Sex Differences in Risk for Alcohol Abuse

This study will determine the neural and hormonal mechanisms underlying sex differences in sensitivity to the disinhibiting effects of alcohol in heavy drinkers.

Alcohol abuse inflicts enormous physical, emotional, and financial burdens on the individual and society at large. Knowing who is at risk for alcohol abuse, and why, is crucial for the development of effective prevention and treatment strategies. Alcohol abuse has been traditionally considered a male-oriented problem and as a consequence research on risk factors specific to women has been minimal. However, the sex gap in substance abuse is closing rapidly, and findings from both animal and human studies suggest that females are actually more vulnerable to drug use than males. As such, there is an urgent need to identify sex differences in risk factors for alcohol abuse in order to develop sex-specific prevention and treatment efforts. One clear candidate risk factor is poor inhibitory control, both in terms of baseline levels of inhibition and sensitivity to the disinhibiting effects of alcohol. Recent studies suggest that sex hormones affect inhibitory control in drug-free individuals, potentially contributing to sex differences in baseline levels of inhibition. However, the degree to which fluctuations in sex hormones influence sex differences in inhibition-related brain function in sober and intoxicated individuals is not known. The proposed project will determine the neural and hormonal mechanisms underlying sex differences in sensitivity to the disinhibiting effects of alcohol in heavy drinkers. The overall objective of the research is to identify hormonal determinants of alcohol effects on brain activation during response inhibition (BARI) in young adult female and male drinkers. BARI will be assessed using functional magnetic resonance imaging (fMRI) during performance of the stop signal task. This task reliably activates right-lateralized prefrontal regions implicated in inhibitory control. This study will assess BARI during IV alcohol (60mg%) and saline infusion in women during the early follicular and mid-luteal phases and in men at matched intervals.

brain activation during response inhibition, BARI, fMRI, stop signal task, sex difference, menstrual, inhibitory control

Participants in this group will be adult female heavy drinkers. Data will be segregated by menstrual cycle phase - the late follicular or mid-luteal phase.

Alcohol will be administered by IV infusion (60mg%). Brain activation during response inhibition (BARI) will be assessed using fMRI during performance of the stop signal task.

Brain activation during response inhibition (BARI) will be assessed using blood oxygenation level dependent (BOLD) fMRI during performance of the stop signal task with alcohol compared to to placebo. Values will be determined by the contrast of BOLD activation during successful inhibition trials relative to go trials.

The Biphasic Alcohol Effects Scale (BAES) is a 14-point self-reporting, unipolar adjective rating scale designed to measure both stimulant and sedative effects of alcohol. Scores range from 0-10 for each of the 14 questions. Higher scores indicate increased stimulation or sedation. Scores will be reported with alcohol comparted to placebo.

Drug Effects Questionnaire (DEQ) consists of simple, face-valid, visual analog scale (VAS) questions on which people report their subjective states after ingesting a substance. The analog scale of responses ranges from "not at all" to "extremely." Scores are measured in millimeters from the scale origin. Higher scores (longer lengths) indicate greater drug effects. Scores will be reported with alcohol comparted to placebo.

Inclusion Criteria: heavy drinking Alcohol Use Disorder Identification Test score above 7 right-handed BMI between 19 and 26 high school education fluent in English women must have regular menstrual cycles not using hormonal contraceptives Exclusion Criteria: drug use disorder (SCID, DSM-5), other than nicotine or caffeine meets withdrawal criteria history of physical or psychiatric disease contraindication for fMRI pregnant or breastfeeding smoking more than 5 cigarettes per day