The Mental Health Social Worker

Overprotective parents slow their children’s brain growth in an area linked to mental illness, a new study asserts. Kosuke Narita of Gunma University, Japan, scanned the brains of 50 people in their 20s and asked them to fill out a survey about their relationship with their parents during their first 16 years. After analyses, it was discovered that those with overprotective parents had less grey matter in a particular area of the prefrontal cortex than those who had had healthy relationships. This part of the prefrontal cortex develops during childhood, and abnormalities there are common in people with schizophrenia and other mental illnesses, according to the results, which are published in the journal Progress in NeuroPsychopharmacology and Biological Psychiatry. (New Scientist, 3/10/10)

ARLINGTON, Va. (March 15, 2010) – Combining the antidepressant sertraline with the alcohol dependence treatment naltrexone produced a 54 percent abstinence rate in patients with both major depression and alcohol dependence, whereas the rates were only 21 to 28 percent for patients taking a placebo, sertraline only, or naltrexone only.
This study shows an important advancement in the treatment of patients who live with both alcoholism and depression because the co-occurrence of these disorders is common in clinical practice, yet antidepressants alone are not sufficient for reducing excessive drinking in these patients.

All 170 patients also received cognitive-behavioral therapy, and the four treatment groups all showed clinical reductions in depressive symptoms over the 14-week study, which was conducted by Helen Pettinati, Ph.D., and colleagues of the University of Pennsylvania.
In addition to a higher abstinence rate, the group receiving combination treatment had a longer interval before resumption of drinking: a median of 61 days compared with 15 days for the other groups combined. Serious adverse events were actually less frequent in the group receiving both medications, since the most common serious event was hospitalization for detoxification or rehabilitation.
“When depression and alcohol dependence occur together, each condition has a negative influence on the outcome of the other, so not only does this pairing of illnesses affect a lot of patients, it also makes the individual disorders worse,” Dr. Pettinati stated. “Combining sertraline and naltrexone could be a practical approach for these patients because both have FDA approval.”
The study will appear on March 15 at AJP in Advance, the online advance edition of The American Journal of Psychiatry (AJP), the official journal of the American Psychiatric Association. Funding for this study was received from the National Institute on Alcohol Abuse and Alcoholism. Pfizer Pharmaceuticals donated sertraline and a matching placebo.
The American Journal of Psychiatry is the oldest continuously published medical specialty journal in the United States and was recently named one of the “Most Influential Journals in Biology & Medicine of the Last 100 Years.” Statements in this press release or the articles in the Journal are not official policy statements of the American Psychiatric Association.
About the American Psychiatric Association:
The American Psychiatric Association is a national medical specialty society whose physician members specialize in the diagnosis, treatment, prevention and research of mental illnesses, including substance use disorders. Visit the APA at www.psych.org and www.HealthyMinds.org.

Studies find facial and vocal expression more difficult to read; deep brain stimulation seems to make it worse

WASHINGTON — Scientists are beginning to find out why people with Parkinson’s disease often feel socially awkward. Parkinson’s patients find it harder to recognize expressions of emotion in other people’s faces and voices, report two studies published by the American Psychological Association.

One of the studies raises questions about how deep brain stimulation, the best available treatment for patients who no longer respond to medication, more strongly affects the recognition of fear and sadness.

A neurodegenerative disorder, Parkinson’s causes tremors, stiffness and balance problems, as well as fairly frequent depression and dementia.

In the March issue of Neuropsychology, Heather Gray, PhD, and Linda Tickle-Degnen, PhD, report that people with Parkinson’s disease, compared with matched controls, often have difficulty discerning how others are feeling.

Their meta-analysis of 34 different studies using data from 1,295 participants shows a robust link between Parkinson’s and specific deficits in recognizing emotions, especially negative emotions, across different types of stimuli and tasks.

The meta-analysis, conducted at Harvard Medical School and Tufts University, found that patients typically had some degree of problem identifying emotion from faces and voices.

Further clarification is provided in a second study that showed that deep-brain stimulation, compared with medication, caused a consistently large deficit in the recognition of fear and sadness – two key facial expressions that, when understood, aid survival. That study is published in the January issue of Neuropsychology.

Researchers led by Julie Péron, PhD, at the Centre Hospitalier Universitaire de Rennes in France, compared the ability of people with Parkinson’s in three different groups to recognize facial emotions: 24 advanced patients implanted with deep-brain stimulators after they didn’t respond or were sensitive to oral levodopa (the usual drug for the disease); 20 advanced patients given apomorphine hydrochloride by injection or infusion pump while they waited an implant; and 30 healthy controls.

Researchers tested all participants using standard photographs of facial expression before and three months after they were treated. Before implantation of the stimulators, all participants read facial expressions equally well.

Patients in the surgical group were implanted with stimulators, electrical devices that prod the brain’s subthalamic nucleus, a small, lens-shaped structure, to normalize the nerve signals that control movement. This nucleus is part of the basal ganglia system, which is thought to integrate movement, cognition and emotion.

Three months after treatment, only the patients with stimulators – not the drug-treated patients or the healthy controls – were significantly worse at recognizing fear and sadness. Patients with stimulators confused those expressions with others, such as surprise, or even no emotion. Medicated patients and healthy controls were either accurate about fear and sadness or occasionally mistook them for other negative emotions, such as disgust.

“Having Parkinson’s predisposes an individual to errors in emotion recognition,” said Gray. “The research in France, along with previous studies, indicates that deep-brain stimulation produces an even more severe deficit.”

Why would treating a movement disorder affect the perception of emotions? Implants affect a part of the brain that reaches across functions, so the authors suggested that the same electrical stimulation that calms over-excited motor activity may also somehow inhibit emotional processing.

Although the impact of Parkinson’s and deep-brain stimulation varies by patient, it’s important to understand. “The first step is to educate patients and their close associates about the potential for emotion recognition difficulties, so they can learn to manage some of the social consequences, such as misunderstanding and frustration,” said Gray and Tickle-Degnen. The next step might be training in emotion recognition, which they said has shown promise.

According to the National Institutes of Health, deep-brain stimulation is used to treat a variety of disabling neurological symptoms, including Parkinson’s and essential tremor, a common neurological movement disorder.

At present, the procedure is used only for patients whose symptoms cannot be adequately controlled with medications. According to Péron, about 15 percent of Parkinson’s disease patients are thought capable of benefiting from the surgery.

