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.

项目摘要 我们在这个新的R 01提案中的目标是描述配偶的物质使用和精神疾病的影响， 他们的伴侣的酒精使用障碍（AUD）的发病，缓解和复发在婚姻期间， 基因信息框架到目前为止，了解配偶对酒精结果的影响的努力已经取得了进展。 主要集中在酒精特定的传染模型，其中一个合作伙伴的酒精使用行为是 通过社交传播给另一个人然而，这种先前的焦点酒精特定的传染是限制性的， 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的 疾病，包括重度抑郁症、广泛性焦虑症、其他药物滥用/依赖， 多动症和反社会人格障碍。我们以这些流行病学发现为基础， 这些其他形式的配偶物质使用和精神疾病之间的联系， 酒精结局包括AUD发作、缓解和复发。我们这样做是在一个基因信息 该框架还承认配偶对疾病的遗传倾向的潜在贡献， 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/她对配偶的障碍有差别地敏感（即，基因-环境交互作用）。相关 该次级数据分析项目的表型和基因型数据来自配偶二对（N = 1，688 作为NIAAA资助的酒精中毒遗传学合作研究（COGA）的一部分。我们 具体目标是：（1）描绘配偶物质之间的时间动态关联 使用和精神障碍诊断（包括大麻使用障碍、其他精神活性药物使用 精神障碍、反社会人格障碍、ADHD、尼古丁依赖、重度抑郁症和PTSD）， 他们的伴侣的AUD发作，缓解和复发;（2）确定配偶的遗传倾向是否 精神疾病（高于诊断本身）与其伴侣的AUD发作相关， 缓解和复发;（3）检查焦点个体的酒精问题的遗传易感性 预测其对配偶物质使用和精神疾病的敏感性的变异性;以及（4）评估 预期效果是否因性别和父母身份而不同。结果可能具有理论上的 扩展AUD的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，这方面的知识预计将有影响的夫妇和家庭系统为基础的 对AUD的预防性干预。更广泛地说，这项工作将有助于合作研究小组的 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的开始、持续和不连续性。