{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T10:26:16Z","timestamp":1775471176701,"version":"3.50.1"},"reference-count":40,"publisher":"Royal College of Psychiatrists","issue":"2","license":[{"start":{"date-parts":[[2025,2,3]],"date-time":"2025-02-03T00:00:00Z","timestamp":1738540800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["no. 82070356"],"award-info":[{"award-number":["no. 82070356"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cambridge.org"],"crossmark-restriction":true},"short-container-title":["BJPsych open"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:sec id=\"S2056472424008354_sec_a1\">\n\t    <jats:title>Background<\/jats:title>\n\t    <jats:p>An increasing number of observational studies have reported associations between frailty and mental disorders, but the causality remains ambiguous.<\/jats:p>\n\t  <\/jats:sec>\n\t  <jats:sec id=\"S2056472424008354_sec_a2\">\n\t    <jats:title>Aims<\/jats:title>\n\t    <jats:p>To assess the bidirectional causal relationship between frailty and nine mental disorders.<\/jats:p>\n\t  <\/jats:sec>\n\t  <jats:sec id=\"S2056472424008354_sec_a3\" sec-type=\"methods\">\n\t    <jats:title>Method<\/jats:title>\n\t    <jats:p>We conducted a bidirectional two-sample Mendelian randomisation on genome-wide association study summary data, to investigate causality between frailty and nine mental disorders. Causal effects were primarily estimated using inverse variance weighted method. Several secondary analyses were applied to verify the results. Cochran's <jats:italic>Q<\/jats:italic>-test and Mendelian randomisation Egger intercept were applied to evaluate heterogeneity and pleiotropy.<\/jats:p>\n\t  <\/jats:sec>\n\t  <jats:sec id=\"S2056472424008354_sec_a4\" sec-type=\"results\">\n\t    <jats:title>Results<\/jats:title>\n\t    <jats:p>Genetically determined frailty was significantly associated with increased risk of major depressive disorder (MDD) (odds ratio 1.86, 95% CI 1.36\u20132.53, <jats:italic>P<\/jats:italic> = 8.1 \u00d7 10<jats:sup>\u22125<\/jats:sup>), anxiety (odds ratio 2.76, 95% CI 1.56\u20134.90, <jats:italic>P<\/jats:italic> = 5.0 \u00d7 10<jats:sup>\u22124<\/jats:sup>), post-traumatic stress disorder (PTSD) (odds ratio 2.56, 95% CI 1.69\u20133.87, <jats:italic>P<\/jats:italic> = 9.9 \u00d7 10<jats:sup>\u22126<\/jats:sup>), neuroticism (<jats:italic>\u03b2<\/jats:italic> = 0.25, 95% CI 0.11\u20130.38, <jats:italic>P<\/jats:italic> = 3.3 \u00d7 10<jats:sup>\u22124<\/jats:sup>) and insomnia (<jats:italic>\u03b2<\/jats:italic> = 0.50, 95% CI 0.25\u20130.75, <jats:italic>P<\/jats:italic> = 1.1 \u00d7 10<jats:sup>\u22124<\/jats:sup>). Conversely, genetic liability to MDD, neuroticism, insomnia and suicide attempt significantly increased risk of frailty (MDD: <jats:italic>\u03b2<\/jats:italic> = 0.071, 95% CI 0.033\u20130.110, <jats:italic>P<\/jats:italic> = 2.8 \u00d7 10<jats:sup>\u22124<\/jats:sup>; neuroticism: <jats:italic>\u03b2<\/jats:italic> = 0.269, 95% CI 0.173\u20130.365, <jats:italic>P<\/jats:italic> = 3.4 \u00d7 10<jats:sup>\u22128<\/jats:sup>; insomnia: <jats:italic>\u03b2<\/jats:italic> = 0.160, 95% CI 0.141\u20130.179, <jats:italic>P<\/jats:italic> = 3.2 \u00d7 10<jats:sup>\u221261<\/jats:sup>; suicide attempt: <jats:italic>\u03b2<\/jats:italic> = 0.056, 95% CI 0.029\u20130.084, <jats:italic>P<\/jats:italic> = 3.4 \u00d7 10<jats:sup>\u22125<\/jats:sup>). There was a suggestive detrimental association of frailty on suicide attempt and an inverse relationship of subjective well-being on frailty.<\/jats:p>\n\t  <\/jats:sec>\n\t  <jats:sec id=\"S2056472424008354_sec_a5\" sec-type=\"conclusions\">\n\t    <jats:title>Conclusions<\/jats:title>\n\t    <jats:p>Our findings show bidirectional causal associations between frailty and MDD, insomnia and neuroticism. Additionally, higher frailty levels are associated with anxiety and PTSD, and suicide attempts are correlated with increased frailty. Understanding these associations is crucial for the effective management of frailty and improvement of mental disorders.<\/jats:p>\n\t  <\/jats:sec>","DOI":"10.1192\/bjo.2024.835","type":"journal-article","created":{"date-parts":[[2025,2,3]],"date-time":"2025-02-03T07:01:21Z","timestamp":1738566081000},"update-policy":"https:\/\/doi.org\/10.1017\/policypage","source":"Crossref","is-referenced-by-count":5,"title":["Casual associations between frailty and nine mental disorders: bidirectional Mendelian randomisation 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