Linkages between ovarian hormones and affective dysfunction with alcohol use, reward and reinforcement

卵巢激素和情感功能障碍与饮酒、奖励和强化之间的联系

基本信息

批准号：
10491688
负责人：
Ana M Abrantes
金额：
$ 21.65万
依托单位：
RUTGERS, THE STATE UNIV OF N.J.
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-22 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10491688
关键词：
Address Affect Affective Age Alcohol consumption Alcoholic beverage heavy drinker Alcohols Allopregnanolone Anti-Anxiety Agents Anxiety Disorders Behavior Control Biological Data Decision Making Depressive disorder Development Distress Drug usage Ecological momentary assessment Emotional Emotional disorder Emotions Environment Estradiol Female Functional disorder Health Heavy Drinking Height Hormones Intervention Knowledge Length Link Luteal Phase Measurement Measures Mediating Mediator of activation protein Menstrual cycle Modeling Motivation Negative Reinforcements Neurobiology Observational Study Outcome Ovarian hormone Patient Self-Report Pharmacology Phase Plasma Population Positive Reinforcements Process Progesterone Proxy Psychological reinforcement Reporting Research Design Rewards Risk Role Salivary Specific qualifier value Stress Study Subject Testing Time Woman Work addiction alcohol craving alcohol demand alcohol effect alcohol intervention alcohol reinforcement alcohol reward alcohol use disorder base behavioral response binge drinking comorbidity craving drinking drug reward emotion dysregulation emotion regulation emotional distress experience flexibility hormonal contraception improved male negative affect novel personalized medicine precision medicine proliferative phase Menstrual cycle receptor response saliva sample sedative sex skills specific biomarkers stress disorder substance misuse

项目摘要

PROJECT SUMMARY/ABSTRACT Emotional disorders (e.g., anxiety, stress, and depressive disorders) are highly comorbid with alcohol use disorder, particularly in females. A core feature of emotional disorders is affective dysfunction, which can be broadly conceptualized as: high levels of emotional distress, heightened reactivity to this distress, and limited ability to utilize adaptive strategies to flexibly modulate the emotional response and/or maintain behavioral control. Affective dysfunction heightens alcohol craving and reward (i.e., positive alcohol reinforcement), effects that are potentiated in females, and is a key driver of negative-reinforcement drinking motivation (e.g., reliance on alcohol to alleviate distress). Ovarian hormones (estradiol, progesterone) are a novel sex-specific biomarker of alcohol reinforcement and affective functioning in females. Estradiol appears to enhance alcohol reinforcement when progesterone is low (i.e., early-mid follicular phase), and declining levels of estradiol and progesterone increase risk for heighted affective dysfunction (i.e., late luteal phase). Thus, frequent fluctuations in estradiol and progesterone during the menstrual cycle may contribute to intermittent periods of exacerbated negative affect and distress, and deplete adaptive emotion regulation abilities, which may make females especially vulnerable to negative-reinforcement drinking. However, existing work has almost exclusively focused on estradiol, despite robust evidence for the role of progesterone in affective dysfunction, a core driver of alcohol reinforcement. Moreover, existing studies have been limited by infrequent measurement of ovarian hormones or reliance of menstrual phases as a proxy for objective hormone measurement, which limits precision in knowledge about how changes or fluctuations in ovarian hormones relate to affect-alcohol linkages. Thus, the proposed study is an observational within-subjects test of 72 biological females with heavy drinking (ages 18-40) with a normal menstrual cycle (25-35 days), not altered by hormonal contraceptive. Over the course of a full menstrual cycle, daily saliva samples will be collected to directly assess progesterone and estradiol, and will be paired with daily ecological momentary assessment (EMA) of affective dysfunction, alcohol use, and alcohol reward reported in “real-time” from females in their natural environments. The aims of this study are to evaluate daily fluctuations in salivary estradiol and progesterone over the course of a female’s complete menstrual cycle and its effect on (a) daily affective processes and (b) alcohol reinforcement as well as to explore the moderating role of alcohol use on these associations. An additional exploratory aim is to explore whether affective processes mediate the link between ovarian hormones and alcohol reinforcement (i.e., feed-forward associations). This study has the potential to improve treatment decision-making for females with heavy drinking around their menstrual cycle, including when in their cycle to intervene, and eventually, for whom specific intervention is most needed (e.g., women with emotional disorders).

项目摘要/摘要情绪障碍（例如焦虑，压力和抑郁症）与酒精使用高度合并疾病，特别是在女性中。情绪障碍的核心特征是情感功能障碍，这可以是广泛地概念化为：高水平的情绪困扰，对这种困扰的反应性增强以及有限利用自适应策略灵活调节情绪反应和/或保持行为的能力控制。情感功能障碍会增强酒精的渴望和奖励（即阳性酒精增强），在女性中潜在的影响，并且是负强调饮酒动机的关键驱动力（例如，依靠酒精来减轻苦难）。卵巢马（雌二醇，孕酮）是一种新颖的性别特定性饮酒的生物标志物和女性情感功能。雌二醇似乎可以增强酒精当孕酮低（即早期卵泡期）时加固，雌二醇和雌二醇水平下降孕酮会增加情感功能障碍增强的风险（即黄体期晚期）。那，频率月经周期期间雌二醇和孕酮的波动可能有助于间歇时间加剧负面影响和困扰，并复制适应性情绪调节能力，这可能使女性特别容易受到负面饮酒的影响。但是，现有工作几乎有仅专注于雌二醇，dospite强大的证据证明了孕激素在情感功能障碍中的作用，一种酒精加固的核心驱动力。此外，现有研究受到不经常测量的限制卵巢马或月经阶段的提醒，作为客观马匹测量的代理限制知识的精度，涉及卵巢激素的变化或与情感饮酒有关的变化或波动链接。这是拟议的研究是对72位生物学女性的观察性内部测试以正常的月经周期（25-35天）的饮酒（18-40岁），未通过激素避孕药改变。超过在整个月经周期的过程中，将收集每日唾液样本，以直接评估孕酮和雌二醇，并将与情感功能障碍的每日生态瞬时评估（EMA）配对，饮酒和酒精奖励在其自然环境中的“实时”中报道了“实时”。目的这项研究是为了评估唾液雌二醇和孕酮的每日波动完成月经周期及其对（a）每日情感过程和（b）酒精增强的影响探索饮酒对这些关联的调节作用。另一个探索目的是探索情感过程是否介导了卵巢激素与酒精增强之间的联系（即，进料联想）。这项研究有可能改善女性的治疗决策在月经周期中大量饮酒，包括何时进行干预，有时甚至是最需要特定干预的人（例如，情绪障碍的女性）。