Ann Yonkers, MD, Yale University associate professor of psychiatry and obstetrics, gynecology and reproductive sciences. “It is our hope that this will be a resource to clinicians who care for pregnant women who have or are at risk of developing major depressive disorder.”

Both depression symptoms and the use of antidepressant medications during pregnancy have been associated with negative consequences for the newborn. Infants born to women with depression have increased risk for irritability, less activity and attentiveness, and fewer facial expressions compared with those born to mothers without depression. Depression and its symptoms are also associated with fetal growth change and shorter gestation periods. And while
available research still leaves some questions unanswered, some studies have linked fetal malformations, cardiac defects, pulmonary hypertension, and reduced birth weight to antidepressant use during pregnancy.

Identifying depression in pregnant women can be difficult because its symptoms mimic those associated with pregnancy, such as changes in mood, energy level, appetite, and cognition. Depressed women are more likely to have poor prenatal care and pregnancy complications, such as nausea, vomiting, and preeclampsia, and to use drugs, alcohol, and nicotine.

“Ob-gyns are the front-line physicians for most pregnant women and may be the first to make a diagnosis of depression or to observe depressive symptoms getting worse. In the past, reproductive health practitioners have felt ill equipped to treat these patients because of the lack of available guidance concerning the management of depressed women during pregnancy,” said ACOG President Gerald F. Joseph, Jr, MD. “This joint report bridges the gap by summarizing
current research on various depression treatment methods and can assist clinicians in decisionmaking. Many people—physicians and women alike—will be glad to know that their choices go beyond ‘medication or nothing.’”

According to the report, some patients with mild-to-moderate depression can be treated with psychotherapy (individual or group) alone or in combination with medication. Additionally, the report discusses the need for ongoing consultation between a patient’s ob-gyn and psychiatrist during pregnancy and presents algorithms for treating patients in common scenarios:

Women thinking about getting pregnant

• For women on medication with mild or no symptoms for six months or longer, it may be appropriate to taper and discontinue medication before becoming pregnant.

• Medication discontinuation may not be appropriate in women with a history of severe, recurrent depression (or who have psychosis, bipolar disorder, other psychiatric illness requiring medication, or a history of suicide attempts).

• Women with suicidal or acute psychotic symptoms should be referred to a psychiatrist for aggressive treatment.
Pregnant women currently on medication for depression

• Psychiatrically stable women who prefer to stay on medication may be able to do so after consultation between their psychiatrist and ob-gyn to discuss risks and benefits.

• Women who would like to discontinue medication may attempt medication tapering and discontinuation if they are not experiencing symptoms, depending on their psychiatric history. Women with a history of recurrent depression are at a high risk of relapse if medication is discontinued.

• Women with recurrent depression or who have symptoms despite their medication may benefit from psychotherapy to replace or augment medication.

• Women with severe depression (with suicide attempts, functional incapacitation, or weight loss) should remain on medication. If a patient refuses medication, alternative treatment and monitoring should be in place, preferably before discontinuation.

Pregnant and not currently on medication for depression

• Psychotherapy may be beneficial in women who prefer to avoid antidepressant medication.

• For women who prefer taking medication, risks and benefits of treatment choices should be evaluated and discussed, including factors such as stage of gestation, symptoms, history of depression, and other conditions and circumstances (eg, a smoker, difficulty gaining weight).

All pregnant women

• Regardless of circumstances, a woman with suicidal or psychotic symptoms shouldimmediately see a psychiatrist for treatment.

Background on the report

APA and ACOG convened a work group to critically evaluate and summarize information about the risks associated with depression and antidepressant treatment during pregnancy. The group included clinical research experts within these two medical specialties and a developmental pediatrician.

Researchers reviewed cumulative existing research relating to antidepressant use in pregnancy; however, available research has not yet adequately controlled for other factors that may influence birth outcomes, including maternal illness or problematic health behaviors that can adversely affect pregnancy.

Limitations of existing research include:

• Few studies of antidepressants and birth outcomes assessed the mothers’ psychiatric condition

• Confounding factors that influence birth outcomes (eg, poor prenatal care and drug/alcohol/nicotine use) were often not controlled

• Pregnancy complications (eg, nausea, preeclampsia) occur at a higher rate in depressed than nondepressed women

The report authors are Kimberly A. Yonkers, MD; Katherine L. Wisner, MD, MS; Donna E.
Stewart, MD, FRCPC; Tim F. Oberlander, MD, FRCPC; Diana L. Dell, MD, FACOG, DFAPA; Nada
Stotland, MD, MPH; Susan Ramin, MD, FACOG; Linda Chaudron, MD, MS; and Charles
Lockwood, MD, FACOG.

