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（由申请人提供）：鼻内催产素（OT）已显示出作为一种药物的前景，可以有效改善以社会行为障碍为特征的疾病（包括精神分裂症）的社会处理。然而，我们对 OT 对精神分裂症的影响的理解存在重大差距。 OT 的一个非常重要的治疗功能可能是其增强社会信息学习的能力，这极大地限制了其作为治疗剂的发展，并且难以解释 OT 的一个非常重要的治疗功能。步骤，在我们开发的手动培训计划中，OT 对精神病患者学习社交认知技能的影响 第一步 (R21) 是证明目标参与度（即，OT 正在进入大脑并影响社交过程）并确定 OT 的最佳剂量。有前途的 OT 目标参与的神经生理学测量包括观察生物运动时的 EEG mu 抑制，以及情绪识别任务期间的瞳孔扩张。 OT 的剂量反应曲线，用于拟议的目标参与措施（即 mu 抑制和瞳孔扩张）。拟议的研究将使用单一给药、受试者内交叉设计来模拟大范围内 OT 的剂量反应。精神分裂症受试者将被随机分配至：8、12、24、36、48、60、72 或 84 IU。 OT（每剂 6 名受试者）。每个受试者将在 OT 给药后间隔 30 分钟接受 OT 和安慰剂，我们还将评估两项测量的数据。 R33 阶段将确定 SCST 会议前 30 分钟的 OT 管理是否可以增强对社会信息的学习。社交认知技能训练（SCST）计划，它将测试 患有精神障碍的受试者将被随机分配到 2×2 析因设计中的一组：OT 与 SCST；安慰剂与 SCST；OT 与训练控制条件；安慰剂与训练控制条件。在基线评估之前，将在 OT 挑战（安慰剂与 OT 相隔一周）中检查 R21 阶段支持的目标参与度以及社会偏好测量，将在基线和中点进行社会认知电池测试。 SCST 6 周后以及 12 周训练完成后，该电池将包括社交线索识别和心理化的测量。