Same Genes Suspected in Both Depression and Bipolar Illness

Increased Risk May Stem From Variation in Gene On/Off Switch
Source: UCSC Genome BrowserResearchers, 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. LPCC Continuing Education
"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

Preference for Moving Shapes vs. People Linked to Autism in Babies

A 1-minute video showing computer screensavers next to videos of dancing children may prove to be a simple, inexpensive screening tool for autism spectrum disorders (ASD) in toddlers. According to an NIMH-funded study, infants as young as 14 months old who had autism spent more time looking at the moving shapes than social images, in contrast to typically developing children and those who had delays but not autism. The study was published online, September 6, 2010, in the Archives of General Psychiatry. Alcoholism and Drug Abuse Counselors Continuing Education


Background
Among the hallmark signs of ASD are repetitive behaviors, which may include persistent and intense preoccupation with objects. For example, a child with ASD may fixate on moving objects or parts of objects, like the moving blade of a fan or spinning tires on a car. Whether this behavior could predict or identify ASD in very young children had not previously been studied.

About the study
To study this phenomenon, Karen Pierce, Ph.D., at the University of California San Diego School of Medicine, and colleagues enrolled 110 toddlers, ages 14-42 months. Of this group, 37 had ASD, 22 were developmentally delayed (DD) but did not have ASD, and 51 had typical development (TD).

The toddlers viewed a 1-minute video showing geometric patterns on one side—basically a computer screensaver—and children exercising, dancing, or otherwise in action on the other side. Using eye tracking technology, the researchers measured how long the toddlers looked at each type of movement and how many times they switched from looking at one type or part of an image to another.

Results
In this study, 40 percent of toddlers with ASD spent significantly more time fixating on moving geometric patterns compared with 9.9 percent in the DD group and 1.9 percent of TD children. The other 60 percent of toddlers with ASD performed similarly to their DD and TD peers, showing a preference for social movement. If a toddler spent more than 69 percent of the time fixating on geometric patterns, ASD could be predicted 100 percent of the time.

While viewing the video, DD and TD children tended to let their eyes wander, changing their focus from one part of an image to another. Among toddlers with ASD, however, those who preferred geometric patterns showed significantly less eye movement when viewing geometric patterns, gazing at only a few parts of an image for extended periods of time. These children also showed significantly more frequent eye movement than DD or TD toddlers when viewing social movement.

A subsample of 41 toddlers were re-tested an average of 8 months later. The researchers found that the toddlers' preferences generally stayed the same between the original study and the follow-up.

Significance
The results suggest that assessing infants' visual preference for geometric vs. social movement, including the amount of time they spend staring at moving geometric patterns, is an inexpensive and easy-to-conduct screening method for ASD.

"What an infant prefers to look at when given a choice between two images may turn out to be a more clearly observable indicator of autism risk than how he or she looks at a single image," Pierce said.

That most of the toddlers with ASD in this study responded in the same way as DD and TD children came as a surprise to the researchers. They suggest that differing patterns of brain activity may underlie toddlers' preference for geometric or social movement. Brain imaging studies would help to confirm whether subgroups of ASD can be distinguished by brain activity patterns.

What's Next
According to the researchers, this screening tool may also be useful in identifying babies who would benefit from further developmental evaluation or even early treatment. The findings also provide new lines of inquiry regarding the role of various brain regions involved in processing social cues and shifting attention in the development of ASD.

Sample "social" image (left) and "geometric" image (right) from Pierce's eye tracking study. Forty percent of babies later diagnosed as having autism preferred to look at the moving geometric images, in contrast to just 2 percent of typically developing babies.

Source: Karen Pierce, Ph.D., UC San Diego

Reference
Pierce K, Conant D, Hazin R, Stoner R, Desmond J. A Preference for Geometric Patterns Early in Life is a Risk Factor for Autism. Arch Gen Psychiatry. 2010 Sep 6. [Epub ahead of print]

Social Phobia Patients Have Heightened Reactions to Negative Comments

In a study using functional brain imaging, NIMH scientists found that when people with generalized social phobia were presented with a variety of verbal comments about themselves and others ("you are ugly," or "he's a genius," for example) they had heightened brain responses only to negative comments about themselves. Knowledge of the social cues that trigger anxiety and what parts of the brain are engaged when this happens can help scientists understand and better treat this anxiety disorder. LPC Continuing Education
Background

Generalized social phobia (GSP) is the most common of all anxiety disorders. It is marked by overwhelming anxiety and self-consciousness in social situations. One approach to understanding anxiety disorders is to use functional brain imaging (fMRI) to explore how the brain responds to different types of social signals. fMRI can provide information on the relative activity—and thus the engagement—of different parts of the brain by tracking the local demands made for oxygen delivered by circulating blood. Scientists using this technology have reported, for example, that people with GSP have heightened responses to a variety of positive, negative, and neutral facial expressions, not just expressions that others perceive as threatening.

