Grant: Peter Lougheed/CIHR New Investigator Canada's Premier Young Researcher

Alcohol dependence is a common, costly disorder with a lifetime prevalence of 10-12% in Canada. Characterizing biological risk factors is critical for identifying high-risk groups and tailoring interventions. One promising approach is to identify endophenotypes that index genetic risk for the disorder and that may provide clues as to neurobiological liability factors. Sensitivity to alcohol is a promising endophenotype that appears to predict future risk for alcohol dependence. However, prior research is characterized by two notable methodological limitations. First, most studies rely on participants' subjective responses to alcohol as the primary phenotype of interest. Second, most studies use oral alcohol administration, which inevitably yields high variability in blood alcohol profiles. These approaches can increase measurement error, reducing sensitivity to detect biological influences. Little is known about neural correlates of alcohol sensitivity. The proposed research will integrate fMRI with novel alcohol administration methods to study neural correlates of alcohol sensitivity. In addition to having expertise in fMRI, our research team is the first in Canada to implement a novel intravenous ethanol infusion protocol (the alcohol clamp) for human studies. This project will integrate fMRI and alcohol clamp methods to allow precise control over brain ethanol exposure. Young social drinkers (N=80) with and without a family history of alcohol dependence will complete alcohol and placebo fMRI sessions. Prospective data will be collected to determine whether neural correlates of alcohol sensitivity predict drinking outcomes. This research may inform future genetic studies and facilitate identification of neurobehavioural markers of alcohol dependence risk. Clarifying neural correlates of alcohol sensitivity may help to identify individuals at relatively greater risk for alcohol dependence, thus informing refinement of diagnostic and treatment approaches.