Article: “Subthalamic Nucleus Stimulation Affects Fear and Sadness Recognition in Parkinson’s Disease,” Julie Péron, PhD, Isabelle Biseul, PhD, and Emmanuelle Leray, PhD, Centre Hospitalier Universitaire de Rennes and Centre Eugène Marquis; Siobhan Vicente, PhD, Centre Hospitalier Universitaire de Rennes and Centre Hospitalier Guillaume Régnier; Florence Le Jeune, MD, PhD, Centre Hospitalier Universitaire de Rennes and Centre Eugène Marquis; Sophie Drapier, MD, Centre Hospitalier Universitaire de Rennes; Dominique Drapier, MD, PhD, Centre Hospitalier Universitaire de Rennes and Centre Hospitalier Guillaume Régnier; Paul Sauleau, MD, PhD, Claire Haegelen, MD, and Marc Vérin, MD, PhD, Centre Hospitalier Universitaire de Rennes; Neuropsychology, Vol. 24, No. 1.

Julie Péron can be reached by e-mail or at 0041 (0)794 54 13 88 (Swiss Centre for Affective Sciences, Geneva University) or 00 33 (0)6 88 31 30 43 (permanent number in France).

Article: “A Meta-Analysis of Performance on Emotion Recognition Tasks in Parkinson’s Disease,” Heather M. Gray, PhD, Cambridge Health Alliance, Harvard Medical School, and Linda Tickle-Degnen, PhD, Tufts University; Neuropsychology, Vol. 24, No. 2.

Heather Gray can be reached by e-mail (Division on Addictions, Cambridge Health Alliance, Harvard Medical School) or by phone at (781) 306-8611.

The offspring of parents with schizophrenia or bipolar disorder are more likely to develop the same illness or another psychiatric condition than those with only one parent with a psychiatric condition, a new study finds. Researchers at the University of Minnesota Medical School examined a population-based cohort of 2.7 million individuals born in Denmark and matched records in a general registry of the population with a database of psychiatric admissions. Their findings, which are published in the Archives of General Psychiatry, show rates of schizophrenia were highest among offspring of two parents with schizophrenia. Of the 196 couples who both had schizophrenia, 27.3 per cent of their children were admitted to a psychiatric facility, increasing to 39.2 per cent when schizophrenia-related disorders were included. This compared with a rate of 7 per cent among offspring of couples in which one parent had schizophrenia and 0.86 per cent in 2.2 million offspring of 1 million couples in which neither parent was admitted for schizophrenia. (HealthDay News, 3/02/10)

Psychologists Study New Treatments for Smokers from Underserved Populations

WASHINGTON – With the national trend toward quitting smoking flat, psychologists are finding some success with treatments aimed at helping smokers from underserved groups, including racial and ethnic minorities and those with psychiatric disorders.

In a special section of this month’s issue of the Journal of Consulting and Clinical Psychology, published by the American Psychological Association, researchers report on several effective treatments that may help these smokers in an effort to increase national smoking cessation rates. The percentage of American smokers rose from 19.8 percent in 2007 to 20.6 percent in 2008, after a 10-year steady decline in smoking rates, according to the latest figures from the Centers for Disease Control and Prevention.

“One of the reasons smoking rates have remained stagnant is because these underserved groups of smokers have not been adequately targeted by research and treatment,” said the special section editor, Belinda Borrelli, PhD, who is with the Centers for Behavioral and Preventive Medicine at Brown University Medical School. Underserved smokers include those who have a 10 percent higher smoking rate than the general population, have less access to treatments, and are more likely to be excluded from long-term treatments trials, according to Borelli.

In one article, researchers found that success in stopping smoking differed for different psychiatric disorders. For example, compared to smokers with no psychiatric disorders, smokers who had an anxiety disorder were less likely to quit smoking six months after treatment.

In the same article, researchers found that people’s barriers to quitting were directly related to what type of psychiatric disorder they had. For example, smokers who had ever been diagnosed with an anxiety disorder reported a strong emotional bond with their cigarettes while smokers ever diagnosed with a substance use disorder reported that social and environmental influences were especially likely to affect their smoking. “This information may help clinicians gauge relapse risk and identify treatment targets among smokers who have ever had psychological illnesses,” said lead author Megan Piper, PhD, from the University of Wisconsin School of Medicine and Public Health.

Evidence-based smoking cessation treatments are addressed in another article in this special section. Researchers from the University of Miami looked at the effect of intensive cognitive-behavioral therapy on African-American smokers. They placed 154 African-American smokers wearing nicotine patches into one of two six-session interventions. Participants in the group using cognitive-behavioral techniques were taught relapse prevention strategies and coping skills, along with other techniques. The other group participated in a health education series that explained general medical conditions that are associated with smoking, such as heart disease and lung cancer.

Compared with general health education, participation in cognitive-behavioral therapy sessions more than doubled the rate of quitting at a six month follow-up, from 14 percent to 31 percent the researchers found. “We know cognitive-behavioral therapy helps people quit, but few studies have examined this treatment’s effect on African-American smokers,” said the study’s lead author, Monica Webb, PhD, of the University of Miami. “Hopefully, our findings will encourage smoking cessation counselors and researchers to utilize cognitive-behavioral interventions in this underserved population.”

Borrelli, the section editor, examined another minority group—Latinos. She measured the amount of second-hand smoke in participants’ homes and gave feedback to smokers about how much smoke their child with asthma was exposed to. For example, they were told that their child was exposed to as much smoke as if the child smoked ‘x’ number of cigarettes him- or herself during the week of the measurement – this was the experimental group. Smokers in the control group underwent standard cognitive-behavioral treatment for smoking cessation. Smokers in the experimental group were twice as likely to quit as the control group, Borrelli found. “The child’s asthma problems may provide a teachable moment for parents whereby they become more open to the smoking cessation messages,” Borrelli said. “Providing treatment that is focused on the health needs of the family, and delivered in a culturally tailored manner, has the potential to address health care disparities for Latino families.”

Special Section: “Smoking Cessation – Innovative Treatments and Understudied Populations,” Section Editor: Belinda Borrelli, PhD, Brown University Medical School and Miriam Hospital; Journal of Consulting and Clinical Psychology, Vol. 78, No. 1.

Contact Dr. Belinda Borrelli by e-mail or her phone number is (401) 741-7994.

