{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T06:45:07Z","timestamp":1793083507527,"version":"4.5.0"},"reference-count":92,"publisher":"Cambridge University Press (CUP)","license":[{"start":{"date-parts":[[2025,2,4]],"date-time":"2025-02-04T00:00:00Z","timestamp":1738627200000},"content-version":"unspecified","delay-in-days":34,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100005416","name":"Norges Forskningsr\u00e5d","doi-asserted-by":"publisher","award":["223273"],"award-info":[{"award-number":["223273"]}],"id":[{"id":"10.13039\/501100005416","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cambridge.org"],"crossmark-restriction":true},"short-container-title":["Psychol. Med."],"published-print":{"date-parts":[[2025]]},"abstract":"<jats:title>Abstract<\/jats:title>\n\t  <jats:sec id=\"S0033291724003271_sec1\">\n\t    <jats:title>Background<\/jats:title>\n\t    <jats:p>The prevalence of youth anxiety and depression has increased globally, with limited causal explanations. Long-term physical health conditions (LTCs) affect 20\u201340% of youth, with rates also rising. LTCs are associated with higher rates of youth depression and anxiety; however, it is uncertain whether observed associations are causal or explained by unmeasured confounding or reverse causation.<\/jats:p>\n\t  <\/jats:sec>\n\t  <jats:sec id=\"S0033291724003271_sec2\" sec-type=\"methods\">\n\t    <jats:title>Methods<\/jats:title>\n\t    <jats:p>Using data from the Norwegian Mother, Father, and Child Cohort Study (MoBa) and Norwegian National Patient Registry, we investigated phenotypic associations between childhood LTCs, and depression and anxiety diagnoses in youth (&lt;19\u00a0years), defined using ICD-10 diagnoses and self-rated measures. We then conducted two-sample Mendelian Randomization (MR) analyses using SNPs associated with childhood LTCs from existing genome-wide association studies (GWAS) as instrumental variables. Outcomes were: (i) diagnoses of major depressive disorder (MDD) and anxiety disorders or elevated symptoms in MoBa, and (ii) youth-onset MDD using summary statistics from a GWAS in iPSYCH2015 cohort.<\/jats:p>\n\t  <\/jats:sec>\n\t  <jats:sec id=\"S0033291724003271_sec3\" sec-type=\"results\">\n\t    <jats:title>Results<\/jats:title>\n\t    <jats:p>Having any childhood LTC phenotype was associated with elevated youth MDD (OR\u00a0=\u00a01.48 [95% CIs 1.19, 1.85], p\u00a0=\u00a04.2\u00d710<jats:sup>\u22124<\/jats:sup>) and anxiety disorder risk (OR\u00a0=\u00a01.44 [1.20, 1.73], p\u00a0=\u00a07.9\u00d710<jats:sup>\u22125<\/jats:sup>). Observational and MR analyses in MoBa were consistent with a causal relationship between migraine and depression (IVW OR\u00a0=\u00a01.38 [1.19, 1.60], p<jats:sub>FDR<\/jats:sub>\u00a0=\u00a01.8x10<jats:sup>\u22124<\/jats:sup>). MR analyses using iPSYCH2015 did not support a causal link between LTC genetic liabilities and youth-onset depression or in the reverse direction.<\/jats:p>\n\t  <\/jats:sec>\n\t  <jats:sec id=\"S0033291724003271_sec4\" sec-type=\"conclusions\">\n\t    <jats:title>Conclusions<\/jats:title>\n\t    <jats:p>Childhood LTCs are associated with depression and anxiety in youth, however, little evidence of causation between LTCs genetic liability and youth depression\/anxiety was identified from MR analyses, except for migraine.<\/jats:p>\n\t  <\/jats:sec>","DOI":"10.1017\/s0033291724003271","type":"journal-article","created":{"date-parts":[[2025,2,4]],"date-time":"2025-02-04T07:26:41Z","timestamp":1738654001000},"update-policy":"https:\/\/doi.org\/10.1017\/policypage","source":"Crossref","is-referenced-by-count":9,"title":["Long-term physical health conditions and youth anxiety and depression: Is there a causal link?"],"prefix":"10.1017","volume":"55","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1412-5413","authenticated-orcid":false,"given":"Amy","family":"Shakeshaft","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica R.","family":"Mundy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3257-5269","authenticated-orcid":false,"given":"Emil M.","family":"Pedersen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7493-2041","authenticated-orcid":false,"given":"Charlotte