We propose to improve the capacity of a psychiatric inpatient facility to foster multidisciplinary collaboration whose goal is to search for biological correlates of psychiatric illness. We will test pharmacological agents whose actions related to specific biological hypotheses of psychopathology. In depression we will measure catecholamine and serotonin metabolites, pituitary thyrotropin response to thyrotropin releasing hormone (TRH), pituitary growth hormone (HGH) response to levodopa, the cortisol response to dexamethasone and the glucose response to glucose and insulin infusion. We then will determine the usefulness of these metabolic tests as predictors of drug-response. In schizophrenia, we propose to look for abnormalities in spinal fluid (CSF) catecholamine and serotonin metabolites, CSF choline and acetylcholine levels, CSF levels of endogenous opiate peptides, platelet monoamine oxidase activity and possible N- or O-methylated indoleamines or phenylethylamines. In patients with tardive dyskinesia, Huntington's disease, schizophrenia, and mania we will test acetylcholine imbalance hypotheses by administering physostigmine and choline chloride. In patients with schizophrenia, we propose to evaluate the role of endogenous opiate peptides by administering short-and long-acting opiate antagonists. We also will use both cross-sectional and longitudinal designs to assess schizophrenic and depressed patients and controls using a battery of event-related brain potentials (ERP's) and clinical techniques. Cortical excitability, stimulus intensity modulation, and various aspects of attention will be assessed. Brain potentials and clinical data will be analyzed cross-sectionally to determine the presence of ERP correlations with diagnostic categories or other clinical variables. The data will be analyzed longitudinally to determine if any of the brain potential measures predict outcome or drug-response. Finally, we hope that the correlation of biochemical, physiological, and clinical variables will improve our understanding of severe mental illness.