Multimodal assessment of neural, neuroendocrine, and immune cue responses in binge drinkers in the laboratory and real world. - Abstract Binge Drinking (BD) is a known risk factor for Alcohol Use Disorders (AUDs). Why some people “mature out” of BD while others persist and develop AUDs may not only be related to the adoption of adult social roles, but may also be due to one’s physiological response to BD. One mechanism contributing to BD appears to be enhanced cue reactivity, i.e., greater craving and alcohol consumption in response to alcohol associated stimuli. We have recently identified several components of a potential multi-attribute biomarker of BD: mPFC activation to cues with concomitant, correlated lower cortisol, higher interleukin 6 (IL-6), and higher craving responses to cues relative to social drinkers, all of which are related to immediate drinking in the laboratory, and future drinking in the real world. The overall goal of this application is to examine neurobiological factors (i.e., neural, neuroendocrine, and immune) associated with BD and cue-induced drinking longitudinally, based on the premise that these neurobiological changes are associated with real world processes that make individuals more vulnerable to drinking in response to alcohol cues in daily life over micro (momentary) and macro (years) time intervals. We aim to replicate and extend our previous findings demonstrating that associated dysregulations in neural, neuroendocrine, immune cue responses constitute a multi-attribute biomarker of BD and are related to craving/drinking in the lab and real world in BD. We will also examine the moderating effects of each individual neurobiological vulnerability (neural, neuroendocrine, immune) and the composite risk propensity score on intraindividual associations between cue exposure in the real world and craving/ drinking in daily life. Furthermore, we aim to characterize the relationships between trajectories of change in individual neurobiological vulnerabilities, including the risk propensity score, with trajectories of change in drinking behavior. Finally, we will examine the moderating effects of sex on the relationship between drinking group membership and neurobiological vulnerabilities with 1) craving/drinking behavior in the laboratory/ real world, 2) the relationship between cue exposure and craving/drinking, and 3) trajectories of BD over 2 years. Successful completion of this project will provide evidence of neurobiological vulnerabilities associated with BD and cue-induced drinking, which could serve as malleable intervention targets prior to the onset of AUD.
