Neural and Hormonal Influences on Sex Differences in Risk for AUD

The sex gap in alcohol consumption is closing rapidly, due to alarming increases among women. From 2002-2013, Alcohol Use Disorder (AUD) increased 84% for women, compared to 35% for men. As such, there is an urgent need to determine the factors underlying sex differences in risk for AUD. Current addiction models propose three domains that drive problematic alcohol use and serve as candidate sex-specific risk factors: executive function, negative emotionality, and incentive salience. Data suggest that poor inhibitory control, a key component of executive function, is a stronger risk factor for women than for men. Moreover, there is have preliminary evidence that female drinkers show less engagement of neural inhibitory circuitry, and that this sex difference is influenced by 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. The goal of this study is to identify the mechanisms underlying sex-specific risk for AUD, and ultimately to help develop sex-specific prevention and treatment efforts. The overall objective of this trial is to determine the neural and hormonal factors contributing to sex-specific risk for AUD in three addiction domains: inhibitory control (executive function), negative emotionality, and alcohol cue reactivity (incentive salience).

Participants in this group will be adult female drinkers. Data will be segregated by menstrual cycle phase.

Participants will complete three experimental sessions. In each session, participants will provide detailed reports of their alcohol consumption over the past five days, and they will provide a blood sample for hormone assays. They will perform tasks during fMRI to assess each of the neurofunctional addiction domains: inhibitory control, negative emotionality, and cue reactivity. Following the fMRI scan, subjects will self-administer intravenous alcohol to provide a controlled assessment of pharmacologically-driven alcohol consumption.

One measure of neural inhibitory function during performance of the stop signal task will be activity (as measured by BOLD % signal change)

The other measure of neural inhibitory function during performance of the stop signal task will be functional connectivity for the StopInh>Go contrast.

One measure of neural negative emotionality during performance of the Emotional Pictures Task will be activity (as measured by BOLD % signal change)

The other measure of neural negative emotionality during performance of the Emotional Pictures Task will be functional connectivity for the Negative>Neutral contrast.

One measure of neural alcohol cue reactivity during performance of the Alcohol Cue Reactivity Task will be activity (as measured by BOLD % signal change)

The other measure of neural alcohol cue reactivity during performance of the Alcohol Cue Reactivity Task will be functional connectivity for the Alcohol>Neutral contrast.

Another measure of IV-ASA will be whether or not a participant reached binge level of alcohol exposure (80mg%)

One measure of current alcohol consumption will be number of binge days (4/5 or more drinks in a sitting for women/men) as determined by responses on the Timeline Followback.

The other measure of current alcohol consumption will be average peak BrAC obtained on drinking days over the past 5 days, as determined by responses on the Timeline Followback.

One measure of prospective alcohol consumption will be number of binge episodes as determined by responses on the 90-day Timeline Followback.

The other measure of prospective alcohol consumption will be drinking days per month, as determined by responses on the 90-day Timeline Followback.

Inclusion Criteria: consume 4/5 drinks per week fluent in English high school education right-handed regular menstrual cycles (women) Exclusion Criteria: serious medical problems body weight <110 or >210 lbs current medical or psychiatric conditions requiring medication for which alcohol is contraindicated substance use disorder other than alcohol current or recent history of inpatient/intensive treatment for addictive behaviors pregnant, nursing, on hormonal contraception contraindications for fMRI smoking > 5 cigarettes per day