International Impact of Bipolar Disorder Highlights Need for Recognition and Better Treatment Availability

The severity and impact of bipolar disorder and bipolar-like symptoms are similar across international boundaries, according to a study partially funded by NIMH. The results were published in the March 2011 issue of the Archives of General Psychiatry. Marriage and Family Therapist Continuing Education

Background
Although several studies report prevalence rates of mental disorders on an international level, the numbers have varied because each study tends to use different methodology and definitions. To remedy this, the World Health Organization’s World Mental Health (WMH) survey initiative used consistent data collection methods in 11 countries in the Americas, Europe, Asia, the Middle East and New Zealand. The survey also applied common diagnostic definitions for mental disorders found in the Diagnostic and Statistical Manual for Mental Disorders (DSM-IV).

NIMH researcher Kathleen Merikangas, Ph.D., and colleagues used WMH data to track prevalence rates of three subtypes of bipolar spectrum disorder—bipolar I, bipolar II and bipolar disorder not otherwise specified (BD-NOS). Bipolar I disorder is considered the classic form of the illness, in which a person experiences recurrent episodes of mania and depression. People with bipolar II disorder experience a milder form of mania called hypomania that alternates with depressive episodes. People with 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 DSM-IV. Yet, BD-NOS can significantly impair those who have it.

Results of the Study
The prevalence rates of bipolar I, bipolar II and BD-NOS were 0.6 percent, 0.4 percent, and 1.4 percent, respectively, with an overall bipolar spectrum rate of 2.4 percent. The United States had the highest prevalence rate of bipolar spectrum (4.4 percent), while India had the lowest rate (0.1 percent). More than half of those with bipolar disorder in adulthood note that their illness began in their adolescent years.

Across all countries studied, 75 percent of those who had bipolar symptoms met criteria for having at least one other disorder. Anxiety disorders, especially panic disorder, were the most common coexisting disorders, followed by behavior disorders and substance use disorders. Patterns of coexisting conditions were similar across countries.

Less than half of those with bipolar symptoms received mental health treatment. In low income countries, only 25 percent reported having contact with a mental health professional.

Significance
This study provides the first international prevalence data on bipolar disorder using reliable, standardized methodology. It highlights the international impact of bipolar disorder and the need for better recognition and treatment availability. The findings also support the notion that, given its multi-dimensional nature, bipolar disorder may be better characterized as a spectrum disorder.

In addition, because so many people note that their illness began in adolescence — a critical time of life for educational, occupational and social development — early detection, intervention, and possibly prevention of subsequent coexisting disorders and complications should be emphasized.

What’s Next
More research is needed to better define the thresholds and boundaries of bipolar symptoms. In addition, further research is needed to better understand why and how the disorder tends to originate in adolescence and persist into adulthood, and how it intersects with coexisting mental disorders.

Reference
Merikangas KR, Jin R, He J, Kessler RC, Lee S, Sampson NA, Viana MC, Andrade LH, Hu C, Karam EG, Mora MEM, Browne MO, Ono Y, Posada-Villa J, Sagar R, Zarkov Z. Prevalence and correlates of bipolar spectrum disorder in the World Mental Health Survey Initiative. Archives of General Psychiatry. March 2011. 68(3):241-251.

Most Teens with Eating Disorders Go Without Treatment

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

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

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

In addition,

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

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

New study shows that most substance abuse treatment programs accept private health insurance

Study indicates that most will be ready to adapt to greater health care coverage provided by the Affordable Care Act and Mental Health Parity and Addiction Equity Act
A new nationwide survey of substance abuse treatment facilities reveals that in 2008 nearly two thirds (65 percent) accepted some private health insurance payment. The survey conducted by the Substance Abuse and Mental Health Services Administration (SAMHSA) also indicated that there were significant differences in the level of private insurance payment acceptance among different types of substance abuse treatment facilities. Professional Counselor Continuing Education
For example, private insurance payment was accepted by 85 percent of facilities with a primary focus on mental health services, 82 percent of facilities offering general health care, and 78 percent of facilities offering a mix of mental health and substance abuse treatment services. On the other hand, private insurance payment was accepted by only 56 percent of facilities primarily focused on substance abuse treatment services and 37 percent of facilities focused on other services (e.g., providing shelter for people experiencing homelessness).

"The ability to bill third party payers including private insurers and Medicaid is critical to the survival of treatment facilities," said SAMHSA Administrator Pamela S. Hyde, J.D. "The dramatic increase in numbers of people covered with health insurance that includes coverage for mental and substance use disorders will revolutionize the behavioral health field. Treatment facilities need to be preparing now and SAMHSA has technical assistance resources available to help."

The study noted that substance abuse treatment facilities that accepted private insurance payments were far more likely than those that did not to accept payment from other sources such as Medicaid (68 percent versus 31 percent), state-financed health insurance (53 percent versus 14 percent) and Medicare (48 percent versus 12 percent).

This capacity of substance abuse programs to bill Medicaid may become more critical as Medicaid’s coverage of substance abuse services becomes more comparable to its coverage of mental health services.

Other significant differences between treatment programs that accepted private insurance payment and those that did not include the use of cognitive-behavioral therapy services at their facilities (70 percent versus 58 percent). Facilities accepting private insurance were more likely than others to accept adolescents into their programs (58 percent versus 33 percent).

The study also showed that treatment facilities located in more central large urban areas were less likely than rurally situated facilities to accept private insurance payment (54 percent versus 78 percent). In general the further away facilities were from central city areas, the more likely they were to accept private insurance payment.

The study, Acceptance of Private Health Insurance in Substance Abuse Treatment Facilities is based on data from SAMHSA’s Treatment Episode Data Set (TEDS) -- a reporting system involving treatment facilities from across the country. The study was developed as part of SAMHSA’s strategic initiative on data, outcomes, and quality -- an effort to inform policy makers and service providers on the nature and scope of behavioral health issues

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.