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

项目摘要/摘要 产前饮酒(PAU)与产科并发症(包括早产)的可能性增加有关 分娩、流产和死产，也是胎儿酒精谱系障碍的直接原因，这是一本集合 神经发育障碍会导致终生神经行为和颅面畸形。在2020年， 疾病控制和预防中心报告称，大约每7名孕妇中就有1人患有 过去一个月的饮酒量与2011年以来的上升趋势一致。因此，PAU是一个主要的 以及日益严重的公共卫生问题，因此必须了解PAU需要告知的风险因素 预防和干预。压力是这样一个关键的风险因素。经常有压力的孕妇有3- 与没有频繁压力的孕妇相比，酗酒的风险要高出一倍。此外，怀孕前 酒精使用一直与PAU有关，这表明了解酒精滥用的病因 孕期外是预防产后溃疡的关键。相应地，压力在酒精中起着至关重要的作用 在怀孕外的女性中使用障碍(AUD)，因为女性更容易在以下情况下复发 相对于男性而言，有压力的诱因。这种脆弱性可能在一定程度上是由性别/性别(SG)差异 AUD中与处理应激相关的神经回路。压力易损性的增加与 “显著网络”(SN)的功能障碍，这是大脑区域的集合，主要是脑岛、背部 前扣带回皮质和顶下小叶，对显著的、潜在的应激刺激做出反应，并 对包括酒精在内的物质使用线索也有很高的反应。此外，社会支持可以作为一种 抵抗压力相关的酒精滥用的弹性因素，特别是在女性身上。社会支持是否以及如何能够 也缓冲了大脑在AUD中对压力的高度易感性，如果在这一效应上存在SG差异， 仍有待检验。此外，压力和社会支持是否同样影响PAU尚不清楚。我的 最重要的假设是，与男性相比，女性更容易受到与压力有关的酒精滥用的影响 通过增强的SN反应性；然而，社会支持对这种关系在 女人。本项目的具体目标是：(1)评估秘书长在SN的角色上的差异 AUD患者的应激反应与酒精使用水平之间的关系，(1B)评估SG在 社会支持是否通过改变压力相关的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。实现这些目标将为科学提供信息-- 在妊娠期和孕期外对女性进行AUD的接地治疗，以及为我的 在学术医学领域成为一名成功的内科医生和科学家。

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.