{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:19:43Z","timestamp":1792790383402,"version":"4.5.0"},"posted":{"date-parts":[[2026,6,29]]},"group-title":"Psychiatry and Clinical Psychology","reference-count":78,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T00:00:00Z","timestamp":1782691200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Deutscher Akademischer Austauschdienst","award":["57645448"],"award-info":[{"award-number":["57645448"]}],"id":[{"id":"https:\/\/ror.org\/039djdh30","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Sleep health and depression are multidimensional constructs, yet their shared determinants remain obscure. We aim to identify the key exposome factors in predicting sleep-related depression (SRD).<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We integrated regularized canonical correlation analysis with machine-learning models within a nested cross-validation to identify a shared phenotype (i.e., sleep-related depression (SRD)) and to predict SRD from exposome factors in the UK Biobank (n = 64,781). The best-performing model was validated in an independent subsample at baseline and follow-up (n = 8,139) and in a clinical depression subsample (n = 3,046) to assess generalizability. Subsequently, we conducted complementary analyses to assess the exposome\u2019s role in other latent phenotypes of sleep and depression.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Findings<\/jats:title>\n                  <jats:p>We identified a robust multivariate association between sleep and depression in GP1 (canonical r = 0.42). Exposome factors moderately predicted SRD (r = 0.25; 95% CI [0.25, 0.26]; R\u00b2 = 0.06; 95% CI [0.06, 0.07]; rMSE = 1.11; 95% CI [1.10, 1.11]). The top predictors were less frequency of confiding in others, less vigorous physical activity, passive smoking exposure, and more sedentary television viewing. Out-of-sample validation of the predictive model showed similar patterns in GP2 at baseline, at follow-up, and in clinical depression subsamples. Similarly, less frequency of confiding in others and greater sedentary television viewing were the main predictors of other depression-related profiles, whereas less walking frequency and less time spent outdoors in winter predicted poor sleep-related profiles.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Interpretation<\/jats:title>\n                  <jats:p>Our generalizable predictive model identifies critical modifiable predictors of the association between sleep health and depression that could serve as potential targets for personalized interventions.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.06.26.26356679","type":"posted-content","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T04:15:25Z","timestamp":1782792925000},"source":"Crossref","is-referenced-by-count":0,"title":["Exposome factors predict the association between sleep health and depression"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-1026-5959","authenticated-orcid":false,"given":"Wen","family":"Liu","sequence":"first","affiliation":[{"name":"Institute of Neuroscience and Medicine, Brain and Behaviour (INM 7), Research Center J\u00fclich, J\u00fclich, Germany"},{"name":"Institute of Systems Neuroscience, Medical Faculty and University Hospital D\u00fcsseldorf, Heinrich Heine University D\u00fcsseldorf, D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9648-0253","authenticated-orcid":false,"given":"Vincent","family":"K\u00fcppers","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience and Medicine, Brain and Behaviour (INM 7), Research Center J\u00fclich, J\u00fclich, Germany"},{"name":"Department of Nuclear Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, 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