Cumulative environmental risk exposure in youth at clinical high-risk for psychosis

项目摘要 了解环境风险暴露对神经和行为发育的影响 对公共卫生政策中有针对性的干预和预防工作至关重要。这种情况尤其适用于 精神障碍，在人群中的发病率为1%，极大地削弱和治疗 抗性(1)。然而，目前对临床高危期环境影响的理解 直接导致精神障碍发作的可能性有限(2)。具体来说，潜在的神经机制 人们对累积环境风险因素暴露的影响知之甚少。重要的是，(A)不平衡 应激暴露的负荷和聚集失调模型表明在研究中有很大的好处 累积风险，因为不同类型的风险暴露可能具有相似的发育后果(3、4)和 (B)已证明，累积模型除了提供更多的预期外，还具有更强的功能 预测优势(3-5)。尽管如此，关于环境风险暴露，文献经常 专注于单一的预测因素。测量多种环境风险暴露对神经的影响 行为结果对于有针对性的干预和预防工作以及对 未来在这一人群中分配治疗和预防资源。目前的提案将衡量 50名健康志愿者和50名健康志愿者在个人和结构水平的累积风险暴露，此外 到纵向预测候选神经机制、症状和社会/职业功能。第一, 这项研究旨在确定慢性阻塞性肺病患者是否经历了更多的累积 环境风险(目标1)。累积环境风险将在个人和结构上衡量 具备结构化面试水平、多名评分者系统社会观察(SSO)软件(6-9)和 人口普查数据的地理编码。然后，该提案将寻求确定累计环境风险 暴露不同程度地影响应激相关区域的神经连通性，并影响CHR的调节 并通常利用结构和功能成像技术发展个体(目标2)。最后， 拟议的项目将检查累积环境风险模型是否与症状相关 和功能，以及他们是否预测这些特征在慢性阻塞性肺疾病患者中的纵向过程(目标 3)。值得注意的是，将进行探索性分析，以分析在不同的 发育期不同地预测感兴趣区域的神经连接。探索性分析将 还应分别检查个人与结构性环境风险因素的暴露情况 群体差异和神经连接。

Project Summary Understanding the effects of environmental risk exposure on neural and behavioral development is essential for targeting intervention and prevention efforts in public health policy. This is especially the case for psychotic disorders, which have a 1% incidence in the population, and are highly debilitating and treatment resistant (1). However, current understanding of environmental influences in the clinical high-risk (CHR) period immediately leading up to psychotic disorder onset is limited (2). Specifically, neural mechanisms underlying the effects of cumulative environmental risk factor exposure are poorly understood. Importantly, (a) allostatic load and aggregate dysregulation models of stress exposure suggest there are strong benefits in studying cumulative risk, as different types of risk exposure may have similar developmental consequences (3, 4) and (b) cumulative models have been shown to be more powerful in addition to offering an increased prospective prediction advantage (3-5). Nonetheless, in regards to environmental risk exposure, the literature has often focused on a single predictor. Measuring the effects of multiple types of environmental risk exposure on neural and behavioral outcomes is essential for targeting intervention and prevention efforts, as well as for informing future allocation of treatment and prevention resources in this population. The current proposal will measure cumulative risk exposure in 50 CHR and 50 healthy volunteers at an individual and structural level, in addition to predicting candidate neural mechanisms, symptoms, and social/occupational functioning longitudinally. First, this study aims to determine whether CHR individuals experience greater exposure to cumulative environmental risk (Aim 1). Cumulative environmental risk will be measured at an individual and structural level with structured interviews, multiple rater systematic social observation (SSO) software (6-9) and geocoding of Census data. Then, the proposal will seek to determine whether cumulative environmental risk exposure differentially affects neural connectivity in regions implicated in stress and affect regulation in CHR and typically developing individuals, using structural and functional imaging technology (Aim 2). Finally, the proposed project will examine whether cumulative environmental risk models are associated with symptoms and functioning, and whether they predict the course of these features longitudinally in CHR individuals (Aim 3). Notably, exploratory analyses will be conducted to analyze whether exposure during different developmental periods differentially predicts neural connectivity in areas of interest. Exploratory analyses will also examine exposure to individual versus structural environmental risk factors separately with regards to group differences and neural connectivity.