{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T13:24:10Z","timestamp":1784035450228,"version":"3.55.0"},"reference-count":56,"publisher":"Royal College of Psychiatrists","issue":"1","license":[{"start":{"date-parts":[[2024,9,30]],"date-time":"2024-09-30T00:00:00Z","timestamp":1727654400000},"content-version":"unspecified","delay-in-days":273,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur. Psychiatr."],"published-print":{"date-parts":[[2024]]},"abstract":"<jats:title>Abstract<\/jats:title>\n\t  <jats:sec id=\"S0924933824017747_sec1\">\n\t    <jats:title>Background<\/jats:title>\n\t    <jats:p>While several risk factors for schizophrenia have been identified, their individual impacts are rather small. The relative independent and cumulative impacts of multiple risk factors on disease risk and age of onset warrant further investigation.<\/jats:p>\n\t  <\/jats:sec>\n\t  <jats:sec id=\"S0924933824017747_sec2\">\n\t    <jats:title>Study design<\/jats:title>\n\t    <jats:p>We conducted a register-based case\u2013control study including all individuals receiving a schizophrenia spectrum disorder in Denmark from 1973 to 2018 (<jats:italic>N<\/jats:italic>\u00a0=\u00a029,142), and a healthy control sample matched 5:1 on age, sex, and parental socioeconomic status (<jats:italic>N<\/jats:italic>\u00a0=\u00a0136,387). Register data included parental history of psychiatric illness, birth weight, gestational age, season of birth, population density of birthplace, immigration, paternal age, and Apgar scores. Data were analysed using logistic regression and machine learning.<\/jats:p>\n\t  <\/jats:sec>\n\t  <jats:sec id=\"S0924933824017747_sec3\" sec-type=\"results\">\n\t    <jats:title>Results<\/jats:title>\n\t    <jats:p>Parental history of psychiatric illness (OR\u00a0=\u00a02.32 [95%CI 2.21\u20132.43]), high paternal age (OR\u00a0=\u00a01.30 [1.16\u20131.45]), and low birth weight (OR\u00a0=\u00a01.28 [1.16\u20131.41]) increased the odds of belonging to the patient group. In contrast, being a second-generation immigrant (OR\u00a0=\u00a00.65 [0.61\u20130.69]) and high population density of the birthplace (OR\u00a0=\u00a00.92 [0.89\u20130.96]) decreased the odds. The findings were supported by a decision tree analysis where parental history, paternal age, and birth weight contributed most to diagnostic classification (ACC<jats:sub>test<\/jats:sub>\u00a0=\u00a00.69, AUC<jats:sub>test<\/jats:sub>\u00a0=\u00a00.59, <jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.001). Twenty percent of patients were child-onset cases. Here, female sex (OR\u00a0=\u00a01.82 [1.69\u20131.97]) and parental psychiatric illness (OR\u00a0=\u00a01.62 [1.49\u20131.77]) increased the odds of receiving the diagnosis &lt;18\u00a0years.<\/jats:p>\n\t  <\/jats:sec>\n\t  <jats:sec id=\"S0924933824017747_sec4\" sec-type=\"conclusions\">\n\t    <jats:title>Conclusion<\/jats:title>\n\t    <jats:p>Multiple early factors contribute independently to a higher psychosis risk, suggesting cumulative effects leading to symptom onset. Routine assessments of the most influential risk factors could be incorporated into clinical practise. Being female increased the risk of diagnosis during childhood, suggesting sex differences in the developmental trajectories of the disorder.<\/jats:p>\n\t  <\/jats:sec>","DOI":"10.1192\/j.eurpsy.2024.1774","type":"journal-article","created":{"date-parts":[[2024,9,30]],"date-time":"2024-09-30T10:44:54Z","timestamp":1727693094000},"source":"Crossref","is-referenced-by-count":6,"title":["Impact of early risk factors on schizophrenia risk and age of diagnosis: A Danish population-based register study"],"prefix":"10.1192","volume":"67","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3647-9709","authenticated-orcid":false,"given":"Cecilie K.","family":"Lemvigh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5638-2357","authenticated-orcid":false,"given":"Karen S.","family":"Ambrosen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2590-5055","authenticated-orcid":false,"given":"Bj\u00f8rn