Three Generations at High and Low Risk for Depression Followed Longitudinally

项目摘要 这是一项为期4年的更新，对高风险和低风险家庭进行了30年的纵向研究。 重度抑郁症（MDD）。该项目在家庭传播艾滋病方面取得了重要成果， 情绪障碍，并有助于该领域的长期时间序列的理解， 从童年到成年的疾病，以及这些过程的神经生物学相关性。然而，在这方面， 尽管取得了这些进展，但家族性风险导致后代受损的机制仍然存在， 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，通过提出功能系统（“结构”），结合联合收割机神经生物学和行为 信息.因此，本次更新旨在前瞻性地测试RDoC构建是否是机制 (i.e.,介体），通过该介体家族史导致成人功能结果和症状轨迹。利用 一个丰富的，30年，3代纵向数据集，我们将整合来自多个分析单元的数据（多个 MRI模态、电生理学、行为和自我报告），以定义对应于3个潜在的 RDoC结构：急性威胁，接近动机和反应抑制。首先，我们将量化 我们的RDoC指标（MRI、生理学、行为等）的重测信度通过重新评估每一个 参与者代表性子样本中的指标（目标1）。这是重要的第一步，因为它将提供强大的 对潜在RDoC结构进行建模并支持RDoC结构是类似特质的前提（即， 稳定）的家庭传播机制。其次，我们将使用结构方程建模来创建3 RDoC结构来自这些指标及其可靠性估计。然后我们将前瞻性地检查 3个潜在的RDoC结构是否实例化了MDD家族史导致 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结构的增量有效性 通过检查其家族传播是否独立于DSM定义的精神病理学， MDD的家族传播（目的3）。总之，这种更新应用程序推进了这种多代研究 对风险机制的关注-开发新的干预措施，以防止负面的关键一步 与家族性抑郁症相关的成年结局。 除了我们的具体目标，这次更新也将提供机会，提供数据，从这个独特的 研究（即，从1982年开始，从家庭中收集了数千个临床和神经生物学数据点， 目前）到NIH RDoC存储库，使这个30年的纵向数据集可供整个 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.