{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:01:34Z","timestamp":1785427294498,"version":"3.56.0"},"reference-count":39,"publisher":"Cambridge University Press (CUP)","license":[{"start":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000},"content-version":"unspecified","delay-in-days":209,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82273748"],"award-info":[{"award-number":["82273748"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cambridge.org"],"crossmark-restriction":true},"short-container-title":["Psychol. Med."],"published-print":{"date-parts":[[2026]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec id=\"S0033291726105248_sec1\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Obesity is a well-established risk factor for major depressive disorder (MDD), yet the risk is not uniform, highlighting the need for precise risk stratification. This study aimed to develop a metabolomics-based prediction model to identify high-risk metabolic phenotypes among obese participants and to elucidate the causal metabolic pathways involved.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"S0033291726105248_sec2\" sec-type=\"methods\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Forty-one-thousand-four-hundred-fifty-nine obese participants were followed for a median of 14.4\u00a0years. We integrated multiple machine learning (ML) algorithms to develop predictive models for 3-, 5-, and 9-year MDD risk, with a temporal validation within the same biobank. Furthermore, we investigated the potential causal relationships within the obesity-metabolite-MDD using mediation Mendelian randomization (MR).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"S0033291726105248_sec3\" sec-type=\"results\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      During follow-up, 3,642 incident MDD cases were documented. The optimized LightGBM model demonstrated superior predictive performance, achieving AUCs of 0.844 (95% CI: 0.773\u20130.914), 0.824 (95% CI: 0.771\u20130.875), and 0.834 (95% CI: 0.796\u20130.871) for 3-, 5-, and 9-year intervals, respectively, significantly outperforming existing clinical models. Temporal validation confirmed the model\u2019s robustness (AUCs: 0.738\u20130.776). MR analysis confirmed that key metabolites causally mediate the pathway from obesity to MDD (mediation proportions: \u221211.5% and \u221235.3%, all\n                      <jats:italic>P<\/jats:italic>\n                      <jats:sub>ME<\/jats:sub>\n                      \u00a0&lt;\u00a00.05).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"S0033291726105248_sec4\" sec-type=\"conclusions\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings challenge the notion of a uniform obesity\u2013MDD association, demonstrating that metabolomic signatures can effectively stratify MDD risk. We present a validated ML framework for the early identification of high-risk individuals with obesity, offering a precision medicine approach to guide targeted metabolic and psychiatric interventions.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1017\/s0033291726105248","type":"journal-article","created":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T05:42:40Z","timestamp":1785303760000},"update-policy":"https:\/\/doi.org\/10.1017\/policypage","source":"Crossref","is-referenced-by-count":0,"title":["Metabolites stratify future major depressive disorder risk in obese population: a longitudinal machine learning analysis"],"prefix":"10.1017","volume":"56","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4575-7360","authenticated-orcid":false,"given":"Xiaobing","family":"Zhai","sequence":"first","affiliation":[{"name":"Macao Polytechnic University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8959-9328","authenticated-orcid":false,"given":"Abao","family":"Xing","sequence":"additional","affiliation":[{"name":"Macao Polytechnic University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaoqi","family":"Deng","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00b30xv10","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi Kin","family":"Lam","sequence":"additional","affiliation":[{"name":"Macao Polytechnic University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lihuan","family":"Wang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0488wz367","id-type":"ROR","asserted-by":"publisher"}],"name":"Wuyi University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Yu","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0488wz367","id-type":"ROR","asserted-by":"publisher"}],"name":"Wuyi University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2687-741X","authenticated-orcid":false,"given":"Henry H.Y.","family":"Tong","sequence":"additional","affiliation":[{"name":"Macao Polytechnic University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nuno","family":"Louren\u00e7o","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04z8k9a98","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Coimbra"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Zhao","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/011ashp19","id-type":"ROR","asserted-by":"publisher"}],"name":"Sichuan University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7233-4347","authenticated-orcid":false,"given":"Kefeng","family":"Li","sequence":"additional","affiliation":[{"name":"Macao Polytechnic University"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"56","published-online":{"date-parts":[[2026,7,29]]},"reference":[{"key":"S0033291726105248_r30","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2023.104643"},{"key":"S0033291726105248_r29","doi-asserted-by":"publisher","DOI":"10.1186\/s12916-023-03148-3"},{"key":"S0033291726105248_r20","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresbull.2025.111191"},{"key":"S0033291726105248_r26","doi-asserted-by":"publisher","DOI":"10.1111\/dom.12227"},{"key":"S0033291726105248_r38","doi-asserted-by":"publisher","DOI":"10.1080\/00207454.2021.1924707"},{"key":"S0033291726105248_r25","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2025.02.109"},{"key":"S0033291726105248_r31","doi-asserted-by":"publisher","DOI":"10.9758\/cpn.2015.13.2.129"},{"key":"S0033291726105248_r13","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(25)00355-1"},{"key":"S0033291726105248_r15","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2013.162"},{"key":"S0033291726105248_r34","unstructured":"World Health Organization. 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Published by Cambridge University Press","name":"copyright","label":"Copyright","group":{"name":"copyright_and_licensing","label":"Copyright and Licensing"}},{"value":"This is an Open Access article, distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives licence (http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0), which permits non-commercial re-use, distribution, and reproduction in any medium, provided that no alterations are made and the original article is properly cited. The written permission of Cambridge University Press or the rights holder(s) must be obtained prior to any commercial use and\/or adaptation of the article.","name":"license","label":"License","group":{"name":"copyright_and_licensing","label":"Copyright and Licensing"}},{"value":"This content has been made available to all.","name":"free","label":"Free to read"}],"article-number":"e244"}}