Why some people are more susceptible to developing drinking problems? Study Finds

Rutgers Health researchers have discovered that brain immune cells from people with a high genetic risk for alcohol use disorder (AUD) behave differently than cells from low-risk people when exposed to alcohol. Their study in Science Advances could help explain why some people are more susceptible to developing drinking problems and potentially lead to more personalized treatments.

The research team took blood samples from two groups of people: those with both high genetic risk for alcohol use disorder and diagnosed alcohol problems and those with low genetic risk and no alcohol problems. They transformed these blood cells into stem cells and made them develop into a type of brain-based immune cell called microglia.

They then exposed these two groups of cells, one from the people with a high genetic risk for alcohol use disorder and one from the people with a low risk of alcohol use disorder, to alcohol levels that mimicked those seen in the blood following alcohol use.

"The microglia with the high genetic risk scores were far more active than the microglia with the low genetic risk scores after the alcohol exposure," said Xindi Li, lead author of the study, a postdoctoral fellow at the Child Health Institute of New Jersey.

The highly active cells engaged in more "synaptic pruning" -- removing connections between neurons in the brain. This increased pruning activity could have significant implications, the researchers said.

"After many years of drinking, people with these genetics may have a greater risk of dementia because the microglia pruned so many more connections," Li said.

"Their overactivity could make neurons less functional."

This work could eventually lead to better treatments for alcohol use disorder. The results suggest that if different genetic variations lead to different cell behavior in the brain, people with different genetic signatures may need different treatments.