Exciting new activities may help prevent relapse

Researchers Evaluated Intervention Focusing on Preventive Health and Future Goal Attainment, Not Moral Choices

Teens who received a behavioral intervention centered on abstinence were more likely to delay first sexual contact than teens who received a control intervention focusing on general health promotion, according to an NIMH-funded study. Though differing from federally funded abstinence-only programs, the researchers describe how an abstinence-based intervention may help delay sexual activity among adolescents in the February 2010 issue of the Archives of Pediatrics and Adolescent Medicine.

Background

Sexually active teens face a broad range of potentially negative outcomes related to HIV and other sexually transmitted infections (STIs) and unplanned pregnancies. In particular, African American teens experience these outcomes at much higher rates than their peers.^1,2,3,4

Studies have shown that behavioral interventions can reduce behaviors related to HIV/STI risk. However, U.S. policymakers do not agree on which type of intervention is most appropriate or most effective for use with teens. Many states have adopted abstinence-only programs in their school systems, which not only lack adequate research showing their efficacy, but have been criticized for inclusion of inaccurate information, negative portrayal of sex, and a moralistic tone.

To address this issue, John B. Jemmott, III, Ph.D., of the University of Pennsylvania, and colleagues recruited 662 students in grades 6 and 7 (ages 10—15) from four, public middle schools serving low-income, African American, urban communities. They were randomly assigned to one of five behavioral interventions:

• Abstinence—based-designed to strengthen beliefs supporting abstinence (e.g., prevent pregnancy and STIs, foster attainment of future goals) and increase skills for resisting pressure to have sex. In addition, the intervention providers were expressly instructed not to discredit use of condoms and to correct false beliefs about the effectiveness of condoms in preventing STIs.
• Safer sex—designed to strengthen beliefs supporting condom use and increase skills to negotiate condom use and use condoms properly.
• 12-hour comprehensive—combined the design and aims of the abstinence-based and safer sex interventions.
• 8-hour comprehensive—provided an abbreviated version of the 12-hour comprehensive intervention. This allowed the researchers to assess whether any benefits of the longer comprehensive intervention could be attributed to the students spending more time in the intervention.
• Health promotion—designed to increase knowledge and motivation regarding general healthful behaviors, such as following a balanced diet and discouraging cigarette smoking. This intervention served as the control condition.

All interventions were designed to increase knowledge about HIV and STIs except for the health promotion intervention. Four of the interventions were provided over two 4-hour weekend sessions (eight hours total). The 12-hour comprehensive intervention was provided over three 4-hour weekend sessions. Participants completed questionnaires at the start of the study, immediately after the last intervention session, and every three months afterwards for up to two years.

In addition, the researchers tested an intervention maintenance program. This program, which was tested in half of the participants, consisted of two 3-hour booster sessions given at six weeks and three months after completion of the initial intervention; six issues of a newsletter; and six brief, one-on-one counseling sessions with the original facilitator provided over a 21-month period.

Results of the Study

At the study’s outset, 23.4 percent of the teens reported that they were already sexually active.

At the two-year follow-up, students who received the abstinence-based intervention and had not been sexually active at the study’s outset were significantly less likely to have initiated sexual activity (33 percent) or to have recently had sex (20 percent) compared to the those who received the health promotion intervention; among students in the control group with no prior sexual activity, 49 percent reported first sexual contact and 29 percent recently had sex. None of the other interventions had a significant effect on the initiation of sexual activity when compared to the control condition. The researchers did not compare the four HIV-prevention interventions with each other on any outcome measures.

Students who received either the 8-hour or 12-hour comprehensive intervention were significantly less likely to report having multiple partners (about 9 percent in each group) than those in the control group (14 percent).

The intervention maintenance program modestly enhanced the effectiveness of the abstinence-based and 12-hour comprehensive interventions at reducing multiple partners, but showed no other benefits.

None of the interventions significantly affected consistent condom use.

Significance

According to the researchers, their study shows that a theory-based, abstinence-only intervention may be an effective method for delaying sexual initiation in middle school students who are not already sexually active. They also emphasized that the abstinence-based intervention used in this study was not designed to meet federal criteria for abstinence-only programs. Thus, it is not subject to the criticisms those programs face. Similarly, the results of the abstinence-based intervention cannot be generalized to all abstinence programs or to all populations.

Also of note, the study did not support a common concern about abstinence-only interventions—that they reduce the likelihood of condom use among teens. Similarly, the other behavioral interventions did not increase sexual activity when compared to the control group, a concern expressed by some regarding comprehensive sex education interventions.

The researchers further cautioned that their findings do not suggest that this or other abstinence-based interventions are the best approach for all adolescents. However, the use of evidence-based abstinence interventions may be an effective means of delaying sexual initiation in some communities for whom abstinence is the only acceptable approach to sex education.

What’s Next

Further work is needed to determine whether the interventions assessed in this study are effective for other teen populations and to determine when they affect biological outcomes such as STI or pregnancy rates. Different methods may be more effective in addressing the specific needs of older youth or teens in committed relationships, for example. The researchers also expressed the need for additional studies to identify ways of prolonging the effectiveness of HIV/STI interventions.

Reference

Jemmott JB, Jemmott LS, Fong GT. Efficacy of a Theory-Based Abstinence-Only Intervention over 24 Months: A Randomized Controlled Trial with Young Adolescents. Arch Pediatr Adolesc Med. 2010 Feb;164(2):152-9.

¹ Centers for Disease Control and Prevention. Sexually transmitted disease surveillance 2006. Atlanta, GA: Division of STD Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, November 2007. Downloaded February 22. 2008 at http://www.cdc.gov/std/.

² Centers for Disease Control and Prevention. HIV/AIDS surveillance in adolescents and young adults (through 2005). Atlanta, GA: Division of HIV/AIDS, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, October 23, 2007. Downloaded February 19, 2008 at www.cdc.gov/hiv/topics/surveillance/resources/slides/adolescents/index.htm.

³ Miller WC, Ford CA, Morris M, Handcock MS, Schmitz, JL, Hobbs MM, Cohen MS, Harris KM, Udry JR. Prevalence of chlamydial and gonococcal infections among young adults in the United States. JAMA. 2004;291:2229-2236.

