The P50 auditory event-evoked potential in adult attention-deficit disorder: comparison with schizophrenia.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) and schizophrenia are both conceptualized as disorders of attention. Failure to inhibit the P50 auditory event-evoked response, extensively studied in schizophrenia, could also occur in ADHD patients, if these two illnesses have common underlying neurobiological substrates. METHODS: This study examined the inhibition of the P50 auditory event-evoked potential in 16 unmedicated adults with ADHD, 16 schizophrenic outpatients, and 16 normal control subjects. Auditory stimuli were presented in a paired stimulus, conditioning-testing paradigm. RESULTS: The amplitude of initial or conditioning P50 response did not differ between the three groups; however, significant effects of psychiatric diagnosis on the amplitude of the test response and the ratio of the test to the conditioning response amplitudes were observed. Schizophrenic patients' P50 ratios and test amplitudes were higher than both the ADHD and normal groups. CONCLUSIONS: Adults with ADHD do not have the inhibitory deficit seen in patients with schizophrenia, suggesting that the mechanism of attentional disturbance in the two illnesses may be fundamentally different.

Auditory P50 in schizophrenics on clozapine: improved gating parallels clinical improvement and changes in plasma 3-methoxy-4-hydroxyphenylglycol.

Schizophrenic patients have decreased inhibition of the P50 auditory evoked potential response to the second of two paired click stimuli delivered 500 ms apart. This deficit in inhibitory gating does not change during treatment with typical neuroleptics. We recently reported that neuroleptic-resistant schizophrenics had enhanced P50 gating after 1 month of clozapine treatment, if they responded with decreased clinical symptoms. This study reports the outcome of more prolonged treatment. Ten treatment-refractory schizophrenic patients were studied at baseline, after 1 month on clozapine, and again after 15 +/- 6.1 (SD) months of clozapine treatment. Eight subjects reached a clinically stable improved state, at which time they had significantly improved P50 auditory gating. One patient had a return of impaired gating after stopping clozapine, as did another during a clinical relapse. Decreasing plasma 3-methoxy-4-hydroxyphenylglycol levels with clozapine treatment were correlated with improved P50 gating and improved Brief Bsychiatric Rating Scale-positive scores. This study provides further evidence that improved P50 gating in schizophrenic patients treated with clozapine coincides with clinical improvement and that this improvement can be sustained for at least 1 year.

Gating of auditory P50 in schizophrenics: unique effects of clozapine.

Schizophrenic patients have a deficit in the ability to filter sensory stimuli, which can be demonstrated in several psychophysiological paradigms. For example, most unmedicated schizophrenic subjects fail to decrement the P50 auditory evoked response to the second of paired stimuli, when the interstimulus interval is 500 msec. This sensory gating deficit persists in schizophrenics treated with typical antipsychotics, even if they show significant clinical improvement. When the interstimulus interval is 100 msec, most schizophrenics exhibit impaired gating while acutely ill, but normalize with treatment. Clozapine, the prototypic atypical antipsychotic medication, is clinically more effective than conventional neuroleptics in a significant proportion of schizophrenics refractory to other drug treatment. Nine schizophrenic subjects who were refractory to conventional neuroleptic treatment were studied while being treated with typical neuroleptics and then restudied after 1 month's treatment with clozapine. In the six clozapine responders, there was significant improvement of P50 gating at the 500 msec interval. At the 100 msec interval there was an inverse relationship between sensory gating of P50 and clozapine dose, independent of clinical response. Thus, although this can only be considered preliminary data because of the small number of subjects, it appears that clozapine, compared to typical neuroleptics, has distinct effects on P50 gating.