A.","family":"Dennison","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5124-5230","authenticated-orcid":false,"given":"Lucy","family":"Riglin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2492-8308","authenticated-orcid":false,"given":"Daniela","family":"Bragantini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0119-157X","authenticated-orcid":false,"given":"Elizabeth C.","family":"Corfield","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ajay K.","family":"Thapar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4461-3568","authenticated-orcid":false,"given":"Ole A.","family":"Andreassen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3586-0927","authenticated-orcid":false,"given":"Evie","family":"Stergiakouli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1407-8314","authenticated-orcid":false,"given":"George","family":"Davey Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3123-5411","authenticated-orcid":false,"given":"Laurie","family":"Hannigan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6198-4953","authenticated-orcid":false,"given":"Katherine L.","family":"Musliner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9268-0423","authenticated-orcid":false,"given":"Alexandra","family":"Havdahl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3689-737X","authenticated-orcid":false,"given":"Anita","family":"Thapar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"56","published-online":{"date-parts":[[2025,2,4]]},"reference":[{"key":"S0033291724003271_r4","first-page":"237","article-title":"Development of a short questionnaire for use in epidemiological studies of depression in children and adolescents","volume":"5","author":"Angold","year":"1995","journal-title":"International Journal of Methods in Psychiatric Research"},{"key":"S0033291724003271_r46","doi-asserted-by":"publisher","DOI":"10.1007\/s10826-021-02079-y"},{"key":"S0033291724003271_r49","doi-asserted-by":"publisher","DOI":"10.1186\/s12916-020-1498-z"},{"key":"S0033291724003271_r5","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddy314"},{"key":"S0033291724003271_r68","first-page":"245","article-title":"Systematic review: Bullying involvement of children with and without chronic physical illness and\/or physical\/sensory disability\u2014a meta-analytic comparison with healthy\/nondisabled peers","volume":"42","author":"Pinquart","year":"2017","journal-title":"Journal of Pediatric Psychology"},{"key":"S0033291724003271_r80","doi-asserted-by":"publisher","DOI":"10.1002\/gepi.22295"},{"key":"S0033291724003271_r89","doi-asserted-by":"publisher","DOI":"10.3390\/nu15010243"},{"key":"S0033291724003271_r54","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyw029"},{"key":"S0033291724003271_r74","unstructured":"R Core Team (2022). R: A language and environment for statistical Computing. R foundation for statistical computing. Vienna, Austria."},{"key":"S0033291724003271_r86","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-020-0648-1"},{"key":"S0033291724003271_r15","doi-asserted-by":"publisher","DOI":"10.1016\/j.psyneuen.2016.04.019"},{"key":"S0033291724003271_r9","doi-asserted-by":"publisher","DOI":"10.1097\/00004583-199704000-00018"},{"key":"S0033291724003271_r27","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2008.08.015"},{"key":"S0033291724003271_r22","doi-asserted-by":"publisher","DOI":"10.1017\/S2040174415007989"},{"key":"S0033291724003271_r20","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-clinpsy-032511-143108"},{"key":"S0033291724003271_r52","doi-asserted-by":"publisher","DOI":"10.1007\/s00787-020-01646-w"},{"key":"S0033291724003271_r53","doi-asserted-by":"publisher","DOI":"10.1111\/cch.12475"},{"key":"S0033291724003271_r47","doi-asserted-by":"publisher","DOI":"10.1136\/archdischild-2018-316702"},{"key":"S0033291724003271_r23","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2019.00246"},{"key":"S0033291724003271_r29","doi-asserted-by":"publisher","DOI":"10.2147\/OARRR.S174408"},{"key":"S0033291724003271_r31","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2019.02.022"},{"key":"S0033291724003271_r65","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2017.196"},{"key":"S0033291724003271_r93","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01507-2019"},{"key":"S0033291724003271_r36","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2214.2003.00324.x"},{"key":"S0033291724003271_r10","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2018-2988"},{"key":"S0033291724003271_r67","