PROJECT SUMMARY Alcohol misuse is rising in females. As females may experience worse health consequences then males and female-specific risks associated with alcohol misuse, elucidating female-specific factors is essential to build a better understanding of alcohol misuse in females and the development of prevention strategies for alcohol misuse in females. A small literature implicates dimensional premenstrual dysphoric disorder (dPMDD)—a mood disorder characterized by clinically significant emotional, behavioral, and physical symptoms during the late luteal that completely resolve by the mid follicular—as a critical female-specific risk factor for alcohol misuse and luteal phase increases in alcohol use. However, no studies to date have evaluated the shared physiological and emotional pathways of dPMDD and alcohol misuse. Emotion regulation encompasses the awareness and identification of emotion, and strategies to modify the emotional response. Emotion regulation may also be physiologically represented. Heart rate variability (HRV), an index of parasympathetic control over heartrate, is considered a peripheral psychophysiological marker of emotion regulation. Reduced subjective and objective (i.e., HRV) emotion regulation has been shown to associate with alcohol misuse. However, studies have not investigated how cyclical changes in emotion regulation may act as a risk factor for alcohol misuse and whether this differs between females with compared to without dPMDD. HRV shows the lowest levels during the luteal phase and our pilot data shows greater luteal phase reductions in HRV map onto more significant increases in luteal phase negative emotion. Our central hypothesis is that females with dPMDD suffer from recurrent luteal phase increases in heavy drinking due to progesterone-related declines in HRV and associated deficits in emotion regulation. The proposed study will recruit premenopausal females with heavy alcohol use (50% dPMDD) who will complete 4 weeks of prospective screening; and 5 weeks of Ecological Momentary Assessment (EMA) and HRV assessment. Aim 1 tests the hypothesis that dPMDD will show larger luteal phase increases in alcohol misuse relative to no dPMDD. Aim 2 tests the hypothesis that cyclical deficits in emotion regulation will predict cyclical increases in alcohol misuse. Aim 3 tests the hypothesis that individual differences in the degree of HRV reduction from the follicular to the luteal phase will predict greater luteal phase increases in alcohol variables. The results of this study will importantly contribute to the NIH strategic plan for research addressing sex/gender differences and female health. Specifically, this study will provide information on cyclical emotion regulation associations with alcohol misuse, which will provide foundational information regarding the influence of emotion regulation in the context of heavy drinking and the etiologic overlap between female alcohol misuse and emotion regulation in dPMDD...