NIMH, the NIH Office of Behavioral and Social Sciences Research, and the National Institute of Justice (NIJ) have announced a significant collaboration on a new 4-year, $6.8 million study called Suicide Prevention for at-Risk Individuals in Transition or “SPIRIT.” The study will address a critical gap in evidence-based suicide prevention and focus on the high-risk individuals who are transitioning from jail to community. The study is NIMH’s largest major investment in suicide prevention in the justice system.

Jennifer E. Johnson, Ph.D ., C. S. Mott Endowed Professor of Public Health, Michigan State University College of Human Medicine, andLauren M. Weinstock,  Ph.D., Associate Professor of Psychiatry and Human Behavior (Research) at Brown University and Clinical Psychologist at Butler Hospital are co-principal investigators on the study.

With nearly 12 million admissions per year and short stays, US jails serve as a catchment area for at-risk individuals at a time of high life stress and high suicide risk, providing an important opportunity for suicide prevention intervention. In fact, about 10 percent of all those who die by suicide are estimated to have had some type of recent criminal legal stressor (often an arrest and jail detention). Recent data from justice settings show high rates of suicide during jail detention (46 deaths per 100,000 people). Studies of post-release detainees find even higher rates (almost 3 times higher) of suicide deaths in the year following release. This study uses the jail setting as an opportunity to prevent suicide among high-risk individuals as they return to the community.

SPIRIT will use trained community mental health center providers to test a practical approach to reducing suicide by comparing it to standard care. SPIRIT researchers plan to enroll 800 detainees as they leave two different community jails: Genesee County Jail in Flint, Michigan and Rhode Island Department of Corrections in Cranston, Rhode Island. Participants will randomly be assigned to either standard care or the Safety Planning Intervention with telephone follow-up. Researchers will track improvements in suicidal behavior, and psychiatric and substance abuse outcomes as well as service use and re-arrest rates for both types of care. Findings from the research comparing the two types of care will help correctional setting and behavioral health program directors identify more effective programs for suicide prevention.

Patients taking medications to treat bipolar disorder are more likely to get well faster and stay well if they receive intensive psychotherapy, according to results from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD), funded by the National Institutes of Health’s (NIH) National Institute of Mental Health (NIMH). The results are published in the April 2007 issue of the Archives of General Psychiatry.Bipolar disorder is a debilitating illness marked by severe mood swings between depression and mania that affects 2.6 percent of Americans in any given year. “We know that medication is an important component in the treatment of bipolar illness. These new results suggest that adding specific, targeted psychotherapy to medication may help give patients a better shot at lasting recovery,” said NIH Director Dr. Elias A. Zerhouni.

“STEP-BD is helping us identify the best tools—both medications and psychosocial treatments—that patients and their clinicians can use to battle the symptoms of this illness,” said NIMH Director Thomas R. Insel, M.D.

Psychotherapy is routinely employed as a means to treat bipolar illness in conjunction with medication, but the extent to which psychotherapy is effective has been unclear. In addition, most psychotherapeutic studies have been limited to a single site and compared only one type of treatment to routine care. Thus, in addition to examining the role of medication, STEP-BD set out to compare several types of psychotherapy and pinpoint the most effective treatments and treatment combinations.

With 293 participants, David Miklowitz, Ph.D., of the University of Colorado and colleagues set out to test the effectiveness of three types of standardized, intensive, nine-month-long psychotherapy compared to a control group that received a three-session, psychoeducational program called collaborative care. The intensive therapies were

• family-focused therapy, which required the participation and input of patients’ family members and focused on enhancing family coping, communication and problem-solving;
• cognitive behavioral therapy, which focused on helping the patient understand distortions in thinking and activity, and learn new ways of coping with the illness; and
• interpersonal and social rhythm therapy, which focused on helping the patient stabilize his or her daily routines and sleep/wake cycles, and solve key relationship problems.

All participants were already taking medication for their bipolar disorder, and most were also enrolled in a STEP-BD medication studyreported in the New England Journal of Medicine on March 28, 2007. The researchers compared patients’ time to recovery and their stability over one year.

Over the course of the year, 64 percent of those in the intensive psychotherapy groups had become well, compared with 52 percent of those in collaborative care therapy. Patients in intensive psychotherapy also became well an average of 110 days faster than those in collaborative care. In addition, patients who received intensive psychotherapy were one and a half times more likely to be clinically well during any month out of the study year than those who received collaborative care. Discontinuation rates among the groups were similar—36 percent of those in the intensive programs discontinued and 31 percent of those in collaborative care discontinued. None of the three intensive psychotherapies appeared to be significantly more effective than the others, although rates of recovery were higher among those in family-focused therapy compared to the other groups.

