{
  "abstract": "Background\n\nAdolescence 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\n\nParticipants 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\n\nTwo 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\n\nPersistent 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.",
  "abstract_shown": true,
  "affiliations": [
    "Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.",
    "Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, China.",
    "Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence, Fudan University, Ministry of Education, Shanghai, China.",
    "Centre for Population Neuroscience and Stratified Medicine, Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, China.",
    "National Institute on Drug Dependence, Peking University, Beijing, China.",
    "Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.",
    "Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.",
    "Discipline of Psychiatry, School of Medicine and Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland.",
    "Physikalisch-Technische Bundesanstalt, Braunschweig and Berlin, Germany.",
    "Departments of Psychiatry and Psychology, University of Vermont, Burlington, Vermont.",
    "Sir Peter Mansfield Imaging Centre School of Physics and Astronomy, University of Nottingham, Nottingham, United Kingdom.",
    "NeuroSpin, Commissariat à l'énergie Atomique et aux Énergies Alternatives, Université Paris-Saclay, Gif-sur-Yvette, France.",
    "Department 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.",
    "Institut 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.",
    "Institut 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.",
    "Department of Child and Adolescent Psychiatry, L'Assistance Publique-Hôpitaux de Paris, Sorbonne Université, Pitié-Salpêtrière Hospital, Paris, France.",
    "Institute of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.",
    "Institute of Medical Psychology and Medical Sociology, University Medical Center Schleswig Holstein, Kiel University, Kiel, Germany.",
    "Department of Child and Adolescent Psychiatry and Psychotherapy, Center for Psychosocial Medicine, University Hospital Heidelberg, Heidelberg, Germany.",
    "Department of Psychiatry and Psychotherapy, Technische Universität Dresden, Dresden, Germany.",
    "Department of Child and Adolescent Psychiatry, Psychotherapy and Psychosomatics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.",
    "Centre for Population Neuroscience and Stratified Medicine, Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Berlin, Germany.",
    "School of Psychology and Global Brain Health Institute, Trinity College Dublin, Dublin, Ireland.",
    "Department of Psychological Medicine, Centre for Research in Eating and Weight Disorders, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.",
    "South London and Maudsley National Health Service Foundation Trust, London, United Kingdom.",
    "Centre for Population Neuroscience and Stratified Medicine, Department of Psychiatry and Neuroscience, Charité Universitätsmedizin Berlin, Berlin, Germany.",
    "Centre for Population Neuroscience and Precision Medicine, Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, China."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 30,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Xinyang Yu"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Shitong Xiang"
    },
    {
      "affs": [
        0,
        1,
        2,
        3
      ],
      "name": "Tianye Jia"
    },
    {
      "affs": [
        0
      ],
      "name": "Zuo Zhang"
    },
    {
      "affs": [
        4
      ],
      "name": "Yan Sun"
    },
    {
      "affs": [
        5
      ],
      "name": "Tobias Banaschewski"
    },
    {
      "affs": [
        6
      ],
      "name": "Gareth J Barker"
    },
    {
      "affs": [
        7
      ],
      "name": "Arun L W Bokde"
    },
    {
      "affs": [
        8
      ],
      "name": "Rüdiger Brühl"
    },
    {
      "affs": [
        9
      ],
      "name": "Hugh Garavan"
    },
    {
      "affs": [
        10
      ],
      "name": "Penny Gowland"
    },
    {
      "affs": [
        11
      ],
      "name": "Antoine Grigis"
    },
    {
      "affs": [
        12
      ],
      "name": "Andreas Heinz"
    },
    {
      "affs": [
        11,
        13
      ],
      "name": "Hervé Lemaître"
    },
    {
      "affs": [
        14
      ],
      "name": "Jean-Luc Martinot"
    },
    {
      "affs": [
        14,
        15
      ],
      "name": "Marie-Laure Paillère Martinot"
    },
    {
      "affs": [
        14
      ],
      "name": "Eric Artiges"
    },
    {
      "affs": [
        5,
        16,
        17
      ],
      "name": "Frauke Nees"
    },
    {
      "affs": [
        11
      ],
      "name": "Dimitri Papadopoulos Orfanos"
    },
    {
      "affs": [
        18
      ],
      "name": "Luise Poustka"
    },
    {
      "affs": [
        19
      ],
      "name": "Michael N Smolka"
    },
    {
      "affs": [
        20
      ],
      "name": "Sarah Hohmann"
    },
    {
      "affs": [
        5
      ],
      "name": "Nathalie Holz"
    },
    {
      "affs": [
        21
      ],
      "name": "Nilakshi Vaidya"
    },
    {
      "affs": [
        12
      ],
      "name": "Henrik Walter"
    },
    {
      "affs": [
        22
      ],
      "name": "Robert Whelan"
    },
    {
      "affs": [
        23,
        24
      ],
      "name": "Ulrike Schmidt"
    },
    {
      "affs": [
        25,
        26
      ],
      "name": "Gunter Schumann"
    },
    {
      "affs": [
        0
      ],
      "name": "Sylvane Desrivières"
    },
    {
      "name": "IMAGEN Consortium"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/4g7273nam9z1w.bib",
  "cited_by": 0,
  "doi": "10.1016/j.bpsgos.2026.100820",
  "fulltext_url": "https://europepmc.org/articles/PMC13693072",
  "id": "4g7273nam9z1w",
  "issns": [
    "2667-1743"
  ],
  "landing_url": "https://europepmc.org/article/MED/42921060",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "3203|Eating Disorders and Behaviors"
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  "openalex": "W7204885958",
  "pdf_url": "https://europepmc.org/articles/PMC13693072?pdf=render",
  "pmcid": "PMC13693072",
  "pmid": "42921060",
  "published": "2026-09-01",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/4g7273nam9z1w.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:21:02Z",
      "native_id": "MED:42921060",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42921060"
    }
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  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:3203|Eating Disorders and Behaviors",
      "subfield": "psychiatry"
    }
  ],
  "title": "Persistent Body Mass Index Profiles During Adolescence: Associations With Brain Maturation and DNA Methylation.",
  "title_text": "Persistent Body Mass Index Profiles During Adolescence: Associations With Brain Maturation and DNA Methylation.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:21:02Z",
  "url": "https://research.draconitic.com/paper/4g7273nam9z1w",
  "venue": "Biological psychiatry global open science",
  "versions": []
}