MAJOR PSYCHOSES

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This is an application for a Specialized Mature Mental Health Center (SMH- CRC). The major theme of the SMH-CRC is the longitudinal study of the pathophysiology and somatic treatments of schizophrenia and mood disorders integrated with informative preclinical research. The major aims of the preclinical research are to investigate the mechanism of action of antipsychotic and thymoleptic drugs and animal models of schizophrenia and mood disorder. The SMH-CRC resources provide infrastructure support to ten core laboratories which facilitate the research of multiple SMH-CRC Investigators. These cores and their major functions are: 1) the Diagnosis and Assessment Core, the functions of which are: a) to recruit schizophrenic and mood disorder patients, related clinical populations and normal controls for participation in multiple, related protocols; b)to provide accurate, standardized diagnosis and assessment of psychopathology over the short and long term; and c) to carry out research or nosology and psychopathology; 2) the Data Management, Analysis and Research Design Core which provides: a) consultation on research design; b) data management and audit; c) a central data bank; and, d) data analysis; 3) the Psychopharmacology Core, which supports and coordinates treatment studies in: a) schizophrenia, especially the effect of clozapine, other atypical antipsychotic drugs, and ECT; and b) studies of drug therapy of mood and related personality disorders (borderline personality disorder, OD); 4) the Neuroendocrinology Core, which supports challenge studies with serotonin (5-HT- and dopamine (DA)-related drugs in schizophrenia, mood disorders, related disorders and normal volunteers; 5) the Neurochemistry Core, which supports post-mortem plasma and CSF neurochemical studies of serotonergic and dopaminergic neurotransmission in schizophrenia, mood disorders and suicide as well as drug plasma level studies; 6) the Brain Imaging Core, which provides; a) CT and MRI measures of brain structure, and b) PET studies of the serotonergic and dopaminergic systems and regional metabolism in schizophrenia and depression; 7) the Neuropsychology Core, which provide measures of cognitive, especially memory, function in schizophrenia; 8) the Psychophysiology Core, which supports eye tracking, motion perception and backward masking studies in schizophrenia and mood disorders; 9) the Neuroscience of Schizophrenia/Antipsychotic Drug Core which supports basic research on the mechanism of action f typical and atypical antipsychotic drugs and animal models of the pathophysiology of schizophrenia, e.g. effect of chronic antipsychotic drugs on neurotransmitters, role of glucocorticoids in neurotoxicity; and 10) the Neuroscience of Mood Disorders/Mood-Drug Core which supports research on the regulation of HPA axis in rodents to determine the basis for HPA abnormalities in major depression and basic studies on the mechanism of action of antidepressants. The SMH-CRC also provides pilot funds for Investigations and has facilitated the training and career development of a large cadre of young investigators.