Utilizing multimodal neuroimaging to identify neurometabolic and neurobehavioral correlates of adolescent binge drinking

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PROJECT SUMMARY/ABSTRACT Adolescent binge drinking (5+ drinks for males, 4+ drinks for females) is problematic and associated with many negative psychosocial consequences, such as progression into early and persistent alcohol use disorder (AUD). Research on neuroscience-informed treatments for adolescent AUD is sparse, but needed, and must be tailored to the adolescent population rather than extrapolating from the adult AUD literature. This requires a comprehensive knowledge of the neurobiological effects of problematic alcohol use in youth, making binge drinking adolescents a critical sample in the adolescent AUD pharmacotherapy development pipeline. Neurobiological research within binge drinking adolescents, as compared to their non-drinking peers, will help to identify mechanisms of alcohol action in the developing brain, which will ultimately translate to targets for pharmacotherapy development for adolescent AUD. Additionally, sex-specific neural effects of binge drinking need to be better understood to ensure efficacious treatments for both males and females. The proposed study employs multimodal neuroimaging (magnetic resonance spectroscopy [MRS] and functional neuroimaging [fMRI]) to investigate the neurometabolic (measured with MRS) and neurobehavioral (measured with fMRI) effects of binge drinking in youth, as compared to non-drinking controls. This project will help to address the current literature gap concerning neurometabolic alterations in glutamate, GABA, and glutathione (all metabolites dysregulated by alcohol use) associated with adolescent binge drinking, and how such changes relate to alcohol cue reactivity and sex as a biological variable (SABV). Aim 1 quantifies glutamate, GABA, and glutathione in the anterior cingulate cortex (ACC) in binge drinkers, as compared to non-drinking controls, using MRS. Aim 2 explores the association between brain metabolite levels (glutamate, GABA, and glutathione) and alcohol cue reactivity measured with fMRI in binge drinking youth, as compared to controls. Aim 3 examines SABV within these neural correlates of adolescent binge drinking, as compared to non-drinking controls. Findings will identify neural targets for the development of pharmacotherapy treatments for adolescent AUD. This F32 application is built upon baseline neuroimaging data from a nearly complete clinical pharmacotherapy trial (PI Squeglia) with an added non-using control group (PI Kirkland; internal pilot project funding), making it highly feasible within the proposed timeline. The research proposed in this F32 application will serve as essential hands-on training to promote the candidate’s career development in adolescent alcohol use disorder neurobiology and neuroimaging research, and it will result in a dataset on which to build an NIH K-award grant application using an advanced multimodal imaging platform to evaluate promising pharmacotherapies for adolescent AUD.