⁴ Ventura SJ, Abma JC, Mosher WD, Henshaw SK. Recent trends in teenage pregnancy in the United States, 1990-2002. Health E-Stats. Hyattsville, MD: National Center for Health Statistics. Released December 2006. Downloaded June 6, 2007 at http://www.csctulsa.org/images/Teen%20Pregnancy%20Trends%201990-2002.pdf

Amidst the background hum of electrical signaling generated by neurons in the brain, scientists have found that local groups of neurons, firing in coordination, sometimes create a signal that is mirrored instantaneously and precisely by other groups of neurons across the brain.  These transient episodes of coherence across different parts of the brain may be an electrical signature of thought and actions.

Background

One of the goals of neuroscience research is to identify how thoughts and actions are encoded in the activity of neurons.  A challenge has been to extract meaningful patterns from the ongoing tumult of electrical activity in the brain.  This global electrical activity is built from the firing of individual neurons.  A single neuron responds to a stimulus in an all or nothing manner—if the stimulus reaches a certain threshold, the neuron “fires” an electrical signal.  Groups of neurons firing in a coordinated way create a local electrical field that is in itself a signal that can vary in pattern.  These local field potentials (LFPs) have been a target of research.

This Study

In this research, Dietmar Plenz and colleagues at NIMH and Duke University pinpointed LFPs in the cortex that surpassed a minimal size threshold, and then searched the rest of the cortex to see what was occurring at the same time.  In each case, they found other answering LFPs across the brain that mimicked each other with high precision: there was no degradation or loss of power (amplitude) in the signal.  Unlike what is observed after dropping a stone in a pond—with wavelets getting smaller farther from the stone—the intensity of the LFPs was the same across the brain.  The investigators call these LFPs coherence potentials.  Although LFPs that occur during these transient episodes of coherence are identical to each other, they are also multidimensional and potentially infinitely diverse, providing a means to encode information.  Most LFPs do not reach the threshold that characterizes a coherence potential but with those that do, propagation of the LFPs across the brain is extraordinarily rapid.  The authors note that the rapid dispersion of such a signal mimics the spread of ideas and behaviors in social networks; a sufficiently provocative idea can spread very swiftly through a population.

Significance

Coherence potentials simultaneously engage groups of neurons in different parts of the brain with diverse functions.  This is consistent with the multi-faceted nature of mental associations and memories—a memory focused on a person or object might conjure various kinds of sensations and thoughts—visual, tactile, auditory, and emotional, for example.

These findings emerged from recent work that demonstrated that, like other systems in nature, the cortex exists at a critical state between stability and instability.  A characteristic of this state in the brain is the presence of neuronal avalanches—if a stimulus reaches a certain threshold, it will set off cascades of neuronal firing.  This dynamic is analogous to when the slope of a sandpile reaches a point at which adding one more grain will trigger an avalanche.  The adherence of the cortex to this critical state ensures that the brain can respond to a wide range of stimuli, but not lapse into a chaos of excess activity (such as the too-synchronous firing during epilepsy).  Coherence potentials emerge predominantly when the cortex is critical, that is, when it displays neuronal avalanches.  Nudging the cortex away from this point, by inhibiting neuronal signaling with medications for example, disrupts these dynamical patterns.

What’s Next

Coherence potentials were present in cells in culture as well as awake monkeys, a robust demonstration that they occur in the functioning cortex.  Future studies will be aimed at monitoring coherence potentials in the context of behavioral function with the ultimate aim of making a connection between specific coherence potentials and behaviors.

Reference

Thiagarajan, T.C., Lebedev, M.A., Nicolelis, M.A., and Plenz, D. Coherence potentials: loss-less, all-or-none network events in the cortex.  PLoS Biology 2010, doi:10.1371/journal.pbio.1000278.

Increased Risk May Stem From Variation in Gene On/Off Switch

Researchers, for the first time, have pinpointed a genetic hotspot that confers risk for both bipolar disorder and depression. People with either of these mood disorders were significantly more likely to have risk versions of genes at this site than healthy controls. One of the genes, which codes for part of a cell’s machinery that tells genes when to turn on and off, was also found to be over-expressed in the executive hub of bipolar patients’ brains, making it a prime suspect. The results add to mounting evidence that major mental disorders overlap at the molecular level.

“People who carry the risk versions may differ in some dimension of brain development that may increase risk for mood disorders later in life,” explained Francis McMahon, M.D., of the NIMH Mood and Anxiety Disorders Program, who led the study.

McMahon and an international team of investigators, supported, in part by NIMH, report on the findings of their genome-wide meta-analysis online January 17, 2010 in the journal Nature Genetics.

Background

Major mood disorders affect 20 percent of the population and are among the leading causes of disability worldwide. It’s long been known that bipolar disorder and unipolar depression often run together in the same families, hinting at some shared lineage. Yet, until now, no common genes or chromosomal locations had been identified.

McMahon and colleagues analyzed data from five different genome-wide association studies (GWAS) totaling more than 13,600 people, and confirmed their results in 3 additional independent samples totaling 4,677 people.

Findings of This Study

Genetic variations on Chromosome 3 were significantly associated with both mood disorders. The suspect gene, called PBRM1, codes for a protein critical for chromatin remodeling, a key process in regulating gene expression. A neighboring gene is involved in the proliferation of brain stem cells.

The researchers pinpointed a “protective” version of the PBRM1 gene that is carried by 41 percent of healthy controls, but only 38 percent of people with bipolar and unipolar depression. The risk version was found in 62 percent of mood disorder cases and 59 percent of controls. The researchers also showed that PBRM1 is expressed more in the prefrontal cortex of people with bipolar disorder than in controls.

Significance

Since mood disorders likely involve altered gene expression during brain development and in response to stress, PBRM1’s profile makes it a good potential candidate gene. This first genetic evidence of unipolar/bipolar overlap is also the first significant genome-wide association with any psychiatric illness in the Chromosome 3p region.

However, the findings underscore limitations of the GWAS approach, which looks for connections to gene versions that are common in the population. Having one copy of this risk variant increases vulnerability for developing a mood disorder by a modest 15 percent. Why do some people with this variant — and presumably other, yet to be discovered, shared risk genes — develop bipolar disorder while others develop unipolar depression or remain healthy? Environmental influences and epigenetic factors may be involved, suggest the researchers, who note that “genetic association findings so far seem to account for little of the inherited risk for mood disorders.”

