Oxytocin Treatment of Social Cognitive and Functional Deficits in Schizophrenia

描述（由申请人提供）：社会功能缺陷是精神分裂症的标志，是这种疾病长期残疾的主要原因，并且对目前可用的抗精神病药物仍然难治。精神分裂症患者的社交功能障碍与社会认知障碍密切相关，社会认知障碍是一系列认知能力，包括情绪识别、归因风格和心理理论。几十年的动物研究表明，催产素（OT）具有许多亲社会效应。OT在精神分裂症动物模型中也有类似抗精神病药物的功效。在最近的人体研究中，鼻内注射OT增加了正常受试者的人际信任和目光接触，并改善了情绪识别和心理理论。基于这些先前的发现，我们假设OT治疗可能改善精神分裂症的社交缺陷和精神病症状。在一项为期两周的随机、双盲、安慰剂对照的初步研究中，我们发现，每天两次鼻内给予OT （N=8)，而不是安慰剂（N=6），显著降低了精神分裂症患者PANSS总分以及怀疑和其他社会功能相关的PANSS项目得分，2）降低了偏执量表的被试评分，3)提高了Br bbbbne心理理论测试中二级错误信念的准确识别。我们现在建议进行一项为期12周的治疗试验，以确定在这段与临床更相关的时间内，OT治疗是否会1)进一步改善社会认知，2)改善社会功能，3)进一步减少其他精神病症状。拟议的研究是具有OT专业知识的基础行为神经科学家（Cort Pedersen博士）和具有精神分裂症社会认知和心理社会治疗专业知识的应用研究科学家（David Penn博士）之间独特的转化合作。该项目可能会证明OT具有优于当前抗精神病药物的治疗效果（特别是在社会认知和社会功能方面的改善），并为精神分裂症的病理生理学研究开辟新的前沿。

DESCRIPTION (provided by applicant): Deficits in social functioning are a hallmark of schizophrenia, the major cause of long-term disability in this disorder, and remain refractory to currently available antipsychotic medications. Social dysfunction in schizophrenia has been strongly linked to impaired social cognition, a set of cognitive abilities that include emotion recognition, attributional style and theory of mind. Oxytocin (OT) has been shown by decades of animal research to have numerous pro-social effects. OT also exerts antipsychotic-like efficacy in animal models of schizophrenia. In recent human studies, intranasal administration of OT increased interpersonal trust and eye contact as well as improved emotion recognition and theory of mind in normal subjects. Based on these prior findings, we hypothesized that OT treatment may improve social deficits and psychotic symptoms in schizophrenia. In a 2-wk randomized, double blind, placebo-controlled pilot study, we found that twice daily intranasal administration of OT (N=8), but not placebo (N=6), significantly 1) decreased PANSS total scores as well as scores on suspiciousness and other social function-relevant PANSS items, 2) decreased subject ratings on the Paranoia Scale and 3) improved accurate identification of second order false beliefs in the Br|ne test of theory of mind, among patients with schizophrenia. We now propose a 12-wk treatment trial to determine over this more clinically relevant period whether OT treatment will 1) further improve social cognition, 2) improve social functioning and 3) further decrease other psychotic symptoms. The proposed research is a unique translational collaboration between a basic behavior neuroscientist with expertise in OT (Dr. Cort Pedersen) and an applied research scientist with expertise in social cognition and psychosocial treatment in schizophrenia (Dr. David Penn). This project may demonstrate that OT has therapeutic effects that are superior to current antipsychotic medications (especially improvement in social cognition and social functioning) and open a new front in the investigation of the pathophysiology of schizophrenia. PUBLIC HEALTH RELEVANCE: This study may demonstrate that oxytocin treatment in schizophrenia is uniquely effective in improving deficits in social cognition (mental abilities necessary for interacting effectively with other people) and deficits in social function. These deficits are the primary causes of disability in this disorder and are not responsive to current antipsychotic medications. Improving social cognition and function with oxytocin treatment may enable patients to more successfully obtain and maintain employment, form and sustain social relationships and live more rewarding lives. Successful outcomes in this study would also lead to new lines of oxytocin- focused research into the biological basis of schizophrenia.