Sex Differences in Risk for Alcohol Use Disorder: Neural and Hormonal Influences

酒精使用障碍风险的性别差异：神经和激素的影响

• 批准号: 10676813
• 负责人: Jessica J Weafer
• 金额: $ 38.44万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10676813
• 关键词: Alcohol abuse; Alcohol consumption; Alcohols; Amygdaloid structure; Anterior; Area; Brain; Corpus striatum structure; Data; Development; Emotional; Estradiol; Female; Functional Magnetic Resonance Imaging; Future; Goals; Gonadal Steroid Hormones; Heavy Drinking; Hormonal; Inferior frontal gyrus; Insula of Reil; Intervention; Intravenous; Laboratories; Link; Luteal Phase; Maintenance; Measures; Medial; Menstrual cycle; Modeling; Motor; Negative Finding; Neurobiology; Neurophysiology - biologic function; Participant; Patient Self-Report; Pattern; Pharmacotherapy; Phase; Prefrontal Cortex; Prevention; Progesterone; Research; Research Personnel; Risk; Risk Factors; Scanning; Self Administration; Sex Differences; Signal Transduction; Smoker; Transcranial magnetic stimulation; Woman; addiction; alcohol abuse therapy; alcohol cue; alcohol intervention; alcohol risk; alcohol use disorder; brain based; career; cingulate cortex; cue reactivity; design; disorder risk; drinking; executive function; follow-up; functional MRI scan; hazardous drinking; incentive salience; innovation; male; men; negative affect; neural; neural circuit; neural correlate; novel; proliferative phase Menstrual cycle; prospective; sex; skills; stimulant user; young woman

PROJECT SUMMARY/ABSTRACT The sex gap in alcohol consumption is closing rapidly, due to alarming increases in alcohol consumption among young women. As such, there is an urgent need to determine the factors underlying sex differences in risk for AUD. Current addiction models propose three neurofunctional domains that drive problematic alcohol use and therefore serve as candidate sex-specific risk factors: executive function, negative emotionality, and incentive salience. Data from our lab and others suggest that poor inhibitory control, a key component of executive function, is a stronger risk factor for women than for men. Moreover, we have preliminary evidence that female drinkers show less engagement of neural circuitry underlying inhibitory control, and that this sex difference is influenced by circulating levels of estradiol. However, the degree to which hormonally-moderated sex differences in executive function extend to the negative emotionality and incentive salience domains, and how these sex differences influence current and future drinking is unknown. Here we will determine: 1) the neurobiological factors contributing to sex-specific risk for AUD in each of these three addiction domains and 2) the degree to which sex differences in each domain influence current and prospective drinking. Female drinkers will undergo fMRI to assess neural correlates of inhibitory control (i.e., executive function), negative emotionality, and alcohol cue reactivity (i.e., incentive salience) at three phases of their menstrual cycle: early follicular phase (low estradiol, low progesterone), late follicular phase (high estradiol, low progesterone), and mid-luteal phase (moderate estradiol, high progesterone). Male drinkers will undergo three fMRI scans at matched intervals. Immediately following each scan, participants will complete a session of free-access intravenous alcohol self-administration. We will then follow participants for 18 months to longitudinally assess changes in drinking patterns. We hypothesize that hormonally-moderated neural function underlying inhibitory control and negative emotionality will be stronger predictors of current and future alcohol consumption in women compared to men, whereas neural alcohol cue reactivity will be a stronger predictor for men. The project capitalizes on the unique skill sets of the PI (an Early Career Investigator) and a strong, collaborative investigative team. The innovative design will provide essential information regarding neural factors influencing development and maintenance of AUD, and, critically, how this risk is influenced by sex and fluctuations in sex hormones. Ultimately, this proposal is a crucial step in a line of research that will lead to the development of sex-specific prevention and treatment efforts for AUD.

项目概要/摘要 由于酒精消费量惊人增加，酒精消费量的性别差距正在迅速缩小 在年轻女性中。因此，迫切需要确定性别差异背后的因素。 澳元的风险。当前的成瘾模型提出了三个导致问题酒精的神经功能域 使用并因此作为候选人特定性别的风险因素：执行功能、消极情绪和 激励显着性。我们实验室和其他实验室的数据表明，不良的抑制控制是 执行功能对女性来说是比男性更强的风险因素。此外，我们还有初步证据 女性饮酒者对抑制控制的神经回路的参与程度较低，而且这种性别 差异受到循环雌二醇水平的影响。然而，荷尔蒙调节的程度 执行功能的性别差异延伸到消极情绪和激励显着领域，并且 这些性别差异如何影响当前和未来的饮酒尚不清楚。在这里我们将确定：1） 在这三个成瘾领域中，神经生物学因素导致 AUD 的性别特异性风险，以及 2) 每个领域的性别差异对当前和未来饮酒的影响程度。女性 饮酒者将接受功能磁共振成像以评估抑制控制（即执行功能）的神经相关性，阴性 月经周期的三个阶段的情绪和酒精暗示反应（即激励显着性）：早期 卵泡期（低雌二醇、低孕酮）、卵泡晚期（高雌二醇、低孕酮）和 黄体中期（中等雌二醇，高孕酮）。男性饮酒者将接受三项功能磁共振成像扫描 匹配的间隔。每次扫描后，参与者将立即完成免费访问的会话 自行静脉注射酒精。然后我们将跟踪参与者 18 个月以进行纵向评估 饮酒方式的改变。我们假设激素调节的神经功能是抑制性的基础 控制力和负面情绪将是当前和未来酒精消费的更强预测因素 与男性相比，女性的酒精提示反应性对男性来说是更强的预测因子。这 项目利用了 PI（早期职业研究者）的独特技能和强大的协作能力 调查组。创新设计将提供有关影响神经因素的重要信息 AUD 的发展和维持，以及最重要的是，这种风险如何受到性别和性别波动的影响 荷尔蒙。最终，该提案是一系列研究中的关键一步，将导致开发 AUD 的针对性别的预防和治疗工作。

项目成果

Effects of a digital cognitive behavioral therapy for insomnia on sleep and alcohol consumption in heavy drinkers: A randomized pilot study.

数字认知行为疗法治疗失眠对重度饮酒者睡眠和饮酒的影响：一项随机试点研究。

• DOI: 10.1111/acer.15209
• 发表时间: 2023
• 期刊: Alcohol, clinical & experimental research
• 作者: Verlinden,JustinJ;Moloney,MaireadE;Vsevolozhskaya,OlgaA;Ritterband,LeeM;Winkel,Fiona;Weafer,Jessica
• 通讯作者: Weafer,Jessica

Sex Differences in the Association Between Poor Sleep Quality and Alcohol-Related Problems Among Heavy Drinkers With Insomnia.

• DOI: 10.3389/fnbeh.2022.875168
• 发表时间: 2022
• 期刊: FRONTIERS IN BEHAVIORAL NEUROSCIENCE
• 影响因子: 3
• 作者: Verlinden, Justin J.;Moloney, Mairead E.;Whitehurst, Lauren N.;Weafer, Jessica
• 通讯作者: Weafer, Jessica