This is a resubmission of a competitive renewal[unreadable] application (ROl MH42261-14) for postmortem studies of the limbic lobe in relation to[unreadable] schizophrenia (SZ) and bipolar disorder (BD). Recent work from this laboratory has[unreadable] demonstrated a series of microscopic anomalies in layer II of the anterior cingulate[unreadable] cortex (ACCx-ll) and sectors CA3 and CA2 of the hippocampal formation (HIPP) in SZs and[unreadable] BDs. These changes have included reductions in interneurons, although an overt loss of[unreadable] GABA cells now appears to be a striking feature of GD, but not SZ. Even so, both SZs and[unreadable] BDs show evidence for a decrease of GABAergic function in ACCx-ll and HIPP. Specific Aim I[unreadable] will test the hypothesis that discrepancies in cell counting data in ACCx and HIPP of SZs[unreadable] and/or BDs can be explained in part by differences in sampling window size employed in 2D[unreadable] vs 3D counting. Specific Aim II will test the hypothesis that there will be a reduction in[unreadable] cells positive for GAD in HIPP sectors CA3 and CA2, as well as layers II and Ill of ACCx[unreadable] in BDs, but not SZs or their family members. In addition, it is also postulated that[unreadable] dopaminergic inputs to GABA cells are in increased in ACCx-ll of SZs, but not BDs.[unreadable] Specific Aim Ill will test the hypothesis that in ACCx and HIPP of SZs and their first[unreadable] degree relatives there will be a decrease of the kainate receptor in PNs, while the NMDA[unreadable] receptor will be decreased in NPs. Specific Aim IV will test the hypothesis that neurons[unreadable] in SZs will show less evidence of apoptosis than patients with BD and this will be[unreadable] especially apparent in interneurons. Taken together, the proposed studies are seeking to[unreadable] identify specific aspects of limbic circuitry that may be involved in the induction of[unreadable] neuronal pathology in SZ and BD. By learning more about the possible role of oxidative[unreadable] stress, novel forms of pharmacotherapy for the major neuropsychiatric disorders may[unreadable] eventually be developed.