Computational examination of RDoC threat and reward constructs in a representative, predominantly low-income, longitudinal sample at increased risk for internalizing disorders

摘要：抑郁和焦虑是一种普遍存在的、使人衰弱的、知之甚少的疾病。RDoC图表 这些条件的性质跨越多个单位，但领域是基于专家的共识， 允许偏见和错失机会。此外，人们对逆境如何影响RDoC知之甚少 构成并促成了精神病理学因此，迫切需要严格评估RDoC 来自不同背景的发展样本中的领域，暴露于逆境的风险增加， 后来的精神病理学。我们将使用数据驱动的分析来设计，应用和验证多层次多模式 威胁和奖励结构模型在现有的纵向队列中的精神病理学风险。到 预测内化症状，我们将确定生物型横截面和检查纵向 RDoC信息生物型的可塑性。恶劣的社会生态条件将得到深入评估， 在多个单位预测内化症状的发作/加剧。我们将评估1,000名年轻人 脆弱家庭和儿童福利研究（FFCWS），一项正在进行的对出生于 主要是低收入家庭。FFCWS的属性是：1）在出生时评估儿童，1，3，5，9， 15年; 2）样本是在城市出生的人的代表，因此，与几乎所有其他人不同， 神经影像学研究，结果是概括性的; 3）虽然代表了全方位的收入， 对低收入和非裔美国人家庭来说，这是一个巨大的财富， 研究;和4）参与者正在进入成年早期，这是精神病理学风险增加的时期。我们 将从四个分析单元评估威胁和回报：症状、基于任务的行为、大脑和基因组学 并将这些单位与逆境联系起来。核心假设是RDoC威胁和奖励 结构将每个集群跨越个人和单位，彼此不同，并具有特定的社会- 生态预测我们将在1000名参与者中检查多通道/多模式数据结构， 213人，纵向参与。我们的跨学科专家团队使我们能够 阐明威胁和奖励结构的结构，并绘制内化生物型的风险图。我们将 大幅扩展我们的既定协议，以协调，聚合，横向和纵向 分析、聚类和可视化高维数据集。使用数据驱动的验证方法， 分析单元，我们将检查三个目标：目标1将检查RDoC威胁结构横截面， 发展上和生态上。目标2将测试RDoC奖励结构的横截面，发展， 和生态。目标3将评估威胁和奖励在横截面上分离的程度， 发展和生态。通过对一个大型队列进行深入的表型分析， 美国参与者，我们将确定威胁/奖励的有效性，并将结果推广到 人口在研究中的代表性不足，受逆境影响的比例过高。

Summary: Depression and anxiety are prevalent, debilitating, and poorly understood disorders. RDoC charts the nature of these conditions across multiple units, but the domains are based on expert consensus, permitting bias and missed opportunities. Moreover, little is known about how adversity affects RDoC constructs and contributes to psychopathology. Thus, there is a critical need to rigorously evaluate RDoC domains in developmental samples from diverse backgrounds at increased risk for exposure to adversity and later psychopathology. We will use data-driven analytics to design, apply and validate multilevel-multimodal models of Threat and Reward constructs in an existing longitudinal cohort at risk for psychopathology. To predict internalizing symptoms, we will identify biotypes cross-sectionally and examine the longitudinal plasticity of RDoC-informed biotypes. Harsh social-ecological conditions will be deeply assessed and used to forecast the onset/intensification of internalizing symptoms at multiple units. We will assess 1,000 young adults from The Fragile Families and Child Wellbeing Study (FFCWS), an ongoing study of children born to predominantly low-income families. Attributes of the FFCWS are: 1) children were assessed at birth, 1, 3, 5, 9, 15 years; 2) the sample is representative of people born in cities and, thus, unlike almost all other neuroimaging research, findings are generalizable; 3) Although a full range of incomes are represented, there is substantial enrichment for low-income and African-American families, populations often under-represented in research; and 4) participants are entering early adulthood, a period of heightened risk for psychopathology. We will assess Threat and Reward at four units of analysis: symptoms, task-based behaviors, brain, and genomics and link these units to exposure to adversity. The central hypothesis is that the RDoC Threat and Reward constructs will each cluster across individuals and units, are distinct from each other, and have specific socio- ecologic predictors. We will examine multisource/multimodal data structure in 1000 participants cross- sectionally and 213 participants longitudinally. Our transdisciplinary team of experts positions us well to elucidate the structure of the Threat and Reward constructs and map risk for internalizing biotypes. We will dramatically expand our established protocol to harmonize, aggregate, cross-sectionally and longitudinally analyze, cluster, and visualize the high-dimensional datasets. Using data-driven validation approaches at four units of analysis, we will examine three aims: Aim 1 will examine RDoC Threat construct cross-sectionally, developmentally, and ecologically. Aim 2 will test RDoC Reward construct cross-sectionally, developmentally, and ecologically. Aim 3 will assess the degree to which Threat and Reward dissociate cross-sectionally, developmentally and ecologically. By deeply phenotyping a large cohort enriched for low income and African American participants, we will determine the validity of Threat/Reward and findings will generalize to a population underrepresented in research and disproportionately affected by adversity.