Alcohol use and brain morphology in adolescence: A longitudinal study in three different cohorts

Hanan El Marroun*, E.T. (Eduard) Klapwijk, Martijn Koevoets, Rachel M. Brouwer, S. (Sabine) Peters, Dennis van't Ent, Dorret I. Boomsma, Ryan L. Muetzel, Eveline A. Crone, Hilleke E. Hulshoff Pol, Ingmar H.A. Franken

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

10 Citations (Scopus)
50 Downloads (Pure)


Alcohol consumption is commonly initiated during adolescence, but the effects on human brain development remain unknown. In this multisite study, we investigated the longitudinal associations of adolescent alcohol use and brain morphology. Three longitudinal cohorts in the Netherlands (BrainScale n = 200, BrainTime n = 239 and a subsample of the Generation R study n = 318) of typically developing participants aged between 8 and 29 years were included. Adolescent alcohol use was self-reported. Longitudinal neuroimaging data were collected for at least two time points. Processing pipelines and statistical analyses were harmonized across cohorts. Main outcomes were global and regional brain volumes, which were a priori selected. Linear mixed effect models were used to test main effects of alcohol use and interaction effects of alcohol use with age in each cohort separately. Alcohol use was associated with adolescent's brain morphology showing accelerated decrease in grey matter volumes, in particular in the frontal and cingulate cortex volumes, and decelerated increase in white matter volumes. No dose–response association was observed. The findings were most prominent and consistent in the older cohorts (BrainScale and BrainTime). In summary, this longitudinal study demonstrated differences in neurodevelopmental trajectories of grey and white matter volume in adolescents who consume alcohol compared with non-users. These findings highlight the importance to further understand underlying neurobiological mechanisms when adolescents initiate alcohol consumption. Therefore, further studies need to determine to what extent this reflects the causal nature of this association, as this longitudinal observational study does not allow for causal inference.

Original languageEnglish
Pages (from-to)6012-6026
Number of pages15
JournalEuropean Journal of Neuroscience
Issue number6
Publication statusPublished - 18 Aug 2021

Bibliographical note

Funding Information:
This work was supported by the Dutch Brain Foundation (De Hersenstichting, project number GH2016.2.01) and Stichting Volksbond Rotterdam, and the NARSAD Young Investigator Grant 27853 from the Brain and Behavior Research Foundation. The BrainTime study was funded by a starting grant of the European Research Council (ERC‐2010‐StG‐263234 awarded to Eveline A. Crone). The BrainSCALE study was funded by Nederlandse Organisatie voor Wetenschappelijk Onderzoek (NWO 51.02.061 to H. H., NWO 51.02.062 to D. B., NWO‐NIHC Programs of excellence 433‐09‐220 to H. H., NWO‐MagW 480‐04‐004 to D. B., and NWO/SPI 56‐464‐14192 to D. B.), FP7 Ideas: European Research Council (ERC‐230374 to D. B.), Universiteit Utrecht (High Potential Grant to H. H.), Netherlands Twin Registry Repository (NWO‐Groot 480‐15‐001/674 to D. B.) and Neuroscience Campus Amsterdam (NCA). The Generation Study was additionally supported by the European Union Horizon 2020's research and innovation programme (Grant agreement 733206 LifeCycle). The funding agencies had no role in the design or conduct of the study, collection, management, analyses or interpretation of the data, or preparation, review or approval of the manuscript or the decision to submit it for publication.

Funding Information:
The Generation R Study is conducted by the Erasmus Medical Centre in close collaboration with the Municipal Health Service Rotterdam area, the Rotterdam Homecare Foundation and the Stichting Trombosedienst & Artsenlaboratorium Rijnmond (STAR), Rotterdam. We gratefully acknowledge the contribution of general practitioners, hospitals, midwives and pharmacies in Rotterdam. Supercomputing computations in the Generation R Study were supported by the NWO Physical Sciences Division: Exacte Wetenschappen, and SURFsara: Lisa computer cluster [ ]. We are grateful to all participants and their parents for their willingness to participate, and we also thank all involved in recruitment and data collection.

Publisher Copyright:
© 2021 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.


Dive into the research topics of 'Alcohol use and brain morphology in adolescence: A longitudinal study in three different cohorts'. Together they form a unique fingerprint.

Cite this