Results of this Study

People with GSP had heightened responses to negative comments (relative to a comparison group without the disorder) in two brain areas: the first, the medial prefrontal cortex (MPFC), is involved in the sense and evaluation of self; the second, the amygdala, is central to emotional processing. The responses revealed by scanning paralleled the participants' self-report of how they felt after seeing the various positive, negative, and neutral comments presented.

Significance

This work, conducted by NIMH intramural investigators Karina Blair, Ph.D., Daniel Pine, M.D., and colleagues, provided information on the specific social cues that trigger anxiety in people with GSP. It adds to previous evidence that the amygdala is involved and, in implicating the MPFC, gives clues for further research to explore on how people with GSP interpret social cues. Functional brain scanning can thus help to define patterns of brain functioning that underlie anxiety disorders, providing information that can inform treatment.

What's Next?

A previous study by these investigators found that the reaction of the brain to facial expressions was different in people with GSP than in those with general anxiety disorder (GAD). This suggests that the two disorders do not represent mild and severe forms in a single spectrum of anxiety disorders, but two neurologically different disorders.

Continuing research will reexamine these differences to see if they occur across different tasks, providing confirmation for understanding them as different disorders, which could lead to more targeted and effective forms of treatment for each disorder. Future studies will also explore more deeply the nature of the thought process underlying the reaction of people with GSP to negative comments about themselves and the interaction of the amygdala and MPFC. Finally, brain scanning offers a means to study the effects of treatment; scanning can, for example, provide information on the effects of medications in these parts of the brain.


Left amygdala (left) and medial prefrontal cortex (circled in yellow, right) activated strongly in people with social phobia (in comparison to those without GSP) in response to criticism of themselves.

References
Blair, K. et al. American Journal of Psychiatry. 2008 Sep;165(9):1193-202. Epub 2008 May 15. PMID: 18483136

Blair, K. et al. Archives of General Psychiatry. 2008 Oct;65(10):1176-1184.

Brain Activity Patterns in Anxiety-Prone People Suggest Deficits in Handling Fear

Anxiety as a personality trait appears to be linked to the functioning of two key brain regions involved in fear and its suppression, according to an NIMH-funded study. Differences in how these two regions function and interact may help explain the wide range of symptoms seen in people who have anxiety disorders. The study was published February 10, 2011 in the journal, Neuron. Social Worker Continuing Education
Background
Anxiety disorders are characterized by an excessive, irrational dread of everyday situations. Some people may experience general, chronic anxiety, while others become anxious in response to one or more specific triggers. Many studies have implicated two brain regions in anxiety—the amygdala in fear responses and the ventral prefrontal cortex (vPFC) in suppressing or regulating fear. Questions remain, however, about how trait anxiety—a person's typical anxiety level on any given day—affects amygdala and vPFC functioning.

To explore these questions, Sonia Bishop, Ph.D., of the University of California Berkeley (at the University of Cambridge (UK) at the time of data collection), and colleagues designed a series of experiments to determine how the amygdala and vPFC responded in three types of situations:

Cued fear—a neutral signal or cue is followed by an aversive event. In this study, the cue was an actor in a video placing his hands over his ears and the aversive event was a loud scream. The cue provided a reliable prediction of the aversive event. Cued fear can be compared to the situation-specific type of anxiety experienced by those with a specific phobia, such as a fear of heights.
Contextual fear—a neutral cue and an aversive event occur independently of each other. The cue did not provide a reliable prediction of the aversive event. Contextual fear may be similar to the non-specific anxiety that affects people with generalized anxiety disorder.
Safety—a neutral signal or cue occurs alone without an aversive event. The safety situation served as a comparison for the other two situations.
The researchers assessed the level of trait anxiety of 23 healthy study participants, ages 18 to 41. Each participant underwent a training session that exposed them to the above conditions. Two days after the training session, participants had their brain activity recorded through functional magenetic resonance imaging (fMRI), a noninvasive imaging method, while re-exposed to the cued fear, contextual fear, and safety conditions in the scanner.

