A Program of Research and Mentorship on Alcohol Use and Intimate Partner Violence

描述（由申请人提供）：我的长期职业目标是提高对药物滥用和亲密伴侣暴力（IPV）之间联系的理解，增加可用的治疗方案，并作为下一代以患者为导向的酒精研究人员的榜样和导师。我的目标是有足够的时间集中精力指导至少10名教师学员，包括至少1名niaaa资助的K01奖获得者，1名nichd资助的K23奖获得者，1名niaaa资助的F-32奖获得者，以及7名最近或正在申请外部资助的助理或副教授。为了我自己的职业发展，我想进行多学科的研究，学习必要的技能，将我的研究项目扩展到酒精治疗和攻击的遗传学。这将包括获得分子遗传学方面的培训，对影响人类行为和精神状况的遗传变异进行高级统计建模，并将注意力集中在进行遗传学研究的伦理后果上。IPV会造成毁灭性的后果，包括身体和精神健康问题、离婚、自杀和杀害配偶。有大量证据表明酒精使用与IPV之间存在关联。最近的研究表明，男性和女性在饮酒日发生IPV的可能性是不饮酒日的5-20倍。在有酒精问题的人群中，研究表明，专门为减少酒精使用而设计的长期干预措施也能降低IPV。然而，研究表明，对因家庭暴力而被捕的人，特别是过度饮酒的人，对IPV的治疗相对无效。对施暴者治疗结果的研究表明，有酗酒问题的男性在干预后再犯暴力的可能性是没有酗酒问题的男性的16倍。迄今为止，关于治疗有害酒精使用将在多大程度上改善殴打者随后的IPV的研究很少。我目前正在进行两项随机临床试验其中男性和女性危险饮酒者因家庭暴力和法院指定的施暴者干预计划而被捕他们被分配到一个简短的，动机集中的酒精干预加上标准施暴者干预或者单独进行标准施暴者干预。在基线、3个月、6个月和12个月的随访中对酒精使用、酒精使用引起的问题以及身体、性和心理攻击进行评估。逮捕记录和保护令是暴力累犯的进一步指标。我们假设，相对于单独的标准治疗，在标准施暴者干预中加入简短的酒精治疗将导致随访中酒精使用和IPV犯罪和受害减少。到目前为止，我们的研究结果支持这些假设。这些赠款侧重于短期酒精干预在减少酒精使用和亲密伴侣暴力（IPV）方面的增量效果，包括确定干预措施的调节者。在这个K24应用程序中，我寻求对生物学驱动途径中经验支持的候选基因进行基因分型的支持，并使用总遗传风险评分（AGRS）方法来检查与酒精相关表型（包括治疗反应）以及ipvv相关表型随时间的遗传关联。研究参与者将从我正在进行的随机临床试验中招募。这个提议的K24奖提供了一个很好的机会来改善我们关于基因、IPV和酒精和暴力治疗结果之间关系的知识库。我建议收集和分析至少175-200名男性施暴者参与者和至少175-200名被捕女性参与者的DNA，以检验经验选择的候选基因在攻击表型和酒精治疗反应中的作用。我们将研究从经验选择的多巴胺能和血清素能系统候选多态性中得出的总体遗传风险评分是否与IPV的频率和严重程度以及药物使用有关，在基线和随时间。我们还将研究GABRA2多态性和单倍型是否与IPV和酒精治疗结果相关。出于探索性目的，我们将研究遗传模型中是否出现性别差异，以及MAO-A基因的性别连锁变异是否与IPV的发生有关。关于暴力和药物使用治疗结果的遗传预测因素的知识可以推进药物使用和攻击的理论模型，并最终可用于患者-治疗匹配。研究结果将极大地促进我们对这些社会问题的生物学基础的理解，并可能建议通过遗传背景针对行为干预的直接转化效益。储存DNA样本将使我们能够检查其他候选基因，因为它们在文献中出现了相关性。确定基因在酒精使用和攻击性行为中的作用将有助于制定更有力的治疗和预防策略。拟议的K24奖将为我提供培养行为遗传学研究知识所需的保护时间，同时让我有足够的时间指导一群优秀的初级同事。

DESCRIPTION (provided by applicant): My long term professional goals are to improve the understanding of the link between substance misuse and intimate partner violence (IPV), to enhance treatment options available, and to serve as a role model and mentor to the next generation of patient-oriented alcohol researchers. My goal is to have protected time to spend focused effort on mentoring at least 10 faculty mentees, including at minimum, one NIAAA-funded K01 award recipient, one NICHD-funded K23 recipient, one NIAAA-funded F-32 recipient, and 7 additional assistant or associate professors who have recently or are in the process of applying for external funding. For my own career development I would like to conduct multidisciplinary research and learn the necessary skills to expand my program of research to the genetics of alcohol treatment and aggression. This will involve obtaining training in molecular genetics, advanced statistical modeling of genetic variants influencing human behavior and psychiatric conditions, and focused attention on the ethical ramifications of conducting genetics research. IPV results in devastating consequences, including physical and mental health problems, divorce, suicide, and spousal homicide. There is substantial evidence for the association between alcohol use and IPV. Recent research has shown that IPV perpetration and victimization by both genders is 5-20 times more likely to occur on a drinking day than on a non-drinking day. In populations of individuals with alcohol problems, research has shown that extended interventions specifically designed to reduce alcohol use also produce decreases in IPV. However, research suggests that treatment for IPV among individuals arrested for domestic violence is relatively ineffective, particularly among individuals who use alcohol excessively. Batterer treatment outcome research has shown that men with alcohol problems are 16 times more likely to recidivate to violence after the intervention than