{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T09:07:35Z","timestamp":1775552855531,"version":"3.50.1"},"reference-count":48,"publisher":"Cambridge University Press (CUP)","license":[{"start":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T00:00:00Z","timestamp":1775520000000},"content-version":"unspecified","delay-in-days":96,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000025","name":"National Institute of Mental Health","doi-asserted-by":"publisher","award":["R01MH122544"],"award-info":[{"award-number":["R01MH122544"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cambridge.org"],"crossmark-restriction":true},"short-container-title":["Psychol. Med."],"published-print":{"date-parts":[[2026]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec id=\"S0033291726104012_sec1\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The individual effects of genetic factors and adverse childhood experiences (ACEs) on risk of psychosis, including schizophrenia (SCZ) and bipolar disorder (BIP), have been widely acknowledged, but their interaction effects on individual psychopathological symptoms remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"S0033291726104012_sec2\" sec-type=\"methods\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Based on data from 163,704 individuals in the UK Biobank, we investigated the joint effects of polygenic risk scores (PRSs) of SCZ and BIP and ACEs on psychopathology. ACEs status and 55 psychopathological symptoms from seven domains were measured retrospectively using an online mental health questionnaire in 2016. Recent genome-wide association studies for SCZ and BIP were combined with genotype data to generate PRSs. Logistic regression analyses were then conducted to explore univariate and joint main effects of PRSs and ACEs on psychopathological symptoms, as well as their additive and multiplicative interaction effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"S0033291726104012_sec3\" sec-type=\"results\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The interaction mechanisms for PRSs and ACEs varied across symptom domains: additive interactions were observed on the depression (RERI\n                      <jats:sub>BIP-ACEs<\/jats:sub>\n                      \u00a0=\u00a00.20\u20130.25), anxiety (RERI\n                      <jats:sub>SCZ-ACEs<\/jats:sub>\n                      \u00a0= 0.20; RERI\n                      <jats:sub>BIP-ACEs<\/jats:sub>\n                      \u00a0=\u00a00.22\u20130.26), help-seeking (RERI\n                      <jats:sub>SCZ-ACEs<\/jats:sub>\n                      \u00a0=\u00a00.24; RERI\n                      <jats:sub>BIP-ACEs<\/jats:sub>\n                      \u00a0=\u00a00.23), and cognition domains (RERI\n                      <jats:sub>SCZ-ACEs<\/jats:sub>\n                      \u00a0=\u00a0\u22120.23 to -0.17), whereas multiplicative interactions were only detected on the psychotic (beta\n                      <jats:sub>SCZ-ACEs<\/jats:sub>\n                      \u00a0=\u00a0\u22120.543; beta\n                      <jats:sub>BIP-ACEs<\/jats:sub>\n                      \u00a0=\u00a0\u22120.181), mania (beta\n                      <jats:sub>BIP-ACEs<\/jats:sub>\n                      \u00a0= \u22120.195), self-harm or suicide (beta\n                      <jats:sub>SCZ-ACEs<\/jats:sub>\n                      \u00a0=\u00a0\u22120.118), and cognitive domains (beta\n                      <jats:sub>SCZ-ACEs<\/jats:sub>\n                      \u00a0=\u00a0\u22120.204 to \u22120.157).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"S0033291726104012_sec4\" sec-type=\"conclusions\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The interplay mechanisms for genetic liability to SCZ and BIP and ACEs vary across symptom domains. This study reveals heterogeneity in gene\u2013ACEs interaction mechanisms underlying psychosis and may provide personalized guidance for psychological care after ACEs.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1017\/s0033291726104012","type":"journal-article","created":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T08:28:54Z","timestamp":1775550534000},"update-policy":"https:\/\/doi.org\/10.1017\/policypage","source":"Crossref","is-referenced-by-count":0,"title":["Joint effects of childhood adversity and genetic risk for psychosis on psychopathology in the UK Biobank"],"prefix":"10.1017","volume":"56","author":[{"given":"Zheng-An","family":"Lu","sequence":"first","affiliation":[{"name":"Karolinska Institute"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5042-8326","authenticated-orcid":false,"given":"Alexander","family":"Ploner","sequence":"additional","affiliation":[{"name":"Karolinska Institute"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5888-0034","authenticated-orcid":false,"given":"Sarah E.","family":"Bergen","sequence":"additional","affiliation":[{"name":"Karolinska