This application seeks continuation support for a NIMH CRC dedicated to the study of major mental disorders of adults and children. In adults these include depression, mania, alcoholism, panic disorder and schizophrenia; in children (or young adults), the sequelae of closed head injury. The theoretical base for the proposed studies consists largely of the principles of neuroendocrinology and psychoendocrinology; also employed are the principles of neurotransmitter physiology, pharmacodynamics and kinetics, immunology, neuropsychology, biostatistics, life history and computer science. Two endocrine faults--the reduced TSH response to TRH and the failure to suppress cortisol after dexamethasone--provide foci for the organization of several proposed clinical studies. Other conceptual themes are: neuroleptic metabolism in schizophrenic patients; responses of depressed and manic patients to drugs that alter cholinergic function; serotonin function in affective disorders. Two studies explore totally new ground: is hypoglycemia necessary to the behavioral effects of insulin; given a tantalizing biochemical relationship, how do chlordiazepoxide and TRH interact on behavior and endocrine function? A study, epidemiologic in design and scheduled to precede others in performance, assesses the incidence and significance of marginal hypothyroidism in psychiatric inpatients. The effects of psychostimulants on patients with late consequences of closed head injury will also be studied. The Center's four basic science sections (one is new) are tied in various ways to each other and to the five clinical sections (two are new). Several studies focus on the HPT axis: with importance for peptide physiology generally, how is TRH synthesized; how do TRH and cholinergic systems interact in a model of depression (Porsolt test); does even slight hypothyroidism increase memory loss in rats after ECT? Some animal studies explore the utility of peptides as markers of adrenergic or cholinergic activity and the effects early separation on later HPT and HPA function. Other studies resonate with our developing interest in schizophrenia: changes in DA metabolism during the reproductive cycle; the effects of gonadal steroids on DAergic activity; the effects of diabetes on DA receptor functions. Six core groups (three are new) support the clinical and basic science sections and enhance each other's work. Teaching and training activities of the Center have increased in parallel with the depth and span of research activities.
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