Three Generations at High and Low Risk for Depression Followed Longitudinally

项目摘要 这是一项对高危和低危家庭进行的为期30年的多代纵向研究的4年续展 重度抑郁症(MDD)。该项目已经取得了关于家族性肺炎传播的重要发现。 情绪障碍，并有助于该领域对长期时间序列的理解 从儿童期到成年期的疾病，以及这些过程的神经生物学相关性。然而， 尽管取得了这些进展，但家族风险导致后代损害的机制仍然存在。 不发达。NIMH的研究领域标准(RDoC)为测试潜力提供了一个引人注目的模型 机制，通过提出结合神经生物学和行为学的功能系统(“构造”) 信息。因此，此次更新旨在前瞻性地测试RDoC构造是否是一种机制 (即，中介物)，通过其家族史导致成人的功能结果和症状轨迹。利用 我们将集成来自多个分析单元(多个)的数据 MRI形式、电生理、行为和自我报告)来定义与3个潜伏期相对应的潜伏期变量 RDoC结构：急性威胁、接近动机和反应抑制。首先，我们将量化 测试-重新测试RDoC指标(MRI、生理、行为等)的可靠性通过重新评估每一项 代表性参与者小样本中的指标(目标1)。这是重要的第一步，因为它将负担起 对潜在的RDoC结构进行建模并支持RDoC结构是类似特征的前提(即， 稳定)家族性传播机制。其次，我们将使用结构方程建模来创建3 RDoC根据这些指标及其可靠性估计进行构建。然后我们将前瞻性地检查 3个潜伏的RDOC是否构建了MDD家族史导致MDD的实例化机制 成年期的负面结果(目标2)。第三，我们将利用我们的多代数据集来检查 RDoC结构的代际传递。我们将测试RDoC构造的增量有效性 Over DSM通过检查其家族传播是否独立于DSM定义了精神病理学 MDD的家族传播(目标3)。总而言之，这一续订申请推进了这项多代研究 将重点放在风险机制上--开发新的干预措施以防止负面影响的关键一步 成年期结局与家族性抑郁症有关。 除了我们的具体目标外，此次续签还将提供机会，从这一独特的 研究(即从1982年的家庭收集的数千个临床和神经生物学数据点- 目前)到NIH RDoC存储库，使整个30年的纵向数据集可用 科学界。

Project Summary This is a 4-year renewal for a multi-generation, 30-year longitudinal study of families at high- and low-risk for Major Depressive Disorder (MDD). The project has yielded important findings on the familial transmission of mood disorders and has contributed to the field's understanding of the long-term temporal sequences of disorders from childhood to adulthood, as well as the neurobiological correlates of these processes. However, despite these advances, the mechanisms through which familial risk leads to offspring impairment remains underdeveloped. NIMH's Research Domain Criteria (RDoC) offers a compelling model for testing potential mechanisms, by proposing functional systems (“constructs”) that combine neurobiological and behavioral information. This renewal therefore aims to prospectively test whether RDoC constructs are mechanisms (i.e., mediators) through which family history leads to adult functional outcomes and symptom trajectories. Leveraging a rich, 30-year, 3-generation longitudinal dataset, we will integrate data from multiple units of analysis (multiple MRI modalities, electrophysiology, behavior, and self-report) to define latent variables corresponding to 3 latent RDoC constructs: Acute Threat, Approach Motivation, and Response Inhibition. First, we will quantify the test-retest reliability of our RDoC indicators (MRI, physiology, behavior, etc.) by re-assessing each of these indicators in a representative subsample of participants (Aim 1). This is an important first step as it will afford robust modeling of the latent RDoC constructs and bolster the premise that the RDoC constructs are trait-like (i.e., stable) mechanisms of familial transmission. Second, we will use structural equation modeling to create the 3 RDoC constructs from these indicators and their reliability estimates. We will then prospectively examine whether the 3 latent RDoC constructs instantiate mechanisms by which family history of MDD leads to negative outcomes in adulthood (Aim 2). Third, we will leverage our multigenerational dataset to examine the inter-generational transmission of the RDoC constructs. We will test the incremental validity of the RDoC constructs over DSM defined psychopathology by examining whether their familial transmission is independent of the familial transmission of MDD (Aim 3). In sum, this renewal application advances this multi-generation study toward a focus on mechanisms of risk – a critical step to developing novel interventions to prevent negative adulthood outcomes associated with familial depression. In addition to our Specific Aims, this renewal will also afford the opportunity to furnish the data from this unique study (i.e., many thousands of clinical and neurobiological data points collected from families from 1982– present) onto the NIH RDoC repository, making this 30-year longitudinal dataset available to the entire scientific community.