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、且知之甚少的疾病。RDOC图表 这些情况的性质跨越多个单位，但领域是基于专家共识， 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 构筑并促成了精神病理学的发展。因此，迫切需要严格评估RDoC 来自不同背景的发育样本中的领域暴露于逆境和 后来的精神变态学。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 存在精神病风险的现有纵向队列中威胁和奖励结构的模型。至 预测内化症状，我们将横断面鉴定生物型并检查纵向 RDoC信息生物型的可塑性。将深入评估恶劣的社会生态条件，并用于 预测多个单元的内在化症状的开始/加剧。我们将评估1000名年轻人 来自脆弱家庭和儿童福祉研究(FFCWS)，这是一项正在进行的关于出生于 主要是低收入家庭。FFCWS的属性是：1)儿童在出生时进行评估，1，3，5，9， 15岁；2)样本代表了出生在城市的人，因此，与几乎所有其他样本不同 神经成像研究，结果是可以概括的；3)虽然代表了全方位的收入，但 对于低收入和非裔美国家庭来说，这是一大笔财富，这些人口在 研究；4)参与者正在进入成年期早期，这是精神病理学的高风险时期。我们 将通过四个分析单元评估威胁和奖励：症状、基于任务的行为、大脑和基因组学 并将这些单位与暴露在逆境中联系起来。中心假设是RDoC的威胁和奖励 每个构造物将跨越个人和单位聚集，彼此不同，并具有特定的社会- 生态预测因子。我们将在1000名参与者中研究多源/多模式数据结构 纵向上有213人参加。我们的跨学科专家团队使我们能够很好地 阐明威胁和奖励结构的结构，并绘制用于内化生物型的风险图。我们会 极大地扩展我们的既定协议，以协调、聚合、横向和纵向 分析、聚集和可视化高维数据集。在四个阶段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将横截面检查RDoC威胁结构， 无论是在发展上还是在生态上。目标2将对RDoC奖励结构进行横断面、发展性、 从生态角度来看。目标3将评估威胁和奖励的横向分离程度， 在发展上和生态上。通过对一大群低收入和非洲人进行深度表型分析 美国参与者，我们将确定威胁/奖励的有效性，并将调查结果概括为 人口在研究中的代表性不足，并且不成比例地受到逆境的影响。

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.