{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T01:51:36Z","timestamp":1788486696976,"version":"build-2803163510"},"reference-count":0,"publisher":"Royal College of Psychiatrists","issue":"5","license":[{"start":{"date-parts":[[2024,4,23]],"date-time":"2024-04-23T00:00:00Z","timestamp":1713830400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["cambridge.org"],"crossmark-restriction":true},"short-container-title":["Br J Psychiatry"],"published-print":{"date-parts":[[2024,5]]},"abstract":"<jats:sec id=\"S0007125024000308_sec_a1\"><jats:title>Background<\/jats:title><jats:p>A significant proportion of people with clozapine-treated schizophrenia develop \u2018checking\u2019 compulsions, a phenomenon yet to be understood.<\/jats:p><\/jats:sec><jats:sec id=\"S0007125024000308_sec_a2\"><jats:title>Aims<\/jats:title><jats:p>To use habit formation models developed in cognitive neuroscience to investigate the dynamic interplay between psychosis, clozapine dose and obsessive\u2013compulsive symptoms (OCS).<\/jats:p><\/jats:sec><jats:sec id=\"S0007125024000308_sec_a3\" sec-type=\"methods\"><jats:title>Method<\/jats:title><jats:p>Using the anonymised electronic records of a cohort of clozapine-treated patients, including longitudinal assessments of OCS and psychosis, we performed longitudinal multi-level mediation and multi-level moderation analyses to explore associations of psychosis with obsessiveness and excessive checking. Classic bivariate correlation tests were used to assess clozapine load and checking compulsions. The influence of specific genetic variants was tested in a subsample.<\/jats:p><\/jats:sec><jats:sec id=\"S0007125024000308_sec_a4\" sec-type=\"results\"><jats:title>Results<\/jats:title><jats:p>A total of 196 clozapine-treated individuals and 459 face-to-face assessments were included. We found significant OCS to be common (37.9%), with checking being the most prevalent symptom. In mediation models, psychosis severity mediated checking behaviour indirectly by inducing obsessions (<jats:italic>r<\/jats:italic> = 0.07, 95% CI 0.04\u20130.09; <jats:italic>P<\/jats:italic> &lt; 0.001). No direct effect of psychosis on checking was identified (<jats:italic>r<\/jats:italic> = \u22120.28, 95% CI \u22120.09 to 0.03; <jats:italic>P<\/jats:italic> = 0.340). After psychosis remission (<jats:italic>n<\/jats:italic> = 65), checking compulsions correlated with both clozapine plasma levels (<jats:italic>r<\/jats:italic> = 0.35; <jats:italic>P<\/jats:italic> = 0.004) and dose (<jats:italic>r<\/jats:italic> = 0.38; <jats:italic>P<\/jats:italic> = 0.002). None of the glutamatergic and serotonergic genetic variants were found to moderate the effect of psychosis on obsession and compulsion (SLC6A4, SLC1A1 and HTR2C) survived the multiple comparisons correction.<\/jats:p><\/jats:sec><jats:sec id=\"S0007125024000308_sec_a5\" sec-type=\"conclusions\"><jats:title>Conclusions<\/jats:title><jats:p>We elucidated different phases of the complex interplay of psychosis and compulsions, which may inform clinicians\u2019 therapeutic decisions.<\/jats:p><\/jats:sec>","DOI":"10.1192\/bjp.2024.30","type":"journal-article","created":{"date-parts":[[2024,4,23]],"date-time":"2024-04-23T14:13:58Z","timestamp":1713881638000},"page":"164-169","update-policy":"https:\/\/doi.org\/10.1017\/policypage","source":"Crossref","is-referenced-by-count":6,"title":["The role of psychosis and clozapine load in excessive checking in treatment-resistant schizophrenia: longitudinal observational study"],"prefix":"10.1192","volume":"224","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4128-8955","authenticated-orcid":false,"given":"Emilio","family":"Fernandez-Egea","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4724-4892","authenticated-orcid":false,"given":"Shanquan","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Estela","family":"Sang\u00fcesa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Gass\u00f3","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marjan","family":"Biria","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Plaistow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isaac","family":"Jarratt-Barnham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nuria","family":"Segarra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3336-6298","authenticated-orcid":false,"given":"Sergi","family":"Mas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria-Pilar","family":"Ribate","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina B.","family":"Garc\u00eda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naomi A.","family":"Fineberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulia","family":"Worbe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rudolf N.","family":"Cardinal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trevor W.","family":"Robbins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"170","published-online":{"date-parts":[[2024,4,23]]},"container-title":["The British Journal of Psychiatry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.cambridge.org\/core\/services\/aop-cambridge-core\/content\/view\/S0007125024000308","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,23]],"date-time":"2024-04-23T14:14:01Z","timestamp":1713881641000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.cambridge.org\/core\/product\/identifier\/S0007125024000308\/type\/journal_article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,23]]},"references-count":0,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2024,5]]}},"alternative-id":["S0007125024000308"],"URL":"https:\/\/doi.org\/10.1192\/bjp.2024.30","relation":{},"ISSN":["0007-1250","1472-1465"],"issn-type":[{"value":"0007-1250","type":"print"},{"value":"1472-1465","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,23]]},"assertion":[{"value":"Copyright \u00a9 The Author(s), 2024. Published by Cambridge University Press on behalf of Royal College of Psychiatrists","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"}]}}