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Am J Psychiatry 1991; 148:1474-1486
Copyright © 1991 by American Psychiatric Association
Dopamine in schizophrenia: a review and reconceptualization
KL Davis, RS Kahn, G Ko and M Davidson
Department of Psychiatry, Mount Sinai Hospital and School of Medicine, New York, NY 10029-6574.
OBJECTIVE: The initial hypothesis that schizophrenia is a manifestation of
hyperdopaminergia has recently been faulted. However, several new findings
suggest that abnormal, although not necessarily excessive, dopamine
activity is an important factor in schizophrenia. The authors discuss these
findings and their implications. METHOD: All published studies regarding
dopamine and schizophrenia and all studies on the role of dopamine in
cognition were reviewed. Attention has focused on post-mortem studies,
positron emission tomography, neuroleptic drug actions, plasma levels of
the dopamine metabolite homovanillic acid (HVA), and cerebral blood flow.
RESULTS: Evidence, particularly from intracellular recording studies in
animals and plasma HVA measurements, suggests that neuroleptics act by
reducing dopamine activity in mesolimbic dopamine neurons. Post-mortem
studies have shown high dopamine and HVA concentrations in various
subcortical brain regions and greater than normal dopamine receptor
densities in the brains of schizophrenic patients. On the other hand, the
negative/deficit symptom complex of schizophrenia may be associated with
low dopamine activity in the prefrontal cortex. Recent animal and human
studies suggest that prefrontal dopamine neurons inhibit subcortical
dopamine activity. The authors hypothesize that schizophrenia is
characterized by abnormally low prefrontal dopamine activity (causing
deficit symptoms) leading to excessive dopamine activity in mesolimbic
dopamine neurons (causing positive symptoms). CONCLUSIONS: The possible
co-occurrence of high and low dopamine activity in schizophrenia has
implications for the conceptualization of dopamine's role in schizophrenia.
It would explain the concurrent presence of negative and positive symptoms.
This hypothesis is testable and has important implications for treatment of
schizophrenia and schizophrenia spectrum disorders.
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