“Intensive psychotherapy, when used as an adjunctive treatment to medication, can significantly enhance a person’s chances for recovering from depression and staying healthy over the long term,” said Dr. Miklowitz. “It should be considered a vital part of the effort to treat bipolar illness.”

A new study supports earlier estimates of the prevalence of bipolar disorder in the U.S. population, and suggests the illness may be more accurately characterized as a spectrum disorder. It also finds that many people with the illness are not receiving appropriate treatment. The study, published in the May 2007 issue of Archives of General Psychiatry, analyzed data from the National Comorbidity Survey Replication (NCS-R), a nationwide survey of mental disorders among 9,282 Americans ages 18 and older. The NCS-R was funded by the National Institutes of Health’s National Institute of Mental Health (NIMH).

NIMH researcher Kathleen Merikangas, Ph.D. and colleagues identified prevalence rates of three subtypes of bipolar spectrum disorder among adults. Bipolar I is considered the classic form of the illness, in which a person experiences recurrent episodes of mania and depression. People with bipolar II experience a milder form of mania called hypomania that alternates with depressive episodes. People with bipolar disorder not otherwise specified (BD-NOS), sometimes called subthreshold bipolar disorder, have manic and depressive symptoms as well, but they do not meet strict criteria for any specific type of bipolar disorder noted in the Diagnostic and Statistical Manual for Mental Disorders (DSM-IV), the reference manual for psychiatric disorders. Nonetheless, BD-NOS still can significantly impair those who have it.

The results indicate that bipolar I and bipolar II each occur in about 1 percent of the population; BD-NOS occurs in about 2.4 percent of the population. The findings support international studies suggesting that, given its multi-dimensional nature, bipolar disorder may be better characterized as a spectrum disorder.

“Bipolar disorder can manifest itself in several different ways. But regardless of type, the illness takes a huge toll,” said NIMH Director Thomas R. Insel, M.D. “The survey’s findings reiterate the need for a more refined understanding of bipolar symptoms, so we can better target treatment.”

Most respondents with bipolar disorder reported receiving treatment. Nearly everyone who had bipolar I or II (89 to 95 percent) received some type of treatment, while 69 percent of those with BD-NOS were getting treatment. Those with bipolar I or II were more commonly treated by psychiatric specialists, while those with BD-NOS were more commonly treated by general medical professionals.

However, not everyone received treatment considered optimal for bipolar disorder. Up to 97 percent of those who had some type of bipolar illness said they had coexisting psychiatric conditions, such as anxiety, depression or substance abuse disorders, and many were in treatment for those conditions rather than bipolar disorder. The researchers found that many were receiving medication treatment considered “inappropriate” for bipolar disorder, e.g., they were taking an antidepressant or other psychotropic medication in the absence of a mood stabilizing medication such as lithium, valproate, or carbamazepine. Only about 40 percent were receiving appropriate medication, considered a mood stabilizer, anticonvulsant or antipsychotic medication.

“Such a high rate of inappropriate medication use among people with bipolar spectrum disorder is a concern,” said Dr. Merikangas. “It is potentially dangerous because use of an antidepressant without the benefit of a mood stabilizer may actually worsen the condition.”

Merikangas and colleagues speculate that as people seek treatment for anxiety, depression or substance abuse disorders, their doctors, especially if they are not mental health specialists, may not be detecting an underlying bipolar condition in their patients.

“Because bipolar spectrum disorder commonly coexists with other illnesses, it is likely underrecognized, and therefore, undertreated. We need better screening tools and procedures for identifying bipolar spectrum disorder, and work with clinicians to help them better spot these bipolar symptoms,” concluded Dr. Merikangas.

Reference

Merikangas KR, et al. Lifetime and 12-Month Prevalence of Bipolar Spectrum Disorder in the National Comorbidity Survey Replication.Archives of General Psychiatry. May 2007; 64.

Two new studies provide additional details on best practices for treating people with bipolar disorder, a sometimes debilitating illness marked by severe mood swings between depression and mania. The two studies are part of the NIMH-funded Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). Both were published in the September 2007 issue of the American Journal of Psychiatry.

Antidepressants provide no added benefit for people with mixed symptoms, and may worsen existing mania

Among STEP-BD participants who experienced manic symptoms while also in the midst of a depressive episode, those who received antidepressant medication along with a mood stabilizer recovered no faster than those who received a mood stabilizer plus placebo (sugar pill). The results, reported by Joseph Goldberg, M.D, of the Mount Sinai School of Medicine, and colleagues, are consistent with the March 2007 STEP-BD results that indicated a mood stabilizer alone appears to be just as effective as a mood stabilizer plus antidepressant for treating bipolar patients in a major depressive episode.

