Category: Bipolar Disorder

Children with bipolar disorder respond differently to facial expressions than children without psychiatric disorders, according to a new study led by a Bradley Hospital researcher. These findings provide additional insight into the neurobiology of pediatric bipolar disorder. 

"Although we know a great deal clinically about bipolar disorder in kids, our understanding of its neurobiology is quite limited, making it difficult to design targeted treatments," said lead author Daniel P. Dickstein, M.D., director of the pediatric mood, imaging and neurodevelopment program at Bradley Hospital. "We used neuroimaging technology to study the brain-behavior interactions of children with bipolar disorder in hopes of shedding some light on this relatively unknown area."

Dickstein, who is also an assistant professor of psychiatry and human behavior at The Warren Alpert Medical School of Brown University, led this research while with the National Institute of Mental Health.

The study included 23 children with bipolar disorder and 22 typically developing children without psychiatric disorders between the ages of 7 and 17. Dickstein and his team used functional magnetic resonance imaging (MRI), a non-invasive technique that localizes regions of the brain activated during cognition and experience, to scan the children while they "encoded" different facial expressions.

During the MRI scan, the children viewed photos of 32 different actors — eight actors each displaying one of four emotions (angry, fearful, happy and neutral) — from standard gray-scale photograph sets of facial expressions. After seeing the photos four times, they rated each face by answering questions such as "How afraid are you?" "How hostile is the face?" and "How wide is the nose?"

Thirty minutes after the MRI scan, children were given a surprise out-of-scanner memory task, during which they viewed 48 actors (half of which were seen previously during the MRI and half that were not previously viewed). They were then asked whether they recalled seeing the face during the earlier test.

During the encoding of "happy" faces, researchers observed increased activity in the region of the brain (striatum) associated with rewards in the children with bipolar disorder. Increased activity was also found in the part of the brain (orbitofrontal cortex) liked to irritability when the same children encoded "angry" faces. Brain activity in both instances was significantly greater than in children without bipolar disorder.

Based on the number of correct identifications during the memory task, Dickstein and colleagues also found that children with bipolar disorder demonstrated reduced memory for emotional faces as compared to children without bipolar disorder — particularly with "fearful" faces.

"This study suggests a neural basis for mania in children, which typically involves unusually irritable or excessively happy moods, and raises questions about whether treatments, therapy or medication could address these brain changes," Dickstein said.

The authors say further research is required to determine the impact of mood state, medication and the presence of an additional illness, such as attention deficit hyperactivity disorder, on these findings.

The study is published in the November issue of the journal Bipolar Disorders.

The National Institute of Mental Health (NIMH) funded the study. Co-authors were Brendan A. Rich, Lisa Berghorst, Deborah Vinton, Daniel S. Pine and Ellen Leibenluft from the Division of Intramural Research Program at NIMH; and Roxann Roberson-Nay from Virginia Commonwealth University Medical College.

 Young people with asthma are about twice as likely to suffer from depressive and anxiety disorders than are children without asthma, according to a study by a research team in Seattle. Previous research had suggested a possible link in young people between asthma and some mental health problems, such as panic disorder, but this study is the first showing such a strong connection between the respiratory condition and depressive and anxiety disorders.

The study was conducted by researchers at the University of Washington School of Medicine, Group Health Cooperative, and Seattle Children's Hospital Research Institute. The researchers interviewed more than 1,300 youths, ages 11 to 17, who were enrolled in the Group Health Cooperative health maintenance organization. Of the participants, 781 had been diagnosed with or treated for asthma, and the rest were randomly selected youths with no history of asthma.

About 16 percent of the young people with asthma had depressive or anxiety disorders, the researchers found, compared to about 9 percent of youth without asthma. When controlling for other possible variables, youth with asthma were about 1.9 times as likely to have such depressive or anxiety disorders.

Researchers tested for several depressive and anxiety disorders, including depression, a mood disorder called dysthymia, panic disorder, generalized anxiety disorder, separation anxiety, social phobia, and agoraphobia. These disorders are somewhat common in youth, and are associated with high risk for school problems, early pregnancy, adverse health behaviors like smoking or lack of exercise, and suicide.

