This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. OBJECTIVE: The phosphoinositol (PI) pathway may be abnormal in bipolar disorder, and this could be an important mechanism involved in its pathophysiology and the mechanisms of action of lithium and other treatments for this condition. This study will investigate in vivo the intracellular PI pathway in bipolar disorder patients, and examine the hypothesis of a dysfunction in this pathway in patients suffering from this disorder. RESEARCH PLAN: We will recruit 90 unmedicated bipolar subjects (30 depressed, 30 euthymic, 30 manic), 30 lithium-treated euthymic patients, and 60 matched healthy controls over the course of a 5 year period. Patients will be diagnosed according to the DSM-IV criteria and need to meet diagnostic criteria for bipolar disorder type I. METHODS: Patients will provide blood samples for determination of platelet membrane phosphoinositides, which will be done with two-dimensional thin-layer chromatography followed by scanning laser densitometry. They will also undergo a 1.5T proton magnetic resonance spectroscopy (MRS) brain scan, which will allow the quantitation of may-inositol in a single voxel placed in the frontal cortex. Correlations will be examined between brain myo-inositol and platelet phosphoinositide levels and between these measurements and specific disease states. The impact of lithium treatment will also be examined. CLINICAL
This study may result in substantial contributions to the understanding of the pathophysiology of bipolar disorder and ultimately contribute to the development of new treatments for this condition.
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