Oxytocin Treatment of Social Cognitive and Functional Deficits in Schizophrenia

催产素治疗精神分裂症的社会认知和功能缺陷

• 批准号: 8087450
• 负责人: CORT ANDREW PEDERSEN
• 金额: $ 54.49万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-15 至 2014-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8087450
• 关键词: Acute; Aftercare; Animal Experimentation; Animal Model; Antipsychotic Agents; Anxiety; Applied Research; Behavior; Belief; Biological; Clinic; Cognition; Cognitive; Collaborations; Disease; Double-Blind Method; Effectiveness; Emotions; Empathy; Employment; Exhibits; Eye; Face; Functional disorder; Human; Impairment; Individual; Intervention; Intervention Studies; Intranasal Administration; Investigation; Lead; Life; Link; Measures; Mind; Motivation; National Institute of Mental Health; Neuropeptides; Outcome; Oxytocin; Paranoia; Patients; Perception; Performance; Pharmaceutical Preparations; Pilot Projects; Placebo Control; Placebos; Play; Process; Psyche structure; Randomized; Refractory; Reporting; Research; Resources; Rewards; Role; Schizophrenia; Scientist; Social Functioning; Strategic Planning; Study Section; Symptoms; Testing; Therapeutic Effect; Time; Trust; base; clinically relevant; digital; disability; follow-up; improved; informant; innovation; mental health center; placebo controlled study; pre-clinical; psychosocial; response; social; social cognition; social skills; theories; therapy design; treatment duration; treatment program; treatment trial; week trial

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.

描述(由申请人提供)：社会功能缺陷是精神分裂症的一个特征，精神分裂症是这种疾病长期残疾的主要原因，并且仍然对目前可用的抗精神病药物难以治疗。精神分裂症的社会功能障碍与社会认知受损密切相关，社会认知受损是一组认知能力，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)具有许多亲社会作用。OT还在精神分裂症的动物模型中发挥抗精神病药物样的疗效。在最近的人体研究中，鼻腔给药OT增加了人与人之间的信任和眼神接触，并改善了正常受试者的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会缺陷和精神症状。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，在精神分裂症患者中，每天两次鼻腔注射OT(N=8)而不是安慰剂(N=6)，显著1)降低PANSS总分以及猜疑和其他与社会功能相关的PANSS项目的分数，2)降低偏执量表上的受试者评级，3)提高对BR|Ne心理理论测试中二级错误信念的准确识别。我们现在提议一项为期12周的治疗试验，以确定在这段更具临床意义的时期内，OT治疗是否将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。拟议的研究是一位在OT方面有专长的基本行为神经科学家(Cort Pedersen博士)和一位在精神分裂症的社会认知和心理社会治疗方面有专长的应用研究科学家(David Penn博士)之间独特的翻译合作。本项目可能证明OT的治疗效果优于目前的抗精神病药物(特别是在改善社会认知和社会功能方面)，并为精神分裂症的病理生理学研究开辟一条新的战线。 公共卫生相关性：这项研究可能证明，催产素治疗精神分裂症在改善社会认知缺陷(与他人有效互动所必需的精神能力)和社会功能缺陷方面独一无二有效。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，可能使患者更成功地获得和维持就业，形成和维持社会关系，并过上更有意义的生活。这项研究的成功结果也将导致以催产素为重点的精神分裂症生物学基础的新研究。