“Our results support the growing view that there aren’t common genes with large effects that confer increased risk for mood disorders,” said McMahon. “If there were, in this largest sample to date, we would have found them. The disorders likely involve many genes with small effects — and different genes in different families — complicating the search. Rarer genes with large effects may also exist.”

What’s Next?

Ultimately, findings such as these may lead to identification of common biological pathways that may play a role in both unipolar and bipolar illness and suggest strategies for better treatment, said McMahon. The results add to other evidence of overlap that is spurring a new NIMH initiative to make sense of research findings that don’t fit neatly into current diagnostic categories. See: Genes and Circuitry, Not Just Clinical Observation, to Guide Classification for Research.

Bipolar disorder and unipolar depression often run in the same families, as this pedigree diagram illustrates. The new study is the first to trace both illnesses to a shared chromosomal hotspot.

Source: NIMH Genetics Initiative Bipolar Disorder Consortium

Reference

Meta-analysis of genome-wide association data identifies a risk locus for major mood disorders on 3p21.1.the Bipolar Disorder Genome Study (BiGS) Consortium, McMahon FJ, Akula N, Schulze TG, Muglia P, Tozzi F, Detera-Wadleigh SD, Steele CJ, Breuer R, Strohmaier J, Wendland JR, Mattheisen M, Mühleisen TW, Maier W, Nöthen MM, Cichon S, Farmer A, Vincent JB, Holsboer F, Preisig M, Rietschel M. Nat Genet. 2010 Jan 17. [Epub ahead of print]PMID: 20081856

Samples included in the meta-analysis:

dbGaP National Institute of Mental Health bipolar disorder
Genetic Association Information Network MDD
Wellcome Trust Case Control Consortium
German sample
Systematic Treatment Enhancement Program for Bipolar Disorder

More Receive Psychotherapy than Medication; Study Provides New Detail on Disparities

Overall, only about half of Americans diagnosed with major depression in a given year receive treatment for it, and even fewer—about one fifth—receive treatment consistent with current practice guidelines, according to data from nationally representative surveys supported by NIMH. Among the ethnic/racial groups surveyed, African Americans and Mexican Americans had the lowest rates of use of depression care; all groups reported higher use of past-year psychotherapy vs. medication for depression.

Background

Depression is a leading cause of disability in the United States. Past research has found that many people with depression never received treatment, and that the percentage of those receiving treatment varies with ethnicity and race. In order to provide comprehensive and up-to-date information on depression care, with a particular emphasis on minority groups, NIMH’s Collaborative Psychiatric Epidemiology Surveys initiative (CPES) has combined data from three nationally representative studies: the National Survey of American Life, the National Comorbidity Survey-Replication, and the National Latino and Asian American Study.

This Study

Scientists at Wayne State University, Detroit, MI; the University of Michigan, Ann Arbor; the University of California, Los Angeles; and the Harvard School of Public Health, Boston, MA, carried out the current study, which reports on data from CPES collected between February 2001 and November 2003 from 15,762 residents 18 years and older. The size of the sample makes it possible to examine health care use in ethnic/racial groups with a new level of detail, distinguishing between groups often surveyed as one population. The investigators were able to break out types of care used, and to assess to what extent the care used was consistent with the American Psychiatric Association (APA) Practice Guidelines for the Treatment of Patients with Major Depressive Disorder. Finally, they examined how factors enabling healthcare access—insurance, education, and household income—influenced rates of care.

A central finding was that overall, 51 percent of all those in the study who met criteria for major depression during the prior year received some kind of treatment for it, with only 21 percent receiving care that was consistent with the APA Guidelines.

Other key study findings addressed disparities, types and quality of care received, and factors that enable access to healthcare.

• Prevalence and severity of major depression was similar among the five studied ethnic/racial groups—Mexican Americans, Puerto Ricans, Caribbean Blacks, African Americans, and non-Latino Whites. However, African Americans and Mexican Americans were least likely to receive any care or care consistent with practice guidelines. Compared with non-Latino Whites for example, of whom 54 percent with depression received care, 40 percent of African Americans and 34 percent of Mexican Americans did. The rate of care for Puerto Ricans was close to that of Whites, 50 percent.
• Across these population groups, psychotherapy was used more frequently than medications (pharmacotherapy). Overall, 34 percent received pharmacotherapy; 45 percent psychotherapy. Psychotherapy was more likely to be consistent with APA guidelines than pharmacotherapy, suggesting that adherence—the extent to which patients completed the recommended therapy—was greater for psychotherapy than pharmacotherapy. The contrast between the rates of Guideline-consistent psychotherapy and pharmacotherapy use was greatest among Caribbean Blacks, African Americans, and Mexican Americans.
• Puerto Ricans had rates of treatment use, and treatment that was consistent with care guidelines, that were similar to, or higher than, non-Latino Whites.
• Differences in factors enabling healthcare access appeared to contribute substantially to disparities in mental healthcare use, particularly for Mexican Americans. When differences in these enabling factors were controlled for statistically—so in effect, the population groups being compared had the same rates of enabling factors—the degree of disparities in use of care by Mexican Americans was reduced. For Caribbean Blacks and African Americans, statistical control of enabling factors reduced disparities in psychotherapy use, but not use of pharmacotherapy.
• Health insurance coverage was associated with a greater likelihood of depression care, but not guideline consistent care. The pattern with education was reversed: education was associated with a greater likelihood of care that was consistent with the APA Guidelines, but not with greater use of care in general.

Significance

This study, with its large sample size and emphasis on minority groups, provides a more nuanced and detailed picture of the care received for major depression among different ethnic/racial groups and of factors that contribute to disparities. Lead author Hector González at Wayne State University said that Mexican-Americans make up over two-thirds of Latinos in the U.S.: “We found in our study that there are some really distinctive differences in mental healthcare use between Mexican Americans and other Latino subgroups that have not been previously reported.” Estimates suggest that Latinos will make up close to one-third of the U.S. population by mid-century; the study findings suggest that Mexican Americans should be a focus of efforts to reduce health disparities to ensure the nation’s health in coming decades.

All groups were more likely to have received psychotherapy than pharmacotherapy. Caribbean Blacks and African Americans were particularly unlikely to receive pharmacotherapy consistent with APA guidelines; enabling factors such as education, health insurance, and income did not explain the lower rates of medication use. The authors note possible reasons for this, including research indicating that perceived discrimination can shape health care seeking. They speculate that the non-immigrant status of Puerto Ricans—and with that, greater predominance of English language use within this group—may be factors in their relatively high rates of health care use.

