Genetic Moderators of Divorce Adjustment: A Pilot Investigation

离婚调整的遗传调节因素：试点调查

• 批准号: 8045339
• 负责人: DAVID A SBARRA
• 金额: $ 20万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-15 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8045339
• 关键词: Adult; American; Animals; Applications Grants; Area; Behavior; Behavioral; Biological; Blood Pressure; C-reactive protein; Candidate Disease Gene; Cardiovascular system; Caucasians; Caucasoid Race; Consensus; DNA; Data; Data Analyses; Divorce; Emotional; Emotions; Environment; European; Event; Exploratory/Developmental Grant; Frequencies; Genes; Genetic; Genetic Polymorphism; Genetic Risk; Genotype; Goals; Grant; Health; Heterogeneity; Inflammation; Institute of Medicine (U.S.); Interleukin-6; Investigation; Laboratories; Life; Literature; Major Depressive Disorder; Marital separation; Marriage; Measurement; Measures; Mental Depression; Mental Health; Mental disorders; Molecular; Molecular Genetics; Monoamine Oxidase A; Moods; Morbidity - disease rate; NIH Program Announcements; Nature; Noise; Outcome; Participant; Pathway interactions; Pattern; Persons; Phenotype; Pilot Projects; Prevention program; Probability; Psychiatric Diagnosis; Psychiatry; Psychological Stress; Psychology; Psychosocial Assessment and Care; Psychosomatic Medicine; Public Health; Recommendation; Recovery; Reporting; Research; Risk; Role; Sampling; Sampling Studies; Serotonin; Serotonin Receptor 5-HT1A; Serotonin Receptor 5-HT2A; Severities; Single Nucleotide Polymorphism; Social Environment; Stress; Symptoms; System; Time; Tumor Necrosis Factor-alpha; Withdrawal; Work; Writing; base; coping; cost effective; cytokine; design; disturbance in affect; divorce/separation; environmental stressor; experience; genetic epidemiology; improved; insight; interdisciplinary collaboration; interest; physical conditioning; programs; prospective; psychologic; psychosocial; resilience; response; serotonin transporter; simulation; social; stressor; treatment program

DESCRIPTION (provided by applicant): The proposed research investigates the potential genetic moderators of psychological and physical adjustment to the common life stressor of divorce. Although most people are resilient in the face of divorce, a subset of adults becomes stuck on pathways toward maladaptive outcomes, making the association between divorce, mood disturbances, and physical health a significant public health concern. The primary goal of this project is to collect deoxyribonucleic acid (DNA) from 190 adults (156 of Caucasian/European American descent) who have experienced a recent marital separation in order to (1) investigate candidate polymorphisms in four serotonin genes that may interact with the psychosocial context of marital separation to moderate changes in mood symptoms over a 9-month period and (2) investigate the role of genes within the inflammation system that may moderate changes in blood pressure (BP) reactivity to a divorce-specific laboratory challenge paradigm. By studying the potential genetic moderators of divorce adjustment, this work can provide new insights into who fares well or poorly following the end of marriage. There is consensus in the fields of genetic epidemiology and molecular psychiatry that the study of genotypic effects on psychological and biological end- points of interest can be greatly enhanced through improved measurement of the psychosocial environment. Thus, by carefully measuring adults' psychological responses to their separation and degree of reported stress, this work has the potential to enhance what is known about the effects of gene-environment (G X E) interactions on psychological and health-related phenotypes of interest. The proposed research is one the first prospective investigations of how G X E interactions may limit or promote emotional and biological recovery over time. Using a planned missingness design (intended to decrease participant attrition), adults will be studied at four occasions over a 9-month period. Simulation studies of this sampling approach reveal that the proposed study will be adequately powered to detect small G X E interaction effects on changes in mood symptoms and BP reactivity. In combination, the study of genes in both the serotonin and inflammation systems, the detailed assessment of the psychosocial context of divorce, and the prospective sampling and data analyses will make the proposed study unique to the existing literature and one with potential for high scientific yield in an understudied area of public health significance. This research will contribute to the growing effort to identify the precise effect size estimates in G X E studies of mood disturbances, as well as newly emerging research in psychosomatic medicine that combines genes, psychological variables, and biological response patterns of interest. There are many reasons to believe that genes in the emotion and inflammation systems interact to produce both increased depression and heightened BP responses, and the proposed investigation has promise to make timely and important contributions to this growing area of research. PUBLIC HEALTH RELEVANCE: Divorce is among the most stressful life events a person can experience, and a significant proportion of adults develop diagnosable mental and physical health problems following the end of marriage. By collecting deoxyribonucleic acid (DNA) from 190 recently separated adults, this project seeks to determine if some people are at unique risk for poor outcomes in the wake of this stressful experience. A better understanding of the associations between the psychological stress of divorce, genetic risk, and health is critical for developing improved prevention and treatment programs.

描述（由申请人提供）：拟议的研究调查了对离婚常见生活压力源进行心理和身体调整的潜在遗传调节因素。尽管大多数人在面对离婚时都能适应，但仍有一部分成年人陷入了适应不良结果的困境，这使得离婚、情绪障碍和身体健康之间的联系成为一个重要的公共卫生问题。该项目的主要目标是从最近经历过婚姻分居的 190 名成年人（156 名白种人/欧洲裔美国人后裔）收集脱氧核糖核酸 (DNA)，以便 (1) 研究可能与婚姻分居的心理社会背景在 9 个月内调节情绪症状的变化，以及 (2) 研究炎症系统中可能调节血压变化的基因的作用（BP）对离婚特定实验室挑战范式的反应。通过研究离婚调整的潜在遗传调节因素，这项工作可以为了解婚姻结束后谁过得好或不好提供新的见解。遗传流行病学和分子精神病学领域达成共识，通过改进心理社会环境的测量，可以大大加强基因型对心理和生物学终点的影响的研究。因此，通过仔细测量成年人对分离的心理反应和报告的压力程度，这项工作有可能增强人们对基因-环境（G X E）相互作用对心理和健康相关表型的影响的了解。这项拟议的研究是关于 G X E 相互作用如何随着时间的推移限制或促进情绪和生物恢复的前瞻性研究之一。采用有计划的缺失设计（旨在减少参与者流失），将在 9 个月的时间内对成年人进行四次研究。这种抽样方法的模拟研究表明，所提出的研究将有足够的动力来检测 G X E 相互作用对情绪症状和血压反应性变化的微小影响。结合起来，对血清素和炎症系统中基因的研究、对离婚心理社会背景的详细评估以及前瞻性抽样和数据分析将使拟议的研究在现有文献中独一无二，并且具有高科学产出的潜力在具有公共卫生意义的尚未研究的领域。这项研究将有助于不断努力确定情绪障碍 G X E 研究中精确效应大小估计，以及结合基因、心理变量和感兴趣的生物反应模式的心身医学新兴研究。有很多理由相信，情绪和炎症系统中的基因相互作用，会导致抑郁症增加和血压反应增强，而拟议的研究有望为这一不断发展的研究领域做出及时而重要的贡献。 公共卫生相关性：离婚是一个人可能经历的压力最大的生活事件之一，很大一部分成年人在婚姻结束后出现可诊断的精神和身体健康问题。该项目通过收集 190 名最近失散的成年人的脱氧核糖核酸 (DNA)，旨在确定某些人在经历这种压力经历后是否会面临导致不良后果的独特风险。更好地了解离婚心理压力、遗传风险和健康之间的关联对于制定改进的预防和治疗计划至关重要。