men without alcohol problems. To date, there is minimal research on the extent to which treatment for hazardous alcohol use will ameliorate subsequent IPV in batterers. I am currently conducting two randomized clinical trials wherein male and female hazardous drinkers who have been arrested for domestic violence and court-referred to batterer intervention programs are assigned to either a brief, motivationally focused alcohol intervention plus standard batterer intervention or standard batterer intervention alone. Alcohol use, problems arising from alcohol use, and physical, sexual, and psychological aggression are assessed at baseline, 3-, 6-, and 12-month follow-up. Arrest records and protection orders are obtained as further indices of violence recidivism. We hypothesize that adding a brief alcohol treatment to standard batterer intervention will result in less alcohol use and IPV perpetration and victimization at follow-up, relative to standard care alone. To date, our findings support these hypotheses. These grants focus on the incremental efficacy of a brief alcohol intervention in reducing alcohol use and by extension intimate partner violence (IPV), including the identification of moderators of the interventions. In this K24 application, I seek support for genotyping empirically-supported candidate genes in biologically driven pathways and using an aggregate genetic risk score (AGRS) approach to examining genetic associations with alcohol-related phenotypes (including treatment response) as well as IPV-related phenotypes over time. Research participants will be recruited from my ongoing randomized clinical trials. This proposed K24 award affords an excellent opportunity to improve our knowledge base regarding the association between genes, IPV, and alcohol and violence treatment outcome. I propose to collect and analyze DNA from a minimum of 175-200 male batterer participants and at least 175-200 arrested women participants to examine the role of empirically selected candidate genes in association with phenotypes of aggression and alcohol treatment response. We will examine whether aggregate genetic risk scores derived from empirically- selected candidate polymorphisms in the dopaminergic and serotonergic systems are associated with the frequency and severity of IPV, and substance use, at baseline and over time. We will also examine whether GABRA2 polymorphisms and haplotypes are associated with IPV and alcohol treatment outcome. For exploratory purposes, we will investigate whether gender differences emerge in genetic models, and whether sex-linked variation in the MAO-A gene is associated with IPV perpetration over time. Knowledge regarding genetic predictors of violence and substance use treatment outcomes could advance theoretical models of substance use and aggression and could ultimately be used for patient-treatment matching. Results will significantly contribute to our understanding of the biological underpinnings of these societal problems, and may suggest immediate translational benefits to targeting behavioral interventions by genetic background. Banking the DNA samples will allow us to examine other candidate genes as their relevance emerges in the literature. Identifying the role of genetics in alcohol use and aggressive behavior will facilitate the development of more robust treatments and prevention strategies. The proposed K24 award will provide the protected time required to cultivate my knowledge of behavioral genetics research, while allowing me considerable time to mentor an outstanding group of junior colleagues.