Clues To Rapid Cycling Bipolar Disease

German researchers have devised a way to follow gene expression over time in a 64-year-old woman who developed rapid-cycling bipolar illness in her mid-40s. Over a 16-year period, the woman logged in 108 cycles in her diary. Rapid-cycling bipolar illness is characterized by four or more episodes of depression and/or mania in a given year.



Martin Begemann, MD, and his colleagues at the Max Planck Institute of Experimental Medicine and the University of Göttingen in Germany had in their hands a unique opportunity to draw blood from this patient over two consecutive days during two episodes of depression and two episodes of mania. They used microarrays to study gene expression during these disparate episodes, in addition to polymerase chain reaction techniques. One-to-two years later, blood was collected again to validate their original findings.


Results of the study were published this month in the journal Molecular Medicine, published by The Feinstein Institute for Medical Research.


During depression, there was an elevation of prostaglandin D synthetase and prostaglandin D2 11-ketoreductase. These genes are known to be associated with the seasons of hibernation in some species.


Based on the finding, they treated the patient with celecoxib, a cyclooxygenase inhibitor, for five months and found a surprising reduction in the severity of her symptoms of depression. It also seemed to alter the severity of her manic episodes. The scientists concluded that rapid cycling bipolar affective disorders "resemble hibernation" and that prostaglandins play a role in mediating this biological response in the brain.


The scientists said they, "Were able to obtain an episode-specific gene expression profile on an identical genetic background" and found significant differences during the depression and manic episodes. "The gene expression differences were small but significant, and would not have been recognized in a pool of patients or in comparison with healthy controls," they wrote. "In principle, such as approach could be employed as a screening strategy for genes in any condition with temporal periodic behavior."


They are now repeating these studies on other rapid cycling patients. They are also trying to figure out what the increased gene expression means to the workings of the nervous system, and how it might set the stage for the symptoms of psychiatric conditions.


Other major studies in the September/October issue include:


- A collaborative multi-center study of cytokine activity in severe burn patients shows that adults produce more cytokines (harmful products of the body's immune response) than children. This could explain why morbidity and mortality rates are higher in adults. Results could pave the way for new interventions in acute burn patients.


- In another study involving a multi-site collaborative effort with Feinstein geneticist Peter K. Gregersen, MD, scientists identified genetic variants (using genome-wide association studies) that explain why some patients with rheumatoid arthritis respond to anti-TNF therapy and others don't. The results suggest that SNP analysis may one day be useful in predicting responses to anti-TNF therapy.


To get copies of these or other studies visit molmed/.


Molecular Medicine