Role of Dysregulated Endocannabinoid Signaling in Bipolar Disorder

Project Description Narrative:

Bipolar disorder is one of the most severely debilitating of all psychiatric illnesses, directly affecting the lives of 1% of Wisconsin residents. This number is an underestimate of the total health cost of the disease because the quality of life of the family members of affected patients is also reduced. Recent studies indicate that for a large percentage of bipolar patients, outcomes are poor. Patients with bipolar disorder generally experience high rates of relapse, lingering residual symptoms, psychosocial disability, and diminished well-being. In addition, it is becoming increasingly apparent that bipolar disorder is not just a psychological disorder, but it is also frequently associated with cardiovascular disease, diabetes mellitus, obesity, metabolic disorder, and thyroid disease. Despite its impact on health, little is known about the precise neurobiological underpinnings of bipolar disorder, which is hampering the development of therapies that are effective and work rapidly with fewer side effects than those currently available. Bipolar disorder needs additional preclinical research to develop novel treatment approaches.

The risk factors for bipolar disorder include a strong genetic component as well as environmental factors. Clinical data suggest that disrupted circadian rhythms are involved in the pathogenesis of bipolar disorder in humans. There is clear evidence that marijuana use is higher among patients with bipolar disorder than the general population, and animal data also support the hypothesis that altered cannabinoid receptor signaling produces changes in mood. The researchers hypothesize that endogenous CB1 cannabinoid receptor activity is hypoactive in patients with bipolar disorder and that this dysregulation contributes to the disruption of circadian rhythmicity in the disorder. The objectives of this project are to acquire preliminary data to support or refute this hypothesis.