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Original Investigation
December 30, 2020

Association of Heavy Drinking With Deviant Fiber Tract Development in Frontal Brain Systems in Adolescents

Author Affiliations
  • 1Department of Psychiatry & Behavioral Sciences, Stanford University School of Medicine, Stanford, California
  • 2Center for Health Sciences, SRI International, Menlo Park, California
  • 3Department of Psychiatry & Behavioral Sciences, Duke University, Durham, North Carolina
  • 4Department of Radiology, Duke University, Durham, North Carolina
  • 5Department of Psychology, University of North Carolina, Wilmington
  • 6Department of Psychiatry, University of California San Diego, La Jolla
  • 7Department of Psychology, University of California San Diego, La Jolla
  • 8Division of Biostatistics, Department of Family Medicine and Public Health, University of California San Diego, La Jolla
  • 9Departments of Psychiatry and Behavioral Neuroscience, Oregon Health & Sciences University, Portland
  • 10Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania
JAMA Psychiatry. 2021;78(4):407-415. doi:10.1001/jamapsychiatry.2020.4064
Key Points

Question  Is heavy alcohol drinking associated with altered adolescent microstructural brain development, and is that alteration age dependent?

Findings  In this case-control study of 451 adolescents, heavy drinkers exhibited significant reduction of whole-brain fractional anisotropy. The disruption occurred after the onset of drinking and was more pronounced in younger rather than older adolescents.

Meaning  Study results suggest that alcohol consumption is associated with deleterious outcomes on white matter microstructural maturation, supporting the concept of heightened vulnerability associated with alcohol use in early adolescence.


Importance  Maturation of white matter fiber systems subserves cognitive, behavioral, emotional, and motor development during adolescence. Hazardous drinking during this active neurodevelopmental period may alter the trajectory of white matter microstructural development, potentially increasing risk for developing alcohol-related dysfunction and alcohol use disorder in adulthood.

Objective  To identify disrupted adolescent microstructural brain development linked to drinking onset and to assess whether the disruption is more pronounced in younger rather than older adolescents.

Design, Setting, and Participants  This case-control study, conducted from January 13, 2013, to January 15, 2019, consisted of an analysis of 451 participants from the National Consortium on Alcohol and Neurodevelopment in Adolescence cohort. Participants were aged 12 to 21 years at baseline and had at least 2 usable magnetic resonance diffusion tensor imaging (DTI) scans and up to 5 examination visits spanning 4 years. Participants with a youth-adjusted Cahalan score of 0 were labeled as no-to-low drinkers; those with a score of greater than 1 for at least 2 consecutive visits were labeled as heavy drinkers. Exploratory analysis was conducted between no-to-low and heavy drinkers. A between-group analysis was conducted between age- and sex-matched youths, and a within-participant analysis was performed before and after drinking.

Exposures  Self-reported alcohol consumption in the past year summarized by categorical drinking levels.

Main Outcomes and Measures  Diffusion tensor imaging measurement of fractional anisotropy (FA) in the whole brain and fiber systems quantifying the developmental change of each participant as a slope.

Results  Analysis of whole-brain FA of 451 adolescents included 291 (64.5%) no-to-low drinkers and 160 (35.5%) heavy drinkers who indicated the potential for a deleterious association of alcohol with microstructural development. Among the no-to-low drinkers, 142 (48.4%) were boys with mean (SD) age of 16.5 (2.2) years and 149 (51.2%) were girls with mean (SD) age of 16.5 (2.1) years and 192 (66.0%) were White participants. Among the heavy drinkers, 86 (53.8%) were boys with mean (SD) age of 20.1 (1.5) years and 74 (46.3%) were girls with mean (SD) age of 20.5 (2.0) years and 142 (88.8%) were White participants. A group analysis revealed FA reduction in heavy-drinking youth compared with age- and sex-matched controls (t154 = –2.7, P = .008). The slope of this reduction correlated with log of days of drinking since the baseline visit (r156 = –0.21, 2-tailed P = .008). A within-participant analysis contrasting developmental trajectories of youths before and after they initiated heavy drinking supported the prediction that drinking onset was associated with and potentially preceded disrupted white matter integrity. Age-alcohol interactions (t152 = 3.0, P = .004) observed for the FA slopes indicated that the alcohol-associated disruption was greater in younger than older adolescents and was most pronounced in the genu and body of the corpus callosum, regions known to continue developing throughout adolescence.

Conclusions and Relevance  This case-control study of adolescents found a deleterious association of alcohol use with white matter microstructural integrity. These findings support the concept of heightened vulnerability to environmental agents, including alcohol, associated with attenuated development of major white matter tracts in early adolescence.

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