Drinking for two? Prenatal alcohol exposure rewires the brain and fuels compulsive behavior, new study finds

Fetal Alcohol Spectrum Disorders (FASD), a leading cause of neurodevelopmental disorders, may affect as many as 1 in 20 school-aged children in the United States. Despite its prevalence, the exact brain circuit responsible for FASD’s hallmark symptom — cognitive inflexibility, or the inability to adjust thoughts and behaviors to new environments — has largely remained a mystery.

A new study led by Dr. Jun Wang and co-authored by Dr. Rajesh Miranda, professors at Texas A&M University’s Naresh K. Vashisht College of Medicine, observed that alcohol consumption both during pregnancy and around the time of birth significantly impairs an offspring’s brain development — particularly in regions that govern decision-making — while also increasing the risk of compulsive alcohol use later in life.

“It’s exciting,” Wang said. “We’ve identified a specific brain cell in offspring affected by early alcohol exposure that’s directly linked to problems with flexible thinking and impulse control, and this gives us a clear target for better understanding and eventually developing more effective treatments of FASD.”

Targeted treatments and a call for awareness

By pinpointing the exact brain circuits affected by prenatal alcohol exposure, the study opens possibilities for targeted therapies aimed at restoring normal cognitive and behavioral flexibility in individuals with FASD.

"Our findings represent a major step forward in FASD research. By uncovering how early alcohol exposure changes brain chemistry, we’re able to move from describing symptoms to transitioning into treating root causes," Wang said.

The findings also reinforce longstanding public health messages about the risks of drinking alcohol during pregnancy or around the time of birth.

“Even limited alcohol consumption during sensitive developmental windows can have profound and lifelong consequences,” Wang said.

Neuron damage in key brain regions

Published in Neuropharmacology and supported by the National Institute on Alcohol Abuse and Alcoholism (NIAAA), the study explored the impact of early alcohol exposure on a specific type of brain cell known as cholinergic interneurons, or CINs — important regulators of learning, behavioral flexibility and impulse control within the brain’s decision-making hub, the striatum

“CINs are like the conductors of the brain’s decision-making orchestra,” Wang explained. “They are largely responsible for the decision-making network in the brain.”

Using high-resolution imaging techniques, the team not only discovered a sharp reduction in the number of CINs in prenatal alcohol-exposed offspring, but they also observed a marked decrease in their firing activity and release of acetylcholine, an essential chemical for learning and adaptive behavior.

“Alcohol exposure during pregnancy or around the time of birth disrupts these conductors,” Wang said. “This impairs the brain’s ability to make critical decisions, learn from feedback and adjust to change.”

These disruptions and deficits help explain why individuals with FASD struggle with cognitive flexibility.

“Cognitive flexibility is our mental ability to learn, adapt and adjust to new or unexpected situations,” Wang said. “It can be significantly impaired in FASD groups.”

The lack of cognitive flexibility was clearly demonstrated in behavioral experiments when the researchers trained and compared two groups—one prenatal alcohol-exposed offspring, one control — to press two distinct levers, each associated with a different food reward.

When the levers were reversed, the prenatal alcohol-exposed group struggled to adjust their responses, continuing to press the old lever despite the change.

“This highlights how prenatal alcohol exposure can have lasting effects on a brain’s flexibility and adaptability to new environments,” Wang said.

From brain chemistry to real-world behavior

Beyond brain changes, the researchers explored how early alcohol exposure might influence behavior later in life — specifically compulsive alcohol drinking, a known risk factor for FASD populations.

Strikingly, they found that the prenatal alcohol-exposed offspring showed compulsive drinking in adulthood, continuing to drink alcohol even when it was mixed with a bitter substance designed to make it unpalatable.

"When key decision-making brain cells are compromised, they don’t just stop at brain chemistry. They manifest in real-world behaviors, like addiction and compulsive behavior," Wang said.

Urgency for prevention, emphasis on intervention

By identifying specific brain circuits disrupted by early alcohol exposure, the research highlights the importance of early prevention, intervention and education of alcohol use during pregnancy and the perinatal period.

“This is a preventable disorder,” Wang emphasized. “There is no safe amount, no safe time, to consume alcohol during pregnancy.”

As the research team continues to uncover brain mechanisms behind FASD, the message is clear: alcohol and pregnancy don’t mix.

For more information about Wang, visit his faculty page.

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