Neurophysiological evidence for a defect in inhibitory pathways in schizophrenia: comparison of medicated and drug-free patients.

Central nervous system inhibitory neuronal mechanisms were assessed in clinically stable chronic schizophrenic patients treated with neuroleptic drugs to provide data for comparison with those obtained previously from acutely psychotic, unmedicated patients. An early positive component of the auditory average evoked response recorded at the vertex 50 msec after a click stimulus (P50) was studied. After stimuli were delivered at 10-sec intervals to establish a baseline response, inhibitory mechanisms were assessed in a conditioning-testing paradigm, by measuring the change in response to a second stimulus following the first at either 0.5-, 1.0-, or 2.0-sec intervals. At the 0.5-sec interval, normal controls had over an 80% mean decrement in response, whereas schizophrenics showed a mean decrement of less than 10% but there was no significant difference in suppression between medicated and unmedicated patients. However, the amplitude of P50, which was smaller in unmedicated schizophrenics than in normal subjects, was significantly increased in the medicated patients. The data suggest that inhibitory mechanisms which are dysfunctional in acutely psychotic.