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一个标志，是这种疾病长期残疾的主要原因，目前可用的抗精神病药物仍然难以治疗。精神分裂症的社会功能障碍与受损的社会认知密切相关，社会认知是一组认知能力，包括情感识别，归因风格和心理理论。几十年的动物研究表明，催产素（OT）具有许多亲社会的作用。OT还在精神分裂症的动物模型中发挥抗精神病样功效。在最近的人类研究中，鼻内施用OT增加了正常受试者的人际信任和眼神接触，以及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治疗可以改善精神分裂症的社会缺陷和精神病性症状。在一项为期2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1）降低PANSS总评分以及怀疑和其他社会功能相关PANSS项目的评分，2）降低了偏执量表的受试者评分，3）提高了对Br中二阶错误信念的准确识别|心理理论的一项测试，在精神分裂症患者中。我们现在提出了一个12周的治疗试验，以确定在这个更临床相关的时期，OT治疗是否会1）进一步改善社会认知，2）改善社会功能和3）进一步减少其他精神病症状。拟议的研究是具有OT专业知识的基本行为神经科学家（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（大卫佩恩博士）之间的独特翻译合作。该项目可能证明OT具有上级当前抗精神病药物的治疗效果（特别是社会认知和社会功能的改善），并在精神分裂症的病理生理学研究中开辟了一个新的前沿。 公共卫生相关性：这项研究可能表明，催产素治疗精神分裂症在改善社会认知缺陷（与他人有效互动所需的心理能力）和社会功能缺陷方面是独特有效的。这些缺陷是这种疾病残疾的主要原因，对目前的抗精神病药物没有反应。通过催产素治疗改善社会认知和功能，可以使患者更成功地获得和维持就业，形成和维持社会关系，过上更有意义的生活。这项研究的成功结果也将导致对精神分裂症生物学基础的新的以催产素为重点的研究。

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.