Association of Heavy Drinking With Deviant Fiber Tract Development in Frontal Brain Systems in Adolescents
Open accessAbstract
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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Adolescent alcohol exposure has deleterious effects on white matter microstructural integrity.
“Other recent reports have confirmed that AAE has deleterious effects on white matter microstructural integrity [98, 99].”
From Consequences of adolescent drug use (2023) · cites this paper as [98]
The Key Points and Discussion report reduced fractional anisotropy and a detrimental association between adolescent heavy drinking and white matter microstructural development. The paper describes these findings as associations from a case-control study, so the citing sentence overstates them as confirmed effects of alcohol exposure. (LLM, conf=0.87)
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Consequences of adolescent drug use
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“Other recent reports have con fi rmed that AAE has deleterious effects on white matter microstructural integrity [98, 99].”
Background
- Authors
- Zhao, Q., Sullivan, E. V., Honnorat, N., Adeli, E., Podhajsky, S., De Bellis, M. D., Voyvodic, J., Nooner, K. B., Baker, F. C., Colrain, I. M., Tapert, S. F., Brown, S. A., Thompson, W. K., Nagel, B. J., Clark, D. B., Pfefferbaum, A., & Pohl, K. M.
- Affiliations
- Stanford Medicine (US)
- SRI International (US)
- Department of Psychiatry & Behavioral Sciences, Duke University, Durham, North Carolina
- Duke University (US)
- University of North Carolina Wilmington (US)
- University of California San Diego (US)
- Oregon Health & Science University (US)
- University of Pittsburgh (US)
- Corresponding author
- Pfefferbaum, Adolf
- ORCID
- Venue
- JAMA Psychiatry
- Publisher
- American Medical Association (AMA)
- Published
- 2021-04-01
- Volume
- 78
- Issue
- 4
- Pages
- 407
- ISSN
- 2168-622X (ISSN-L)
- PMC
- PMC7774050
- OpenAlex
- W3117276841
- Cited by
- 50
- References
- 52
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 9 · 2023: 6 · 2022: 13 · 2021: 8
- FWCI
- 4.84
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- JAMA Psychiatry (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Alcohol Abuse and Alcoholism (K99AA028840, U01AA021681, P60AA010760)
- Topics
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- heavy drinking, adolescent alcohol use, white matter microstructure, fractional anisotropy, frontal lobe, brain development, alcohol use disorder risk, diffusion tensor imaging, sex differences, adolescent substance use
- MeSH terms
- Underage Drinking, Adolescent, Adult, Alcoholism, Child, Female, Frontal Lobe, Humans, Longitudinal Studies, Male, Neural Pathways, Case-Control Studies, Anisotropy, Adolescent Development, Young Adult, Diffusion Tensor Imaging, White Matter
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