Genes, Gendered Contexts, and Substance Use Outcomes

基因、性别背景和药物使用结果

• 批准号: 8048856
• 负责人: EDELYN VERONA
• 金额: $ 18.41万
• 依托单位: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-15 至 2013-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8048856
• 关键词: Address; Adolescent; Adult; Alcohol or Other Drugs use; Behavior; Biological; Biology; Brain; Child Abuse; Child Sexual Abuse; Childhood; Country; Crime; DRD4 gene; Data; Development; Disadvantaged; Drug abuse; Drug usage; Economics; Education; Electroencephalography; Environment; Environmental Risk Factor; Etiology; Female; Future; Gender; Gene Expression; Genes; Genetic; Genotype; Goals; Individual; Intervention; Measures; Mediating; Mediator of activation protein; Mental Depression; Modeling; Monoamine Oxidase A; Neighborhoods; Outcome; Outcome Measure; Pathway interactions; Pharmaceutical Preparations; Pharmacological Treatment; Prostitution; Psychopathology; Psychophysiology; Recording of previous events; Relative (related person); Research; Risk Factors; Rosa; Sex Characteristics; Social Problems; Specific qualifier value; Symptoms; Woman; Work; anti social; drug relapse; follow-up; innovation; intimate partner violence; male; men; monoamine; neuromechanism; offspring; prospective; psychosocial; serotonin transporter; sex; statistics; treatment program; trend

DESCRIPTION (provided by applicant): It is becoming increasingly clear that risk factors for use and trajectories toward desistance may differ significantly for men and women (e.g., Westermeyer & Boedicker, 2000). For example, recent work has uncovered different effects of monoamine genotypes (e.g., serotonin transporter, MAO-A) on male and female psychopathology and behavior (Sjoberg et al., 2007a; Verona, Joiner, Johnson & Bender, 2006). In addition, there is evidence that pubertal onset, childhood sexual abuse, and intimate partner violence (IPV) constitute unique risk factors for antisocial behavior and drug use among women compared to men (Dick, Rose, Kaprio, & Viken, 2000) and can predict drug relapse in women many years later in adulthood (Hyman, Garcia, & Sinha, 2006). Thus, a primary goal of the present application is to identify gender differences in biological and environmental risk factors for substance use outcomes as a way of advancing nuanced conceptualizations of female drug problems. The current project intends to (1) explore various gene by environment (GxE) effects on drug use outcomes, by examining different monoamine genes (5HTT, DRD4, MAO-A) and incorporating gendered environmental risk factors that are not commonly included in studies of drug use (e.g., intimate partner violence), (2) examine the extent to which GxE effects or individual risk factors are specific to substance use outcomes in women relative to men, and (3) identify multivariate models involving GxE effects and mediators of these effects to predict substance use pathways in men and women. The goal is to examine not only GxE effects (e.g., gene-by-abuse, gene-by-IPV) that directly influence substance use outcomes, but identify potential mediators (pubertal development, internalizing symptoms) in an effort to understand nuanced pathways for female substance use. The ultimate goal is to help in the development of tailored interventions to address gender-specific manifestations and etiologies. PUBLIC HEALTH RELEVANCE: Women's drug arrests have increased in the last two decades, whereas men's arrests have decreased. Thus, women's drug use has become a significant social problem. An innovative aspect of the project is the attempt to identify genetic and environmental factors that are female specific for substance use outcomes. Given important sex differences in biology, gene expression, and motives, this project can inform psychosocial and pharmacological treatments for substance use so that they are tailored to address gender-specific issues.

描述（由申请人提供）：越来越明显的是，男性和女性的使用风险因素和戒烟轨迹可能存在显着差异（例如，Westtermeyer & Boedicker，2000）。例如，最近的工作揭示了单胺基因型（例如，血清素转运蛋白，MAO-A）对男性和女性精神病理学和行为的不同影响（Sjoberg et al., 2007a; Verona, Joiner, Johnson & Bender, 2006）。此外，有证据表明，与男性相比，青春期开始、儿童期性虐待和亲密伴侣暴力 (IPV) 构成女性反社会行为和吸毒的独特危险因素 (Dick, Rose, Kaprio, & Viken, 2000)，并且可以预测女性成年后多年吸毒的复发 (Hyman, Garcia, & Sinha, 2006)。因此，本申请的主要目标是确定物质使用结果的生物和环境风险因素中的性别差异，作为推进女性毒品问题的细致概念化的一种方式。当前项目打算 (1) 通过检查不同的单胺基因（5HTT、DRD4、MAO-A）并纳入吸毒研究中不常见的性别环境风险因素（例如亲密伴侣暴力），探索各种基因环境 (GxE) 对吸毒结果的影响，(2) 检查 GxE 影响或个人风险因素对女性物质使用结果的特定程度（相对于女性） (3) 确定涉及 GxE 效应和这些效应中介因素的多变量模型，以预测男性和女性的物质使用途径。目标不仅是检查直接影响物质使用结果的 GxE 效应（例如基因滥用、基因 IPV），还要确定潜在的中介因素（青春期发育、内化症状），以努力了解女性物质使用的微妙途径。最终目标是帮助制定量身定制的干预措施，以解决特定性别的表现和病因。 公共卫生相关性：过去二十年，女性因毒品被捕的人数有所增加，而男性因毒品被捕的人数有所减少。因此，妇女吸毒已成为一个重大的社会问题。该项目的一个创新方面是尝试确定女性特有的物质使用结果的遗传和环境因素。鉴于生物学、基因表达和动机方面存在重要的性别差异，该项目可以为药物滥用的心理社会和药物治疗提供信息，以便针对特定性别的问题进行定制。