杰出学者973项目解析精神分裂症

　　

生物通报道：来自中科院心理所的消息，心理所心理健康院重点实验室神经心理学与应用认知科学实验室与汕头大学精神卫生中心的研究人员考查了不同抗精神病药对首发未服药精神分裂症病人P50的影响，发现精神分裂症的P50缺损是由疾病本身而不是由药物造成的。这一研究成果公布在爱思唯尔期刊《精神分裂症研究》（Schizophrenia Research）上。

领导这一研究的是中科院心理所的陈楚侨研究员，其早年毕业于香港大学，拥有康复科学专业资格,并曾在香港多间医院机构工作，专心于中风、脊椎受损、其它神经系统引发的疾病的患者及其家人的心理卫生、适应过程、生活素质等问题。近年他主要致力于神经心理学及认知神经科学研究，在2008年取得了多项研究成果，还获得了澳大利亚格里菲斯大学杰出学者奖。

精神分裂症的感觉门控功能（由P50反映）存在障碍。虽然有很多证据表明典型抗精神病药物所引起的感觉门控障碍是无法逆转的，但关于非典型抗精神病药物所引起的精神分裂症病人的P50缺损是否可以逆转结果不太一致。以前的大部分研究都存在一些局限，如研究是横断面设计或收集的病例是服多种药物的。

研究人员考查了不同抗精神病药对首发未服药精神分裂症病人P50的影响。研究对65个首发未服药的精神分裂症病人进行了基线和药物治疗6周后（舒必利24人，维斯通24人，氯氮平17人）进行了P50诱发电位的记录，62个健康控制组进行了基线P50的记录。结果发现首发未服药的病人和健康控制组相比存在感觉门控的障碍（均值分别为94.19% [SD=61.31%]，41.22% [SD=33.82%]）。检验刺激S2的波幅在精神分裂症病人中显著高于控制组。精神分裂症病人在基线时条件刺激S1的波幅及阳性症状与P50门控比相关。P50在服用不同药物的3组病人在基线（F（2，62）=1.074，p=0.348）及服药后（F（2，62）=0.441，p=0.646）都没有显著差异。本研究的一个优点是收集了首发未服药的精神分裂症病人来考查非典型抗精神病药物对P50的影响，这样，就能知道抗精神病药对精神分裂症P50的真正的影响。即，本研究的结果说明精神分裂症的P50缺损是由疾病本身而不是由药物造成的。

本研究的另一个优点是可以确定不同抗精神病药对P50的影响，进而可以为临床医生提供证据，告诉病人及他们的家属药物治疗在神经生理缺损方面带来的影响。总之，本研究结果表明，P50在首发未服药的精神分裂症病人中存在缺损，非典型抗精神病药对该类缺损没有影响。精神分裂症P50的缺损可能可以作为它的一个内表型标记。进一步的更严格的前瞻性跟踪研究设计，以及把被试扩展到病人未发病的家属可以为该推测提供更有力的证据。

原文摘要：

Neuroleptic effects on P50 sensory gating in patients with first-episode never-medicated schizophrenia

Sensory gating deficit, as reflected by P50 suppression, has been demonstrated in schizophrenia. Despite extensive evidence of the irreversible effects of typical neuroleptics on this deficit, recent studies of atypical neuroleptics have produced inconsistent findings on the reversibility of P50 suppression in schizophrenia. As the majority of these studies were limited by either their cross-sectional design or the recruitment of patients on multiple medications, the current study was designed to examine the effects of different neuroleptic medications on the P50 sensory gating index in patients with first-episode, never-medicated schizophrenia. P50-evoked potential recordings were obtained from 62 normal controls when they entered the study and from 65 patients with first-episode, never-medicated schizophrenia at baseline and after six weeks of different neuroleptic treatments (sulpiride [n = 24], risperidone [n = 24] and clozapine [n = 17]). The first-episode, never-medicated schizophrenia patients had impaired sensory gating relative to the normal controls (mean = 94.19% [SD = 61.31%] versus mean = 41.22% [SD = 33.82%]). The test amplitude S2 was significantly higher in the schizophrenia patients than in the normal controls. The conditioning amplitude S1 and the positive symptom scores were related to the P50 gating ratios in schizophrenia at baseline. There was no change in P50 sensory gating (P > 0.10) and a significant improvement in the clinical ratings (P > 0.10) after six-week neuroleptic treatment for schizophrenia. P50 sensory gating was not significant for the patients who received sulpiride, risperidone or clozapine at baseline (F = 1.074, df = 2, 62, P = 0.348) or at endpoint (F = 0.441, df = 2, 62, p = 0.646). Our findings indicate that there is P50 sensory gating impairment in first-episode, never-medicated schizophrenia and that treatment with typical and atypical antipsychotics has no significant impact on such gating in this illness.