Testing Neurobiological Models of Alcohol Use Disorder Through Real World Cue Reactivity and Mood - PROJECT SUMMARY/ ABSTRACT The neuroscientific understanding of alcohol use disorder (AUD) has advanced tremendously over the past three decades. However, translation from preclinical models to clinical studies lags behind the evolving neuroscience literature. Two of the most prominent neurobiological models of addiction are the allostatic model and the incentive-sensitization model. The allostatic model focuses on the transition from positive to negative reinforcement as addiction progresses. The incentive-sensitization model also emphasizes dynamic processes in addiction and focuses primarily on the transition from ‘liking’ to ‘wanting’ a substance. Given that the clinical application of these two prominent models is underway, understanding the forward translation (pre-clinical to clinical) of these neurobiological models is more important than ever before. Moreover, identifying demographic moderators of the interaction between these models is a crucial next step in understanding the potential application of these findings in treatment development. Further, these two prominent neurobiological models are being used to inform precision medicine approaches even though the predictive utility of these models on alcohol consumption is limited. Therefore, innovative methodology is necessary to increase the translational efficacy of neurobiological models to human clinical samples. This proposal is based on recent indications that there is an interactive effect between the allostatic model and incentive-sensitization model. Specifically, a preliminary study in the Sponsor’s laboratory focused on the allostatic model and incentive- sensitization model. Their combined effect showed that there is an interactive effect of negative mood and cue exposure on drinking among individuals with AUD. The objective of this NRSA application is to foster the applicant’s development as a clinical scientist with a focus on neurobiological models of addiction, translational science of addiction, and quantitative methods. This proposal aims to fill the gap in the literature by examining the interaction between the allostatic model and incentive-sensitization model, identifying moderators of this interaction, and testing the predictive utility of these models. Specifically, Aim #1 tests the effects of negative mood and cue exposure on same-day alcohol craving and alcohol use. Aim #2 tests the predictive effects of the allostatic model and incentive-sensitization model on longitudinal alcohol use. Exploratory Aim tests demographic moderators of the relationship between negative mood and cue reactivity. To address these Aims 64 individuals (32 females) with current AUD (mild to severe) will complete daily diary assessments of mood, craving, cue-exposure, and drinking for 14 days and will complete remote follow-up visits at 4, 8, and 12-weeks post daily diary. A sophisticated analytic approach including longitudinal multilevel modeling and multilevel moderation will be used to test these aims. The present study represents an important step in furthering the translation of neurobiological constructs of AUD and, with the support of the mentoring team, the applicant’s scientific development as an independent researcher with an interest in translational science of addiction.