Young people with depressive and anxiety disorders often find it harder to manage their asthma and describe more impaired physical functioning because of the combination of asthma and a depressive or anxiety disorder, the researchers said. Youth with asthma and one of the disorders are also more likely to smoke, making their asthma more difficult to treat.

"Physicians treating young people with asthma should realize that those children are at a greater risk of depressive and anxiety disorders, and should try to educate patients and their families about this increased risk," said Dr. Wayne Katon, professor and vice-chair of psychiatry at the UW School of Medicine, and corresponding author of the study. "The primary care system is correctly identifying only about 40 percent of the cases in which children with asthma also have a psychiatric disorder. We should improve our screening for these disorders, and develop effective treatment programs for affected patients that address both asthma and the depressive or anxiety disorder."

In addition to exploring the link between asthma and depressive and anxiety disorders, researchers found other variables that further increase the risk of such disorders. Female respondents were at a greater risk of depressive and anxiety disorders, as were youth living in a single-parent household, those who had been diagnosed with asthma more recently, and those with more impairment in asthma-related physical health.

The findings appear in the November issue of the Journal of Adolescent Health.

The research team also included Dr. Paula Lozano of the UW Department of Pediatrics, Group Health Cooperative, and Children's Hospital and Regional Medical Center; Dr. Joan Russo of the UW Department of Psychiatry; Dr. Elizabeth McCauley of the UW Department of Psychiatry and Seattle Children's Hospital Research Institute; Dr. Laura Richardson of the UW Department of Pediatrics and Children's Hospital and Regional Medical Center; and Dr. Terry Bush of Group Health Cooperative.

NewsPsychology (Sep. 14, 2007) — The medication tamoxifen, best known as a treatment for breast cancer, dramatically reduces symptoms of the manic phase of bipolar disorder more quickly than many standard medications for the mental illness, a new study shows.

Researchers at the National Institutes of Health’s National Institute of Mental Health (NIMH) who conducted the study also explained how: Tamoxifen blocks an enzyme called protein kinase C (PKC) that regulates activities in brain cells. The enzyme is thought to be over-active during the manic phase of bipolar disorder.

By pointing to PKC as a target for new medications, the study raises the possibility of developing faster-acting treatments for the manic phase of the illness. Current medications for the manic phase generally take more than a week to begin working, and not everyone responds to them.

Tamoxifen itself might not become a treatment of choice, though, because it also blocks estrogen — the property that makes it useful as a treatment for breast cancer — and because it may cause endometrial cancer if taken over long periods of time. Currently, tamoxifen is approved by the Food and Drug Administration for treatment of some kinds of cancer and infertility, for example. It was used experimentally in this study because it both blocks PKC and is able to enter the brain.

Results of the study were published in Bipolar Disorders by Husseini K. Manji, MD, Carlos A. Zarate Jr., MD, and colleagues.

Almost 6 million American adults have bipolar disorder, whose symptoms can be disabling. They include profound mood swings, from depression to vastly overblown excitement, energy, and elation, often accompanied by severe irritability. Children also can develop the illness.

During the manic phase of bipolar disorder, patients are in “overdrive” and may throw themselves intensely into harmful behaviors they might not otherwise engage in. They might indulge in risky pleasure-seeking behaviors with potentially serious health consequences, for example, or lavish spending sprees they can’t afford. The symptoms sometimes are severe enough to require hospitalization.

“People think of the depressive phase of this brain disorder as the time of risk, but the manic phase has its own dangers,” said NIMH Director Thomas R. Insel, MD. “Being able to treat the manic phase more quickly would be a great asset to patients, not just for restoring balance in mood, but also because it could help stop harmful behaviors before they start or get out of control.”

The three-week study included eight patients who were given tamoxifen and eight who were given a placebo (a sugar pill); all were adults and all were having a manic episode at the time of the study. Neither the patients nor the researchers knew which of the substances the patients were getting.

