Biobehavioral inflexibility and risk for juvenile-onset depression

这份修订后的竞争性续签申请建立在我们最近对SAD联合监管的研究基础上， 烦躁不安(情绪修复)和自主神经系统(ANS)功能的心脏指数(包括 呼吸窦性心律不齐(RSA)在不同抑郁风险水平的年轻人中。为回应这一事件 IRG的评论，我们提供了关于我们评估和抽样的协变量的进一步信息 特征；协变量对关键结果的影响；进一步阐述研究的意义；注意 方法的变化，并总结新的发现。使用高风险家庭设计，我们一直在研究 有青少年起病抑郁(JOD)病史的青少年先证者的临床样本，他们从来没有。 抑郁(高危)兄弟姐妹和健康对照。我们提出3项协同研究作为下一步的合乎逻辑的步骤， 基于我们的发现和最近的文献。研究1解决了日常烦躁情绪的程度 生活反映了个体在情绪修复反应和/或背景方面的差异，以及情绪修复的效果如何 同时，基于实验室的情绪修复评估和RSA与现实生活中的情绪修复相关。在实验室之后- 礼仪、情感和自然主义情绪修复将在100年通过生态瞬时评估进行采样 先证者、100名高危兄弟姐妹和100名对照；7天的采样间隔将与每个受试者的 生日保证了一个具有潜在情感意义的统一的生活事件。研究2调查机制：IT 检验这样一种假设，即将注意力从导致抑郁的物质和 关联性焦虑症是适应性情绪修复的关键机制，受个体差异的影响。 生物行为功能。采用“概念证明”的方法，先证者(n=160)将被随机分配到 伪装注意力训练或训练，以提高将注意力从负面材料上转移的能力；效果 关于情绪修复的注意力训练将在RSA档案和之前的情绪修复的背景下进行审查 成功。延长了先前研究的随访期的研究3提出，非典型RSA特征 (休息RSA+RSA对悲伤情绪的反应的非规范组合)和低积极情感是 首发抑郁症的真实、发病前危险因素：将包括175名高危兄弟姐妹和175名 在他们最后一次研究评估中还没有临床抑郁症的健康对照组。作为次要目标， 我们将描述情绪修复曲目从儿童后期到新兴阶段的发展轨迹 成人期。使用多水平建模，研究结果将进一步阐明情绪修复何时(以及如何)失败 (或成功)，注意力作为一种机制，以及ANS功能的作用。结果也将有助于确定 抑郁症风险的可修改的发病前预测因子和发育以及背景调节因子 临床结果。因此，总体而言，拟议的研究将有助于病因学模型的演变。 还有助于推进抑郁症的个性化治疗和预防干预， 造福公众健康的最终目标。

This REVISED competing renewal application builds on our recent study of the joint regulation of sad, dysphoric affect (mood repair) and cardiac indexes of autonomic nervous system (ANS) functioning (including respiratory sinus arrhythmia, RSA) among youths at varying levels of depression risk. In response to the IRG's comments, we provide information further on about the covariates we assess and sample characteristics; the effects of covariates on key outcomes; explicate further the study's significance; note changes in the Methods, and summarize new findings. Using a high-risk family design, we have been studying a clinical sample of adolescent probands with juvenile-onset depression (JOD) histories, their never- depressed (high-risk) siblings, and healthy controls. We propose 3 synergistic studies as the logical next step, based on our findings and the recent literature. Study 1 addresses the extent to which dysphoric mood in daily life reflects individual differences in features of mood repair responding and/or context, and how well contemporaneous lab-based assessment of mood repair and RSA relate to real-life mood repair. After a lab- protocol, affect and naturalistic mood repair will be sampled via Ecological Momentary Assessment in 100 probands, 100 high-risk siblings, and 100 controls; the 7-day sampling interval will overlap with each subject's birthday to assure a uniform life event with potential affective significance. Study 2 investigates mechanisms: it examines the hypothesis that the capacity to switch attention away from depressogenic material and associated dysphoria is a key mechanism of adaptive mood repair, subject to individual differences in biobehavioral functioning. Using a “proof of concept” approach, probands (n=160) will be randomly assigned to sham attention training or training to improve the ability to switch attention away from negative material; effects of attention training on mood repair will be examined in the context of RSA profiles and prior mood repair success. Study 3, which extends the follow-up period of the prior study, proposes that atypical RSA profiles (non-normative combinations of resting RSA+RSA response to sad mood) and low positive affectivity are bona fide, pre-morbid risk factors for first-onset depression: it will include 175 high-risk siblings and 175 healthy controls who did not yet have clinical depression at their last research evaluation. As a secondary goal, we will characterize developmental trajectories of mood repair repertoires from late childhood into emerging adulthood. Using multilevel modeling, study results will shed further light on when (and how) mood repair fails (or succeeds), attention as a mechanism, and the role of ANS functioning. Results also will serve to identify modifiable pre-morbid predictors of depression risk and developmental as well as contextual moderators of clinical outcomes. Overall therefore, the proposed study will contribute to evolving models of the etiology depression, and also help advance personalized therapeutic and preventive interventions for depression, with the ultimate goal of benefitting public health.