Acute Alcohol Response In Bipolar Disorder: a Longitudinal Alcohol Administration/fMRI Study

The PI is currently investigating subjective response to alcohol in bipolar disorder and typical developing young adults (n=60; 50% with bipolar disorder) using placebo-controlled alcohol administration with baseline structural/functional MRI assessments collected with her K01. The proposed work will extend this active study to enroll 100 new young adults (50% with bipolar disorder) to complete baseline clinical, MRI, and placebo-controlled alcohol administration sessions. The PI's K01 is focused on investigating differences in subjective and neural response to alcohol between bipolar disorder and typical developing young adults. The proposed study will focus on investigating changes in subjective response to alcohol, placebo response, and relations with neural trajectories, the role(s) of stress, and prediction of alcohol problems over a two-year period. Longitudinal follow-up (clinical, detailed assessment of alcohol use, and MRI) will occur on average 1- and 2-years following enrollment. Participants enrolled on the PI's K01 will be brought back for longitudinal assessments to reach N=80 per group with longitudinal data (50% female; aged 21-26)]. At 2-year follow-up, placebo-controlled alcohol administration sessions will be repeated to test if sensitivity to alcohol changes over time-and if change in sensitivity to alcohol is associated with progressive neural changes in corticolimbic brain networks during young adulthood-and associations with alcohol use and symptoms of AUDs over time, and interactions with bipolar disorder. Changes in placebo-response and if changes are predictive of increased alcohol use and symptoms of AUDs will also be modeled. At one-year follow-up, a subset of participants will be invited to complete a psychosocial stress and neutral fMRI task on separate days (counter balanced; n=40 per group). Participants will immediately complete an alcohol session following the fMRI tasks and stress-induced changes in subjective response to alcohol and interactions with group will be modeled.

Inclusion criteria

Inclusion criteria

for all participants:

• between 21 and 26 years of age
• having consumed at least 4 (men) or 3 (women) drinks on a single occasion over the last year
• euthymic at the time of enrollment

Inclusion criteria

for bipolar disorder participants:

• Meeting Diagnostic and Statistical Manual-5 Research Version (DSM-V-RV) diagnostic criteria for bipolar disorder, confirmed by structured interview

Exclusion criteria

For all subjects exclusion criteria include:

• history of significant medical illness, particularly if possible changes in cerebral tissue
• neurologic abnormality including significant head trauma (loss of consciousness of ≥5-min)
• full Scale intelligence quotient (IQ) <85
• contraindication to MRI scanning
• positive pregnancy test
• current cannabis use disorder>moderate
• history of severe AUDs
• scores > 15 on the alcohol Use Disorders Identification Test (AUDIT; part of phone screen)
• ever being in an abstinence-oriented treatment program for alcohol use
• reporting wanting to quit drinking but not being able to
• any medical, religious, or other reasons for not drinking alcohol
• history of heart attack, heart trouble, high blood pressure, diabetes, or liver disease
• an adverse reaction to alcoholic beverages
• reporting never consuming 4 (men) or 3 (women) or more drinks on a single occasion over the last year
• unwillingness to have a friend or family member drive them home after the alcohol administration sessions
• a past year substance use disorder (other than alcohol, cannabis, or nicotine)

Additional exclusion criteria for bipolar disorder participants:

• not taking medications for greater than or equal to 4 weeks (i.e. participants must be stable on medications)

Additional exclusion criteria for healthy comparison subjects also include:

• any prior psychiatric hospitalizations
• lifetime history of a neurodevelopmental disorder, affective disorder, psychotic disorder, eating disorder
• greater than 1 month of lifetime psychotropic medication.