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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH032666-08
Application #
3375359
Study Section
(PCBB)
Project Start
1978-09-01
Project End
1987-08-31
Budget Start
1985-09-01
Budget End
1986-08-31
Support Year
8
Fiscal Year
1985
Total Cost
Indirect Cost
Name
University of Cincinnati
Department
Type
Schools of Medicine
DUNS #
City
Cincinnati
State
OH
Country
United States
Zip Code
45221
Garver, D L; Bissette, G; Yao, J K et al. (1991) Relation of CSF neurotensin concentrations to symptoms and drug response of psychotic patients. Am J Psychiatry 148:484-8
Garver, D L; Kelly, K; Fried, K A et al. (1988) Drug response patterns as a basis of nosology for the mood-incongruent psychoses (the schizophrenias). Psychol Med 18:873-85
Zemlan, F P; Hirschowitz, J; Sautter, F et al. (1986) Relationship of psychotic symptom clusters in schizophrenia to neuroleptic treatment and growth hormone response to apomorphine. Psychiatry Res 18:239-55
Zemlan, F P; Hirschowitz, J; Garver, D L (1986) Relation of clinical symptoms to apomorphine-stimulated growth hormone release in mood-incongruent psychotic patients. Arch Gen Psychiatry 43:1162-7
Hitzemann, R J; Garver, D L; Mavroidis, M et al. (1986) Fluphenazine activity and antipsychotic response. Psychopharmacology (Berl) 90:270-3
Hitzemann, R J; Hirschowitz, J; Garver, D L (1986) On the physical properties of red cell ghost membranes in the affective disorders and psychoses. A fluorescence polarization study. J Affect Disord 10:227-32
Hitzemann, R; Mark, C; Hirschowitz, J et al. (1985) Characteristics of phospholipid methylation in human erythrocyte ghosts: relationship(s) to the psychoses and affective disorders. Biol Psychiatry 20:397-407
Zemlan, F P; Hitzemann, R J; Hirschowitz, J et al. (1985) Down-regulation of central dopamine receptors in schizophrenia. Am J Psychiatry 142:1334-7