CHILDHOOD SEXUAL ABUSE AND PROBLEM DRINKING IN WOMEN: NEUROBEHAVIORAL MECHANISMS

摘要（Project Summary） 该项目的总体目标是阐明神经行为机制， 儿童期性虐待史（CSA）与酒精和其他物质使用之间的关系 妇女的成果。有CSA病史的女性有更早的酒精滥用和更高的酒精率 即使在控制了影响CSA暴露和问题的家庭背景因素后， 饮酒，如家族酗酒史。越来越多的证据表明，CSA及其后果 大脑发育可能构成了女性酗酒的独特病因学途径。然而，神经， 认知、情感和行为过程以及CSA和酒精之间联系的潜在机制 虐待行为并没有得到很好的理解。关于CSA神经行为后果的现有研究通常 依赖于小样本和不充分匹配的对照组，限制了对家族水平混杂因素的控制 因素和因果推理。拟议的研究旨在解决这些知识差距， 方法上的挑战，通过利用一个独特的资源，包括几个大的，良好的特点， 纵向样本和实施一套模型驱动的实验范式来检验假设 CSA+女性的饮酒问题是由偏见的情感处理和认知功能障碍介导的， 控制，导致失调的影响，因此，应对饮酒的动机。拟议的研究 这些理论都有很强的基础，并得到了我们的初步研究结果的支持。 实验室有早期CSA病史的年轻成年女性（n=80）和倾向评分匹配的对照组 （n=120，包括来自CSA-不一致MZ双胞胎对的40名CSA-共双胞胎）将参加实验室会议 包括面对面的访谈，行为和认知测试，以及定量脑电图的记录， 几种行为范式中的ERP。具体目标如下：1）阐明行为 以及CSA、酒精和其他物质之间关系的心理生理机制 使用女性的结果，2）检查CSA+和CSA-女性的酒精提示反应（ACR）及其 与饮酒动机和问题饮酒的关系，以及3）确定观察到的差异是否 与CSA相关的漏洞代表滥用的后果，而不是使用 cotwin控制设计总而言之，拟议的项目旨在弥合知识和技术方面的重大差距， 将是第一个对神经行为通路进行有力和良好控制的调查， 女性酗酒的重要病因学途径的潜在机制。的诸多方面都 提出的研究是特别新颖的：使用倾向评分匹配和不一致的双胞胎分析， 控制潜在的混杂变量，重点关注女性酗酒的特定病因学途径; 解释CSA和酒精问题之间联系的神经行为机制。

Abstract (Project Summary) The overall goal of the proposed project is to elucidate neurobehavioral mechanisms underlying the relationships between a history of childhood sexual abuse (CSA) and alcohol and other substance use outcomes in women. Women with CSA history have earlier onset of alcohol misuse and higher rates of alcohol use disorders, even after controlling for family background factors influencing both CSA exposure and problem drinking, such as family history of alcoholism. Converging evidence suggests that CSA and its consequences for brain development may constitute a distinct etiological pathway to alcoholism in women. However, neural, cognitive, affective, and behavioral processes and mechanisms underlying the link between CSA and alcohol abuse are not well understood. Existing research on neurobehavioral consequences of CSA have typically relied on small samples and insufficiently matched control groups limiting control for family-level confounding factors and causal inferences. The proposed study seeks to address these gaps in knowledge and methodological challenges by utilizing a unique resource consisting of several large, well-characterized, longitudinal samples and implementing a model-driven set of experimental paradigms to test the hypothesis that problem drinking in CSA+ women is mediated by biased affective processing and dysfunction in cognitive control, leading to dysregulated affect and, consequently, coping motives for drinking. The proposed studies are strongly grounded in the current theories of addiction and supported by preliminary findings from our laboratory. Young adult women with a history of early CSA (n=80) and propensity score-matched controls (n=120, including 40 CSA- co-twins from CSA-discordant MZ twin pairs) will participate in a laboratory session involving face-to-face interviews, behavioral and cognitive testing, and the recording of quantitative EEG and ERPs in several behavioral paradigms. The following Specific Aims will be pursued: 1) to elucidate behavioral and psychophysiological mechanisms underlying the relationship between CSA, alcohol, and other substance use outcomes in women, 2) to examine alcohol cue reactivity (ACR) in CSA+ and CSA- women and its relationship with drinking motives and problem drinking, and 3) to determine whether observed differences associated with CSA represent consequences of abuse rather than pre-existing vulnerabilities by using the cotwin control design. In summary, the proposed project is aimed at bridging important gaps in knowledge and will be one of the first well-powered and well-controlled inquiries into the neurobehavioral pathways and mechanisms underlying an important etiological pathway to alcoholism in women. Several aspects of the proposed research are particularly novel: the use of propensity score matching and discordant twin analyses to control for potential confounding variables, focus on a specific etiological pathway to alcoholism in women; and explication of neurobehavioral mechanisms underlying the link between CSA and alcohol problems.