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Which came first: Brain size or drinking propensity?

For years, researchers have observed that the consumption of alcohol is associated with reduced brain volume.

But new research turns that theory on its head, suggesting that reduced brain volume may represent a genetically-conferred predispositional risk factor for heavier alcohol consumption.

"Our results suggest that associations between alcohol consumption and reduced brain volume are attributable to shared genetic factors," said Ryan Bogdan, associate professor of psychological and brain sciences in the University of Washington. Louis, where the research is based. "Lower brain volume in specific regions may predispose 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," he said.

The study, recently published online in the journal Biological Psychiatry, based on longitudinal and family data from three independent brain imaging studies – including the comparison of drinking behaviors in twin and non-twin siblings; longitudinal research within children who were never exposed to alcohol at baseline; and gene expression analyzes 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," said David Baranger, Bogdan's lab.

"These findings do not discount the hypothesis that alcohol abuse may further reduce gray matter volumes, but it does suggest that brain volumes begin to lower with the beginning," said Baranger. "As a result, brain volumes may also serve as useful biological markers.

Baranger, who is now a postdoctoral scholar at the University of Pittsburgh, led by the research project, which included other Arts & Sciences psychology graduate students and faculty from Washington University School of Medicine. Louis; Duke University; and the Medical University of South Carolina.

Researchers used data from the Duke Neurogenetics Study, the Human Connectome Project, and the Teen Alcohol Results, to confirm that greater alcohol consumption was associated with lower gray matter volume in the two brain regions, the dorsolateral prefrontal cortex, and the insula , memory, reward, cognitive control and decision making.

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

To further confirm genetic links between the lower brain volumes and the consumption of alcohol, the team examined data from different and non-twin siblings with differing histories of alcohol consumption. When compared with siblings, a history of low alcohol use, siblings who drank more heavily had lower gray matter volumes. Interestingly, the study found no differences in gray matter volume in the same-family siblings where one drank more heavily than the other – both looked like heavy-drinkers. This finding provides additional evidence that a lower gray matter volume is a pre-existing vulnerability factor.

Finally, the research team used to explore the human brain.

Baranger and colleagues found that genomic risk for alcohol consumption is enriched for genes that are preferentially expressed in the dorsolateral prefrontal cortex. Further, they found that the expression of specific genes in this region are associated with the risk of alcohol consumption. These data provide additional convergent evidence that it is biologically plausible that lower gray matter volume in the frontal cortex.

"Our analyzes in three independent samples provide unique convergent evidence that associations between middle / superior frontal gray matter volume and alcohol use are genetically-conferred and predictive future use and initiation," the study concludes.

"Taken alongside evidence that heavy alcohol consumption induces gray matter volume reductions, our data raise the intriguing possibility that genetically-conferred reductions in regional gray matter volumes may promote alcohol use from adolescence to young, which may, in turn, lead to accelerated atrophy within these and other regions, "the authors wrote

The results may be due to the same genetic factors.


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