Effects of clozapine on auditory event-related potentials in schizophrenia

Background: Schizophrenia is associated with cognitive deficits that are an intrinsic component of the disorder. Clozapine is an atypical antipsychotic that is superior to typical agents in the treatment of positive symptoms. The degree to which clozapine ameliorates cognitive deficits, however, is still controversial. Mismatch negativity (MMN), N200 (N2), and P300 (P3) are cognitive event-related potentials (ERPs) that index preattentive (MMN) and attention-dependent information processing (N2, P3) and provide a measure of cognitive deficits associated with schizophrenia. In schizophrenic patients deficient generation of MMN, N2, and P3 has been observed, suggesting impairments of discrete stages of information processing. Methods: This study investigates the effects of clozapine treatment on MMN, N2, and P3 generation. Patients were recruited from a haloperidol-controlled, double-blind treatment study of clozapine in chronic schizophrenia. ERPs were obtained at the beginning of the study and after 9 weeks (4 patients) and 16 weeks (13 patients) of treatment. Results: Clozapine treatment was associated with a significant increase of P3 amplitude, which was not observed in the haloperidol group; however, clozapine treatment did not affect deficits in MMN and N2. Conclusions: These findings suggest that clozapine—in contrast to conventional antipsychotics—improves electrophysiological measures of attention-dependent information processing, but does not ameliorate preattentive deficits