Results from the Study
Participants with high trait anxiety showed greater amygdala response to cued fear situations compared to those with low trait anxiety. According to the researchers, this finding suggests that individual differences in amygdala response may contribute to differences in vulnerability to cue-specific anxiety disorders, such as specific phobia.

Participants with low trait anxiety showed increased vPFC activity in response to cued fear and more strongly sustained vPFC activity during contextual fear situations, compared to those with high trait anxiety. Notably, vPFC activity in participants with low trait anxiety occurred before the aversive event had ceased. The researchers suggest that this process—engaging brain areas that help to suppress fear even when the source of fear is still present—may help to protect against chronic anxiety disorders even when stressful life events are ongoing.

Significance
The study's findings support a potential role of the amygdala in vulnerability to anxiety disorders and a potential role of the vPFC in protection against them.

"Individual differences in the functioning of one or both of these brain regions may help account for the variability in symptoms across different anxiety disorders," said Bishop. "A better understanding of these processes may help inform treatment choice and predict treatment response."

This study was supported in part by a Biobehavioral Research Award for Innovative New Scientists (BRAINS) from NIMH. Dr. Bishop was one of 12 researchers to receive this award in 2010.

Reference
Indovina I, Robbins TW, Núñez-Elizalde AO, Dunn BD, Bishop SJ. Fear-Conditioning Mechanisms Associated with Trait Vulnerability to Anxiety in Humans. Neuron. 2011 Feb 10;69(3):563-71.

Family-Focused Therapy Effective in Treating Depressive Episodes of Bipolar Youth

Adolescents with bipolar disorder who received a nine-month course of family-focused therapy (FFT) recovered more quickly from depressive episodes and stayed free of depression for longer periods than a control group, according to an NIMH-funded study published September 2008 in the Archives of General Psychiatry. MFT Continuing Education
In FFT, the patient and his or her family are heavily involved in psychosocial treatment sessions. They learn to identify the symptoms of bipolar disorder, its course, and how to spot impending episodes or relapses. Patients and families also learn communication and problem-solving skills, and illness management strategies. For this trial, David Miklowitz, Ph.D., of the University of Colorado, and colleagues adapted the therapy to the needs of adolescents and their families.

The 58 participants, ages 12 to 17, were recruited from the University of Colorado and the University of Pittsburgh, and randomly assigned to either 21 50-minute sessions of FFT or to a control intervention called enhanced care (EC). EC included three 50-minute sessions with patients and their families that focused on relapse prevention planning, taking medication as directed, and dealing with conflict at home. All participants took mood-stabilizing medication such as lithium as well. Participants were evaluated every three months during the first year of the two-year study and every six months in the second year.

Although the rate of recovery was high for all participants—91.4 percent—participants in the FFT group recovered faster from depressive symptoms than the EC group. This was especially pronounced in youths who were in the midst of a major depressive episode at the beginning of the study. In the FFT group, the average time to recovery from major depression was 10 weeks, compared to 14 weeks for the EC group. The FFT group also spent less time depressed—about three weeks compared to the EC group’s five weeks—and had less severe depressive symptoms over the two years than the EC group.

The results are similar to those of the NIMH-funded Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD), which found that adult participants who received up to 30 sessions of FFT, cognitive behavioral therapy, or interpersonal therapy plus mood stabilizing medications recovered more rapidly from depressive episodes than the participants who received only three psychoeducational sessions in addition to medication.

The adolescent participants in the new study eventually recovered from manic symptoms as well, but neither of the treatments showed a statistically significant advantage in treating mania, a finding also consistent with STEP-BD results. The researchers conclude that for full recovery from adolescent bipolar disorder, FFT may need to be augmented with psychoeducational interventions that are effective against mania symptoms.

Reference
Miklowitz DJ, Axelson DA, Birmaher B, George EL, Taylor DO, Schneck CD, Beresford CA, Dickinson M, Craighead WE, Brent DA. Family-focused treatment for adolescents with bipolar disorder. Archives of General Psychiatry. 2008 Sept; 65(9).

