The neural mechanisms of risk for alcohol use disorder among college students

PROJECT SUMMARY/ABSTRACT
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.