Dopaminergic mechanisms in the pathogenesis of schizophrenia

The dopamine hypothesis of schizophrenia has been the dominant theoretical construction guiding research and treatment of the schizophrenic disorders over the past generation. This hypothesis, in its simplest guise, posits the presence of a functional alteration in central dopaminergic systems in the brains of schizophrenic patients. Recent findings have resulted in a greater understanding of the complexity of the central dopaminergic systems and have led to revisions of the hypothesis of a simple functional hyperactivity of central dopaminergic systems. These recent data suggest that there may be regionally restricted changes in the function of the mesotelencephalic dopamine system, and that these changes may be in opposite directions. Such changes may be associated with dysfunctions of interactions between distinct dopaminergic terminal field regions, and may be subserved by functional derangements in other transmitter systems or reflect regionally restricted changes in expression or function of distinct dopamine receptors or catecholamine synthetic enzymes. A recent FASEB symposium reviewed new advances in molecular biology, biochemistry, pharmacology, anatomy, and systems neuroscience as they relate to schizophrenia, and discussed the implications of these data for guiding future research and treatment strategies.