Key Molecule in Inflammation-Related Depression Confirmed

Scientists have confirmed the role of an immune-activated enzyme in causing inflammation-related depression-like symptoms in mice. The work clarifies how the immune system can trigger depression and, more broadly, demonstrates the potential of this animal model for exploring the relationship between chronic inflammation—a common feature of diseases such as heart disease, cancer, and diabetes—and depression. LPC Continuing Education
Background

When an individual is infected with viruses or bacteria, cells of the immune system respond by secreting proteins called cytokines. These cytokines not only trigger inflammation and orchestrate the body's immune response against the infection, but they also cause changes in behavior, such as fatigue and withdrawal. Beyond these commonly experienced behavioral signs of illness, previous research has shown that cytokines can also cause depression in people with physical illnesses but who have no prior history of mental illness. For instance, around one-third of patients receiving the cytokine interferon-α for treatment of cancer or hepatitis C develop major depression. Clinical evidence has suggested that an enzyme (IDO) activated by these same cytokines might be a key player.

This Study

In this work, scientists used a weakened form of the tuberculosis relative, bacille Calmette-Guérin (BCG), to model chronic inflammation. This strain of bacteria is used outside the U.S. as a vaccine for tuberculosis. Infection of mice with high doses of BCG persistently activates the immune system; as a consequence, the mice develop depressive-like behavior after initial signs of illness have subsided. This study demonstrated that mice in which the gene for IDO is knocked out, or in which IDO is chemically blocked, do not exhibit depressive-like effects. The authors conclude that IDO is a necessary step in the development of this immunity-related depression.

Significance

The compound used in this work to block IDO may have potential as a treatment for depression in instances when immunotherapy such as interferon-α is used. In addition, chronic, low-grade inflammation is a feature not only of infectious diseases, but conditions like cancer, diabetes, obesity, and heart disease. Depression co-occurs frequently with these common diseases and is associated with poorer prospects for future health. Work in this animal model has the potential to provide insight into the role of chronic inflammation in precipitating depression that is often associated with these chronic conditions.

Scientists at the University of Illinois, Urbana-Champaign, led by Jason O'Connor, Robert Dantzer, and Keith Kelley, conducted this work with collaborators at the Centre National de la Recherche Scientifique, Bordeaux, France, and Miles Herkenham at the National Institute of Mental Health. The National Institute of Mental Health and the National Institute on Aging funded this research.

What's Next

The use of BCG in this mouse model offers a means to explore the molecular cascade induced by IDO that leads to inflammation-associated depression. The exact mechanism by which IDO causes these depressive behaviors is not yet clear; exploration of the downstream effects of IDO may provide additional avenues for developing approaches to blocking the development of immune-related depression.

Reference
O'Connor, J.C., Lawson, M.A., Andre, C., Briley, E.M., Szegedi, S.S., Lestage, J., Castanon, N., Herkenham, M., Dantzer, R., and Kelley, K.W. Induction of IDO by Bacille Calmette-Guerin Is Responsible for Development of Murine Depressive-Like Behavior. Journal of Immunology 2009 Mar 1;182(5):3202-12. PMID: 19234218

Combination Treatment for Psychotic Depression Holds Promise

A combination of an atypical antipsychotic medication and an antidepressant known as a selective serotonin reuptake inhibitor (SSRI) may be more effective in treating psychotic depression than an atypical antipsychotic alone, according to results from an NIMH-funded clinical study. Social Worker Continuing Education
Background
Psychotic depression is characterized by major depression accompanied by symptoms such as hallucinations, delusions, and breaks with reality. A person with psychotic depression may be unwilling or unable to care for him or herself and often is admitted to the hospital. Typically, psychotic depression is treated with electroconvulsive therapy (ECT), known to be effective but not always acceptable to patients and their families. It is less commonly treated with an antipsychotic or an antipsychotic plus an antidepressant.

Results of the Study
In a 12-week trial, all 259 participants were required to have psychotic depression with at least one delusion or irrational belief, although not all had hallucinations. Participants were randomly assigned to one of two treatments—the atypical antipsychotic olanzapine (Zyprexa) plus the SSRI sertraline (Zoloft) (combination therapy), or to olanzapine plus a placebo, or inactive, pill (monotherapy). Barnett S. Meyers, M.D., of Cornell University, and colleagues compared rates of remission and side effects among the participants. They also compared the responses of the 117 patients younger than 60 with the responses of the 142 patients older than 60 to determine if the two age groups responded differently.

