Positive valence systems engagement during social reward exposure psychotherapy for mid- and late-life depression

项目摘要/摘要 拟议的K23以患者为导向的研究职业发展奖旨在提供 具有独立职业生涯所需的概念性知识和技术技能的候选人 研究人员关注个性化过程中行为和神经网络目标的参与 治疗中晚期抑郁症的心理疗法。候选人将在以下地点进行培训和研究活动 威尔康奈尔老年精神病学研究所的快活中心。 该提议的前提是识别特定的行为和神经网络目标 可以指导简化干预措施的开发，具有广泛的可扩展性和覆盖面。“参与”，a 对晚年抑郁症的简化治疗，其主要干预措施是“奖励暴露”，可能会改变 正价系统(PVS)函数。候选人的初步研究表明，早期增加的 PVS结构在“接合”期间的静息状态功能连接性(RsFC)预测增加的行为 激活。此外，与单独愉快的活动相比，接触有益的社交活动 在“参与”过程中，行为激活度的增加和抑郁严重程度的降低。最后， 应聘者进行的一项机器学习分析表明，低感知社会支持是 心理治疗早期不良反应的最强预测者。这些发现与动物和人类的研究结果一致。 证明社会奖励的保护作用的研究。基于这些观察，候选人 开发了《敬业S》，这是一个基于社会回报的版本，旨在增加接触有意义的人 与他人的社交互动。 培训研究建议考察《接洽-S》中的社会回报暴露是否会提高PVS 反常和改善中老年抑郁症。参与者将是60岁以上的中年人 患有严重抑郁症的成年人(年龄为≥50)，他们将被随机分成两组，一组接受9周的S治疗，另一组接受症状治疗 复习与心理教育(SRP)对照情况。在治疗期间，我们将检查靶点 PVS与rsFC的参与度、行为激活量表(BADS)，以及在新型社交媒体上的表现 奖励模式分别为基线、5周和9周。我们将使用计算方法来识别 与治疗反应相关的神经成像和行为特征。 培训计划由正式课程、结构化教程和实践方法培训组成 这将为应聘者提供以下方面的知识和技能：1)抑郁症和衰老的功能神经解剖学；2) 在中老年抑郁症的心理治疗中使用功能磁共振成像评估目标投入；3) 用于识别治疗反应的临床和神经成像预测因素的计算模型 可用于个性化心理治疗；以及4)为R系列实验生成初步数据 治疗公司的目标是参与应用。

PROJECT SUMMARY/ ABSTRACT The proposed K23 Patient-Oriented Research Career Development Award is designed to provide the candidate with the conceptual knowledge and technical skills needed for a career of an independent investigator focused on the engagement of behavioral and neural network targets during personalized psychotherapies for mid- and late depression. The candidate will conduct her training and research activities at the ALACRITY Center of the Weill Cornell Institute of Geriatric Psychiatry. The proposal is based on the premise that identifying specific behavioral and neural network targets can guide development of streamlined interventions with potential for broad scalability and reach. “Engage”, a streamlined therapy for late-life depression, whose principal intervention is “reward exposure”, may change Positive Valence Systems (PVS) functions. Preliminary studies by the candidate show that early increase in resting state functional connectivity (rsFC) of PVS structures during “Engage” predicts increased behavioral activation. Additionally, compared to solitary pleasant activities, exposure to rewarding social interactions during “Engage” leads to greater increase in behavioral activation and reduction of depression severity. Finally, a machine learning analysis conducted by the candidate showed that low perceived social support is the strongest predictor of poor response early in psychotherapy. These findings are in line with animal and human studies demonstrating the protective role of social rewards. Based on these observations, the candidate developed “Engage-S”, a social-reward based version of “Engage”, aimed to increase exposure to meaningful social interactions with others. The training study proposes to examine whether social reward exposure in “Engage-S” enhances PVS abnormalities and improves mid- and late-life depression. The participants will be 60 middle-aged and older adults (age ≥ 50) with major depression who will be randomized to 9-weeks of “Engage-S” or to a Symptom Review and Psychoeducation (SRP) comparison condition. During treatment, we will examine target engagement of the PVS with rsFC, a behavioral activation scale (BADS), and performance on a novel social reward paradigm at baseline, 5 weeks, and 9 weeks. We will use computational methods to identify neuroimaging and behavioral profiles associated with treatment response. The training plan consists of formal courses, structured tutorials, and hands-on methodological training that will offer the candidate knowledge and skills in: 1) Functional neuroanatomy of depression and aging; 2) Use of fMRI to assess target engagement during psychotherapies for mid- and late-life depression; 3) Computational modeling for the identification of clinical and neuroimaging predictors of treatment response that can be used to personalize psychotherapy; and 4) Generate preliminary data for an R-series experimental therapeutics target engagement application.