WASHINGTON, DC—Although exercise is good for your health, extreme exercise may be physically addicting. Rats given a drug that produces withdrawal in heroin addicts went into withdrawal after running excessively in exercise wheels, according to new research. Rats that ran the hardest had the most severe withdrawal symptoms.

The scientists who conducted the study reason that if excessive exercise is addicting, then maybe, to feel good, addicts could take moderate exercise instead of drugs. The findings also shed light on the potentially fatal eating disorder called anorexia athletica, in which exercise undertaken to shed pounds becomes as compulsive as taking drugs, resulting in even greater weight loss.

“Excessive running shares similarities with drug-taking behavior,” the researchers wrote in the August issue of Behavioral Neuroscience, published by the American Psychological Association.

For those looking for an excuse to hit the couch, however, this study looked at excessive, not moderate, exercise. “As with food intake and other parts of life, moderation seems to be the key. Exercise, as long as it doesn’t interfere with other aspects of one’s life, is a good thing with respect to both physical and mental health,” said lead author Robin Kanarek, PhD, of Tufts University.

For several weeks, 44 male and 40 female rats were allowed to either run in exercise wheels or remain inactive. To simulate anorexia athletica, the researchers divided the active and inactive rats into groups whose members were either given food for one hour a day or around the clock. Rats in all four groups were then given naloxone, a medicine for heroin overdose that produces immediate withdrawal symptoms.

Active and inactive rats responded very differently to naloxone, which was given in proportion to their weight. The active rats showed withdrawal symptoms like those seen in narcotics addicts: trembling, writhing, teeth chattering, and drooping eyelids.

The active rats who had access to food for only one hour a day both ran the most and displayed the most severe withdrawal symptoms. Like people with anorexia athletica, they ran so much that they lost significant amounts of weight. Additionally, the more a given rat had run, the worse its withdrawal symptoms after naloxone. In contrast, regardless of how much they ate, inactive rats responded very little to the drug.

Because of the way the active rats responded to naloxone, they seemed to have undergone the same changes in the brain’s reward system as rats addicted to drugs. “Exercise, like drugs of abuse, leads to the release of neurotransmitters such as endorphins and dopamine, which are involved with a sense of reward,” noted Kanarek.

Insights into behaviors that trigger the release of the brain’s “reward” chemicals may lead to addiction treatments that incorporate moderate exercise, according to the researchers. The findings also suggest that active rats given limited food may make a good experimental model for studying and developing treatments for anorexia athletica, added Kanarek.

Because rats and humans share many nervous-system traits, researchers frequently carry laboratory findings like these out into the real world.

Article: “Running and Addiction: Precipitated Withdrawal in a Rat Model of Activity-Based Anorexia,” Robin B. Kanarek, PhD, Kristen E. D’Anci, PhD, Nicole Jurdak, MS, and Wendy Foulds Mathes, PhD, Tufts University; Behavioral Neuroscience, Vol. 123, No. 4.

(Full text of the article is available from the APA Public Affairs Office and at http://www.apa.org/journals/releases/bne1234905.pdf)

Robin Kanarek can be reached at e-mail. Her office number is (617) 627-5902. During the first two weeks of August, she can be reached by cell phone at (978) 835-9132.

Making evidence-based mental health services accessible to everyone in a disaster-stricken area would have substantial public health benefits, according to a statistical model developed by NIMH-funded researchers. Rough estimates of cost show such comprehensive care would be within the range of other accepted medical practices. However, given the considerable costs and resources required, further studies are needed to determine whether such broader efforts are advisable and, if so, to what degree. The study was published in the August 2009 issue of the Archives of General Psychiatry.

Background

Research on survivors of Hurricanes Katrina and Rita show that this population continues to face many persistent mental health issues. These issues may at times be worsened by lack of availability or access to proper mental health care services. To help inform future disaster plans, a group of researchers led by Kenneth B. Wells, M.D., MPH, of RAND Corporation and UCLA Semel Institute, Health Services Research Center, developed a model to estimate the costs and outcomes of providing enhanced, evidence-based mental health care in a post-disaster setting.

