Early Stress and Suicidal Behavior

描述（由申请人提供）：自杀行为给个人、家庭和社会带来了巨大的负担。虽然以前的研究已经确定了许多自杀行为的风险因素，但为了最有效地预防自杀行为，需要对这些风险因素进行强有力的因果推论的研究。几个基因信息，瑞典人口登记处将合并形成一个前所未有的数据集，其中包括1973年至1996年在瑞典出生的每个人（210万瑞典克朗），这个数据集足够大，足以调查相对罕见但代价高昂的自杀行为。需要检查的早期风险因素包括母亲的压力暴露、妊娠期、产前和产后头4年。压力被定义为母亲的一级亲属或伴侣死亡或住院。自杀行为结果包括明确的和不确定的自杀企图、自杀完成和意外死亡。首先，将采用Cox比例生存分析来检验压力暴露时间与自杀行为之间的关系。早期后代、家庭和社区水平的风险（如父母年龄和社会经济地位）将被纳入协变量。确定处于高度脆弱性的早期发育阶段将为支持或拒绝不同的自杀病因假说提供有用的信息。其次，将检验统计关联的其他假设。我们将研究早期压力暴露如何与其他已知的自杀行为风险因素（包括母亲和父亲的自杀行为）共同变化。此外，由于数据集包括每个人与其所有家庭的生物关系信息，当前的项目还将利用强大的基于家庭的准实验方法来解释其他因果假设。特别是，兄弟姐妹比较设计，通过检查不同暴露的兄弟姐妹，将提供更好的控制未测量的背景因素（环境和遗传），这些因素可能影响早期母亲压力和后代自杀之间的关系。第三，研究不良出生结局（如早产和低出生体重）的潜在中介作用，进一步阐明早期应激暴露与后来自杀行为之间的关系。该培训计划将支持先进的准实验和流行病学方法的教学，包括早期应激动物研究在内的转化研究和理论的教育，以及与相关人群的实际临床工作。当前项目的研究结果将为改进预防方案提供信息，并增加我们对自杀行为病因的理解。

DESCRIPTION (provided by applicant): Suicidal behavior places a staggering burden on individuals, families, and society. Although previous research has identified numerous risk factors for suicidal behavior, research that can draw strong causal inferences about such risk factors is needed for the most effective prevention of suicidal behavior. Several genetically-informed, Swedish population registries will be merged to form an unprecedented dataset of every individual born in Sweden from 1973 to 1996 (NH2,100,000) that is large enough to investigate the relatively rare, yet costly suicidal behavior. Early risk factors to be examined include maternal stress exposure pregestation, prenatally, and during the first 4 years of postnatal life. Stress is defined as the death or hospitalization of a first degree relative or partner of the mother. Suicidal behavior outcomes include definite and uncertain suicide attempts, suicide completions and accidental deaths. First, Cox Proportional Survival Analyses will be employed to examine the association between timing of stress exposure and suicidal behavior. Measures of early offspring, family, and community- level risks (e.g. parental age and socioeconomic status) will be included as covariates. Identifying periods of early development that are at heightened vulnerability would provide useful information for the support or rejection of different etiological hypotheses of suicide. Second, alternative hypotheses of the statistical associations will be tested. We will examine how early stress exposure covaries with other known risk factors for suicidal behavior, including maternal and paternal suicidal behavior. Further, because the dataset includes information on the biological relatedness of each individual with all of their family, the current project will also utilize powerful family-based, quasi-experimental methods to account for alternative causal hypotheses. In particular, the sibling comparison design, by examining differentially exposed siblings, will provide increased control of unmeasured background factors (both environmental and genetic) that may influence the association between early maternal stress and offspring suicidality. Third, the potential mediating effects of adverse birth outcomes, such as preterm birth and low birth weight, will be examined to further clarify the relations between early stress exposure and later suicidal behavior. The training plan will support instruction in advanced quasi- experimental and epidemiological methods, education in translational research and theory including animal studies of early stress, and hands-on clinical work with relevant populations. Findings from the current project will provide information to improve prevention programs and increase our understanding of the etiology of suicidal behavior. PUBLIC HEALTH RELEVANCE: Suicide reduction is a public health priority, but the effective prevention of suicidal behavior requires the identification of risk factors that are causally linked to suicidal behaviors. Previous research has been unable to draw strong causal inferences regarding risk factors because of empirical restrictions and limited data. In order to improve prevention programs and our understanding of the etiology of suicidal behavior, the current proposal uses novel analytical and methodological approaches to understand early risk factors for suicidal behavior in a study of every individual in Sweden from 1973 to 1996 (NH2,100,000).