Convergent Evidence for Predispositional Effects of Brain Gray Matter Volume on Alcohol Consumption.

Journal Article (Journal Article)


Alcohol use has been reliably associated with smaller subcortical and cortical regional gray matter volumes (GMVs). Whether these associations reflect shared predisposing risk factors or causal consequences of alcohol use remains poorly understood.


Data came from 3 neuroimaging samples (N = 2423), spanning childhood or adolescence to middle age, with prospective or family-based data. First, we identified replicable GMV correlates of alcohol use. Next, we used family-based and longitudinal data to test whether these associations may plausibly reflect a predispositional liability for alcohol use or a causal consequence of alcohol use. Finally, we used heritability, gene-set enrichment, and transcriptome-wide association study approaches to evaluate whether genome-wide association study-defined genomic risk for alcohol consumption is enriched for genes that are preferentially expressed in regions that were identified in our neuroimaging analyses.


Smaller right dorsolateral prefrontal cortex (DLPFC) (i.e., middle and superior frontal gyri) and insula GMVs were associated with increased alcohol use across samples. Family-based and prospective longitudinal data suggest that these associations are genetically conferred and that DLPFC GMV prospectively predicts future use and initiation. Genomic risk for alcohol use was enriched in gene sets that were preferentially expressed in the DLPFC and was associated with replicable differential gene expression in the DLPFC.


These data suggest that smaller DLPFC and insula GMV plausibly represent genetically conferred predispositional risk factors for, as opposed to consequences of, alcohol use. DLPFC and insula GMV represent promising biomarkers for alcohol-consumption liability and related psychiatric and behavioral phenotypes.

Full Text

Duke Authors

Cited Authors

  • Baranger, DAA; Demers, CH; Elsayed, NM; Knodt, AR; Radtke, SR; Desmarais, A; Few, LR; Agrawal, A; Heath, AC; Barch, DM; Squeglia, LM; Williamson, DE; Hariri, AR; Bogdan, R

Published Date

  • April 2020

Published In

Volume / Issue

  • 87 / 7

Start / End Page

  • 645 - 655

PubMed ID

  • 31699293

Pubmed Central ID

  • PMC7412715

Electronic International Standard Serial Number (EISSN)

  • 1873-2402

International Standard Serial Number (ISSN)

  • 0006-3223

Digital Object Identifier (DOI)

  • 10.1016/j.biopsych.2019.08.029


  • eng