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: This study will examine the existence of particular in vivo neurochemical and morphometric brain abnormalities in unipolar mood disorder subjects, and their potential involvement in the pathophysiology of this illness. We will also examine potential in vivo brain correlates of prior suicidal behavior in this patient population. RESEARCH PLAN: We will investigate regional brain myo-inositol and platelet membrane phosphoinositide levels in 30 unmedicated unipolar patients (15 depressed and 15 in the remitted state) and 30 age, sex, educational level, and race-matched healthy controls. In addition to that, we will examine brain morphometry of key brain regions involved in mood regulation, to attempt to determine their relationship with illness symptoms. We will also examine brain correlates of suicide behavior by comparing patients with prior suicide attempts and the ones without such attempts. METHODS: All subjects undergo a 1.5T proton MIR/MRS brain scan, which allows the quantitation of myoinositol in 8cc brain voxels located in the frontal cortex, medial temporal lobe, and basal ganglia. At the same time, subjects provide a blood sample for platelet determination of membrane phosphoinositides, which is done with two-dimensional thin layer chromatography, followed by scanning laser densitometry. This research holds substantial promise to contribute to a better understanding of the biochemical brain dysfunction underlying mood disorders, and ultimately guide future efforts towards the development of new treatments for these conditions. CLINICAL RELEVANCE: This study will allow examination of involvement of abnormalities in the phosphoinositol (PI) pathway in pathophysiology of depression and mood disorders. It will also allow examination of anatomical involvement of specific brain regions participating in mood regulation in the pathophysiology of mood disorders. It could also possibly aid in development of new ways to identify depressed unipolar patients at high risk for suicide.