The role of stress, social support, and brain function on alcohol misuse in women

项目总结/摘要 产前饮酒（PAU）与产科并发症的可能性增加有关，包括早产 分娩，流产和死胎，也是胎儿酒精谱系障碍的直接原因， 导致终生神经行为和颅面畸形的神经发育障碍。在2020年， 疾病控制和预防中心报告说，大约七分之一的孕妇 在过去一个月里，消费酒精，这符合自2011年以来的增长趋势。因此，PAU是一个主要的 和日益严重的公共卫生问题，因此必须了解PAU的风险因素， 预防和干预。压力就是这样一个关键的风险因素。经常有压力的孕妇有3- 酗酒的风险比没有频繁压力的孕妇高出一倍。此外，怀孕前 酒精使用与PAU相关，这表明了解酒精滥用的病因 妊娠期外预防对预防PAU至关重要。相应地，压力在酒精中起着至关重要的作用。 使用障碍（AUD）在怀孕以外的妇女，因为妇女更容易复发， 相对于男性的压力触发器。这种脆弱性可能部分是由性别/性别（SG）差异造成的， 与AUD中加工应激相关的神经回路。压力脆弱性的增加与 在“显着网络”（SN）功能障碍，这是一个大脑区域的集合，主要是脑，背， 前扣带皮层和顶下小叶，对显著的、潜在的压力刺激做出反应， 也对包括酒精在内的物质使用线索反应强烈。此外，社会支持可以作为 对与压力有关的酒精滥用的弹性因素，特别是在妇女。社会支持是否以及如何能够 也缓冲了大脑对AUD压力的高度脆弱性，如果这种影响存在SG差异， 还有待研究。此外，压力和社会支持是否同样影响PAU尚不清楚。我 总体假设是，女性相对于男性更容易受到与压力相关的酒精滥用的影响 通过增强SN反应性;然而，社会支持将对这种关系产生更强的缓冲作用， 妇女本项目的具体目标是：（1A）评估秘书长在卫星网络作用方面的差异， AUD患者的应激反应性和酒精使用水平之间的关系，（1B）评估 社会支持是否通过改变与压力相关的SN反应性来防止酒精滥用，以及（2） 确定产前饮酒的风险和保护因素。实现这些目标将科学地告知- 在怀孕期间和怀孕之外的女性中，AUD的基础治疗，以及为我准备一个 在学术医学领域作为一名医生科学家的成功职业生涯。

PROJECT SUMMARY/ABSTRACT Prenatal alcohol use (PAU) is associated with increased likelihood of obstetric complications, including preterm labor, miscarriage, and stillbirth, and is also the direct cause of Fetal Alcohol Spectrum Disorders, a collection of neurodevelopmental disorders that cause lifelong neurobehavioral and craniofacial abnormalities. In 2020, the Center for Disease Control and Prevention reported that approximately 1 in 7 pregnant women had consumed alcohol in the past month, which is in line with increasing trends since 2011. Thus, PAU is a major and growing public health problem, so it is imperative to understand the risk factors for PAU to inform prevention and intervention. Stress is one such key risk factor. Pregnant women with frequent stress have a 3- fold higher risk of binge drinking than pregnant women without frequent stress. Furthermore, pre-pregnancy alcohol use is consistently associated with PAU, suggesting that understanding the etiology of alcohol misuse outside of pregnancy is essential for preventing PAU. Correspondingly, stress plays a crucial role in Alcohol Use Disorder (AUD) in women outside of pregnancy, as women are more vulnerable to relapse following stressful triggers relative to men. This vulnerability may in part be driven by sex/gender (SG) differences in neurocircuitry related to processing stress in AUD. Increased stress vulnerability has been linked to dysfunction in the “salience network” (SN), which is a collection of brain regions, primarily the insula, the dorsal anterior cingulate cortex, and inferior parietal lobule, that responds to salient, potentially stressful stimuli and is also highly reactive to substance use cues, including alcohol. Furthermore, social support may serve as a resilience factor against stress-related alcohol misuse, particularly in women. If and how social support can also buffer the brain’s heightened vulnerability to stress in AUD, and if there are SG differences in this effect, remains to be examined. Moreover, whether stress and social support similarly affect PAU is unclear. My overarching hypothesis is that women, relative to men, are more vulnerable to stress-related alcohol misuse via enhanced SN reactivity; however, social support will have a stronger buffering effect on this relationship in women. The specific aims of this project are to (1A) assess SG differences in the role of the SN on the relationship between stress reactivity and alcohol use levels in people with AUD, (1B) assess SG differences in whether social support protects against alcohol misuse by altering stress-related SN reactivity, and (2) determine risk and protective factors for prenatal alcohol use. Achieving these goals will inform scientifically- grounded treatments for AUD in women during and outside of pregnancy, as well as prepare me for a successful career as a physician-scientist in academic medicine.