Alterations in functions of the brain dopamine (DA) system have been implicated in the pathophysiology of schizophrenia and in the therapeutic action of neuroleptic drugs. Detailed understanding of these changes in brain DA function have been limited by the absence of an accurate and easily repeatable measure of brain DA activity in man. Plasma levels of the main DA metabolite, homovanillic acid (HVA) may be such a measure. In animals, pHVA accurately reflects changes in the brain DA functions. Reflections of brain DA activity by pHVA measurements in human subjects requires the elimination of confounding variables affecting these measurements. The previous grant application developed methods for controlling these variables and identified abnormal pHVA concentrations in schizophrenic patients. The present grant application propose to identify additional confounding factors affecting pHVA measurements in man, improve the methodology of controlling these factors, and apply this information to the study of schizophrenia and other neuropsychiatric disorders. The effect of age, weight, seasonality, and previous pharmacological treatment on pHV will be examined in human subjects. An improvement in the control of confounding variables will consist of developing a pharmacological method to suppress peripheral HVA production. This method will be based on pretreatment with the MAO inhibitor debrisoquin. Using the optimal method for reflecting brain DA activity, pHVA will be measured in remitted, exacerbated, and treatment resistant schizophrenic patients. The ability to perform serial evaluations of dopaminergic activity may help elucidate the role of this neurotransmitter in schizophrenics.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH037922-05
Application #
3376413
Study Section
(PCBB)
Project Start
1983-09-15
Project End
1988-08-31
Budget Start
1987-09-01
Budget End
1988-08-31
Support Year
5
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Mount Sinai School of Medicine
Department
Type
Schools of Medicine
DUNS #
City
New York
State
NY
Country
United States
Zip Code
10029
Stern, R G; Kahn, R S; Davidson, M et al. (1994) Early response to clozapine in schizophrenia. Am J Psychiatry 151:1817-8
Serper, M R; Davidson, M; Harvey, P D (1994) Attentional predictors of clinical change during neuroleptic treatment in schizophrenia. Schizophr Res 13:65-71
Davidson, M; Kahn, R S; Stern, R G et al. (1993) Treatment with clozapine and its effect on plasma homovanillic acid and norepinephrine concentrations in schizophrenia. Psychiatry Res 46:151-63
Stern, R G; Kahn, R S; Harvey, P D et al. (1993) Early response to haloperidol treatment in chronic schizophrenia. Schizophr Res 10:165-71
Kahn, R S; Davidson, M; Hirschowitz, J et al. (1992) Nocturnal growth hormone secretion in schizophrenic patients and healthy subjects. Psychiatry Res 41:155-61
Keefe, R S; Lobel, D S; Mohs, R C et al. (1991) Diagnostic issues in chronic schizophrenia: kraepelinian schizophrenia, undifferentiated schizophrenia, and state-independent negative symptoms. Schizophr Res 4:71-9
Harvey, P D; Davidson, M; Powchik, P et al. (1991) Time course and clinical predictors of treatment response in schizophrenia. Schizophr Res 5:161-6
Davis, K L; Kahn, R S; Ko, G et al. (1991) Dopamine in schizophrenia: a review and reconceptualization. Am J Psychiatry 148:1474-86
Davidson, M; Kahn, R S; Knott, P et al. (1991) Effects of neuroleptic treatment on symptoms of schizophrenia and plasma homovanillic acid concentrations. Arch Gen Psychiatry 48:910-3
Harvey, P D; Putnam, K M; Davidson, M et al. (1991) Brief neuroleptic discontinuation and clinical symptoms in Kraepelinian and non-Kraepelinian chronic schizophrenic patients. Psychiatry Res 38:285-92

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