Persistent Body Mass Index Profiles During Adolescence: Associations With Brain Maturation and DNA Methylation.
27 affiliations
- 1Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
- 2Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, China.
- 3Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence, Fudan University, Ministry of Education, Shanghai, China.
- 4Centre for Population Neuroscience and Stratified Medicine, Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, China.
- 5National Institute on Drug Dependence, Peking University, Beijing, China.
- 6Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
- 7Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
- 8Discipline of Psychiatry, School of Medicine and Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland.
- 9Physikalisch-Technische Bundesanstalt, Braunschweig and Berlin, Germany.
- 10Departments of Psychiatry and Psychology, University of Vermont, Burlington, Vermont.
- 11Sir Peter Mansfield Imaging Centre School of Physics and Astronomy, University of Nottingham, Nottingham, United Kingdom.
- 12NeuroSpin, Commissariat à l'énergie Atomique et aux Énergies Alternatives, Université Paris-Saclay, Gif-sur-Yvette, France.
- 13Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Charité Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
- 14Institut des Maladies Neurodégénératives, Unité Mixte de Recherche 5293, Centre National de la Recherche Scientifique, Commissariat à l'énergie Atomique et aux Énergies Alternatives, Université de Bordeaux, Bordeaux, France.
- 15Institut National de la Santé et de la Recherche Médicale, U1299 Developmental Trajectories & Psychiatry, Université Paris-Saclay, Université Paris Cité, École Normale Supérieure Paris-Saclay, Centre National de la Recherche Scientifique, Centre Borelli Unité Mixte de Recherche 9010, Gif-sur-Yvette, France.
- 16Department of Child and Adolescent Psychiatry, L'Assistance Publique-Hôpitaux de Paris, Sorbonne Université, Pitié-Salpêtrière Hospital, Paris, France.
- 17Institute of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
- 18Institute of Medical Psychology and Medical Sociology, University Medical Center Schleswig Holstein, Kiel University, Kiel, Germany.
- 19Department of Child and Adolescent Psychiatry and Psychotherapy, Center for Psychosocial Medicine, University Hospital Heidelberg, Heidelberg, Germany.
- 20Department of Psychiatry and Psychotherapy, Technische Universität Dresden, Dresden, Germany.
- 21Department of Child and Adolescent Psychiatry, Psychotherapy and Psychosomatics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
- 22Centre for Population Neuroscience and Stratified Medicine, Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Berlin, Germany.
- 23School of Psychology and Global Brain Health Institute, Trinity College Dublin, Dublin, Ireland.
- 24Department of Psychological Medicine, Centre for Research in Eating and Weight Disorders, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
- 25South London and Maudsley National Health Service Foundation Trust, London, United Kingdom.
- 26Centre for Population Neuroscience and Stratified Medicine, Department of Psychiatry and Neuroscience, Charité Universitätsmedizin Berlin, Berlin, Germany.
- 27Centre for Population Neuroscience and Precision Medicine, Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, China.
Abstract
Background
Adolescence is a critical period for the emergence of obesity and disordered eating behaviors, yet the biological mechanisms underlying persistent differences in body mass index (BMI) development remain poorly understood. We investigated whether longitudinal BMI profiles are associated with behavioral, neurodevelopmental, and epigenetic variation during adolescence.Methods
Participants from the IMAGEN cohort (N = 1296) were followed from ages 14 to 23 years. Latent profile analysis identified longitudinal BMI profiles. Disordered eating behaviors were repeatedly assessed across adolescence. Structural magnetic resonance images acquired at ages 14 and 23 characterized longitudinal changes in gray matter volume (GMV), cortical thickness (CT), and sulcal depth. Genome-wide DNA methylation (DNAm) was measured in whole blood at age 14. We conducted epigenome-wide association studies (EWASs) and functional enrichment analyses and evaluated a DNAm-based BMI risk score (bmiMRS).Results
Two distinct BMI profiles were identified: a persistently overweight group and a persistently normal-weight group. Adolescents with persistent overweight showed progressively increasing BMI; greater eating-, weight-, and shape-related concerns; and more frequent dieting and binge-eating behaviors. They also exhibited atypical cortical maturation, characterized by attenuated cortical thinning, accelerated reductions in sulcal depth, and reduced gray matter volume loss within frontal and temporal association cortices. EWAS identified 29 BMI-associated CpGs (Bonferroni-corrected p < 1.3 × 10⁻⁷), enriched for genes involved in adipogenesis, immune and inflammatory signaling, type 2 diabetes, and brain-related biological processes. The bmiMRS predicted BMI, cumulative BMI across adolescence, and membership of the persistently overweight group and remained significantly associated with BMI in an independent cohort. Longitudinal analyses further suggested reciprocal associations between BMI and brain maturation, with higher BMI in early adolescence predicting subsequent regional GMV changes, whereas lower baseline CT predicted greater BMI increases independently of baseline BMI.Conclusions
Persistent adolescent overweight is associated with distinct behavioral, neurodevelopmental, and peripheral epigenetic signatures. Integrating longitudinal neuroimaging and DNAm identifies molecular biomarkers and brain developmental features associated with sustained BMI elevation, providing a framework for earlier risk stratification and informing biologically grounded approaches to obesity prevention.
