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

项目摘要/摘要 情绪障碍(如焦虑、压力和抑郁障碍)与饮酒高度并存 失调症，尤指女性。情绪障碍的一个核心特征是情感障碍，这可能是 广义的概念是：高水平的情绪痛苦，对这种痛苦的高度反应，以及有限的 能够利用适应性策略灵活地调节情绪反应和/或维持行为 控制力。情感障碍会加剧酒精渴望和奖励(即积极的酒精强化)， 在女性中增强的影响，是负面强化饮酒动机的关键驱动因素(例如， 依赖酒精来缓解痛苦)。卵巢激素(雌二醇、孕酮)是一种新的性别特异性激素 女性酒精强化和情感功能的生物标志物。雌二醇似乎可以提高酒精含量 当黄体酮水平较低时(即卵泡早期和中期)增强，雌二醇和 黄体酮增加了高度情感功能障碍(即黄体晚期)的风险。因此，频繁地 月经周期中雌二醇和孕酮的波动可能导致间歇性月经周期 加剧消极情绪和痛苦，耗尽适应性情绪调节能力，这可能会使 女性尤其容易受到负面强化饮酒的影响。然而，现有的工作几乎已经 专门关注雌二醇，尽管有强有力的证据表明黄体酮在情感障碍中的作用， 酒精强化的核心驱动力。此外，现有的研究受到不频繁测量的限制。 卵巢激素或月经时相作为客观荷尔蒙测量的替代指标， 限制了有关卵巢激素的变化或波动如何与酒精有关的知识的精确度 联系。因此，这项拟议的研究是对72名患有重病的生物女性进行的观察性受试者内测试。 饮酒(年龄18-40岁)，月经周期正常(25-35天)，不受激素避孕药影响。完毕 在整个月经周期中，每天都会采集唾液样本，以直接评估黄体酮和 雌二醇，并将与情感障碍的日常生态瞬时评估(EMA)相结合， 酒精使用和酒精奖励是由自然环境中的女性“实时”报告的。的目标是 这项研究是为了评估一名女性在月经过程中唾液中雌二醇和孕酮的每日波动。 完整的月经周期及其对(A)日常情感过程和(B)酒精强化的影响 以探索酒精使用对这些联系的调节作用。另一个探索性目标是 探讨情感过程是否在卵巢激素和酒精强化之间的联系中起中介作用 (即前馈关联)。这项研究有可能改善女性的治疗决策。 在他们的月经周期期间大量饮酒，包括在他们的周期中进行干预，并最终 谁最需要具体的干预(例如，患有情绪障碍的妇女)。

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).