The researchers conducted assessments at the beginning of the trial, weekly for the first six weeks, and then every other week until week 12. They found that 42 percent of those on combination therapy remitted compared to 24 percent of those on the monotherapy, with no significant differences in remission rates between age groups. Combination therapy's superiority became most evident between weeks eight and 12 of the trial.

Overall, the two age groups experienced comparable side effects. Both groups experienced significant increases in cholesterol and triglyceride levels, and both gained weight. However, the younger age group gained twice as much on average—about 14 pounds—compared to the older group, which gained an average of 7 pounds. This finding is consistent with other reports that have found older adults tend to gain less weight with atypical antipsychotics, specifically olanzapine, the researchers said. However, older participants also tended to be on lower doses of the antipsychotic than the younger adults, which may partially explain the disparity in weight gain, according to the researchers.

Unexpectedly, older participants had no more difficulty tolerating the medications than younger participants, nor were they any more likely to experience falls, sedation or have greater movement disorder symptoms than younger participants.

Overall, about 45 percent of participants dropped out of the study, although the drop-out rate was lower in the combination treatment group (37 percent) compared to the monotherapy group (53 percent).

Significance
Because the drop-out rate was relatively high and no follow-up data on those who discontinued were collected, the authors caution against applying the study's results to clinical practice prematurely. Still, the authors suggest that combination therapy holds promise as an alternative therapy to ECT. "Psychotic depression is difficult to treat," said NIMH Director Thomas R. Insel, M.D. "This study provides insight into one approach to treatment that may be a valid alternative for many patients who cannot or will not undergo ECT."

What's Next
Longer-term studies are needed to evaluate side effects. "Future research must weigh the benefits of continuing atypical antipsychotic medication beyond 12 weeks against the risks of associated metabolic side effects," lead author Meyers concluded.

Reference
Meyers BS, Flint AJ, Rothschild AJ, Mulsant BH, Whyte EM, Peasley-Miklus C, Papademetriou E, Leon AC, Heo M for the STOP-PD study group. A double-blind randomized controlled trial of olanzapine plus sertraline versus olanzapine plus placebo for psychotic depression—The Study of Pharmacotherapy of Psychotic Depression (STOP-PD). Archives of General Psychiatry. 2009;66(3):838-847.

Air Force Suicide Prevention Program Reduces Suicide Rate

U.S. Air Force Photo/ Staff Sgt. Angelita M. LawrenceA U.S. Air Force suicide prevention program is associated with reduced suicide rates among Air Force personnel during times in which the program was rigorously implemented and monitored, according to an NIMH-funded study published online ahead of print May 13, 2010, in the American Journal of Public Health. LCSW CEUs
Background
The Air Force Suicide Prevention Program (AFSPP) was implemented in 1997. Based on the premise that individuals at risk for suicide exhibit early warning signs, AFSPP emphasizes leadership and community involvement in reducing suicide by encouraging Air Force leaders to actively support and get involved with suicide prevention efforts. It trains commanders in how and when to seek out mental health services for their troops, provides training to all military and civilian personnel in suicide prevention, and incorporates other community-based components.

Kerry Knox, Ph.D., of the University of Rochester Medical Center, and colleagues studied the impact of AFSPP in reducing suicide among Air Force personnel from 1997 until 2008. They examined suicide rates from 1981 to 2008 to provide historical context during three military conflicts, and a downsizing of the Air Force that occurred in the 1990s.

Results of the Study
The researchers found that suicide rates were significantly lower after the program was launched than before—an average of two suicides per 100,000 per quarter occurred during the intervention period compared to three suicides per 100,000 per quarter prior to the intervention rollout. During the third quarter of 2004, however, suicide rates increased. Knox and colleagues suggest that the upward spike may have been the result of a diminished implementation of ASFPP due to increased demands from the two ongoing wars in Iraq and Afghanistan. In response, Air Force leadership took steps to strengthen implementation of the program and ensure compliance of its components, according to the authors.

Significance
The results suggest that the program is effective but its success is contingent on continuous implementation efforts and ongoing monitoring. The program cannot be maintained by "inherent momentum," the authors concluded.