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BibTeX
@article{yu2026persistent,
title = {{Persistent Body Mass Index Profiles During Adolescence: Associations With Brain Maturation and DNA Methylation.}},
author = {Xinyang Yu and Shitong Xiang and Tianye Jia and Zuo Zhang and Yan Sun and Tobias Banaschewski and Gareth J Barker and Arun L W Bokde and Rüdiger Brühl and Hugh Garavan and Penny Gowland and Antoine Grigis and Andreas Heinz and Hervé Lemaître and Jean-Luc Martinot and Marie-Laure Paillère Martinot and Eric Artiges and Frauke Nees and Dimitri Papadopoulos Orfanos and Luise Poustka and Michael N Smolka and Sarah Hohmann and Nathalie Holz and Nilakshi Vaidya and Henrik Walter and Robert Whelan and Ulrike Schmidt and Gunter Schumann and Sylvane Desrivières and IMAGEN Consortium},
journal = {Biological psychiatry global open science},
year = {2026},
month = sep,
doi = {10.1016/j.bpsgos.2026.100820},
url = {https://europepmc.org/article/MED/42921060},
note = {CC BY},
}
RIS
TY - JOUR
TI - Persistent Body Mass Index Profiles During Adolescence: Associations With Brain Maturation and DNA Methylation.
AU - Xinyang Yu
AU - Shitong Xiang
AU - Tianye Jia
AU - Zuo Zhang
AU - Yan Sun
AU - Tobias Banaschewski
AU - Gareth J Barker
AU - Arun L W Bokde
AU - Rüdiger Brühl
AU - Hugh Garavan
AU - Penny Gowland
AU - Antoine Grigis
AU - Andreas Heinz
AU - Hervé Lemaître
AU - Jean-Luc Martinot
AU - Marie-Laure Paillère Martinot
AU - Eric Artiges
AU - Frauke Nees
AU - Dimitri Papadopoulos Orfanos
AU - Luise Poustka
AU - Michael N Smolka
AU - Sarah Hohmann
AU - Nathalie Holz
AU - Nilakshi Vaidya
AU - Henrik Walter
AU - Robert Whelan
AU - Ulrike Schmidt
AU - Gunter Schumann
AU - Sylvane Desrivières
AU - IMAGEN Consortium
PY - 2026
DA - 2026/09/01
JO - Biological psychiatry global open science
DO - 10.1016/j.bpsgos.2026.100820
UR - https://europepmc.org/article/MED/42921060
AB - Background Adolescence is a critical period for the emergence of obesity and disordered eating behaviors, yet the biological mechanisms underlying persistent differences in body mass index (BMI) development remain poorly understood. We investigated whether longitudinal BMI profiles are associated with behavioral, neurodevelopmental, and epigenetic variation during adolescence.Methods Participants from the IMAGEN cohort (N = 1296) were followed from ages 14 to 23 years. Latent profile analysis identified longitudinal BMI profiles. Disordered eating behaviors were repeatedly assessed across adolescence. Structural magnetic resonance images acquired at ages 14 and 23 characterized longitudinal changes in gray matter volume (GMV), cortical thickness (CT), and sulcal depth. Genome-wide DNA methylation (DNAm) was measured in whole blood at age 14. We conducted epigenome-wide association studies (EWASs) and functional enrichment analyses and evaluated a DNAm-based BMI risk score (bmiMRS).Results Two distinct BMI profiles were identified: a persistently overweight group and a persistently normal-weight group. Adolescents with persistent overweight showed progressively increasing BMI; greater eating-, weight-, and shape-related concerns; and more frequent dieting and binge-eating behaviors. They also exhibited atypical cortical maturation, characterized by attenuated cortical thinning, accelerated reductions in sulcal depth, and reduced gray matter volume loss within frontal and temporal association cortices. EWAS identified 29 BMI-associated CpGs (Bonferroni-corrected p < 1.3 × 10⁻⁷), enriched for genes involved in adipogenesis, immune and inflammatory signaling, type 2 diabetes, and brain-related biological processes. The bmiMRS predicted BMI, cumulative BMI across adolescence, and membership of the persistently overweight group and remained significantly associated with BMI in an independent cohort. Longitudinal analyses further suggested reciprocal associations between BMI and brain maturation, with higher BMI in early adolescence predicting subsequent regional GMV changes, whereas lower baseline CT predicted greater BMI increases independently of baseline BMI.Conclusions Persistent adolescent overweight is associated with distinct behavioral, neurodevelopmental, and peripheral epigenetic signatures. Integrating longitudinal neuroimaging and DNAm identifies molecular biomarkers and brain developmental features associated with sustained BMI elevation, providing a framework for earlier risk stratification and informing biologically grounded approaches to obesity prevention.
SN - 2667-1743
ER -