The psychoses are a heterogeneous group of disorders. Systematic separation of several relatively homogeneous groups of psychotic diseases from one another and from the residium of other psychotic disorders has been/is the aim of this series of investigations of illness symptoms, illness course, associated familial psychopathology, biologic markers and treatment response. Utilizing treatment response criteria as the primary independent variable, the present proposal will extend studies of a previously described lithium responsive psychotic cohort. It will examine the course of subsequent illness in such psychotics, especially whether abnormal/normal biologic markers studied at index admission are predictive of the ultimate illness course. Transmission patterns of such biological markers will be studied in family members of the lithium responsive probands together with lifetime patterns of psychiatric illness to determine the form(s) of psychiatric illness associated with both particular trait markers in family members, and with different courses of subsequent illness of the initially lithium responsive probands. Three psychotic patient populations will also be discriminated by means of remission time course during treatment with classical neuroleptic drug: (1) a rapid responder group will be studied for evidence of functional DA receptor supersensitivity on neuroendocrine measures and for abnormalities of membrane composition and function, including variant plasma/RBC haloperidol ratios, RBC lithium ratios, counterflow and leak, and membrane phospholipid composition; (2) a neuroleptic drug nonresponder group will be defined following 5 or more weeks of dose adjusted treatment and will be studied for evidence of increased brain ventricular ratios (BVR); (3) a residual, traditional responder group (2 to 5 weeks) will undergo trials (a) to verify previously suggested optimal plasma therapeutic ranges and (b) to study the effect of adjusting drug plasma levels to optimal ranges with respect to speed and completeness of antipsychotic response. Family studies will examine patterns of illness in each of the three proband subgroups of psychotics as defined by such remission parameters. Longitudinal prospective studies will determine if patients remain stable within the same psychotic subtype, or whether in the course of similar treatment of subsequent episodes, patients drift toward a less rapidly responsive/nonresponsive chronic subtype. Relationships between lithium responsive and rapid neuroleptic responsive psychotics will be studied to determine if they are identical groups.