Findings from this study will inform future research on adherence to various depression therapies, and the factors that shape differences in care among racial/ethnic groups. “Future studies,” say the authors, “should explore the extent to which patients’ subjective experiences of racial bias may affect their access and utilization of mental healthcare.”

Reference

González, H.M., Vega, W.A., Williams, D.R., Tarraf, W., West, B.T., and Neighbors, H.W. Archives of General Psychiatry 2010;67(1):37-4

Wellstone-Domenici Act Goes Into Effect January 1

Contact: Steve Vetzner, (703) 797-2588 or svetzner@mentalhealthamerica.net

ALEXANDRIA, Va. (December 28, 2009) – Mental Health America today called for intensive education efforts to inform the public about the benefits of the new federal mental health parity law (the Paul Wellstone and Pete Domenici Mental Health Parity and Addiction Equity Act ), which becomes fully effective this Friday, January 1.

The law, which Congress passed in October of 2008, broadly outlaws health insurance discrimination against Americans with mental health and substance use conditions in employer-sponsored health plans.

It bans employers and insurers from imposing stricter limits on coverage for mental health and substance use conditions than those set for other medical conditions. The law benefits 82 million Americans covered by self-insured plans and another 31 million in plans that are subject to state regulation. (Fact sheets and background information can be viewed here.)

Mental Health America, which worked for years to pass the law, said public education efforts will ensure Americans are aware of their rights. A recent review of the experience with California’s mental health parity law concluded that public education campaigns are needed to inform individuals about the law and that those efforts could also help reduce the stigma around mental health conditions. It also recommended a system be established to monitor not only cost and coverage issues, but access to and quality of care.

“Parity is a milestone, but given how integral mental health is to overall health we have to raise public awareness,” said David L. Shern, Ph.D., president and CEO of Mental Health America. “With economic problems making it even harder for Americans to afford treatment and driving up rates of depression and family difficulties, the new law is especially important.”

Mental Health America has also urged the three federal departments charged with writing implementing regulations (Labor, Health and Human Services, and Treasury) to reflect the clear Congressional intent of the law. The regulations, which were expected to be published by this fall, are now not likely to be issued until January.

Dr. Shern said employers should embrace parity and recognize the value of providing mental health and substance use care. The findings of at least one recent survey suggest that few employers will drop mental health coverage because of the new law.

“The passage of parity recognized that we have to address mental health and substance use issues with same urgency and on the same level as other medical problems,” he said. “Those who believe parity is costly are making a huge mistake. The real cost is not treating mental health and substance use conditions.”

A number of studies have found that equalizing specialty behavioral health and general medical benefits will not increase total health care expenses at all or will increase them by only a very modest amount. In a landmark report, the National Business Group on Health said the indirect costs associated with mental health and substance use conditions-excess turnover, lost productivity, absenteeism and disability-commonly meet or exceed the direct treatment costs, and have been estimated to be at lest $105 billion annually.

Dr. Shern said the passage of parity has helped elevate the attention paid to mental health and substance use during the health reform debate. Both the House and Senate health reform bills would require that newly issued health plans offer an essential benefits package that includes mental health and substance use services.  A parity requirement would also apply to these new plans.

ARLINGTON, Va. (Dec. 15, 2009) – A nationwide study found that suicide rates for HIV patients in Switzerland decreased by more than half, after 1996 when the highly active antiretroviral therapy (HAART) was introduced. Despite the dramatic decrease, the suicide rate among HIV-infected individuals still significantly exceeded that of the general population. The study also showed that the majority of HIV patients who died by suicide (62%) had a mental illness diagnosis.

The findings from this nationwide Swiss study by Olivia Keiser, Ph.D., and colleagues from the University of Bern will appear on December 15 at AJP in Advance, the online advance edition of The American Journal of Psychiatry (AJP), the official journal of the American Psychiatric Association.

Keiser et al. found that the reduction in suicide risk after the introduction of retroviral therapy was associated with an increase in CD4 white blood cells, indicating an improvement in HIV disease status. In the pre-HAART era, high suicide rates were driven by disease progression, which at that time could not be prevented.

Although suicide rates have declined, there still remains a serious public health concern that HIV patients are not receiving proper mental health treatment. . Substantial proportions of HIV patients—both before and after antiretroviral therapy was introduced —had not been treated for their mental condition.

“HAART is not a cure,” Keiser explained “Even though the rates of suicide and untreated mental illness in HIV patients have declined, they’re both still high and warrant increases in mental health screening and access to pharmacological and psychological treatment for these patients,”

Data was provided by the Swiss National Cohort and the Swiss HIV Cohort Study, which are funded by the Swiss National Science Foundation. The Swiss HIV Cohort Study is one of the oldest HIV cohort studies worldwide and includes about 40% of all HIV-positive patients in Switzerland and about 70% of all patients with AIDS.

The American Journal of Psychiatry is the oldest continuously published medical specialty journal in the United States and was recently named one of the “Most Influential Journals in Biology & Medicine of the Last 100 Years.” Statements in this press release or the articles in the Journal are not official policy statements of the American Psychiatric Association.

The American Psychiatric Association is a national medical specialty society whose 38,000 physician members specialize in diagnosis, treatment, prevention and research of mental illnesses including substance use disorders. Visit the APA at www.psych.org and www.HealthyMinds.org.

Deleting one type of neurotransmitter receptor in a specific population of brain cells can induce schizophrenia-like behavior in mice, but only when the receptor is deleted early in development, according to a study by NIMH intramural scientists. The work provides strong support for previous observations implicating these receptors in psychosis; further, the mice provide a model of how psychotic symptoms can arise from a disruption in neuronal development, consistent with observations of how schizophrenia emerges in humans.

Background

Glutamate is the brain’s chief excitatory signaling molecule, or neurotransmitter, lowering the threshold at which neurons will fire and send a signal to adjacent neurons. Past studies have shown that drugs that shut down a specific type of receptor for glutamate—the NMDA receptor (NMDAR)—cause psychotic symptoms that resemble schizophrenia. That observation has led to a theory that psychosis in schizophrenia can be traced to reduced NMDAR function. Past work has also implicated a specific population of cells—interneurons—in schizophrenia. Interneurons function as integrating connectors between other neurons. Signaling by interneurons characteristically involves the inhibitory neurotransmitter GABA, which, contrary to glutamate, acts to slow the pace of neuronal activity.

