Diabetes, Depression, and the Contextual Environment: A Multilevel Analysis

描述（由申请人提供）：流行病学和临床研究已经确定，重度抑郁症（MD）经常与晚年的医疗状况同时发生，包括2型糖尿病（T2DM）。MD和T2DM之间的关系可能是双向的。事实上，基于人群的队列研究中有一致的证据表明，MD与T2DM的风险和死亡率增加相关，T2DM与MD的发作和复发相关。然而，前瞻性研究无法明确区分MD是否是T2DM的独特风险因素，或者这种现象是否是由于MD和T2DM共有的共同因素，如遗传易感性或环境背景。本研究的目的是利用一个大的，以人群为基础的样本，前瞻性地调查的动态作用的背景环境，家族遗传风险，以及他们的相互作用的发展共病T2DM和MD。数据来自瑞典国家多代住院、门诊和药房登记处，这些登记处与瑞典全国代表性的初级保健中心样本相关联，这些样本代表了自2001年以来收集的100多万人。这些数据已被地理编码为社区一级的物理和社会背景环境数据。本研究利用多层次纵向结构方程模型来研究具体目标，即：1）研究情境环境特征（例如，社区社会经济贫困、犯罪、靠近公园或快餐店、社会混乱）和T2DM和MD共病; 2）检查家族遗传对T2DM和MD共病的贡献; 3）检查遗传风险和周围环境对T2DM和MD发展的相互作用。遗传信息设计提供了一个独特的机会，探索竞争的背景环境和遗传风险之间的关系T2DM-MD共病的病因模型。使用家庭设计，我们可以估计一个人的遗传易感性T2DM和MD，从而进行更直接和公正的检查的上下文环境因素，有助于这种合并症。本申请的目的是明确纳入上下文环境因素到我们的理解如何表达和调节遗传易感性的环境，研究结果将提供深入了解广泛的病因机制，环境背景如何影响T2DM和MD的风险。公共卫生意义：该研究计划解决了两种常见的和使人衰弱的健康状况的交叉点，T2DM和MD，这是美国和全球医疗保健成本和公共卫生负担的主要来源。了解遗传风险、环境背景及其相互作用在T2DM和MD共病发展中的动态作用，将为反映这种复杂性的创新计划提供信息，以便更有效地促进公共卫生和指导临床护理。

DESCRIPTION (provided by applicant): Epidemiologic and clinical studies have established that Major Depression (MD) often co-occurs with medical conditions in later life, including Type 2 Diabetes Mellitus (T2DM). The relationship between MD and T2DM is likely bi-directional. Indeed, there is consistent evidence from population-based cohort studies that MD is associated with increased risk of and mortality from T2DM, and that T2DM is associated with onset and recurrence of MD. However, prospective studies cannot definitively distinguish whether MD is a unique risk factor for T2DM, or if this phenomenon is due to a common factor shared by both MD and T2DM such as genetic liability or environmental context. The goal of this study is to utilize a large, population-based sample to prospectively investigate the dynamic roles of the contextual environment, familial genetic risk, and their interplay on the development of comorbid T2DM and MD. Data come from Swedish national multi-generational inpatient, outpatient, and pharmacy registries, which have been linked to a nationally-representative sample of primary care centers in Sweden representing over 1 million individuals, collected since 2001. These data have been geocoded to neighborhood-level physical and social contextual environment data. This research utilizes multi-level longitudinal and structural equation modeling to investigate the specific aims, which are to: 1) investigate the association between contextual environmental characteristics (e.g., neighborhood socioeconomic deprivation, crime, proximity to parks or fast food restaurants, social disorganization) and comorbid T2DM and MD; 2) examine the familial genetic contributions to the comorbidity between T2DM and MD; and 3) examine the interplay between genetic risk and the contextual environment on development of T2DM and MD. Genetically-informative designs provide a unique opportunity for exploring competing etiologic models of the relationships between the contextual environment and genetic risk for comorbid T2DM-MD. Using family designs we can estimate an individual's genetic liability for T2DM and MD, and thus conduct a more direct and unbiased examination of the contextual environmental factors that contribute to this comorbidity. This application aims to explicitly incorporate contextual environmental factors into our understanding of how genetic liability is expressed and moderated by the environment, and the findings will provide insight into the broad etiologic mechanisms of how environmental context influences risk of T2DM and MD. Public health significance: The research plan addresses the intersection of two common and debilitating health conditions, T2DM and MD, that are leading sources of healthcare costs and public health burden in the US and globally. Understanding the dynamic roles that genetic risk, environmental context, and their interaction play in development of comorbid T2DM and MD will inform innovative programs that reflect this complexity in order to more effectively promote public health and guide clinical care.