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However, the causal mechanisms, particularly the role of mental health disorders, remain elusive.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this Mendelian randomization (MR) study, we leveraged genome\u2010wide association study data from multiple sources. Age at first sexual intercourse (AFSI) statistics were derived from the UK Biobank, encompassing up to 406,457 participants of European ancestry. Intentional self\u2010harm (ISH) genome\u2010wide association study (GWAS) data were obtained from the FinnGen Biobank, comprising 218,792 European\u2010descent individuals. We investigated the causal relationship between AFSI and ISH and quantified the mediating effects of major depressive disorder (MDD; <jats:italic>n<\/jats:italic>\u00a0=\u00a0173,005), schizophrenia (SCZ; <jats:italic>n<\/jats:italic>\u00a0=\u00a0127,906), and attention deficit hyperactivity disorder (ADHD; <jats:italic>n<\/jats:italic>\u00a0=\u00a055,374). Both two\u2010step and multivariable MR approaches were employed to estimate the mediation effects of these psychiatric disorders.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The <jats:italic>F<\/jats:italic>\u2010statistics of all retained SNPs are over 10, indicating our study has no weak instrument bias. The odds ratio (OR) indicated that early sexual intercourse substantially increases the risk of ISH (IVW: OR\u00a0=\u00a00.60, 95% CI\u00a0=\u00a00.54\u20130.66, <jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.05). Specifically, MDD was found to mediate 31% of this effect and SCZ 12%, collectively accounting for 46% of the total effect.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Early sexual intercourse is associated with an increased risk of intentional self\u2010harm, potentially mediated by psychiatric disorders. These findings emphasize the need for mental health screening and early intervention in adolescents with early sexual debuts.<\/jats:p><\/jats:sec>","DOI":"10.1002\/brb3.70124","type":"journal-article","created":{"date-parts":[[2024,12,4]],"date-time":"2024-12-04T06:47:22Z","timestamp":1733294842000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Investigating the Mediating Role of Mental Disorders in the Relationship Between Early Sexual Intercourse and Intentional Self\u2010Harm: A Two\u2010Step and Multivariable Mendelian Randomization Study"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-9157-9436","authenticated-orcid":false,"given":"Dameng","family":"Dong","sequence":"first","affiliation":[{"name":"School of Public Health Zhejiang Chinese Medical University Hangzhou Zhejiang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7183-0082","authenticated-orcid":false,"given":"Saboor","family":"Saeed","sequence":"additional","affiliation":[{"name":"School of Medicine Zhejiang University Hangzhou Zhejiang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rucheng","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Public Health Zhejiang Chinese Medical University Hangzhou Zhejiang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9419-8254","authenticated-orcid":false,"given":"An","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Public Health, Faculty of Medicine University of Helsinki Helsinki Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weijun","family":"Zheng","sequence":"additional","affiliation":[{"name":"School of Public Health Zhejiang Chinese Medical University Hangzhou Zhejiang China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,12,3]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)61141-6"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyv080"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/gepi.21965"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyr036"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1192\/j.eurpsy.2022.18"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10654\u2010021\u201000757\u20101"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/children10071270"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu14204434"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddu328"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.k601"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2023.1192123"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaac.2018.06.018"},{"key":"e_1_2_10_14_1","unstructured":"Global Burden of Disease Collaborative Network.2019. \u201cGlobal Burden of Disease Study 2019 (GBD 2019) results.\u201d Last modified October 15 2020.https:\/\/www.thelancet.com\/infographics\u2010do\/gbd\u20102019."},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12888\u2010020\u201002583\u20103"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/s2215\u20100366(14)70240\u20108"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.34408"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2023\u2010064800"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpsychires.2023.05.066"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600\u20100447.2004.00384.x"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.3349\/ymj.2010.51.1.18"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(22)00173-8"},{"key":"e_1_2_10_23_1","first-page":"2","article-title":"Overview of the Youth Risk Behavior Surveillance System","volume":"108","author":"Kolbe L. 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