438 The Dopamine Hypothesis: An Overview of Studies With Schizophrenic Patients

For the past decade, the dopamine hypothesis of schizophrenia has been the predominant biochemi-cal theory of schizophrenia. De-spite the extensive study of tissue samples obtained from schizo-phrenics, indirect pharmacologi-cal evidence still provides the ma-jor support for the hypothesis. Direct support is either uncom-pelling or has not been widely replicated. The dopamine hypoth-esis is limited in theoretical scope and in the range of schizophrenic patients to which it applies. No comprehensive biological scheme has yet been proposed to draw to-gether the genetic, environmental, and clinical features of schizo-phrenia. Recent refinements of the dopamine hypothesis may aid in the delineation of biologically homogeneous subgroups. Positive symptoms (e.g., hallucinations, delusions) and negative sympto-matology (e.g., affective flat-tening, social withdrawal) may result from different pathophysi-ological processes. Schizophrenia research might benefit from an increased attention to neuro-physiological adaptations. The dopamine (DA) hypothesis of schizophrenia was founded on in-direct pharmacological evidence. Early observations suggested a dopaminergic hyperactivity in schizophrenia: the symptoms of acute paranoid schizophrenia re-semble the psychosis induced in nonschizophrenics by ampheta-mine, an indirect DA agonis