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The Switch that Activates Alcoholism

Researchers will explore uncontrolled drinking’s ties to genetic expression


hy are some people unable to control their drinking? A team of Miller School researchers has been awarded a five-year, $2.1 million grant from the National Institutes of Health to explore whether it may be due to the impact of stress or environmental influences on genes in their brain.

“Our goal is to find the underlying drivers for alcohol use disorder in the hope of eventually developing some type of treatment,” said Claes Wahlestedt, M.D., Ph.D., professor of psychiatry and behavioral sciences, director of the Center for Therapeutic Innovation, and associate dean for therapeutic innovation.

Dr. Wahlestedt, the principal investigator, will conduct the laboratory study with departmental colleagues Zane Zeier, Ph.D., associate professor, and Luis Tuesta, Ph.D., assistant professor, in collaboration with researchers at Linkoping University in Sweden.

Dr. Wahlestedt noted that this will be the among the first alcohol use disorder studies to focus on epigenetic drivers — modifications of gene expression due to stress or environmental factors rather than direct alterations of the genetic code. “We have long hypothesized that compulsive drinking and addiction relate to epigenetic changes in the brain, almost like if a switch has been turned on or off,” he said. “This study will help test that hypothesis and examine where in the brain this happens, and which specific molecular pathways play key roles.”

Previous research by Dr. Wahlestedt and his collaborators has shown that behavioral changes associated with alcohol addiction are evident in signaling networks in specific brain regions, such as the amygdala, which is activated in response to threatening or dangerous stimuli.

“A key feature of alcohol use disorder is compulsive drinking despite negative consequences or at the expense of other rewards,” Dr. Wahlestedt said. “These clinically significant compulsive behaviors occur in a minority of individuals who consume alcohol — a strong indication that epigenetic vulnerabilities are at the core of the disease. Hopefully, this new study will point to new therapeutic targets within the brain’s signaling system.”