White matter neural substrates in alcohol dependence with genetic risk and their role in pathological reward process

Studies have revealed significant evidence of white matter (WM) microstructural and network connectome abnormalities in alcohol use disorder (AUD). However, the neuroimaging characteristics of alcohol dependence (AD) patients with a family history of AUD and the role of these changes in pathological craving remain unclear. Investigating the heritability of AUD is crucial for identifying genetic predispositions and informing targeted prevention strategies. The study recruited 51 patients for AD, 21 patients with a family history positive (FHP), 30 patients with a family history negative (FHN), and 25 healthy controls (HC). We compared fractional anisotropy (FA) and mean diffusivity (MD) of striatal circuits and topological properties of the reward system between the three groups. Then, covariates of alcohol use characteristics (duration and severity of AD) were controlled between FHP and FHN. We found abnormal topological properties of hippocampus in AD with FHP compared to HC. After controlling for covariates, there were still disruptions of topology organization in FHP compared to FHN, such as lower nodal betweenness, nodal degree and higher shortest path of right hippocampus. The nodal topological properties of right hippocampus were significantly correlated with self-reported craving in AD. Our findings provide robust evidence for WM neural abnormalities in AD with high genetic risk. We also found the disrupted topological properties of the right hippocampus associated with craving level.