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2214.2012.01397.x"},{"key":"S0033291724003271_r12","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyv080"},{"key":"S0033291724003271_r58","doi-asserted-by":"publisher","DOI":"10.2105\/AJPH.2009.180943"},{"key":"S0033291724003271_r85","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(22)01012-1"},{"key":"S0033291724003271_r7","doi-asserted-by":"publisher","DOI":"10.1093\/jpepsy\/jsz004"},{"key":"S0033291724003271_r19","doi-asserted-by":"publisher","DOI":"10.1111\/jcpp.12372"},{"key":"S0033291724003271_r32","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwm165"},{"key":"S0033291724003271_r61","doi-asserted-by":"publisher","DOI":"10.5324\/nje.v24i1-2.1755"},{"key":"S0033291724003271_r62","article-title":"Trends in comorbid physical and mental health conditions in children from 1999 to 2017 in England","author":"Panagi","year":"2022a","journal-title":"European Child and Adolescent Psychiatry"},{"key":"S0033291724003271_r56","doi-asserted-by":"publisher","DOI":"10.1016\/j.rasd.2017.08.002"},{"key":"S0033291724003271_r72","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-019-0559-1"},{"key":"S0033291724003271_r55","doi-asserted-by":"publisher","DOI":"10.1016\/S2215-0366(23)00193-1"},{"key":"S0033291724003271_r90","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-018-0099-7"},{"key":"S0033291724003271_r11","doi-asserted-by":"publisher","DOI":"10.1136\/archdischild-2012-303396"},{"key":"S0033291724003271_r79","article-title":"Strengthening the reporting of observational studies in epidemiology using mendelian randomisation (STROBE-MR): Explanation and elaboration","volume":"375","author":"Skrivankova","year":"2021","journal-title":"BMJ"},{"key":"S0033291724003271_r87","doi-asserted-by":"publisher","DOI":"10.1017\/S0033291718003896"},{"key":"S0033291724003271_r24","doi-asserted-by":"publisher","DOI":"10.1016\/j.ecresq.2019.10.011"},{"key":"S0033291724003271_r16","doi-asserted-by":"publisher","DOI":"10.1101\/2020.11.30.20237768"},{"key":"S0033291724003271_r45","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2021.807563"},{"key":"S0033291724003271_r75","volume-title":"State of child health","year":"2020"},{"key":"S0033291724003271_r34","doi-asserted-by":"publisher","DOI":"10.1097\/DBP.0000000000000898"},{"key":"S0033291724003271_r48","first-page":"1866","article-title":"Triangulation in aetiological epidemiology","volume":"45","author":"Lawlor","year":"2016","journal-title":"International Journal of Epidemiology"},{"key":"S0033291724003271_r8","doi-asserted-by":"publisher","DOI":"10.1097\/00004583-199910000-00011"},{"key":"S0033291724003271_r25","doi-asserted-by":"publisher","DOI":"10.1002\/ppul.23689"},{"key":"S0033291724003271_r51","doi-asserted-by":"publisher","DOI":"10.2337\/dc21-1347"},{"key":"S0033291724003271_r76","doi-asserted-by":"publisher","DOI":"10.1038\/s43586-021-00092-5"},{"key":"S0033291724003271_r21","doi-asserted-by":"publisher","DOI":"10.1101\/2022.06.23.496289"},{"key":"S0033291724003271_r43","doi-asserted-by":"publisher","DOI":"10.1038\/s41539-020-00080-6"},{"key":"S0033291724003271_r60","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2020-042297"},{"key":"S0033291724003271_r77","doi-asserted-by":"publisher","DOI":"10.1016\/j.acap.2011.10.004"},{"key":"S0033291724003271_r81","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyg070"},{"key":"S0033291724003271_r92","doi-asserted-by":"publisher","DOI":"10.12740\/PP\/OnlineFirst\/143982"},{"key":"S0033291724003271_r69","doi-asserted-by":"publisher","DOI":"10.1111\/j.1651-2227.2011.02223.x"},{"key":"S0033291724003271_r30","doi-asserted-by":"publisher","DOI":"10.1001\/jamapediatrics.2022.3940"},{"key":"S0033291724003271_r1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)32129-3"},{"key":"S0033291724003271_r33","doi-asserted-by":"publisher","DOI":"10.1111\/cch.12910"},{"key":"S0033291724003271_r35","doi-asserted-by":"publisher","DOI":"10.2337\/db19-0831"},{"key":"S0033291724003271_r13","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddz161"},{"key":"S0033291724003271_r38","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-021-00990-0"},{"key":"S0033291724003271_r17","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpsychires.2013.10.015"},{"key":"S0033291724003271_r59","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.20220906"},{"key":"S0033291724003271_r64","doi-asserted-by":"crossref","first-page":"1449","DOI":"10.1038\/ng.3424","article-title":"Multi-ancestry