What's Next
The authors suggest that the program, if maintained and monitored for compliance, can continue to keep suicide rates low in the Air Force. They also suggest that the program could be implemented in other communities and organizations to prevent suicide and reduce the stigma associated with the mental and psychosocial problems that often precipitate suicide attempts.

Reference
Knox K, Pflanz S, Talcott GW, Campise RL, Lavigne JE, Bajorska A, Tu X, Caine ED. The US Air Force Suicide Prevention Program: Implications for Public Health Policy. American Journal of Public Health. Online ahead of print May 13, 2010.

Study Identifies Three Effective Treatments for Childhood Anxiety Disorders

Treatment that combines a certain type of psychotherapy with an antidepressant medication is most likely to help children with anxiety disorders, but each of the treatments alone is also effective, according to a new study funded by the National Institutes of Health’s National Institute of Mental Health (NIMH). The study was published online Oct. 30, 2008, in the New England Journal of Medicine. MFT Continuing Education


“Anxiety disorders are among the most common mental disorders affecting children and adolescents. Untreated anxiety can undermine a child’s success in school, jeopardize his or her relationships with family, and inhibit social functioning,” said NIMH Director Thomas R. Insel, M.D. “This study provides strong evidence and reassurance to parents that a well-designed, two-pronged treatment approach is the gold standard, while a single line of treatment is still effective.”

The Child/Adolescent Anxiety Multimodal Study (CAMS) randomly assigned 488 children ages 7 years to 17 years to one of four treatment options for a 12-week period:

Cognitive behavioral therapy (CBT), a specific type of therapy that, for this study, taught children about anxiety and helped them face and master their fears by guiding them through structured tasks;
The antidepressant sertraline (Zoloft), a selective serotonin reuptake inhibitor (SSRI);
CBT combined with sertraline;
pill placebo (sugar pill).
The children, recruited from six regionally dispersed sites throughout the United States, all had moderate to severe separation anxiety disorder, generalized anxiety disorder or social phobia. Many also had coexisting disorders, including other anxiety disorders, attention deficit hyperactivity disorder, and behavior problems.

John Walkup, M.D., of Johns Hopkins Medical Institutions, and colleagues found that among those in combination treatment, 81 percent improved. Sixty percent in the CBT-only group improved, and 55 percent in the sertraline-only group improved. Among those on placebo, 24 percent improved. A second phase of the study will monitor the children for an additional six months.

“CAMS clearly showed that combination treatment is the most effective for these children. But sertraline alone or CBT alone showed a good response rate as well. This suggests that clinicians and families have three good options to consider for young people with anxiety disorders, depending on treatment availability and costs,” said Walkup.

Results also showed that the treatments were safe. Children taking sertraline alone showed no more side effects than the children taking the placebo and few children discontinued the trial due to side effects. In addition, no child attempted suicide, a rare side effect sometimes associated with antidepressant medications in children.

CAMS findings echo previous studies in which sertraline and other SSRIs were found to be effective in treating childhood anxiety disorder. The study’s results also add more evidence that high-quality CBT, with or without medication, can effectively treat anxiety disorders in children, according to the researchers.

“Further analyses of the CAMS data may help us predict who is most likely to respond to which treatment, and develop more personalized treatment approaches for children with anxiety disorders,” concluded Philip C. Kendall, Ph.D., of Temple University, a senior investigator of the study. “But in the meantime, we can be assured that we already have good treatments at our disposal.”

The six CAMS sites were Duke University; New York State Psychiatric Institute/Columbia University Medical Center; Johns Hopkins University; Temple University/University of Pennsylvania; University of California, Los Angeles; and the Western Psychiatric Institute and Clinic/University of Pittsburgh Medical Center.



Reference
Walkup JT, Albano AM, Piacentini J, Birmaher B, Compton SN, Sherrill J, Ginsburg GS, Rynn MA, McCracken J, Waslick B, Iyengar S, March JS, Kendall PC. Cognitive-behavioral therapy, sertraline and their combination for children and adolescents with anxiety disorders: acute phase efficacy and safety. New England Journal of Medicine. Online ahead of print 30 Oct 2008.

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

The National Institutes of Health (NIH) — The Nation’s Medical Research Agency — includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit the NIH website.