Role of Metal Ion Transporter ZIP8 in Alcohol-Related Behaviors

Eligibility Criteria

• 1. Male and female participants between 21-60 years of age. \[Based on: identification provided to Clinical Center Admissions office\].
• 2. Non-smokers with no history of smoking in the past year and not a daily smoker for more than 1 month in their lifetime. \[Based on: smoking history questionnaire, Additional History Form\]
• 3. Participants of European ancestry: the minor T allele of rs13107325, has a frequency of 0.08 in European ancestry, but is almost absent in Asian and African populations (http://www.ensembl.org). Due to the rare occurrence of the T allele and to avoid populations stratification in this small sample-sized study, only participants with European ancestry will be enrolled in this study.
• 4. Inclusion criteria for persons of childbearing potential: Use of adequate method of birth control during the study, if participant is sexually active and is not surgically sterilized. Adequate methods of contraception include use of oral contraceptives; use of barrier method of contraceptive; use of an approved IUD or other long-acting reversible contraceptive (LARC); have a male sexual partner who is surgically sterilized; or have exclusively same-sex sexual partner(s). Justification: To minimize the risk of administering alcohol to pregnant persons of childbearing potential, given the known effects of alcohol exposure on fetuses. \[Based on: medical history\].
• 5. Ability to understand the written consent form and willing to sign it. \[Based on: consent quiz\].
• 1. Current history (past 12 months) of major medical illness, including CNS, cardiovascular, respiratory, gastrointestinal, hepatic, renal, endocrine, or reproductive disorders, or positive hepatitis (A, B antigen, or C), or HIV test. Justification: Many illnesses may alter the neuropsychological effects of alcohol as well as MRI measures. Hepatitis can alter liver function and alcohol pharmacokinetics. HIV infection can alter brain function. \[Based on: clinically significant findings on medical history and physical exam, ECG, laboratory tests\].
• 2. Current history of psychiatric disorders, including depressive disorder, bipolar disorder, or anxiety disorders. Justification: Concurrent psychopathology can alter brain function and alcohol response. \[Based on: SCID interview\]
• 3. Lifetime history of psychotic disorders, obsessive compulsive disorder (OCD), posttraumatic stress disorder (PTSD), or eating disorder. Justification: These disorders can have long-term effects on brain function and alcohol response. \[Based on: SCID interview\]
• 4. Current or lifetime diagnosis of alcohol or substance use disorder. Past mild AUD or past mild SUD with no current symptoms for at least 2 years will not be exclusionary. Justification: History of moderate to severe alcohol or substance use disorder will impact brain function and alcohol response We do not anticipate past mild AUD or SUD in remission for 2+ years would have such impact on brain function and alcohol response. We will examine this in an exploratory analysis. We will also do a follow-up telephone/telehealth visit with these participants to assess any changes in alcohol or substance use or problems related to their participation in the study. \[Based on: SCID interview\].
• 5. Currently seeking treatment for alcohol use disorders. Justification: It would be unethical to administer alcohol to individuals seeking treatment for alcohol problems. Also, this study does not provide treatment for individuals with alcohol use disorder. \[Based on: medical history\]
• 6. Non-drinkers (alcohol-naive individuals or current abstainers) or individuals with no experience drinking 5 or more drinks on one occasion in their lifetime. Justification: It would be unethical to administer alcohol to individuals that do not drink alcohol. \[Based on: medical history\].
• 7. Current or prior history of alcohol-induced flushing reactions, including rapid reddening of the face, rapid heart rate and breathing, and nausea after 1 or 2 drinks. Justification: It would not be safe to administer alcohol to individuals with the highly aversive flushing response to alcohol. \[Based on: alcohol flushing questionnaire\].
• 8. Positive result on urine drug screen or positive breathalyzer during screening visit. Positive urine drug screen or breathalyzer reading during more than 1 study visit will result in participant withdrawal from the study. Justification: Current or recent exposure to alcohol or drugs of abuse could impact brain function and alcohol response. \[Based on: laboratory tests and breathalyzer test\].
• 9. History of significant withdrawal symptoms or presence of clinically significant withdrawal symptoms (Clinical Institute Withdrawal Assessment (CIWA) score \> 8) at screening. Justification: Withdrawal symptoms would be indicative of alcohol use disorder, which is already an exclusion criterion. Additionally, withdrawal symptoms would be a major safety concern for participants, and a major confound in the assessment of alcohol response and brain function. \[Based on: CIWA assessment\].
• 10. Medication