Biobehavioral inflexibility and risk for juvenile-onset depression

摘要 在这个修订后的应用程序中，它侧重于生物行为的可识别性作为一个框架，以确定风险因素 对于青少年抑郁症（juvenile-onset depression，JOD），我们对IRG的每一个问题都做出了回应。具体而言，我们：a）提供 我们的模型，假设和统计方法的更明确的公式，B）解决可能的 环境调节剂，和c）提出新的试点研究的结果，这表明我们有能力诱导和 纠正匈牙利受试者的烦躁情绪，并支持使用心脏迷走神经的躯体探针 控制年轻人。在这个应用中，我们建议研究当前和未来JOD之间的关系 风险和两个功能重要的生物行为系统：心脏迷走神经控制（CVC）和情绪修复。到 表征CVC的可接受性，我们将评估CVC在不同实验挑战中的功能 （躯体与心理）;在一种类型的挑战的版本内（例如，替代心理任务）;以及 在CVC的不同方面（静息与CVC反应性和恢复）。为了描述僵硬情绪修复的特征， 我们将评估受试者在消极情绪挑战后减弱烦躁情绪的能力， 实施2种不同的情绪修复策略（积极的自传体回忆与分散注意力）， 不同的情绪修复机会（实验控制与非结构化）。我们的样本（11-18岁 入组时）将包括200名患有JOD的先证者，200名尚未受JOD影响的高危兄弟姐妹，以及100名 从不生病的控制。先证者（和兄弟姐妹）将从一个仔细诊断和良好表征的 700多例年轻JOD患者（每个人至少有一个兄弟姐妹）的样本，代表了一个国家，临床 在匈牙利的样本，谁参加了最近的计划项目。设计包括横截面 评估CVC、情绪修复、精神状态和心理社会功能，以及纵向临床 随访我们提出：（1）生理可操作性（操作为受损CVC的指标）和 行为能力（可操作为受损情绪修复的指标），以及它们的组合（全球生物- 行为能力指数），将横截面区分先证者，在风险的兄弟姐妹，和控制同行 以及（2）总体生物行为能力指数将前瞻性地预测临床过程（升高 抑郁症状，JOD先证者的复发性抑郁发作， 以前未受影响的兄弟姐妹）。我们还将在以下情况下测试我们的全球可接受性模型的要素： 环境调节剂。我们的研究意义重大，因为抑郁症是导致残疾的主要原因 国际吧此外，JOD是一种严重和复发性的抑郁症，占约50%的抑郁症患者。 年轻人的抑郁症。我们的研究是创新的，因为它：（a）整合了生物学和 与抑郁症相关的具有现成翻译潜力的行为指标，（B）使用以下替代探针： 跨多个刺激条件的CVC和情绪修复，以获得这些结构的更丰富的表征， 以及（c）其生物行为目标可以为检测、预防和治疗抑郁症的改进工作提供信息。

Abstract In this revised application, which focuses on bio-behavioral inflexibility as a framework to identify risk factors for juvenile-onset depression (JOD), we responded to each of the IRG's concerns. In particular, we: a) offer more explicit formulations of our model, hypotheses, and statistical approaches, b) address possible environmental moderators, and c) present the results of new pilot studies, which show our ability to induce and remediate dysphoric mood in Hungarian subjects and support the use of somatic probes of cardiac vagal control in youths. In this application, we propose to study the relation between current and prospective JOD risk and two functionally important bio-behavioral systems: cardiac vagal control (CVC) and mood repair. To characterize CVC inflexibility, we will assess CVC functioning across different experimental challenges (somatic vs. psychological); within versions of one type of challenge (e.g., alternative psychological tasks); and across different facets of CVC (resting vs. CVC reactivity and recovery). To characterize inflexible mood repair, we will assess subjects' ability to attenuate dysphoric mood subsequent to negative mood challenges by implementing 2 different mood repair strategies (positive autobiographical recall vs. distraction) and across different mood repair opportunities (experimentally controlled vs. unstructured). Our sample (11-18 years old at entry) will include 200 probands with JOD, 200 of their at-risk siblings not yet affected by JOD, and 100 never-ill controls. Probands (and siblings) will be recruited from a carefully diagnosed and well-characterized sample of 700+ young patients with JOD (each with at least one sibling), representing a national, clinical sample in Hungary, who participated in a recent Program Project. The design includes cross-sectional assessment of CVC, mood repair, psychiatric status, and psychosocial functioning, and longitudinal clinical follow-up. We propose that: (1) physiological inflexibility (operationalized as indices of impaired CVC) and behavioral inflexibility (operationalized as indices of impaired mood repair), and their combinations (global bio- behavioral inflexibility indices), will cross-sectionally distinguish probands, at-risk siblings, and control peers and that (2) global bio-behavioral inflexibility indices will prospectively predict clinical course (elevated depressive symptoms, recurrent depressive episodes in JOD probands, onset of first depressive episode in previously unaffected siblings). We also will test elements of our global inflexibility models in the presence of environmental moderators. Our study is significant because depression is a leading cause of disability worldwide. Moreover, JOD is a severe and recurrent form of depression that accounts for about 50% of the cases of depression in young adults. Our study is innovative because it: (a) integrates biological and behavioral indices relevant to depression that have ready translational potential, (b) uses alternate probes of CVC and mood repair across multiple stimulus conditions to obtain a richer characterization of these constructs, and (c) its bio-behavioral targets can inform improved efforts to detect, prevent, and treat depression.