Moreover, Goldberg and colleagues found that at the three-month follow-up, manic symptoms were more severe among those who had received the antidepressant, compared to those who had received the placebo. Hence, the researchers caution that adjunctive antidepressant medication may actually exacerbate existing manic symptoms.

Intensive psychotherapies improve relationships and life skills

STEP-BD participants who received intensive psychotherapy in addition to medication reported better life satisfaction and better relationship skills than those who received only brief therapy and medication. However, patients in intensive psychotherapy fared no better in vocational skills.

David Miklowitz, PhD., of the University of Colorado, and colleagues evaluated participants’ improvements in relationship, life and work skills over a nine-month period of psychotherapy. Participants received one of three types of psychotherapy:

• Family-focused therapy (FFT), which required the participation and input of participants’ family members and focused on enhancing family coping with the illness, communication, and problem-solving.
• Cognitive behavioral therapy (CBT), which focused on helping the person understand distortions in thinking and activity, and learn new ways of coping with the illness.
• Interpersonal and social rhythm therapy (IPSRT), which focused on helping the participant stabilize his or her daily routines and sleep/wake cycles, and solve key relationship problems.

All three therapies incorporated ways to overcome life challenges, such as finding a place to live, finding a satisfying job, or improving personal finances. They also taught participants strategies for managing mood states that interfere with enjoyment of activities.

Previous STEP-BD results reported in April 2007 revealed that those participants who received any of the three intensive psychotherapies recovered from depression faster and stayed well longer than those who received a brief, three-session educational program. In this follow-up study, the researchers found that although relationship skills improved and participants felt more satisfied with life overall, they reported little or no improvement in their work functioning.

Miklowitz and colleagues suggest that a different approach that targets specific vocational skills may be necessary. For example, certain vocational rehabilitation programs designed for people with schizophrenia may be adapted to the needs of people with bipolar disorder.

Colleen Labbe

Five major mental disorders share some of the same genetic risk factors, the largest genome-wide study of its kind has found. Evidence for such genetic overlap had previously been limited to pairs of disorders.

National Institutes of Health-funded researchers discovered that people with disorders traditionally thought to be distinct – autism, ADHD, bipolar disorder, major depression and schizophrenia – were more likely to have suspect genetic variation at the same four chromosomal sites. These included risk versions of two genes that regulate the flow of calcium into cells.

“These results will help us move toward diagnostic classification informed by disease cause,” said Jordan Smoller, M.D. , of Massachusetts General Hospital, Boston, a coordinator of the study, which was supported by NIH’s National Institute of Mental Health. “Although statistically significant, each of these genetic associations individually can account for only a small amount of risk for mental illness, making them insufficient for predictive or diagnostic usefulness by themselves.”

Smoller, Kenneth Kendler, M.D., , Virginia Commonwealth University, Richmond; Nicholas Craddock, PhD. , Cardiff University, England;Stephan Ripke, M.D. , Massachusetts General, Patrick Sullivan, M.D. , University of North Carolina at Chapel Hill, and colleagues in the Cross-Disorder Group of the Psychiatric Genomics Consortium, report on their findings February 28, 2013 in The Lancet.

Prior to the study, researchers had turned up evidence of shared genetic risk factors for pairs of disorders, such as schizophenia and bipolar disorder, autism and schizophrenia and depression and bipolar disorder. Such evidence of overlap at the genetic level has blurred the boundaries of traditional diagnostic categories and given rise to research domain criteria, or RDoC, an NIMH initiative to develop new ways of classifying psychopathology for research based on neuroscience and genetics as well as observed behavior.

To learn more, the consortium researchers analyzed the five key disorders as if they were the same illness. They screened for evidence of illness-associated genetic variation across the genomes of 33,332 patients with all five disorders and 27,888 controls, drawing on samples from previous consortium mega-analyses.

For the first time, specific variations significantly associated with all five disorders were among several suspect genomic sites that turned up. These included variation in two genes that code for the cellular machinery for regulating the flow of calcium into neurons. Variation in one of these, called CACNA1C, which had previously been implicated in susceptibility to bipolar disorder, schizophrenia and major depression, is known to impact brain circuitry involved in emotion, thinking, attention and memory – functions disrupted in mental illnesses. Variation in another calcium channel gene, called CACNB2, was also linked to the disorders.

Alterations in calcium-channel signaling could represent a fundamental mechanism contributing to a broad vulnerability to psychopathology, suggest the researchers.

They also discovered illness-linked variation for all five disorders in certain regions of chromosomes 3 and 10. Each of these sites spans several genes, and the specific causal factors within them remain elusive. However, one region, called 3p21, which produced the strongest signal of illness association, harbors suspect variations identified in previous genome-wide studies of bipolar disorder and schizophrenia.

References

Cross-Disorder Group of the Psychiatric Genomics Consortium. Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis. The Lancet, February 28, 2013