Developmentally moderated expressions of the neuropathology underlying schizophrenia.

Abstract

A gradually accumulating body of literature suggests that behavioral dysfunction precedes the onset of the schizophrenic syndrome by many years. Thus, a comprehensive neurodevelopmental model of schizophrenia must encompass these early manifestations of dysfunction as well as the postmorbid period. This article draws on previous research findings as well as recently proposed neurodevelopmental models to offer some further hypotheses about the neurodevelopmental process underlying the changing life-course manifestations of the diathesis for schizophrenia. It is proposed that normal maturational events in the central nervous system moderate the behavioral expression of a congenital neuropathology that affects subcortical regions of the brain that are part of multiple neural circuits. Specifically, it is suggested that the diathesis for schizophrenia involves a functional excess of dopamine activity in the basal ganglia that serves to disrupt these circuits. Findings from empirical research suggest a modal developmental trajectory for schizophrenia in which neuromotor dysfunction is most pronounced in early childhood and late in life, whereas florid psychotic symptomatology is most pronounced in late adolescence and early adulthood. The literature on normal central nervous system development suggests that the feedback circuit linking motor cortex with subcortical structures is maximally metabolically activated, relative to other circuits, early and late in the life course. Thus, subcortical dopamine excess may be predominantly expressed in motoric symptoms during these periods. In contrast, late adolescence and early adulthood are marked by low motor cortex metabolic activity relative to other cortical regions, in particular limbic and frontal regions. In addition, hormonal changes appear to result in a maximal activation of the dopamine system during this developmental period. Thus, it is hypothesized that during this period the neural circuitry abnormality will be primarily behaviorally expressed in psychotic symptoms. Some implications of the model for the study of movement abnormalities and psychotic symptoms are discussed.