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; 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.

项目摘要/摘要 由于饮酒的增加，饮酒的性别差距正在迅速结束 在年轻女性中。因此，迫切需要确定性别差异的因素 aud的风险。当前的成瘾模型提出了三个驱动有问题的酒精的神经功能域 使用并因此充当特定于性别的风险因素：执行功能，负面情绪和 激励显着性。我们实验室和其他人的数据表明，抑制性较差，这是 执行功能是女性的危险因素，而不是男性。而且，我们有初步证据 那个女性饮酒者表现出较少的抑制性控制神经回路的参与，这种性别 差异受雌二醇循环水平的影响。但是，荷尔蒙修饰的程度 执行功能的性别差异扩展到负面情绪和激励显着领域，以及 这些性别差异如何影响当前和未来的饮酒是未知的。在这里我们将确定：1） 在这三个成瘾领域中的每个领域中的每一个，有助于特定性别风险的神经生物学因素，2） 每个领域的性别差异影响当前和前瞻性饮酒程度。女性 饮酒者将接受fMRI以评估抑制性控制的神经相关性（即执行功能），负面 情绪和酒精提示反应性（即激励显着性）在其月经周期的三个阶段：早期 卵泡期（低雌二醇，低孕酮），晚卵泡期（高雌二醇，低孕酮）和 中间体相（中度雌二醇，高孕酮）。男性饮酒者将在 匹配的间隔。每次扫描之后，参与者将立即完成免费访问会议 静脉酒精自我管理。然后，我们将关注参与者18个月进行纵向评估 饮酒方式的变化。我们假设抑制性荷尔蒙修饰的神经功能 控制和负面情绪将是对当前和未来饮酒量的更强有力的预测指标 与男性相比，女性，而神经酒精提示反应性将是男性的更强预测指标。这 项目将PI的独特技能（早期职业调查员）和强大的协作式资本化。 调查团队。创新设计将提供有关影响神经因素的基本信息 AUD的开发和维护，并且在批判性的情况下，这种风险如何受到性别的影响 激素。最终，该提议是一项研究的关键步骤，这将导致发展 特定于性别的预防和AUD治疗工作。