{
  "abstract": "Introduction\n\nEarly-life emotional and behavioral difficulties increase vulnerability to later psychopathology, but it remains unclear whether a biological footprint is detectable in early childhood.Objectives\n\nWe aimed to identify serum- and urine-based metabolite signatures of internalizing, externalizing, and attention-deficit/hyperactivity disorder (ADHD) traits in 6-year-old children and examine their associations with traits through adolescence.Methods\n\nWe analyzed 196 participants of the Rhea cohort (Greece), with serum and urine metabolomics at age 6 and internalizing, externalizing, and ADHD traits assessed at ages 6, 11, and 15. Trait- and biofluid-specific metabolite signatures were identified using elastic net regression with cross-validation. Associations with subsequent traits at repeated time points were evaluated using confounder-adjusted linear mixed-effects models.Results\n\nMetabolite signatures comprising amino acids, acylcarnitines, phosphatidylcholines, and gut microbiota-related metabolites were identified for internalizing, externalizing, and ADHD traits. Serum metabolite scores were associated with increased internalizing (β = 0.40; 95% CI 0.14-0.68) and externalizing traits (β = 0.83; 95% CI 0.56-1.1). Urine metabolite scores were associated with internalizing (β = 0.42; 95% CI 0.16-0.68) and externalizing traits (β = 0.69; 95% CI 0.43-0.95), while the association with ADHD traits was nominal (β = 0.25; 95% CI: 0.006-0.502; nominal p = 0.045; BH-FDR p = 0.054). Associations were stable over time for internalizing and ADHD but weakened with age for externalizing traits.Conclusions\n\nThis proof-of-concept study shows that complementary serum and urine metabolomic profiles in early childhood are associated with subsequent internalizing and externalizing trait trajectories, while a nominal longitudinal association was observed between the urine metabolite profile and ADHD traits. These findings warrant evaluation in larger independent studies.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Hygiene, Social-Preventive Medicine & Medical Statistics, Medical School, Aristotle University of Thessaloniki, University Campus, Thessaloniki, Greece.",
    "Department of Psychology, School of Social Sciences, University of Crete, Rethymno, Crete, Greece.",
    "Faculty of Medicine, Clinic of Preventive Medicine and Nutrition, University of Crete, Heraklion, Greece.",
    "Nutrition and Metabolism Branch, International Agency for Research On Cancer (IARC-WHO), Lyon, France.",
    "Department of Epidemiology and Biostatistics, School of Public Health, Faculty of Medicine, Imperial College London, London, UK.",
    "Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece.",
    "Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Madrid, Spain.",
    "Barcelona Institute for Global Health, Barcelona, Spain.",
    "Universitat Pompeu Fabra, Barcelona, Spain.",
    "Department of Surgery & Cancer, Faculty of Medicine, Imperial College London, London, UK.",
    "The Department of Paediatrics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands. m.karachaliou@erasmusmc.nl.",
    "Department of Nutrition and Dietetics Sciences, School of Health Sciences, Hellenic Mediterranean University, Sitia, Crete, Greece.",
    "Clinical and Epidemiological Neuroscience (NeuroÈpia), Institut d'Investigació Sanitària Pere Virgili (IISPV), Reus, Spain."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 14,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Eleni Barmpa"
    },
    {
      "affs": [
        1
      ],
      "name": "Katerina Koutra"
    },
    {
      "affs": [
        1
      ],
      "name": "Chrysi Mouatsou"
    },
    {
      "affs": [
        2
      ],
      "name": "Katerina Margetaki"
    },
    {
      "affs": [
        2
      ],
      "name": "Mariza Kampouri"
    },
    {
      "affs": [
        2
      ],
      "name": "Ariadni Konopidou"
    },
    {
      "affs": [
        3
      ],
      "name": "Anastasia Chrysovalantou Chatziioannou"
    },
    {
      "affs": [
        4,
        5
      ],
      "name": "Konstantinos K Tsilidis"
    },
    {
      "affs": [
        6,
        7,
        8
      ],
      "name": "Martine Vrijheid"
    },
    {
      "affs": [
        6,
        7,
        8
      ],
      "name": "Lea Maitre"
    },
    {
      "affs": [
        9
      ],
      "name": "Hector C Keun"
    },
    {
      "affs": [
        7
      ],
      "name": "Manolis Kogevinas"
    },
    {
      "affs": [
        10
      ],
      "name": "Marianna Karachaliou",
      "orcid": "0000-0002-3014-0747"
    },
    {
      "affs": [
        11,
        12
      ],
      "name": "Christopher Papandreou"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/1an61aafx1etk.bib",
  "cited_by": 0,
  "doi": "10.1007/s11306-026-02550-1",
  "fulltext_url": "https://europepmc.org/articles/PMC13722752",
  "id": "1an61aafx1etk",
  "issns": [
    "1573-3882",
    "1573-3890"
  ],
  "landing_url": "https://europepmc.org/article/MED/42961540",
  "language": "eng",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Original Article"
    ],
    [
      "openalex",
      "1312|Metabolomics and Mass Spectrometry Studies"
    ]
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  "openalex": "W7224734502",
  "pdf_url": "https://europepmc.org/articles/PMC13722752?pdf=render",
  "pmcid": "PMC13722752",
  "pmid": "42961540",
  "published": "2026-10-30",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/1an61aafx1etk.ris",
  "sources": [
    {
      "first_seen": "2026-11-02T03:21:21Z",
      "native_id": "MED:42961540",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42961540"
    },
    {
      "first_seen": "2026-11-04T12:21:31Z",
      "native_id": "PMC13722752",
      "source": "pmc",
      "url": "https://doi.org/10.1007/s11306-026-02550-1"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Metabolomics and Mass Spectrometry Studies",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Early childhood serum and urine metabolite signatures of internalizing, externalizing, and ADHD traits and their trajectories to adolescence: the Rhea mother-child cohort.",
  "title_text": "Early childhood serum and urine metabolite signatures of internalizing, externalizing, and ADHD traits and their trajectories to adolescence: the Rhea mother-child cohort.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-04T12:21:31Z",
  "url": "https://research.draconitic.com/paper/1an61aafx1etk",
  "venue": "Metabolomics : Official journal of the Metabolomic Society",
  "versions": []
}