H.","family":"Ebdrup","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3056-7262","authenticated-orcid":false,"given":"Birte Y.","family":"Glenth\u00f8j","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6921-220X","authenticated-orcid":false,"given":"Merete","family":"Osler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4547-2944","authenticated-orcid":false,"given":"Birgitte","family":"Fagerlund","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"170","published-online":{"date-parts":[[2024,9,30]]},"reference":[{"key":"S0924933824017747_r9","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.179.1.46"},{"key":"S0924933824017747_r39","first-page":"2825","article-title":"Scikit-learn: Machine learning in Python","volume":"12","author":"Pedregosa","year":"2011","journal-title":"J Mach Learn Res."},{"key":"S0924933824017747_r30","doi-asserted-by":"publisher","DOI":"10.1007\/s10654-018-0356-1"},{"key":"S0924933824017747_r42","doi-asserted-by":"publisher","DOI":"10.1016\/j.socscimed.2004.02.004"},{"key":"S0924933824017747_r45","unstructured":"[45] Statistics Denmark. Byopg\u00f8relsen 1. januar 2023: F\u00e6rre bor p\u00e5 landet. 2023."},{"key":"S0924933824017747_r14","doi-asserted-by":"publisher","DOI":"10.1017\/S0033291707009944"},{"key":"S0924933824017747_r7","article-title":"The relative and interactive impact of multiple risk factors in schizophrenia spectrum disorders: A combined register-based and clinical twin study","author":"Lemvigh","year":"2021","journal-title":"Psychol Med"},{"key":"S0924933824017747_r52","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.159.7.1080"},{"key":"S0924933824017747_r53","doi-asserted-by":"publisher","DOI":"10.1016\/j.schres.2011.06.017"},{"key":"S0924933824017747_r11","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.60.7.673"},{"key":"S0924933824017747_r6","doi-asserted-by":"publisher","DOI":"10.1002\/wps.20490"},{"key":"S0924933824017747_r56","doi-asserted-by":"publisher","DOI":"10.1007\/s11920-019-1091-3"},{"key":"S0924933824017747_r18","doi-asserted-by":"publisher","DOI":"10.1016\/j.schres.2014.01.008"},{"key":"S0924933824017747_r12","doi-asserted-by":"publisher","DOI":"10.1001\/jamapsychiatry.2013.441"},{"key":"S0924933824017747_r33","doi-asserted-by":"publisher","DOI":"10.1007\/s10654-014-9930-3"},{"key":"S0924933824017747_r1","doi-asserted-by":"publisher","DOI":"10.1093\/schbul\/sbx121"},{"key":"S0924933824017747_r37","first-page":"691","article-title":"Committee opinion: the Apgar score","volume":"126","year":"2015","journal-title":"Obstet Gynecol."},{"key":"S0924933824017747_r8","doi-asserted-by":"publisher","DOI":"10.1016\/j.schres.2011.09.020"},{"key":"S0924933824017747_r51","doi-asserted-by":"publisher","DOI":"10.1007\/s00787-017-1102-z"},{"key":"S0924933824017747_r17","doi-asserted-by":"publisher","DOI":"10.1017\/S003329171700383X"},{"key":"S0924933824017747_r27","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0447.2000.101004293.x"},{"key":"S0924933824017747_r4","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2017.08.017"},{"key":"S0924933824017747_r13","doi-asserted-by":"publisher","DOI":"10.1017\/S0033291717000162"},{"key":"S0924933824017747_r49","first-page":"60","article-title":"The validity of the schizophrenia diagnosis in the Danish Psychiatric Central Research Register is good","author":"Uggerby","year":"2013","journal-title":"Dan Med J."},{"key":"S0924933824017747_r54","doi-asserted-by":"publisher","DOI":"10.1017\/S0033291709991966"},{"key":"S0924933824017747_r55","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1038\/nature13595","article-title":"Biological insights from 108 schizophrenia-associated genetic loci","volume":"511","author":"Ripke","year":"2014","journal-title":"Nature."},{"key":"S0924933824017747_r31","doi-asserted-by":"publisher","DOI":"10.1177\/1403494810395825"},{"key":"S0924933824017747_r28","doi-asserted-by":"publisher","DOI":"10.1016\/j.schres.2007.07.018"},{"key":"S0924933824017747_r22","doi-asserted-by":"publisher","DOI":"10.1001\/jamapsychiatry.2014.16"},{"key":"S0924933824017747_r3","first-page":"1","article-title":"Schizophrenia","author":"Kahn","year":"2015","journal-title":"Nat Rev Dis Primers."