Institute"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"56","published-online":{"date-parts":[[2026,4,7]]},"reference":[{"key":"S0033291726104012_r38","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2024.11.067"},{"key":"S0033291726104012_r46","doi-asserted-by":"publisher","DOI":"10.2174\/1381612825666191216153508"},{"key":"S0033291726104012_r9","doi-asserted-by":"publisher","DOI":"10.1002\/gepi.22339"},{"key":"S0033291726104012_r6","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.2018.89"},{"key":"S0033291726104012_r37","doi-asserted-by":"publisher","DOI":"10.1186\/s12939-023-02017-y"},{"key":"S0033291726104012_r13","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.25690"},{"key":"S0033291726104012_r4","doi-asserted-by":"publisher","DOI":"10.1001\/jamapsychiatry.2019.0097"},{"key":"S0033291726104012_r19","doi-asserted-by":"publisher","DOI":"10.1080\/00223980.2018.1476316"},{"key":"S0033291726104012_r28","doi-asserted-by":"publisher","DOI":"10.1017\/S0033291721001252"},{"key":"S0033291726104012_r11","doi-asserted-by":"publisher","DOI":"10.1001\/jamapsychiatry.2024.0039"},{"key":"S0033291726104012_r34","doi-asserted-by":"publisher","DOI":"10.1016\/j.brat.2019.103413"},{"key":"S0033291726104012_r25","doi-asserted-by":"publisher","DOI":"10.1001\/archgenpsychiatry.2011.12"},{"key":"S0033291726104012_r29","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-08468-9"},{"key":"S0033291726104012_r22","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyr218"},{"key":"S0033291726104012_r3","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.adf4428"},{"key":"S0033291726104012_r17","doi-asserted-by":"publisher","DOI":"10.1097\/00001648-199209000-00012"},{"key":"S0033291726104012_r48","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2023.1247063"},{"key":"S0033291726104012_r33","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2022.104806"},{"key":"S0033291726104012_r18","doi-asserted-by":"publisher","DOI":"10.1177\/17455057231184325"},{"key":"S0033291726104012_r8","doi-asserted-by":"publisher","DOI":"10.1017\/S0033291714000129"},{"key":"S0033291726104012_r15","first-page":"109","article-title":"A brief instrument for the assessment of childhood abuse and neglect: The childhood trauma screener (CTS)","volume":"39","author":"Grabe","year":"2012","journal-title":"Psychiatrische Praxis"},{"key":"S0033291726104012_r1","doi-asserted-by":"publisher","DOI":"10.1017\/S0033291721003664"},{"key":"S0033291726104012_r16","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2017.08.017"},{"key":"S0033291726104012_r7","doi-asserted-by":"publisher","DOI":"10.1093\/gigascience\/giz082"},{"key":"S0033291726104012_r44","doi-asserted-by":"publisher","DOI":"10.1093\/schbul\/sbs050"},{"key":"S0033291726104012_r21","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dym157"},{"key":"S0033291726104012_r24","doi-asserted-by":"publisher","DOI":"10.1093\/epirev\/mxn001"},{"key":"S0033291726104012_r45","doi-asserted-by":"publisher","DOI":"10.1093\/schbul\/sbac049"},{"key":"S0033291726104012_r14","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0231627"},{"key":"S0033291726104012_r30","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.88117.4"},{"key":"S0033291726104012_r2","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-024-03149-7"},{"key":"S0033291726104012_r32","first-page":"1","article-title":"The association of adverse childhood experiences with long-term outcomes of psychosis: A 21-year prospective cohort study after a first episode of psychosis","author":"Peralta","year":"2024","journal-title":"Psychological Medicine"},{"key":"S0033291726104012_r20","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2013.09.006"},{"key":"S0033291726104012_r43","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-04434-5"},{"key":"S0033291726104012_r36","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2021.686666"},{"key":"S0033291726104012_r31","doi-asserted-by":"publisher","DOI":"10.1093\/geront\/gnac041"},{"key":"S0033291726104012_r35","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.2018.227"},{"key":"S0033291726104012_r5","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0579-z"},{"key":"S0033291726104012_r39","doi-asserted-by":"publisher","DOI":"10.1016\/j.euroneuro.2021.05.007"},{"key":"S0033291726104012_r12","doi-asserted-by":"publisher","DOI":"10.3389\/fsoc.2022.833987"},{"key":"S0033291726104012_r23","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.2023.128"},{"key":"S0033291726104012_r27","article-title":"Assessing additive interactions between protective factors using relative risk reduction due to interaction","volume":"60","author":"Nova","year":"2024","journal-title":"Medicina (Kaunas, Lithuania)"},{"key":"S0033291726104012_r42","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0163319"},{"key":"S0033291726104012_r47","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2023.08.116"},{"key":"S0033291726104012_r10","first-page":"49","article-title":"Schizophrenia and bipolar disorder: The road from similarities and clinical heterogeneity to neurobiological types","volume":"449","author":"Dacquino","year":"2015","journal-title":"the International Journal of Clinical Chemistry"},{"key":"S0033291726104012_r40","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2022.110612"},{"key":"S0033291726104012_r41","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awy279"},{"key":"S0033291726104012_r26","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-021-00857-4"}],"container-title":["Psychological Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.cambridge.org\/core\/services\/aop-cambridge-core\/content\/view\/S0033291726104012","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T08:28:56Z","timestamp":1775550536000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.cambridge.org\/core\/product\/identifier\/S0033291726104012\/type\/journal_article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026]]},"references-count":48,"alternative-id":["S0033291726104012"],"URL":"https:\/\/doi.org\/10.1017\/s0033291726104012","relation":{},"ISSN":["0033-2917","1469-8978"],"issn-type":[{"value":"0033-2917","type":"print"},{"value":"1469-8978","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026]]},"assertion":[{"value":"\u00a9 The Author(s), 2026. 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":"e92"}}