By the end of the study, 63 percent of the patients taking tamoxifen had reduced manic symptoms, compared with only 13 percent of those taking a placebo. Patients taking tamoxifen responded by the fifth day — which corresponds with the amount of time needed to build up enough tamoxifen in the brain to dampen PKC activity.

The researchers decided to test tamoxifen’s effects on the manic phase of bipolar disorder because standard medications used to treat this phase, specifically, are known to lower PKC activity — but they do it through a roundabout biochemical route that takes time. Tamoxifen is known instead to block PKC directly. As the researchers suspected would happen, tamoxifen’s direct actions on PKC resulted in much faster relief of manic symptoms, compared with some of the standard medications available today.

“We now have proof of principle. Our results show that targeting PKC directly, rather than through the trickle-down mechanisms of current medications, is a feasible strategy for developing faster-acting medications for mania,” said Manji. “This is a major step toward developing new kinds of medications.”

Findings from another recent NIMH study strengthen the results. This previous study showed that the risk of developing bipolar disorder is influenced by a variation in a gene called DGKH. The gene makes a PKC-regulating protein known to be active in the biochemical pathway through which standard medications for bipolar disorder exert their effects — another sign that PKC is a promising direct target at which to aim new medications for the illness.

“Mania isn’t just your average mood swing, where any of us might feel upbeat in response to something that happens. It’s part of a brain disorder whose behavioral manifestations can severely undermine people’s jobs, relationships, and health,” said Zarate. “The sooner we can help patients get back on an even keel, the more we can help them avoid major disruptions to their lives and the lives of people around them.”

Reference: Zarate Jr. CA, Singh JB, Carlson PJ, Quiroz J, Jolkovsky L, Luckenbaugh DA, Manji HK. Efficiency of a Protein Kinase C Inhibitor (Tamoxifen) in the Treatment of Acute Mania: A Pilot Study. Bipolar Disorders, online ahead of print, September 2007.

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The above story is reprinted (with editorial adaptations by newsPsychology staff) from materials provided by NIH/National Institute of Mental Health, via EurekAlert!, a service of AAAS.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of NewsPsychology or its staff.

— Melbourne mental health researchers have succeeded in halving the number of relapses experienced by people with bipolar disorder which strikes two in 100 Australians, accounts for 12 per cent of suicides each year and costs the country at least $1.5 billion annually.*

With funding from the MBF Foundation and Beyond Blue, a team led by the Mental Health Research Institute of Victoria has developed an innovative structured group program to help people with bipolar disorder to better manage their condition.

The 12-session program, led by trained mental health clinicians, enables people battling the disorder to effectively monitor their mood, assess personal triggers and early warning signs of oncoming illness and take the necessary steps to stay well.

In a controlled randomised study of 84 people diagnosed with bipolar disorder, those on the special intervention program had half the number of relapses after 12 months as the control group which continued with normal treatment. Even with modern drug therapies that act as mood stabilisers, relapse rates for people with bipolar disorder are as high as 40 per cent in the first year and almost 75 per cent over five years.

MBF general manager health product, Michael Carafillis, said the new program provides a much-needed bridge between the mental health services that treat people when they are acutely ill and the GPs and private psychiatrists who provide ongoing care.

"Bipolar is a complicated disease involving periods of depression and mania and its sufferers don't always take their medications when they should," said Mr Carafillis.

"People with the condition straddle the divide between public and private systems resulting in poor continuity of care for many sufferers. They tend to gain access to the public system in the most severely disabling phase of their illness, typically mania, and are often too ill and the disorder too complex to be easily managed in primary care."

Professor David Castle at the Mental Health Research Institute of Victoria said providing people with bipolar disorder with the right tools and strategies to better self-manage their disease in a supportive group environment can substantially reduce the burden on individuals, their families and the health system.

Buoyed by the exciting results, the research team is now training clinicians in metropolitan and regional Victoria. The development of an accompanying service delivery framework, already being implemented in parts of Victoria, South Australia and the ACT, will enable the program to be rolled out in other states.

* Access Economics report (2003) commissioned by SANE Australia