White Matter Connectometry Among Individuals with Self-Reported Family History of Drug and Alcohol Use Disorders

Heredity is an important risk factor for alcoholism. Several studies have been conducted on small groups of alcohol naive adolescents which show lowered fractional anisotropy of frontal white matter in FH+ groups. We sought to compare large FH+ and FH- groups using white matter connectometry, as opposed to the previously used global tractography method, as it is more sensitive to regional variability. Imaging and behavioral data from the Human Connectome Project (WU-MINN HCP 1200) was used. Groups of participants were positive (n=109) and negative (n=109) for self-reported drug and alcohol use disorders in at least one parent. Groups were matched on gender, age, education, current alcohol usage, and alcohol use disorders (AUD). Connectometry was performed on diffusion MRI in DSI-Studio using q-space diffeomorphic reconstruction, and multiple regression was completed with 5000 permutations. Analyses showed decreased major tract (>40 mm) connectivity in the FH+ group in left inferior longitudinal fasciculus, bilateral cortico-striatal pathway, left cortico-thalamic pathway, and corpus callosum, compared to the FH- group. For cognitive tasks related to reward processing, inhibition, and monitoring, there were a number of interactions, such that the relationship between identified networks and behavior differed significantly between groups. Positive self-report of family history of alcoholism was associated with decreased connectivity in reward signaling pathways, controlling for alcohol consumption and AUD. This is the first connectometry study of FH+, and extends the neural basis of the hereditary diathesis of alcoholism beyond that demonstrated with global tractography. Regions associated with FH+ are similar to those associated with AUD.