Individuals with a history of childhood trauma are at an increased risk of developing an alcohol use disorder (AUD), a susceptibility that is further enhanced if they have a family history of this disorder. In fact, approximately 50% of the risk for developing an alcohol use disorder (AUD) is driven by genetic factors. Thus, evidence suggests that both genetic and environmental risk factors contribute to AUD and that these factors likely exert combined effects. However, the neural mechanisms by which these risk factors contribute to the development of AUD are not yet understood. Research in individuals with a family history of AUD suggests that this genetic predisposition produces increased behavioral impulsivity. Previous research in victims of childhood maltreatment has likewise identified cognitive and affective consequences of childhood stress, including increased impulsivity. It is noteworthy that impulsive behavior is not only characteristic of individuals with a current AUD, but is also a predictor later life alcohol use among adolescents, suggesting these behaviors precede the development of AUD. This proposed training and research study are built on the hypothesis that impulsivity functions as an intermediate phenotype that mediates the relationship between genetic and environmental risk factors for AUD and problem drinking. The training project will focus on two domains of impulsivity ? discounting of delayed rewards and response inhibition ? based on strong evidence supporting their link to both AUD and its risk factors.
The first Aim will include a neuroimaging investigation of the these two tasks of impulsivity and an examination of the large-scale neural network correlates of risk factors for AUD. Longitudinal analyses (Aim 2) will examine the predictive relationship between neural measures of impulsivity on these tasks and changes in alcohol consumption over a three year follow-up timeline. Finally, Aim 3 is dedicated to examining the sex-dependent neural alterations associated with risk for AUD and well as sex-dependent relationships between the brain and alcohol use trajectories. The candidate?s prior training in the neurodevelopmental consequences of childhood trauma, cognitive neuroscience of addiction, sex differences, advanced statistical approaches, and neuroimaging methodologies provide a strong foundation for the proposed research project. The proposed training experiences will fill additional gaps through a combination of mentoring, didactic coursework, seminars, and conferences. The training plan is particularly tailored to provide additional support in alcoholism research and provides an extension into the study of addiction genetics. The training experience will be led by Dr. Charlotte Boettiger, an expert in behavioral and neuroimaging biomarkers of addiction, and supported by co-mentors Dr. Fulton Crews, an expert in the neurobiology of AUD, and Dr. Kirk Wilhelmsen, an expert in addiction genetics. The completion of this training will provide a strong foundation enabling the candidate to pursue independent research and will provide adequate knowledge, publications, and pilot data to be competitive for future grant applications focused on elucidating the neural basis of risk for AUD.
Epidemiologic evidence indicates that 7% of adults in the US meet criteria for an alcohol use disorder with most cases developing between 18-21 years of age. An examination of the neural and behavioral mediators between risk factors (genetic and environmental) and the development of pathological alcohol use will offer neural and behavioral endophenotypes of this disorder and inform prevention strategies for at-risk individuals.
