Dopamine in schizophrenia: a review and reconceptualization.
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.


METHODS
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.
Davis
K L
KL
Department of Psychiatry, Mount Sinai Hospital and School of Medicine, New York, NY 10029-6574.
Kahn
R S
RS
Ko
G
G
Davidson
M
M
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D001921:Brain / Q000378:metabolism / Q000503:physiopathology*; D003071:Cognition / Q000502:physiology; D004298:Dopamine / Q000378:metabolism / Q000502:physiology*; D005625:Frontal Lobe / Q000378:metabolism / Q000503:physiopathology; D006719:Homovanillic Acid / Q000097:blood; D006801:Humans; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D012559:Schizophrenia / Q000175:diagnosis / Q000378:metabolism / Q000503:physiopathology*; D012565:Schizophrenic Psychology; D014055:Tomography, Emission-Computed
D014150:Antipsychotic Agents; D011954:Receptors, Dopamine; D004298:Dopamine; D006719:Homovanillic Acid