A genetically informative approach to understanding the impact of spousal psychiatric disorders on alcohol use disorder onset, remission, and relapse

一种了解配偶精神疾病对酒精使用障碍发作、缓解和复发影响的遗传信息方法

• 批准号: 10718384
• 负责人: JESSICA E SALVATORE
• 金额: $ 35.33万
• 依托单位: RUTGERS BIOMEDICAL AND HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10718384
• 关键词: Affect; African ancestry; Alcohol abuse; Alcohol consumption; Alcohols; Antisocial Personality Disorder; Attention deficit hyperactivity disorder; Behavior; Couples; Data; Data Analyses; Dependence; Diagnosis; Disease; Disease remission; Drug Use Disorder; Drug abuse; Environmental Risk Factor; Epidemiology; European ancestry; Family; Female; Funding; Generalized Anxiety Disorder; Genetic; Genetic Predisposition to Disease; Genetic study; Genotype; Goals; Husband; Illicit Drugs; Individual; Knowledge; Major Depressive Disorder; Marriage; Mental disorders; Mission; Modeling; National Institute on Alcohol Abuse and Alcoholism; Nature; Nicotine Dependence; Onset of illness; Outcome; Phenotype; Post-Traumatic Stress Disorders; Predisposition; Psychotropic Drugs; Public Health; Recording of previous events; Relapse; Research; Sampling; Spouses; Stress; System; Testing; United States National Institutes of Health; Work; alcohol risk; alcohol use disorder; anti social; behavior influence; contagion; cost; gene environment interaction; genetics of alcoholism; genome wide association study; innovation; marijuana use disorder; member; preventive intervention; psychosocial stressors; sex; social; social genomics; social stress; substance use; symptomatology; theories; transmission process

Project Summary Our objective in this new R01 proposal is to delineate the impact of a spouse’s substance use and psychiatric disorders on their partner’s alcohol use disorder (AUD) onset, remission, and relapse during marriage within a genetically informative framework. To date, efforts to understand spousal influences on alcohol outcomes have largely focused on alcohol-specific contagion models, whereby alcohol use behaviors in one partner are socially transmitted to the other. Yet, this prior focus alcohol-specific contagion is restrictive in view of epidemiological evidence that spouses of AUD-affected individuals also tend to suffer from other common disorders, including major depressive disorder, generalized anxiety disorder, other drug abuse/dependence, ADHD, and antisocial personality disorder. We build on these epidemiological findings to clarify the nature of the associations between these other forms of spousal substance use and psychiatric disorders and key alcohol outcomes including AUD onset, remission, and relapse. We do this within a genetically informative framework that also recognizes the potential contributions of a spouse’s genetic propensity for a disorder even in the absence of a diagnosis (i.e., social genetic effects), as well as how the focal individual’s genotype may differentially sensitize him/her to a spouse’s disorder (i.e., gene-environment interaction effects). Relevant phenotypic and genotypic data for this secondary data analysis project come from spousal dyads (N = 1,688 dyads) collected as part of the NIAAA-funded Collaborative Study on the Genetics of Alcoholism (COGA). Our specific aims are to: (1) Delineate the temporal dynamics underlying associations between spousal substance use and psychiatric disorder diagnoses (inclusive of cannabis use disorder, other psychoactive drug use disorder, antisocial personal disorder, ADHD, nicotine dependence, major depressive disorder, and PTSD) and their partner’s AUD onset, remission, and relapse; (2) Identify whether a spouse’s genetic propensity for psychiatric disorders (above and beyond a diagnosis itself) is associated with their partner’s AUD onset, remission, and relapse; (3) Examine whether the focal individual’s genetic predisposition for alcohol problems predicts variability in their sensitivity to spousal substance use and psychiatric disorders; and (4) Evaluate whether the expected effects differ as a function of sex and parenthood. The results may have theoretical implications for expanding social stress models of AUD to include spousal substance use and psychiatric disorders, and in turn this knowledge is anticipated to have implications for couples and family systems-based preventive interventions for AUD. More broadly, this work will contribute to the collaborative research team’s long-term goal to elucidate how genetic factors and close relationship factors come together to influence the onset, persistence, and discontinuity of AUD.

项目概要 我们在这项新 R01 提案中的目标是描述配偶物质使用和精神疾病的影响 婚姻期间伴侣酒精使用障碍 (AUD) 发病、缓解和复发的影响 迄今为止，人们已经努力了解配偶对酒精结果的影响。 主要关注酒精特定的传染模型，因此一个伴侣的饮酒行为是 然而，考虑到这种先前关注的酒精特定传染性是有限制性的。 流行病学证据表明，受 AUD 影响的个人的配偶也往往患有其他常见疾病 疾病，包括重度抑郁症、广泛性焦虑症、其他药物滥用/依赖， 我们根据这些流行病学发现来阐明多动症和反社会人格障碍的本质。 这些其他形式的配偶物质使用与精神疾病之间的关联以及关键 酒精结果，包括 AUD 发病、缓解和复发，我们在遗传信息范围内进行此研究。 该框架还认识到配偶的遗传倾向对某种疾病的潜在贡献，甚至 在没有诊断的情况下（即社会遗传效应），以及焦点个体的基因型如何可能 使他/她对配偶的疾病有不同的敏感性（即基因-环境相互作用的影响）。 该二级数据分析项目的表型和基因型数据来自配偶二人组（N = 1,688 dyads）作为 NIAAA 资助的酒精中毒遗传学合作研究（COGA）的一部分收集。 具体目标是： (1) 描绘配偶实质之间关联的时间动态 使用和精神疾病诊断（包括大麻使用障碍、其他精神药物使用） 障碍、反社会人格障碍、多动症、尼古丁依赖、重度抑郁症和创伤后应激障碍）和 其伴侣的 AUD 发病、缓解和复发； (2) 确定配偶是否有 AUD 的遗传倾向； 精神疾病（超出诊断本身）与其伴侣的 AUD 发病有关， (3) 检查焦点个体是否有酗酒问题的遗传倾向 预测他们对配偶物质使用和精神疾病的敏感性的变化；以及 (4) 评估 预期效果是否因性别和父母身份而异。结果可能具有理论意义。 扩大 AUD 社会压力模型以包括配偶物质使用和精神疾病的影响 疾病，反过来，这些知识预计会对基于夫妻和家庭系统的夫妇和家庭产生影响 更广泛地说，这项工作将有助于合作研究团队的预防干预。 长期目标是阐明遗传因素和密切关系因素如何共同影响 AUD 的发生、持续和间断。