This Study

To explore whether reduced NMDAR function in interneurons could cause psychosis, scientists in NIMH’s intramural program, led by Dr. Kazu Nakazawa, used a technique that allowed them to create mouse lines in which an essential subunit of the NMDA receptor was deleted (“knocked out”), but only in interneurons in areas of the brain (the cortex and hippocampus) that are thought to be particular targets of reduced NMDAR function. The method they used allowed them to create mouse lines in which they could vary the timing of the deletion: in one mouse line, the deletion was evident early in postnatal development; in the other, the deletion took place after the mice had reached adulthood.

By four weeks of age, a time period that corresponds roughly to infancy in humans, NMDA receptors were knocked out in one of the mouse lines. After a delay of several weeks, testing showed a number of types of behaviors analogous to schizophrenia in humans. As in humans, there was a latency, or prodromal period, before signs of abnormal behavior became apparent.

In tests of exploratory behavior, the knockout mice showed signs of hyper-reactivity and increased anxiety. They also showed reduced appetite for sweet solutions and deficits in nesting and mating, all signs that parallel the negative symptoms seen in schizophrenia: a lack of pleasure in everyday activities, and a reduced ability to plan and carry out tasks. Social and working memory were also affected in the mice. In another parallel to human schizophrenia, symptoms showed up earlier in mice that had been raised for several weeks in isolation, a form of social stress. Finally, no symptoms appeared in mice in which the NMDA receptors were knocked out after 12 weeks.

Significance

In this study, reduced function of NMDA receptors in a specific population of cells was sufficient to cause symptoms resembling schizophrenia in humans, providing the first direct evidence that these cell receptors are central in the origin of psychosis. The fact that the symptoms developed over time, and only when the receptors were deleted in younger mice, also depicts a process consistent with the view of schizophrenia as a disease in which a failure in one type of neuronal signaling throws off the normal formation of neuronal connections (synapses) and leads to disease.

What’s Next

This knockout mouse provides a model for exploring the role of NMDA receptors in schizophrenia. Future studies will address what could cause reduced NMDAR function in people with schizophrenia; how disrupted regulation of this receptor causes symptoms and how stress exacerbates them; and how currently-used medications work to alleviate symptoms. Ultimately, understanding these processes will provide the basis for developing new, targeted medications.

A provocative aspect of these results is that deleting the receptor in adult mice failed to cause symptoms, a surprise given the fact that drugs with an analogous effect on the receptor cause symptoms in adult humans and animals. A question for future research is whether the drugs that target NMDA receptors also have broader actions that explain their ability to cause psychosis. In addition, the study found that deleting a receptor for glutamate—which is excitatory—resulted in increased, not decreased, activity of neurons in the cortex. The explanation may be related to regulation by glutamate of interneuron activity, which is in turn GABA-based and inhibitory.

Reference

Belforte, J.E., Zsiros, V., Sklar, E.R., Jiang, Z., Yu, G., Li, Y., Quinlan, E.M. and Nakazawa, K. Postnatal NMDA receptor ablation in corticolimbic interneurons confers schizophrenia-like phenotypes. Nature Neuroscience published online 11/15/2009; doi: 10.1038/nn.2447

Treatment that includes medication plus a structured training program for parents reduces serious behavioral problems in children with autism and related conditions, according to a study funded by the National Institute of Mental Health (NIMH). The study, which was part of the NIMH Research Units on Pediatric Psychopharmacology (RUPP) Autism Network, was published in the December 2009 issue of the Journal of the American Academy of Child and Adolescent Psychiatry.

Results from a previous RUPP study reported in 2002 showed that the antipsychotic medication risperidone (Risperdal) reduced such behavior problems as tantrums, aggression and self-injury in children with autism. However, most children’s symptoms returned when the medication was discontinued. Although effective, risperidone is associated with adverse effects such as weight gain, which can lead to metabolic changes, obesity and related health problems.

“Medication alone has been shown to help with some symptoms of autism, but its potential is limited,” said NIMH Director Thomas R. Insel. “This study shows promise of a more effective treatment protocol that could improve life for children with autism and their families.”

In the study, the RUPP group tested the benefits of medication alone compared to medication plus a parent training program that actively involves parents in managing their children’s severely disruptive and noncompliant behavior. Parents were taught to modify their children’s behavior and learned to enhance their children’s daily living skills.

The 24-week, three-site trial included 124 children ages 4 to 13 with pervasive developmental disorders (PDD) such as autism, Asperger’s or related disorders accompanied by tantrums, aggression and self-injury. The children were randomized to a combination of risperidone and parent training, or to risperidone only. Parents in combination therapy received an average of 11 sessions of training over the course of the study.

Although both groups improved over the six-month trial, the group receiving combination therapy showed greater reduction in behavioral problems like irritability, tantrums and impulsiveness compared to the group receiving medication only. The combination therapy group also ended the trial taking an average dose of 1.98 milligrams (mg) per day of risperidone, compared to 2.26 mg/day in the medication-only group—a 14-percent lower dose. However, children in both groups gained weight, indicating “a need to learn more about the metabolic consequences of medications like risperidone,” said the authors.

“The combination group was able to achieve its gains with a lower dose of medication. Plus, it appeared that the benefits of added behavioral treatment increased over time, a strong signal that actively including parents in the treatment of children with PDD could only benefit families, ” said lead author Michael Aman, Ph.D., of the Ohio State University.

“Future studies will evaluate whether the benefits of parent training endure over a long period of time,” concluded the authors. The investigators also plan to apply the parent training to younger children with PDD to prevent the evolution of serious behavioral problems. Future studies may also look for ways in which the parent training program can be used in schools and community clinics.

Reference

Aman MG, McDougle CJ, Scahill L, Handen B, Arnold LE, Johnson C, Stigler KA, Bearss K, Butter E, Swiezy NB, Sukhodolsky DD, Ramadan Y, Pozdol SL, Nikolov R, Lecavalier L, Kohn AE, Koenig K, Hollway JA, Korzekwa P, Gavaletz A, Mulick JA, Hall KL, Dziura J, Ritz L, Trollinger S, Yu S, Vitiello B, Wagner A, for the Research Units on Pediatric Psychopharmacology Autism Network. Medication and parent training in children with pervasive developmental disorders and serious behavior problems: results from a randomized clinical trial. Journal of the American Academy of Child and Adolescent Psychiatry. 2009 Dec. 48(12):1143-1154.

