Neurological signs and involuntary movements in schizophrenia: intrinsic to and informative on systems pathobiology.

While it has long been considered whether the pathobiology of schizophrenia extends beyond its defining symptoms to involve diverse domains of abnormality, in the manner of a systemic disease, studies of neuromotor dysfunction have been confounded by treatment with antipsychotic drugs. This challenge has been illuminated by a new generation of studies on first-episode schizophrenia before initiation of antipsychotic treatment and by opportunities in developing countries to study chronically ill patients who have remained antipsychotic naive due to limitations in provision of psychiatric care. Building from studies in antipsychotic-naive patients, this article reviews 2 domains of neuromotor dysfunction in schizophrenia: neurological signs and involuntary movements. The presence and characteristics of neurological signs in untreated vis-à-vis treated psychosis indicate a vulnerability marker for schizophrenia and implicate disruption to neuronal circuits linking the basal ganglia, cerebral cortex, and cerebellum. The presence and characteristics of involuntary movements in untreated vis-à-vis treated psychosis indicate an intrinsic feature of the disease process and implicate dysfunction in cortical-basal ganglia-cortical circuitry. These neuromotor disorders of schizophrenia join other markers of subtle but pervasive cerebral and extracerebral, systemic dysfunction, and complement current concepts of schizophrenia as a disorder of developmentally determined cortical-basal ganglia-thalamo-cortical/cerebellar network disconnectivity.