Starting with a population of around 11 million in the hurricane-affected areas (based on U.S. Census & Area Resources File¹ data), the researchers focused on medium-term mental health response, which starts around seven months post-disaster. They chose this period because fewer strategies have been developed for medium-term response, compared with the immediate post-disaster response (zero to six months), which mainly involves humanitarian efforts such as life-saving care and crisis counseling. Wells and colleagues modeled service use through 24 months post-disaster and measured outcomes up to 30 months out.

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A single-session, online, multimedia intervention effectively reduced risky sexual behaviors among young men who have sex with men, a group at high risk for HIV/AIDS and other sexually transmitted infections. Such low-cost programs may help reverse the steady rise in HIV diagnoses among this population. The study was published online ahead of print on June 5, 2009, in the journal, AIDS and Behavior.

Background

Based on the Information-Motivational-Behavioral Skills (IMB) model for reducing HIV risk,
Kelly M. Carpenter, Ph.D., of Talaria, Inc., and colleagues developed a multimedia, online intervention that aimed to:

• Increase knowledge of risk factors
• Provide skills training for safer sex behaviors
• Increase motivation for behavior change.

The researchers recruited 112 men who have sex with men, ages 18–39. Participants were HIV negative or did not know their status and had engaged in unprotected sex within the preceding three months. All participants completed a 25-minute baseline assessment and then were randomly assigned to the experimental intervention or a control group program. Both the intervention and control program required 1.5–2 hours to complete, though participants had up to a week to finish. Participants were asked to return to the study Web site three months later to complete a 20-minute follow-up questionnaire.

The intervention presented a variety of interactive exercises, multimedia clips, quizzes, and other materials that provided information about safer sex practices and tested participants’ knowledge of HIV risk factors. Those in the control group completed an online stress reduction program that described the effects of stress on the body and health reasons for reducing stress, in addition to leading participants in relaxation exercises, such as deep breathing and guided imagery. The control program did not include any sexual risk reduction information.

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A combination of an atypical antipsychotic medication and an antidepressant known as a selective serotonin reuptake inhibitor (SSRI) may be more effective in treating psychotic depression than an atypical antipsychotic alone, according to results from an NIMH-funded clinical study.

Background

Psychotic depression is characterized by major depression accompanied by symptoms such as hallucinations, delusions, and breaks with reality. A person with psychotic depression may be unwilling or unable to care for him or herself and often is admitted to the hospital. Typically, psychotic depression is treated with electroconvulsive therapy (ECT), known to be effective but not always acceptable to patients and their families. It is less commonly treated with an antipsychotic or an antipsychotic plus an antidepressant.

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The transition from teen to young adult involves many highly anticipated rites of passage. However, for youths with developmental disorders, coming of age may signal the sudden end of coverage for education and training programs, health insurance, and youth-oriented services. For teens with autism spectrum disorders (ASD) and their families, this transition may be especially difficult. To better understand this issue and how best to address it, NIMH has awarded a five-year grant to Paul T. Shattuck, Ph.D., of the George Warren Brown School of Social Work at Washington University in St. Louis.

With this grant, Dr. Shattuck and his colleagues will pursue a study of socioeconomically and racially diverse adolescents and adults with ASD. The researchers will assess data gathered on 922 people with ASD who participated in the U.S. Department of Education’s (ED) National Longitudinal Transition Study 2. The 10-year ED study included a nationally representative study population of nearly 12,000 youth, ages 13-17 at the start of the study in 2000. In particular, the Shattuck study will focus on:

• Outlining changes in service needs, service use, and health insurance coverage as youths with ASD enter adulthood
• Identifying resources and barriers associated with use of, and continuity in, health care and other services
• Detailing young adult outcomes (such as employment, housing, independent living, health, and community participation) and examining how these may be linked with prior measures of need, service use, resources, and barriers.

The study also meets a research objective in the Interagency Autism Coordinating Committee’s (IACC) Strategic Plan for Autism Spectrum Disorder Research “to support at least two studies [by 2011] to assess and characterize service access, health, and functional outcomes” among diverse demographic groups. Comprising representatives of federal agencies and members of the public, the IACC coordinates efforts within the U.S. Department of Health and Human Services concerning ASD.

“This study will help us one day answer one of the most pressing issues in treating ASD,” said NIMH Director Thomas R. Insel, M.D. “Bridging the gap in health care, service use, and insurance coverage as these young people leave the school systems and enter adulthood may help prevent lapses in behavioral, social, and occupational skills that they and their families have worked so hard to achieve.”

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