},{"key":"S0924933824017747_r34","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.schbul.a007030"},{"key":"S0924933824017747_r35","doi-asserted-by":"publisher","DOI":"10.1016\/j.schres.2009.06.017"},{"key":"S0924933824017747_r38","first-page":"6","article-title":"Unconditional or conditional logistic regression model for age-matched case\u2013control data?","author":"Kuo","year":"2018","journal-title":"Front Public Health"},{"key":"S0924933824017747_r29","doi-asserted-by":"publisher","DOI":"10.1177\/1403494811399956"},{"key":"S0924933824017747_r41","doi-asserted-by":"publisher","DOI":"10.1093\/schbul\/sbs096"},{"key":"S0924933824017747_r44","first-page":"68","article-title":"A comparison of selected risk factors for unipolar depressive disorder, bipolar affective disorder, schizoaffective disorder, and schizophrenia from a Danish population-based cohort","author":"Laursen","year":"2007","journal-title":"J Clin Psychiatry."},{"key":"S0924933824017747_r5","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(200021)97:1<12::AID-AJMG3>3.0.CO;2-U"},{"key":"S0924933824017747_r20","doi-asserted-by":"publisher","DOI":"10.1016\/S2215-0366(14)70379-7"},{"key":"S0924933824017747_r24","doi-asserted-by":"publisher","DOI":"10.1016\/j.eurpsy.2011.11.001"},{"key":"S0924933824017747_r43","first-page":"58","article-title":"Evidence of a dose-response relationship between urbanicity during upbringing and schizophrenia risk","author":"Pedersen","year":"2001","journal-title":"Arch Gen Psychiatry."},{"key":"S0924933824017747_r15","doi-asserted-by":"publisher","DOI":"10.1016\/j.schres.2008.04.011"},{"key":"S0924933824017747_r32","doi-asserted-by":"publisher","DOI":"10.2147\/CLEP.S91125"},{"key":"S0924933824017747_r19","doi-asserted-by":"publisher","DOI":"10.1016\/j.schres.2016.10.014"},{"key":"S0924933824017747_r36","doi-asserted-by":"publisher","DOI":"10.1017\/S0033291710001406"},{"key":"S0924933824017747_r23","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.157.10.1652"},{"key":"S0924933824017747_r25","doi-asserted-by":"publisher","DOI":"10.1016\/j.comppsych.2017.09.009"},{"key":"S0924933824017747_r47","doi-asserted-by":"publisher","DOI":"10.1016\/j.schres.2016.06.023"},{"key":"S0924933824017747_r48","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2022.10.009"},{"key":"S0924933824017747_r50","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0447.1994.tb01577.x"},{"key":"S0924933824017747_r16","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2016.03.017"},{"key":"S0924933824017747_r46","unstructured":"[46] Statistics Denmark. Byopg\u00f8relsen 1. januar 2015 F\u00e6rre p\u00e5 landet-flere i de st\u00f8rre byer. 2015."},{"key":"S0924933824017747_r40","doi-asserted-by":"publisher","DOI":"10.1145\/2939672.2939785"},{"key":"S0924933824017747_r26","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2017.04.002"},{"key":"S0924933824017747_r2","doi-asserted-by":"publisher","DOI":"10.3390\/brainsci11020275"},{"key":"S0924933824017747_r10","doi-asserted-by":"publisher","DOI":"10.1111\/j.1601-5215.2010.00498.x"},{"key":"S0924933824017747_r21","doi-asserted-by":"publisher","DOI":"10.1016\/j.schres.2009.03.005"}],"container-title":["European Psychiatry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.cambridge.org\/core\/services\/aop-cambridge-core\/content\/view\/S0924933824017747","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,30]],"date-time":"2024-09-30T10:45:00Z","timestamp":1727693100000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.cambridge.org\/core\/product\/identifier\/S0924933824017747\/type\/journal_article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024]]},"references-count":56,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024]]}},"alternative-id":["S0924933824017747"],"URL":"https:\/\/doi.org\/10.1192\/j.eurpsy.2024.1774","relation":{},"ISSN":["0924-9338","1778-3585"],"issn-type":[{"value":"0924-9338","type":"print"},{"value":"1778-3585","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024]]},"article-number":"e64"}}