Remitted bipolar disorder patients have unique dysfunctional beliefs compared with unipolar patients and healthy individuals, say UK scientists who believe the findings could help the development of specific behavioral therapies.

To date, cognitive behavioral therapy modified for bipolar disorder has yielded disappointing results. While differences in dysfunctional beliefs noted between unipolar and bipolar patients have been identified that could improve therapeutic approaches, until recently there has been no reliable method of assessing beliefs in remitted bipolar disorder patients.

Y Alatiq and colleagues from the University of Oxford therefore administered the Hypomanic Attitudes and Positive Prediction Inventory (HAPPI), as well as the Dysfunctional Attitudes Scale (DAS) to 40 remitted bipolar disorder patients, 20 remitted unipolar patients, and 20 healthy controls.

There were no significant differences in terms of the history of depression or current depressive mood symptoms between bipolar and unipolar patients, both scoring significantly more than controls. Bipolar patients scored more highly on current manic symptoms than both unipolar patients and controls, with no significant differences between the latter.

There were no significant differences between the groups in DAS scores, whether in terms of total scores of any of the subscales, or after taking age into account, the team reports in the Journal of Affective Disorders.

Bipolar patients had significantly higher HAPPI scores than unipolar patients and controls in terms of total scores as well as scores on the self-catastrophic beliefs, other negative beliefs, and response style, even after controlling for age. There were no significant differences between unipolar patients and controls.

The team writes: “To conclude, the study has confirmed that bipolar patients when in remission hold dysfunctional beliefs related to the elevated mood experience which are found to be specific to bipolar disorder.”

They add: “Further study is now needed to look at whether cognitive behavioural therapy for bipolar disorder might benefit from working on such beliefs.”

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a part of Springer Science+Business Media. © Current Medicine Group Ltd; 2009

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Children aged 8??”12 years with major mood disorders experience improved outcomes with brief, adjunctive multifamily psychoeducational group psychotherapy, conclude US researchers.

Mood disorders in youth are a major health concern, yet there are few established treatments. Psychosocial treatments are recommended for childhood depression and bipolar disorder; however, evidence to support these recommendations is lacking.

To investigate the benefits of adjunctive multifamily psychoeducational psychotherapy, Mary Fristad, from Ohio State University in Columbus, and colleagues randomly assigned 165 children aged 8??”12 years with depression or bipolar disorder to receive multifamily psychoeducational psychotherapy plus treatment as usual or a wait-list control condition plus treatment as usual.

The treatment consisted of eight 90-minute sessions with the child and at least one parent, combining psychoeducation, family systems, and cognitive behavioral psychotherapy in order to learn about mood disorders and their treatment, gain support from other families, and build skills. Participants were assessed at baseline and after 6, 12, and 18 months, with the intervention applied to the treatment group between baseline and 6 months, and between 12 and 18 months for the control group.

On intention-to-treat analysis, intervention patients experienced a 6.48-point greater decrease in Mood Severity Index (MSI) scores over the first 12 months compared with controls, at an effect size of 0.53. Although control patients experienced a nonsignificant increase in scores over the final 6 months of treatment, the rate of improvement was similar to that seen in the intervention group, at 7.00 and 6.48 points per year, respectively.

Focusing on patients who completed treatment, the team found similar results to those observed on the intention-to-treat analysis, but with a larger effect, such that intervention patients had an 8.17-point greater decrease in MSI scores versus controls over the first 12 months, at an effect size of 0.68.

Noting the benefits of the intervention, the team concludes in the Archives of General Psychiatry: “Clinicians who treat children can incorporate cognitive behavior and family systems components of multifamily psychoeducational psychotherapy into their practice.

“Researchers who investigate psychosocial interventions for mood disorders may consider comparing the relative efficacy of multifamily psychoeducational psychotherapy with that of other psychosocial interventions for children with depression and bipolar disorder as well as possible moderators and mediators of treatment.”

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a part of Springer Science+Business Media. © Current Medicine Group Ltd; 2009

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The finding suggests that a single gene, called GSK-3, controls the signals that determine how many neurons actually end up composing the brain. This has important implications for patients with neuropsychiatric illness, as links have recently been drawn between GSK-3 and schizophrenia, depression and bipolar disorder.

In populating the growing brain, neural stem cells must strike a delicate balance between two key processes - proliferation, in which the cells multiply to provide plenty of starting materials - and differentiation, in which those materials evolve into functioning neurons.

If the stem cells proliferate too much, they could grow out of control and produce a tumor. If they proliferate too little, there may not be enough cells to become the billions of neurons of the brain. Researchers at the University of North Carolina at Chapel Hill School of Medicine have now found that this critical balance rests in large part on a single gene, called GSK-3.

The finding suggests that GSK-3 controls the signals that determine how many neurons actually end up composing the brain. It also has important implications for patients with neuropsychiatric illness, as links have recently been drawn between GSK-3 and schizophrenia, depression and bipolar disorder.

One of the genes associated with schizophrenia appears to use GSK-3 as an intermediary to exert its effects on nerve cells. In addition, lithium, a popular treatment for bipolar disorder, acts, in part, by shutting down GSK-3. “I don’t believe anyone would have imagined that deleting GSK-3 would have such dramatic effects on neural stem cells,” said senior study author William D. Snider, M.D., professor of neurology and cell and molecular physiology, and director of the UNC Neuroscience Center. “People will have to think carefully about whether giving a drug like lithium to children could have negative effects on the underlying structure of the nervous system.”

In a study appearing online October 4th in the journal Nature Neuroscience, Snider and his colleagues created a mouse model in which both forms of the GSK-3 gene - designated alpha and beta - had been deleted. They decided to go after GSK-3 - which stands for glycogen synthase kinase 3 - because it is one of the most studied kinases or signaling molecules in all of biology.

The researchers used a “conditional knock-out” strategy to remove GSK-3 at a specific time in the development of the mouse embryo, when a type of cell called a radial progenitor cell had just been formed.

As the brain develops, neural stem cells evolve through three different stages — neural epithelial cells, radial progenitor cells and intermediate neural precursors. The radial progenitor cells are especially important because they are thought to provide the majority of the neurons of the developing brain but also differentiate themselves to give rise to all the cellular elements of the brain. The researchers discovered that deleting GSK-3 during this second phase of development caused the radial progenitor cells to be locked in a constant state of proliferation.

“It was really quite striking,” said Snider. “Without GSK-3, these neural stem cells just keep dividing and dividing and dividing. The entire developing brain fills up with these neural stem cells that never turn into mature neurons.”

GSK-3 is known to coordinate signals for proliferation and differentiation within nerve cells through multiple “signaling pathways.” Thus, the researchers looked to see what effect deleting the molecule had on some of these pathways. They found that every one of the pathways that they studied went awry.

Snider and his colleagues now want to see if adding GSK-3 back to their genetically engineered mice can convert the proliferating stem cells into neurons, possibly resulting in three to four times as many neurons in the mutants as normal.

“I find that quite interesting because I can’t think of any other manipulation that potentially would enable you to simply dial up and down the number of neurons that are generated in the brain,” said Snider.

Funding for the studies led at UNC came from the National Institutes of Health. Study co-authors from Snider’s laboratory at UNC include lead author Woo-Yang Kim, Ph.D., postdoctoral research associate; Xinshuo Wang, graduate student and Yaohong Wu, chief technician. Researchers from the laboratory of James R. Woodgett, Ph.D. at the University of Toronto also collaborated on the project.

Source:
Les Lang

University of North Carolina School of Medicine

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