Adolescents and young adults with alcohol-use disorders have a smaller prefrontal cortex

September 14, 2005

Previous research has shown that alcohol-use disorders (AUDs) are associated with abnormalities of the prefrontal cortex, thalamus and the cerebellar hemispheres in adults. These same brain structures are known to be actively maturing during adolescence. An examination of adolescents and young adults with AUDs has found that a smaller prefrontal cortex is associated with early-onset drinking. Results are published in the September issue of Alcoholism: Clinical & Experimental Research.

"This is the first study to examine the sizes of these brain structures in adolescents and young adults," said Michael D. De Bellis, professor of psychiatry and behavioral sciences and director of the Healthy Childhood Brain Development Research Program at Duke University Medical Center, as well as corresponding author for the study.

"Studies on adults with alcoholism have generally shown smaller brain sizes, but this is after many years of very heavy drinking," added Susan Tapert, associate professor of psychiatry at the University of California at San Diego. "Before this study, it really wasn't clear that adolescents, with briefer drinking histories, would show any differences in brain size. However, with nearly one in three high-school seniors binge drinking at least once per month, it is critical that we understand precisely how drinking affects the brain of these young people."

Researchers used magnetic resonance imaging to measure prefrontal cortex, thalamic, and cerebellar volumes in 14 subjects (8 males, 6 females) with AUDs, and in 28 (16 males, 12 females) sociodemographically similar individuals without AUDs, known as "controls." Adolescents were defined as 13 to 17 years of age, and young adults were defined as 18 to 21 years of age. All of the subjects with AUDs were recruited from substance-abuse treatment programs, and had co-existing mental-health disorders. Controls were recruited from the community via advertisement.

"Our findings show that adolescents and young adults with AUDs had a smaller prefrontal cortex and prefrontal cortex white-matter volumes compared with controls," said De Bellis. "Right, left and total thalamic, pons/brainstem, right and left cerebellar hemispheric, total cerebellar, and cerebellar vermis volumes did not differ between groups. There was a significant sex-by-group effect, in that males with an adolescent-onset AUD compared to control males had smaller cerebellar volumes, whereas the two female groups did not differ in cerebellar volumes. Also, prefrontal cortex volume variables significantly correlated with measures of alcohol consumption. Taken together, these findings suggest that a smaller prefrontal cortex is associated with early-onset drinking in individuals with co-morbid mental disorders, which are very common in adolescents with drinking and drug problems."

"The prefrontal cortex is a key region for complex thinking, planning, inhibition, and emotional regulation," said Tapert. "It could be that, with less white matter in the prefrontal cortex, information does not transfer in this area as rapidly and efficiently as is needed for the sorts of complex decision making young people need to do. It may be harder to inhibit urges, delay gratification, and think clearly about the consequences of actions." She added that the cerebellum, which was smaller among the males with an adolescent-onset AUD, "is a key brain region for motor coordination and timing and also for integrating and managing information and sequencing behavioral responses."

Both De Bellis and Tapert observed that future studies will need to determine if a smaller prefrontal cortex represents a vulnerability to, or a consequence of, early-onset drinking.

"It may be that the adolescent prefrontal cortex is more vulnerable than the adult brain to the negative effects of drinking," said De Bellis. "Or prefrontal-cortex maturation may be impeded by the neurotoxic effects of substances on the adolescent brain. Another explanation for the smaller prefrontal cortex and prefrontal-cortex white-matter volumes of adolescents and young adults with an adolescent onset AUD is an inherent vulnerability for delayed prefrontal cortex maturation that enhances the risk for poorer executive cognitive functioning and adolescent substance-use disorders."

"In addition," said Tapert, "we need to figure out the role of the other mental illnesses in these brain-size abnormalities."

De Bellis and his colleagues are currently examining both brain and cognitive function in adolescents with substance-abuse problems. "We are very interested in studying if adolescent brain and cognitive development normalizes after a time period of sobriety," he said.
Alcoholism: Clinical & Experimental Research (ACER) is the official journal of the Research Society on Alcoholism and the International Society for Biomedical Research on Alcoholism. Co-authors of the ACER paper, "Prefrontal Cortex, Thalamus and Cerebellar Volumes in Adolescents and Young Adults with Adolescent Onset Alcohol Use Disorders and Co-Morbid Mental Disorders," were: Anandhi Narasimhan of Duke University Medical Center; and Dawn L. Thatcher, Matcheri S. Keshavan and Paul Soloff of the University of Pittsburgh Medical Center. The study was funded by the National Institute on Alcohol Abuse and Alcoholism.

Alcoholism: Clinical & Experimental Research

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