genome-wide association study of 21,000 cases and 95,000 controls identifies new risk loci for atopic dermatitis","volume":"47","author":"Paternoster","year":"2015","journal-title":"Nature Genetics"},{"key":"S0033291724003271_r66","doi-asserted-by":"publisher","DOI":"10.1093\/jpepsy\/jst020"},{"key":"S0033291724003271_r82","doi-asserted-by":"publisher","DOI":"10.1007\/s00787-015-0697-1"},{"key":"S0033291724003271_r26","doi-asserted-by":"publisher","DOI":"10.1007\/s11916-015-0479-y"},{"key":"S0033291724003271_r3","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-023-02352-1"},{"key":"S0033291724003271_r6","first-page":"37","article-title":"Why are migraineurs more depressed? A review of the factors contributing to the comorbidity of migraine and depression","volume":"19","author":"Baksa","year":"2017","journal-title":"Neuropsychopharmacologia Hungarica"},{"key":"S0033291724003271_r71","doi-asserted-by":"publisher","DOI":"10.1136\/adc.2008.146571"},{"key":"S0033291724003271_r28","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2021.07.090"},{"key":"S0033291724003271_r37","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-022-01888-z"},{"key":"S0033291724003271_r70","doi-asserted-by":"publisher","DOI":"10.1093\/jpepsy\/jsq104"},{"key":"S0033291724003271_r83","doi-asserted-by":"publisher","DOI":"10.1186\/s12889-021-11038-7"},{"key":"S0033291724003271_r88","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2010.104"},{"key":"S0033291724003271_r42","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2614"},{"key":"S0033291724003271_r73","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2021.646421"},{"key":"S0033291724003271_r84","doi-asserted-by":"publisher","DOI":"10.5888\/pcd13.150535"},{"key":"S0033291724003271_r41","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.34408"},{"key":"S0033291724003271_r44","unstructured":"International League Against Epilepsy Consortium on Complex Epilepsies, Berkovic, S. F. , Cavalleri, G. L. , & Koeleman, B. P . (2022). Genome-wide meta-analysis of over 29,000 people with epilepsy reveals 26 loci and subtype-specific genetic architecture. medRxiv, 2022.06.08.22276120."},{"key":"S0033291724003271_r57","doi-asserted-by":"publisher","DOI":"10.1007\/s00431-008-0697-y"},{"key":"S0033291724003271_r39","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0261952"},{"key":"S0033291724003271_r2","doi-asserted-by":"publisher","DOI":"10.1192\/apt.bp.108.006510"},{"key":"S0033291724003271_r14","doi-asserted-by":"publisher","DOI":"10.1017\/S0954579420000206"},{"key":"S0033291724003271_r18","doi-asserted-by":"publisher","DOI":"10.1097\/MPG.0000000000002407"},{"key":"S0033291724003271_r40","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1007081"},{"key":"S0033291724003271_r50","first-page":"1","article-title":"Childhood sleep: Physical, cognitive, and behavioral consequences and implications","author":"Liu","year":"2022","journal-title":"World Journal of Pediatrics"},{"key":"S0033291724003271_r63","doi-asserted-by":"publisher","DOI":"10.1002\/mpr.1926"},{"key":"S0033291724003271_r78","doi-asserted-by":"publisher","DOI":"10.1007\/s10567-010-0074-z"}],"container-title":["Psychological Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.cambridge.org\/core\/services\/aop-cambridge-core\/content\/view\/S0033291724003271","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,4]],"date-time":"2025-02-04T07:26:50Z","timestamp":1738654010000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.cambridge.org\/core\/product\/identifier\/S0033291724003271\/type\/journal_article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025]]},"references-count":92,"alternative-id":["S0033291724003271"],"URL":"https:\/\/doi.org\/10.1017\/s0033291724003271","relation":{},"ISSN":["0033-2917","1469-8978"],"issn-type":[{"value":"0033-2917","type":"print"},{"value":"1469-8978","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025]]},"assertion":[{"value":"\u00a9 The Author(s), 2025. 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 licence (http:\/\/creativecommons.org\/licenses\/by\/4.0), which permits unrestricted re-use, distribution and reproduction, provided the original article is properly cited.","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":"e7"}}