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For the past decade, the dopamine hypothesis of schizophrenia has been the predominant biochemical theory of schizophrenia. Despite the extensive study of tissue samples obtained from schizophrenics, indirect pharmacological evidence still provides the major support for the hypothesis. Direct support is either uncompelling or has not been widely replicated. The dopamine hypothesis 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 together the genetic, environmental, and clinical features of schizophrenia. Recent refinements of the dopamine hypothesis may aid in the delineation of biologically homogeneous subgroups. Positive symptoms (e.g., hallucinations, delusions) and negative symptomatology (e.g., affective flattening, social withdrawal) may result from different pathophysiological processes. Schizophrenia research might benefit from an increased attention to neurophysiological adaptations.

No current biological hypothesis can assimilate the genetic, environmental, and clinical features of schizophrenia. If, as some authors contend, environmental factors have important effects on the course of schizophrenia, then a fruitful research concern may be the adaptation of neuronal circuitry to environmental changes. The plasticity of neuronal connections has been studied by subjecting animals to neurosurgical lesions, brain electro-stimulation, and a variety of rearing environments. The present article approaches the schizophrenia research literature from a theoretical perspective which takes into account the plasticity of neuronal connections. In a speculative manner, it demonstrates how neural plasticity concepts can be invoked to explain the following seemingly disparate features of schizophrenia: the pharmacological support for the dopamine hypothesis, the delayed onset and offset of neuroleptic antipsychotic action, genetic and environmental influences in schizophrenia, the regional alterations in brain structure and function seen in chronic schizophrenic patients, and the various types of behavioral symptoms exhibited by schizophrenic patients. In view of the explanatory potential of neural plasticity concepts, a research program that focuses on these concepts seems warranted.

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