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证实，严重抑郁症(MD)通常在晚年与包括2型糖尿病(T2 DM)在内的疾病并存。MD与T2 DM之间的关系可能是双向的。事实上，基于人群的队列研究有一致的证据表明，MD与T2 DM的风险和死亡率的增加有关，并且T2 DM与MD的发病和复发有关。然而，前瞻性研究不能明确区分MD是否是T2 DM的独特危险因素，或者这种现象是否是MD和T2 DM共同的因素所致，如遗传易感性或环境背景。本研究的目的是利用一个大的、基于人群的样本，前瞻性地研究周围环境、家族性遗传风险的动态作用，以及它们在T2 DM和MD并存发展中的相互作用。数据来自瑞典国家多代住院、门诊和药房登记处，这些登记处自2001年以来一直与瑞典代表100多万人的具有全国代表性的初级保健中心样本相联系。这些数据已被地理编码为邻居级别的物理和社会上下文环境数据。本研究利用多层次纵向和结构方程模型来研究特定目的：1)调查周边环境特征(如邻里社会经济贫困、犯罪、邻近公园或快餐店、社会组织混乱)与T2 DM和MD共病之间的关系；2)检验家庭遗传因素对T2 DM和MD共病的影响；3)考察遗传风险和周边环境对T2 DM和MD的发展的相互作用。遗传信息设计为探索T2 DM-MD并存的环境和遗传风险之间的相互竞争的病因学模型提供了独特的机会。使用家系设计，我们可以估计个体患T2 DM和MD的遗传风险，从而对导致这种共病的背景环境因素进行更直接和公正的检查。这项应用旨在明确地将背景环境因素纳入我们对环境如何表达和调节遗传易感性的理解中，研究结果将为环境背景如何影响T2 DM和MD风险的广泛病因机制提供洞察。公共卫生意义：该研究计划解决了两种常见且令人衰弱的健康状况--T2 DM和MD的交集，这两种疾病是美国和全球医疗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T2 DM和MD并存发展中的动态作用，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健康和指导临床护理。

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.