Adolescents And Young Adults With Alcohol-use Disorders Have A Smaller Prefrontal Cortex

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

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

"Studies on adults with alcoholism have generally shownsmaller brain sizes, but this is after many years of very heavydrinking," added Susan Tapert, associate professor of psychiatry at theUniversity of California at San Diego. "Before this study, it reallywasn't clear that adolescents, with briefer drinking histories, wouldshow any differences in brain size. However, with nearly one in threehigh-school seniors binge drinking at least once per month, it iscritical that we understand precisely how drinking affects the brain ofthese young people."

Researchers used magnetic resonance imaging to measureprefrontal cortex, thalamic, and cerebellar volumes in 14 subjects (8males, 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, andyoung adults were defined as 18 to 21 years of age. All of the subjectswith AUDs were recruited from substance-abuse treatment programs, andhad co-existing mental-health disorders. Controls were recruited fromthe community via advertisement.

"Our findings show that adolescents and young adults with AUDshad a smaller prefrontal cortex and prefrontal cortex white-mattervolumes compared with controls," said De Bellis. "Right, left and totalthalamic, pons/brainstem, right and left cerebellar hemispheric, totalcerebellar, and cerebellar vermis volumes did not differ betweengroups. There was a significant sex-by-group effect, in that males withan adolescent-onset AUD compared to control males had smallercerebellar volumes, whereas the two female groups did not differ incerebellar volumes. Also, prefrontal cortex volume variablessignificantly correlated with measures of alcohol consumption. Takentogether, these findings suggest that a smaller prefrontal cortex isassociated with early-onset drinking in individuals with co-morbidmental disorders, which are very common in adolescents with drinkingand drug problems."

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

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

"It may be that the adolescent prefrontal cortex is morevulnerable than the adult brain to the negative effects of drinking,"said De Bellis. "Or prefrontal-cortex maturation may be impeded by theneurotoxic effects of substances on the adolescent brain. Anotherexplanation for the smaller prefrontal cortex and prefrontal-cortexwhite-matter volumes of adolescents and young adults with an adolescentonset AUD is an inherent vulnerability for delayed prefrontal cortexmaturation that enhances the risk for poorer executive cognitivefunctioning 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 brainand cognitive function in adolescents with substance-abuse problems."We are very interested in studying if adolescent brain and cognitivedevelopment normalizes after a time period of sobriety," he said.

Alcoholism: Clinical & Experimental Research (ACER) isthe official journal of the Research Society on Alcoholism and theInternational Society for Biomedical Research on Alcoholism. Co-authorsof the ACER paper, "Prefrontal Cortex, Thalamus and Cerebellar Volumesin Adolescents and Young Adults with Adolescent Onset Alcohol UseDisorders and Co-Morbid Mental Disorders," were: Anandhi Narasimhan ofDuke University Medical Center; and Dawn L. Thatcher, Matcheri S.Keshavan and Paul Soloff of the University of Pittsburgh MedicalCenter. The study was funded by the National Institute on Alcohol Abuseand Alcoholism.