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).