Might Aberrant Neuronal “Avalanches” Signal Mental Illness?

Even when we’re not doing much of anything, our brain’s cortex, or outer mantle, is bustling with activity. In fact, scientists for the first time have detected “avalanches” of cortex activity in awake monkeys at rest.

They’ve also discovered that these bursts of synchronous neuronal activity aren’t just random, but rather precisely ordered. Large avalanches are followed by smaller and smaller avalanches, much like the aftershocks of an earthquake. This type of ordering reveals that the normal state of cortex circuitry is at a tipping point: at the edge of instability — like rocks along an earthquake fault.

“Mental illness may involve disturbances in this delicate balance, and abnormal avalanche patterns are potentially detectable,” explained NIMH’s Dietmar Plenz, Ph.D. “Being in such a state of instability allows neurons to telegraph information optimally across varying distances and to quickly adapt to new challenges. This makes it possible for the cortex to grow through development and expand through evolution without changes in its architecture.”

Plenz and colleagues report on their study of neuronal avalanches online during the week of August 24, 2009 in the Proceedings of the National Academy of Sciences.

Background

Understanding the cortex’s complex functional architecture has posed challenges for researchers. Plenz’s earlier studies in cell cultures and brain slices suggested that cortex tissue is organized like grains of sand in a sand pile – with the potential for even a few grains to trigger large avalanches. Periods of relative calm are punctuated by the spontaneous, synchronous avalanches. To confirm these findings in intact, awake animals, Plenz and colleagues recorded electrical signals in different parts of the cortex of two monkeys that were resting in a chair.

Results of This Study

The researchers observed avalanches, synchronous bursts of neural activity across varying expanses of cortex, in a pattern that implies a specific structure. The neuronal avalanches seem to obey laws similar to those that characterize their geological counterparts. Again like earthquakes, smaller avalanches are more common than bigger ones. Their size can range from involving clusters of cells to widespread networks.

“Avalanches function at any scale, bridging a 1 mm distance in the same way as they bridge a 10 mm distance as the brain develops or evolves,” explained Plenz.

Significance

The state of instability appears to be a general property of cortex tissue. There are hints that disorders of thinking, such as schizophrenia, could involve a breakdown in this critical state, leading to aberrant neuronal avalanche activity, say the researchers.

What’s Next?

Plenz and NIMH colleagues are studying this possibility using a non-invasive technique called magnetoencephalography (MEG), which images electrical activity deep in the brain. They are comparing cortex activity in schizophrenia patients and healthy controls, looking for quantifiable neural signatures of abnormal avalanche activity.

“If a brain doesn’t show the normal, synchronous avalanche pattern, this could signal a brain disorder,” said Plenz.

Even though the monkey was just resting in a chair, neuronal avalanches were spontanously sparking in its brain’s outer mantle, or cortex. Electrodes (black dots) detected these synchronous bursts (colored circles) of neural activity. The diameter and color of the circles reflects the varying size of the avalanches, which occurred as disparate clusters of synchronous activity. Despite their irregular appearances, the avalanche patterns are highly organized in space and time obeying precise rules similar to those found for earthquakes. This suggests that the cortex is normally organized in a state with the potential for such critical activity.

Reference

Spontaneous cortical activity in awake monkeys composed of neuronal avalanches. Petermann T, Thiagarajan TC, Lebedev MA, Nicolelis MA, Chialvo DR, Plenz D. Proc Natl Acad Sci U S A. 2009 Aug 26.

WASHINGTON—Every March, most Americans welcome the switch to daylight saving time because of the longer days, but also dread losing an hour of sleep after they move their clocks forward. Now a new study shows that losing just an hour of sleep could pose some dangerous consequences for those in hazardous work environments.

The findings are reported in the September issue of the Journal of Applied Psychology, which is published by the American Psychological Association.

“One hour of lost sleep may not seem like a lot. But our findings suggest it could have an impact on people’s ability to stay alert on the job and prevent serious injuries,” said the article’s lead author, Christopher Barnes, PhD. Barnes and co-author David Wagner, PhD, were both doctoral students in organizational behavior at Michigan State University when they conducted this research.

They analyzed the number of injuries reported to the Mine Safety and Health Administration from 1983 to 2006. The U.S. Department of Labor requires all mine operators to investigate and report all mining-related injuries. The researchers also looked at the number of work days employees missed as a result of their injuries. Across the 24 years, there were 576,292 reported injuries on the job.

On average, there were 3.6 more injuries on the Mondays following the switch to daylight saving time compared to other days, and 2,649 more days of work were lost as a result of those injuries. That’s approximately a 68 percent increase in lost work days. In their analysis, the researchers controlled for weekends and holidays. Work experience did not appear to play a role in the number of injuries suffered.

The researchers also confirmed that people do sleep less in the days after they’re forced to turn their clocks forward. They looked at data from the Bureau of Labor Statistics’ American Time Use Survey, which measures the amount of time Americans spend engaged in various activities, including sleep. For this study, the researchers looked at data from 14,310 interviews from 2004 to 2006. Results showed that after the switch to daylight saving time, people slept an average of 40 minutes less on the Sunday night they switched to daylight saving time.

The researchers did not find any significant changes in the number and severity of workplace injuries on the Mondays after the switch to standard time, when people gained an hour. Further analysis of the American Time Use Survey showed that people had a much easier time adjusting their sleep schedules and did not, on average, sleep less or more after they changed to standard time. These findings would help explain why there were no significant effects, according to Barnes.

The study could have some important practical implications for employers, Barnes said. “We think managers and organizations can use this information to help improve safety in the days following the switch to daylight saving time,” he said. “They can schedule particularly dangerous work on other days, perhaps later in the week after employees have had more time to adjust their sleep schedules.” Another suggestion would be to implement extra safety precautions on those days.

Article: “Changing to Daylight Saving Time Cuts Into Sleep and Increases Workplace Injuries,” Christopher M. Barnes, PhD, and David T. Wagner, PhD, Michigan State University; Journal of Applied Psychology, Vol. 94, No. 5

(Full text of the article is available from the APA Public Affairs Office and at http://www.apa.org/journals/releases/apl9451317.pdf)

Contact Christopher Barnes by e-mail; his phone number is (517) 214-0438.

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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.

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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