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 naïve adolescents which show lowered fractional anisotropy of frontal white matter in individuals with a family history of alcohol and substance use disorder (FH+). We compare large adult FH+ and FH- groups using white matter connectometry, different from 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 analyzed. Groups of participants were positive (n = 109) and negative (n = 109) for self-reported alcohol and substance use disorders in at least one parent, and stringently matched. 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 tracts and behavior differed significantly between groups. Self-reported family history was associated with decreased connectivity in reward signaling pathways, controlling for alcohol consumption and alcohol use disorder. 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 alcohol use disorder.