Quasi-experimental studies of early risk factors for severe psychopathology

严重精神病理学早期危险因素的准实验研究

• 批准号: 7881333
• 负责人: Brian M D'Onofrio
• 金额: $ 35.42万
• 依托单位: TRUSTEES OF INDIANA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-12 至 2014-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7881333
• 关键词: Accounting; Alcohol or Other Drugs use; Alcohols; Area; Basic Science; Biological; Bipolar Disorder; Birth; Cessation of life; Child; Child Development; Communities; Complex; Crime; Data Analyses; Data Set; Development; Distress; Environment; Environmental Risk Factor; Epidemiology; Etiology; Experimental Designs; Exposure to; Family; Family member; Genes; Genetic; Genetic Risk; Grant; Hospitalization; Income; Indiana; Individual; International; Life; Marital Status; Maternal Age; Measures; Mediating; Mental Health; Methods; Murder; Natural experiment; Neighborhoods; Outcome; Overdose; Paternal Age; Performance; Perinatal; Pharmaceutical Preparations; Population; Pregnancy; Prevention; Prevention program; Process; Psyche structure; Psychopathology; Public Policy; Registries; Relative (related person); Research; Research Design; Research Personnel; Research Proposals; Resources; Risk; Risk Factors; Role; Sample Size; Sampling; Schizophrenia; Schools; Second Pregnancy Trimester; Siblings; Societies; Source; Specific qualifier value; Staging; Stress; Suicide; Sweden; Testing; Third Pregnancy Trimester; Time; Twin Multiple Birth; Unemployment; Universities; Validity of Results; Violence; accomplished suicide; adverse outcome; assault; base; child bearing; cost; design; experience; genetic selection; improved; indexing; innovation; manslaughter; maternal cigarette smoking; maternal stress; offspring; prenatal; public health relevance; research study; severe mental illness; theories; trait

DESCRIPTION (provided by applicant): Significance: Crime, substance use problems, suicide, and severe mental illness, such as schizophrenia and bipolar disorder, are associated with enormous personal distress and societal costs. Identifying the causes of these problems, especially very early in life, is a crucial research endeavor. Researchers have identified numerous putative environmental factors that are associated with increased risk for these severe problems, including maternal smoking during pregnancy, maternal stress during pregnancy, maternal age at childbearing, and advancing paternal age at childbearing. We do not know, however, whether these risk factors are casual risk factors for severe forms of psychopathology or are merely indices of family confounding. Our limited understanding of the underlying causal mechanisms is due, in part, to the fact that most existent studies of these risks have failed to use research designs that can test alternative hypotheses, especially the role of environmental and genetic selection factors. Innovation: We propose to utilize powerful quasi-experimental designs, natural experiments that can pull-apart co-occurring risk mechanisms and account for unmeasured genetic and environmental processes, to explore the effects of several putative early risk factors. In particular, we will compare differentially exposed full siblings, an approach that rules out all genetic factors that could account for the statistical association between early putative risks and later outcomes, as well as all environmental factors that siblings share. We will also compare differentially exposed half siblings, offspring of full siblings (full cousins), offspring of half siblings (half cousins), and offspring of twins. These additional comparisons will enable us to provide converging evidence for our findings and identify the source any familial selection factors (genetic and/or environmental). Detailed assessments of offspring, parental, and community- level risks will further enable us to identify the mechanisms through which early risk factors are associated with severe psychopathology. Approach: We propose to analyze a large dataset that includes information on every individual who was born or lived in Sweden from 1940-1995 (NH7,500,000), which includes measures of early environmental risks, correlated familial and community risks, and well-validated indices of severe criminal, substance use, suicide, and mental health problems from Swedish national registries. Because the dataset also includes information on the biological relatedness of each individual with all of their family members, we are able to conduct numerous quasi-experimental studies of the associations by comparing individuals who differ in both their environmental and genetic risk. Environment and Investigators: Our experienced team includes international experts in the risks associated with early prenatal and perinatal factors; the assessment and etiology of severe psychopathology; the use of large, national registries; and the use of quasi-experimental designs to study putative environmental factors. Indiana University and the Karolinska Institutet provide strong environments and relevant resources. PUBLIC HEALTH RELEVANCE: The staggering burden on individuals and society caused by violence, substance use problems, suicide, and severe mental illness has been well documented. Researchers have identified early risk factors that predict these major societal problems, but, it is still unclear whether putative early risks are truly causal or whether part-or most-of the associations with these risks are due to background familial factors. In order to improve prevention programs and our understanding of early risk factors, the current proposal seeks support to analyze a unique resource, a large dataset that includes every individual in Sweden for roughly five decades, relying on natural experiments to rigorously test causal hypotheses.

描述（由申请人提供）：意义：犯罪、药物使用问题、自杀和严重精神疾病（例如精神分裂症和双相情感障碍）与巨大的个人痛苦和社会成本相关。确定这些问题的原因，特别是在生命的早期，是一项至关重要的研究奋进。研究人员已经确定了许多与这些严重问题风险增加相关的假定环境因素，包括母亲在怀孕期间吸烟，母亲在怀孕期间的压力，母亲生育年龄和父亲生育年龄的增加。然而，我们不知道这些危险因素是否是严重精神病理学形式的偶然危险因素，或者仅仅是家庭混杂的指标。我们对潜在因果机制的理解有限，部分原因是大多数现有的这些风险研究未能使用可以测试替代假设的研究设计，特别是环境和遗传选择因素的作用。创新：我们建议利用强大的准实验设计，自然实验，可以拉开共同发生的风险机制，并考虑到不可测量的遗传和环境过程，探索几个假定的早期风险因素的影响。特别是，我们将比较不同暴露的全同胞，这种方法排除了所有可能解释早期推定风险和后期结果之间统计学关联的遗传因素，以及同胞共享的所有环境因素。我们还将比较不同暴露的同父异母兄弟姐妹、同父异母兄弟姐妹的后代（同父异母堂兄弟姐妹）、同父异母兄弟姐妹的后代（同父异母堂兄弟姐妹）和双胞胎的后代。这些额外的比较将使我们能够为我们的发现提供聚合证据，并确定任何家族选择因素（遗传和/或环境）的来源。对后代、父母和社区水平风险的详细评估将进一步使我们能够确定早期风险因素与严重精神病理学相关的机制。方法：我们建议分析一个大型数据集，其中包括1940年至1995年在瑞典出生或生活的每个人的信息（NH 7，500，000），其中包括早期环境风险的措施，相关的家庭和社区风险，以及瑞典国家登记处的严重犯罪，物质使用，自杀和精神健康问题的有效指数。由于数据集还包括每个个体与其所有家庭成员的生物相关性信息，因此我们能够通过比较环境和遗传风险不同的个体来进行大量的准实验研究。环境和研究者：我们经验丰富的团队包括与早期产前和围产期因素相关的风险的国际专家;严重精神病理学的评估和病因学;使用大型国家注册表;以及使用准实验设计来研究推定的环境因素。印第安纳州大学和卡罗林斯卡学院提供了强大的环境和相关资源。 公共卫生关系：暴力、药物使用问题、自杀和严重精神疾病给个人和社会造成的惊人负担已得到充分记载。研究人员已经确定了预测这些主要社会问题的早期风险因素，但是，目前还不清楚是否假定的早期风险是真正的因果关系，或者是否部分或大部分与这些风险的关联是由于背景家庭因素。为了改善预防计划和我们对早期风险因素的理解，目前的提案寻求支持来分析一个独特的资源，一个大型数据集，包括瑞典大约五十年来的每个人，依靠自然实验来严格测试因果假设。