Nagamoto H T, Adler L E, Hea R A, Griffith J M, McRae K A, Freedman R
Department of Psychiatry, Denver Veterans Affairs Medical Center, CO, USA.
Biol Psychiatry. 1996 Aug 1;40(3):181-8. doi: 10.1016/0006-3223(95)00371-1.
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.
精神分裂症患者在过滤感觉刺激的能力方面存在缺陷，这在几种心理生理学范式中都可以得到证明。例如，当刺激间隔为500毫秒时，大多数未服用药物的精神分裂症患者对成对刺激中的第二个刺激的P50听觉诱发电位反应不会减弱。这种感觉门控缺陷在使用典型抗精神病药物治疗的精神分裂症患者中持续存在，即使他们显示出显著的临床改善。当刺激间隔为100毫秒时，大多数精神分裂症患者在急性发病时表现出门控受损，但治疗后恢复正常。氯氮平作为非典型抗精神病药物的原型，在相当一部分对其他药物治疗无效的精神分裂症患者中，临床疗效比传统抗精神病药物更好。对9名对传统抗精神病药物治疗无效的精神分裂症患者进行了研究，他们先接受典型抗精神病药物治疗，然后在接受氯氮平治疗1个月后再次进行研究。在6名对氯氮平有反应的患者中，500毫秒间隔时P50门控有显著改善。在100毫秒间隔时，P50的感觉门控与氯氮平剂量呈负相关，与临床反应无关。因此，尽管由于受试者数量较少，这只能被视为初步数据，但与典型抗精神病药物相比，氯氮平似乎对P50门控有明显影响。
