{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T03:22:34Z","timestamp":1769138554980,"version":"3.49.0"},"posted":{"date-parts":[[2026,1,16]]},"group-title":"Epidemiology","reference-count":79,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T00:00:00Z","timestamp":1768521600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.medrxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,1,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  The plasma metabolome represents a valuable molecular readout of a person\u2019s physiological state, yet its relation to health, stress and lifestyle remains underexplored collectively. Here, we conducted an untargeted metabolomics analysis using 3804 paired samples from 1902 participants of the Netherlands Study of Depression and Anxiety at baseline and 6-year follow-up, quantifying 680 plasma metabolites. We characterised five metabolome profiles using principal component analysis, three with distinct biochemical enrichments related to transmembrane transport, sphingolipid and amino acid metabolism. Metabolite levels showed moderate intrapersonal correlation between baseline and 6-year follow-up (ICC\n                  <jats:sub>median<\/jats:sub>\n                  = 0.482), and only 22% of metabolites showed standardized mean differences greater than 0.2, indicating minimal 6-year population-level change. Multivariate linear modelling on 18 determinants across demographics, psychosocial environment, lifestyle, somatic and mental health explained a maximum of 35% of baseline metabolome profile variance and 12.2% in 6-year changes. Demographic (e.g., sex, age), somatic health (e.g., BMI, medication) and lifestyle factors (e.g., smoking, alcohol intake) demonstrated strong associations, while psychosocial factors and mental health contributed minor explained variance. Altogether, our study provides novel insights into the cross-sectional and longitudinal implications of health, stress and lifestyle exposures for the plasma metabolome, contributing to the understanding of metabolomic signatures in population studies.\n                <\/jats:p>","DOI":"10.64898\/2026.01.14.26344096","type":"posted-content","created":{"date-parts":[[2026,1,17]],"date-time":"2026-01-17T01:50:17Z","timestamp":1768614617000},"source":"Crossref","is-referenced-by-count":0,"title":["Determinants of the plasma metabolome: cross-sectional and longitudinal associations over 6 years in the NESDA cohort"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1333-1103","authenticated-orcid":false,"given":"Dennis","family":"Klose","sequence":"first","affiliation":[{"name":"Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Department of Psychiatry, Amsterdam, The Netherlands"},{"name":"Amsterdam University Medical Center, Amsterdam Public Health 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Netherlands"},{"name":"Amsterdam University Medical Center, Amsterdam Public Health Research Institute, Personalized Medicine and Mental Health Programs, Amsterdam, The Netherlands"},{"name":"Amsterdam University Medical Center, Amsterdam Neuroscience Research Institute, Mood, Anxiety, Psychosis, Sleep & Stress Program and Complex Trait Genetics Program, Amsterdam, The Netherlands, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3235-1633","authenticated-orcid":false,"given":"Nic J A","family":"van der Wee","sequence":"additional","affiliation":[{"name":"Leiden University Medical Center, Universiteit Leiden, Department of Psychiatry and Psychology, Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4666-0923","authenticated-orcid":false,"given":"Matthias","family":"Arnold","sequence":"additional","affiliation":[{"name":"Institute of Computational Biology, Helmholtz Zentrum M\u00fcnchen \u2013 German Research Center for Environmental Health, Neuherberg, Germany"},{"name":"Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5901-638X","authenticated-orcid":false,"given":"Christopher R","family":"Brydges","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siamak Mahmoudian","family":"Dehkordi","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabi","family":"Kastenm\u00fcller","sequence":"additional","affiliation":[{"name":"Institute of Computational Biology, Helmholtz Zentrum M\u00fcnchen \u2013 German Research Center for 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