Reduced Brain Size May Affect Alcohol Consumption

Reduced brain size may suggest a genetic predisposition towards higher alcohol consumption, according to new research.

“Our results suggest that associations between alcohol consumption and reduced brain volume are attributable to shared genetic factors. Lower brain volume in specific regions may predispose a person to greater alcohol consumption. The study is impressive because it uses a variety of approaches and data analysis techniques to reach findings that all converge on the same conclusion,”

says senior author Ryan Bogdan, associate professor of psychological and brain sciences and director of the Brain Lab at Washington University in St. Louis.

Converging Genetic Factors

Longitudinal and family data from three independent brain imaging studies formed the basis of the work. They included the comparison of drinking behaviors in twin and non-twin siblings; longitudinal research within children who never had been exposed to alcohol at baseline; and gene expression analyses using postmortem brain tissue.

“Our study provides convergent evidence that there are genetic factors that lead to both lower gray matter volumes and increased alcohol use. These findings don’t discount the hypothesis that alcohol abuse may further reduce gray matter volumes, but it does suggest that brain volumes started out lower. As a result, brain volumes may also serve as useful biological markers for gene variations linked to increased vulnerability for alcohol consumption,”

says lead author David Baranger.

Data from the Duke Neurogenetics Study, the Human Connectome Project, and the Teen Alcohol Outcomes Study confirmed that higher alcohol consumption is associated with lower gray matter volume in two brain regions. They were the dorsolateral prefrontal cortex and the insula. Both feature prominently in emotion, memory, reward, cognitive control, and decision making.

Analyses of brain imaging and family data spanning childhood to adulthood revealed genetically-conferred reductions in gray matter volume in the frontal cortex and insula. These were, in turn, predictive of future alcohol use, including the initiation of drinking in adolescence and future drinking in young adulthood.

Twin Studies

To further confirm genetic links between lower brain volumes and alcohol consumption, the team examined data from twin and non-twin siblings with differing histories of alcohol consumption. When compared with siblings with a shared history of low alcohol use, siblings who drank more heavily had smaller grey matter volumes.

Interestingly, the study found no differences in gray matter volume in brains of same-family siblings where one drank more heavily than the other — both looked like heavy drinkers. This finding provides additional evidence that lower gray matter volume is a pre-existing vulnerability factor associated with the potential for alcohol use, as opposed to a consequence of alcohol use.

Finally, the research team used data of gene expression in the human brain to explore whether genetic risk for alcohol consumption is enriched for genes expressed in these regions and could be associated with the expression of specific genes.

Baranger and colleagues found enhanced genomic risk for alcohol consumption for genes that express more in the dorsolateral prefrontal cortex relative to other tissues and brain regions.

Further, they found that the expression of specific genes in this region is reliably associated with genomic risk for alcohol consumption. These data provide additional convergent evidence that it is biologically plausible that genetic risk for alcohol consumption may drive lower grey matter volume in the frontal cortex.

“Our analyses in three independent samples provides unique convergent evidence that associations between middle/superior frontal gray matter volume and alcohol use are genetically-conferred and predict future use and initiation,”

the study concludes.

[1] Baranger, David AA. et al. Convergent evidence for predispositional effects of brain gray matter volume on alcohol consumption. Biological Psychiatry, DOI: https://doi.org/10.1016/j.biopsych.2019.08.029