# YALE-SCORE ON SEX DIFFERENCES IN ALCOHOL USE DISORDER

> **NIH NIH U54** · YALE UNIVERSITY · 2020 · $1,675,000

## Abstract

Our proposed Yale-Specialized Center of Research Excellence (SCORE) on sex differences in alcohol use
disorder (AUD) brings together a team of leading basic and clinical science experts to pursue an
interdisciplinary, translational, cross-species program of research aimed at identifying novel therapeutics to
address the recent surge in rates of AUD in women. Over the past 10 years, rates of AUD in women have
increased by 84%, translating to 10.5 million women across the United States. Alcohol use is the third leading
cause of preventable morbidity and mortality in the United States and women drinkers experience exacerbated
health risks associated with alcohol consumption when compared to men. FDA-approved medications for AUD
have relatively low efficacy, all were developed with samples of men, and none target factors that differentially
maintain drinking in women. A considerable body of data identifies that women are more likely to drink to
regulate negative affect and stress, while men are more likely to drink for alcohol-related positive
reinforcement. Koob & Volkow194 have developed a heuristic framework of the addiction cycle, where the
‘withdrawal/negative affect stage’ involves drinking motivated by stress and other negative affect states, also
termed ‘the dark side of addiction’. Neuroadaptations during this stage identify reward deficits and stress
surfeits, which drive compulsive drinking. Using this negative reinforcement model to guide our research, we
plan to target key brain structures, neurochemical systems, HPA-axis activity, neuroimmune function, alcohol
metabolism, and sex steroid hormones, which are hypothesized to differentially motivate alcohol consumption
in women. To date, there has not been a concerted effort to incorporate sex as a biological variable (SABV)
into AUD medication development. Consequently, the focus of our Yale-SCORE represents a high research
priority topic for both NIAAA and ORWH. We propose three Projects that will have inter-related and shared
goals, with each providing unique contributions to inform and expedite the development of AUD therapeutics
for women with AUD. The Projects will be supported by three Cores and an institutional environment with
exceptional resources and infrastructure to support translational science. Our specific aims and objectives of
the Yale-SCORE are to: AIM 1: Use a neurobiologically-informed approach focusing on the ‘dark side of
addiction’ to inform and expedite the development of sex-appropriate therapeutics targeting stress and
negative affect, which differentially maintain drinking in women. AIM 2: Mentor SCORE-Early Investigators to
become the next generation of biomedical and behavioral researchers focused on alcohol and women’s health
spanning the T1 to T4 translational spectrum. AIM 3: Be an institutional, regional, and national resource
galvanizing the study of sex differences in relation to alcohol use across T1 to T4 translation by providing
expert consultation, s...

## Key facts

- **NIH application ID:** 9854087
- **Project number:** 1U54AA027989-01
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Sherry Ann McKee
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,675,000
- **Award type:** 1
- **Project period:** 2020-03-10 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9854087

## Citation

> US National Institutes of Health, RePORTER application 9854087, YALE-SCORE ON SEX DIFFERENCES IN ALCOHOL USE DISORDER (1U54AA027989-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9854087. Licensed CC0.

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