Enhancing Social Cognitive Training with Oxytocin: Linking Target Engagement to Clinical Effects

用催产素增强社会认知训练：将目标参与度与临床效果联系起来

• 批准号: 8953022
• 负责人: STEPHEN R MARDER
• 金额: $ 33.7万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-15 至 2017-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8953022
• 关键词: Behavioral; Biological; Brain; Clinical Trials; Communities; Crossover Design; Cues; Data; Development; Disease; Dose; Drug effect disorder; Electroencephalography; Emotions; Impairment; Individual; Learning; Link; Measures; Mediating; Mediator of activation protein; Modeling; Motion; Outcome; Oxytocin; Patients; Pharmaceutical Preparations; Phase; Placebos; Process; Psychotic Disorders; Randomized; Research; Schizophrenia; Social Behavior; Social Controls; Testing; Therapeutic; Therapeutic Agents; Training; Training Programs; base; clinical effect; cognitive skill; cognitive training; design; improved; neurophysiology; preference; programs; public health relevance; response; skills; skills training; social; social cognition; social learning; treatment effect

 DESCRIPTION (provided by applicant): Intranasal oxytocin (OT) has shown promise as an agent that can effectively improve social processing in disorders that are characterized by impairments in social behaviors, including schizophrenia. However, important gaps in our understanding of OT's effects on the brain have greatly limited its development as a therapeutic agent and made it difficult to interpret mixed research findings. One very important therapeutic function of OT may be its ability to enhance learning of social information. The proposed research will evaluate, in sequential steps, OT's effects on learning social cognitive skills in psychotic patients within a manualized training program that we have developed. The initial step (R21) is to demonstrate target engagement (i.e., that OT is getting to the brain and influencing social processes) and to establish optimal dosing of OT. Promising neurophysiological measures of target engagement for OT include EEG mu suppression while observing biological motion, and pupillary dilation during an emotion recognition task. The R21 phase will determine the dose-response curve to OT for proposed measures of target engagement (i.e., mu suppression and pupillary dilation). The proposed study will use a single administration, within-subjects, crossover design to model the dose-response to OT across a large range of doses. Subjects with schizophrenia will be randomized to either: 8, 12, 24, 36, 48, 60, 72, or 84 IU OT (6 subjects to each dose). Each subject will receive OT and placebo in administrations separated by one week in randomized order. 30 minutes following OT administration, mu suppression and pupillary response will be assessed. We will also collect data on two measures of social salience (operationally defined here as behavioral tasks of social preference) to examine their correlations with measure of target engagement. The R33 phase will determine whether OT administration 30 min before a SCST session enhances the learning of social information in the context of a social cognitive skills training (SCST) program, and it will test a possible mediator of this effect. Subjects with psychotic disorders will be randomized to one of four groups in a 2 by 2 factorial design: OT with SCST; Placebo with SCST; OT with training control condition; placebo with training control condition. Measure(s) of target engagement supported in the R21 phase, as well as measures of social preference, will be examined in an OT challenge (placebo versus OT one week apart) prior to baseline assessment. A social cognition battery will be administered at baseline, at midpoint after 6 weeks of SCST, and at completion of training at 12 weeks. The battery will include measures of social cue identification and mentalizing.

 描述（由适用提供）：鼻内氧（OT）已显示出作为一种有效改善以社会行为障碍（包括精神分裂症）为特征的疾病的社会加工的代理人的承诺。但是，在我们对OT对大脑影响的理解中的重要差距极大地限制了其作为治疗剂的发展，并使很难解释混合研究结果。 OT的一个非常重要的治疗功能可能是它增强社会信息学习的能力。拟议的研究将通过顺序评估OT对我们开发的手动培训计划中精神病患者学习社交认知技能的影响。最初的步骤（R21）是证明目标参与度（即，OT进入大脑并影响社会过程）并建立了OT的最佳剂量。 OT目标参与的有希望的神经生理学测量包括在观察生物运动的同时进行脑电图抑制，以及在情感识别任务中的瞳孔扩散。 R21相将确定剂量响应曲线至OT，以测量目标参与度（即MU抑制和瞳孔扩散）。拟议的研究将使用单个管理，受试者内部的跨界设计，以对大量剂量的OT剂量反应进行建模。精神分裂症的受试者将随机分为：8、12、24、36、48、60、72或84 IU OT（每种剂量的6名受试者）。每个受试者将以随机顺序分开一周的行政部门中的OT和安慰剂。 OT给药后30分钟，将评估MU抑制和瞳孔反应。我们还将收集有关社会显着性的两种量度（此处定义为社会喜好行为任务）的数据，以检查其与目标参与度量度的相关性。 R33阶段将在SCST会议之前30分钟确定在社会认知技能培训（SCST）计划的情况下30分钟的管理，并将测试 这种效果的可能调解人。患有精神疾病的受试者将在2 x 2阶乘设计中随机分为四组之一：与SCST的OT；安慰剂与SCST； OT具有训练控制条件；具有训练控制条件的安慰剂。在基线评估之前，将在OT挑战（安慰剂与一周相隔一周）中检查在R21阶段支持的目标参与度的度量以及社会偏好的测量值。 SCST 6周后，在基线中的中点和12周完成培训后，将在基线，中点进行社会认知电池。电池将包括社会提示识别和心理化的度量。