Sex Differences in Risk for Alcohol Use Disorder: Neural and Hormonal Influences
Project Number5R01AA028503-06
Former Number5R01AA028503-04
Contact PI/Project LeaderWEAFER, JESSICA J
Awardee OrganizationOHIO STATE UNIVERSITY
Description
Abstract Text
PROJECT SUMMARY/ABSTRACT
The sex gap in alcohol consumption is closing rapidly, due to alarming increases in alcohol consumption
among young women. As such, there is an urgent need to determine the factors underlying sex differences in
risk for AUD. Current addiction models propose three neurofunctional domains that drive problematic alcohol
use and therefore serve as candidate sex-specific risk factors: executive function, negative emotionality, and
incentive salience. Data from our lab and others suggest that poor inhibitory control, a key component of
executive function, is a stronger risk factor for women than for men. Moreover, we have preliminary evidence
that female drinkers show less engagement of neural circuitry underlying inhibitory control, and that this sex
difference is influenced by circulating levels of estradiol. However, the degree to which hormonally-moderated
sex differences in executive function extend to the negative emotionality and incentive salience domains, and
how these sex differences influence current and future drinking is unknown. Here we will determine: 1) the
neurobiological factors contributing to sex-specific risk for AUD in each of these three addiction domains and 2)
the degree to which sex differences in each domain influence current and prospective drinking. Female
drinkers will undergo fMRI to assess neural correlates of inhibitory control (i.e., executive function), negative
emotionality, and alcohol cue reactivity (i.e., incentive salience) at three phases of their menstrual cycle: early
follicular phase (low estradiol, low progesterone), late follicular phase (high estradiol, low progesterone), and
mid-luteal phase (moderate estradiol, high progesterone). Male drinkers will undergo three fMRI scans at
matched intervals. Immediately following each scan, participants will complete a session of free-access
intravenous alcohol self-administration. We will then follow participants for 18 months to longitudinally assess
changes in drinking patterns. We hypothesize that hormonally-moderated neural function underlying inhibitory
control and negative emotionality will be stronger predictors of current and future alcohol consumption in
women compared to men, whereas neural alcohol cue reactivity will be a stronger predictor for men. The
project capitalizes on the unique skill sets of the PI (an Early Career Investigator) and a strong, collaborative
investigative team. The innovative design will provide essential information regarding neural factors influencing
development and maintenance of AUD, and, critically, how this risk is influenced by sex and fluctuations in sex
hormones. Ultimately, this proposal is a crucial step in a line of research that will lead to the development of
sex-specific prevention and treatment efforts for AUD.
Public Health Relevance Statement
PROJECT NARRATIVE
The findings from this project will determine sex differences and the influence of sex hormones on neural
function underlying risk for Alcohol Use Disorder (AUD), as well as how sex differences in neural function
influence current and future alcohol consumption. The results will identify novel brain-based targets for sex-
specific prevention and treatment efforts for AUD, and will provide information on the optimal timing of
intervention for women, based on fluctuating sex hormones. As such, the project is a critical step towards the
development of biologically-based, sex-specific interventions for AUD.
National Institute on Alcohol Abuse and Alcoholism
CFDA Code
273
DUNS Number
832127323
UEI
DLWBSLWAJWR1
Project Start Date
01-May-2024
Project End Date
31-July-2025
Budget Start Date
01-August-2024
Budget End Date
31-July-2025
Project Funding Information for 2024
Total Funding
$336,466
Direct Costs
$270,323
Indirect Costs
$66,143
Year
Funding IC
FY Total Cost by IC
2024
National Institute on Alcohol Abuse and Alcoholism
$336,466
Year
Funding IC
FY Total Cost by IC
Sub Projects
No Sub Projects information available for 5R01AA028503-06
Publications
Publications are associated with projects, but cannot be identified with any particular year of the project or fiscal year of funding. This is due to the continuous and cumulative nature of knowledge generation across the life of a project and the sometimes long and variable publishing timeline. Similarly, for multi-component projects, publications are associated with the parent core project and not with individual sub-projects.
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Outcomes
The Project Outcomes shown here are displayed verbatim as submitted by the Principal Investigator (PI) for this award. Any opinions, findings, and conclusions or recommendations expressed are those of the PI and do not necessarily reflect the views of the National Institutes of Health. NIH has not endorsed the content below.
No Outcomes available for 5R01AA028503-06
Clinical Studies
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History
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