DRD2 methylation and regional grey matter volumes in young adult offspring from families at ultra-high risk for alcohol dependence

Dopaminergic alteration is a prominent feature in those with AD and may influence brain development in those with a family history of AD. MRI scans (3T) from 43 HR offspring (27.4 ± 3.6 years) and 45 controls (24.5 ± 4.1 years) provided whole brain (WB) and region of interest (ROI) analyses. The VBM8 toolbox was used for WB analysis (threshold p < 0.005; cluster = 100 voxels); the MarsBaR ROI toolbox provided region of interest data. Pyrosequencing of CpG sites within the DRD2 gene was performed. DRD2 methylation was significantly increased in association with familial high-risk status. Significant familial risk group differences were seen with HR individuals showing reduced volume of the Left Inferior Temporal, Left Fusiform and Left Insula regions relative to LR controls. These regions have previously been linked to social cognition. DRD2 methylation was negatively related to grey matter volumes in these regions. Because these regions, have been previously linked to facial affect perception and social cognition, lesser grey matter volumes in individuals at high-risk for developing AD suggests that neural underpinnings of social cognitive impairment may be a premorbid risk factors for AD.