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.