Biological Risk Factors for the Prospective Development of Alcohol Use Disorders in Young Adults with Bipolar Disorder and Typically Developing Young Adults

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Alcohol use disorders (AUDs) affect up to 60% of individuals with bipolar disorder during their lifetime and is associated with worse illness outcomes, yet few studies have been performed to clarify the causes of this comorbidity. Understanding biological risk factors that associate with and predict the development of AUDs in bipolar disorder could inform interventions and prevention efforts to reduce the rate of this comorbidity and improve outcomes of both disorders. Identifying predictors of risk requires longitudinal studies in bipolar disorder aimed at capturing the mechanisms leading to the emergence of AUDs. Previous work in AUDs suggest that subjective responses to alcohol and stress-related mechanisms may contribute to the development of AUDs. In bipolar disorder, altered developmental trajectory of critical ventral prefrontal networks that modulate mood and reward processing may alter responses to alcohol and stressors; consequently, the disruption in typical neurodevelopment may be an underlying factor for the high rates of comorbidity. No longitudinal data exist investigating if this developmental hypothesis is correct. To address this gap, we will use a multimodal neuroimaging approach, modeling structural and functional neural trajectories of corticolimbic networks over young adulthood, incorporating alcohol administration procedures, clinical phenotyping, and investigating effects of acute stress exposure and early life stress. Research aims are to identify biological risk factors—i.e., changes in subjective response to alcohol and associated neural trajectories—that are associated with the development of alcohol misuse and symptoms of AUDs over a two-year longitudinal period in young adults with bipolar disorder and typical developing young adults. Longitudinal data will be collected on 160 young adults (50% with bipolar disorder, 50% female; aged 21-26). This study is a natural extension of the PI's K01 award. How acute exposure to stress and childhood maltreatment affects subjective response to alcohol and risk for prospective alcohol misuse and symptoms of AUDs will be investigated. We will test our hypothesis that developmental differences in bipolar disorder versus typical developing individuals disrupt corticolimbic networks during young adulthood, increase sensitivity to stress, and lead to changes in subjective response to alcohol and placebo response increasing risk for developing AUDs. This research project will be conducted by a multidisciplinary team of investigators with expertise in bipolar disorder, AUDs, substance use disorders, stress, longitudinal modeling, neuroimaging, and alcohol administration methodology. Essential to successfully improving clinical prognosis in bipolar disorder are research results that enable better prediction, diagnosis, and treatment based on the individual. There is a paucity of human clinical research investigating interactions between subjective response to alcohol/placebo, corticolimbic development during the young adult epoch, and acute exposure to stress and childhood maltreatment. Findings may inform intervention efforts that are more specific and may serve as a model for improving life-long outcomes in bipolar disorder and typical developing youth.