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This study aimed to analyze prevalence of OCS and obsessive\u2013compulsive disorder (OCD) in this subgroup and find possible correlations with different phenotypes. Additionally, this is the first study to examine polygenetic risk scores (PRS) in individuals with SCZ and OCS. A multicenter cohort of 91 individuals with SCZ who were treated with CLZ was recruited and clinically and genetically assessed. Symptom severity was examined using the Positive and Negative Symptom Scale (PANSS), Clinical Global Impression Scale (CGI), the Calgary Depression Scale for Schizophrenia (CDSS), Global Assessment of Functioning Scale (GAF) and Yale\u2013Brown Obsessive\u2013Compulsive Scale (Y-BOCS). Participants were divided into subgroups based on phenotypic OCS or OCD using Y-BOCS scores. Genomic-wide data were generated, and PRS analyses were performed to evaluate the association between either phenotypic OCD or OCS severity and genotype-predicted predisposition for OCD, SCZ, cross-disorder, and CLZ\/norclozapine (NorCLZ) ratio, CLZ metabolism and NorCLZ metabolism. OCS and OCD were frequent comorbidities in our sample of CLZ-treated SCZ individuals, with a prevalence of 39.6% and 27.5%, respectively. Furthermore, the Y-BOCS total score correlated positively with the duration of CLZ treatment in years (<jats:italic>r<\/jats:italic>\u2009=\u20090.28; <jats:italic>p<\/jats:italic>\u2009=\u20090.008) and the PANSS general psychopathology subscale score (<jats:italic>r<\/jats:italic>\u2009=\u20090.23; <jats:italic>p<\/jats:italic>\u2009=\u20090.028). A significant correlation was found between OCD occurrence and PRS for CLZ metabolism. We found no correlation between OCS severity and PRS for CLZ metabolism. We found no correlation for either OCD or OCS and PRS for OCD, cross-disorder, SCZ, CLZ\/NorCLZ ratio or NorCLZ metabolism. Our study was able to replicate previous findings on clinical characteristics of CLZ-treated SCZ individuals. OCS is a frequent comorbidity in this cohort and is correlated with CLZ treatment duration in years and PANSS general psychopathology subscale score. We found a correlation between OCD and PRS for CLZ metabolism, which should be interpreted as incidental for now. Future research is necessary to replicate significant findings and to assess possible genetic predisposition of CLZ-treated individuals with SCZ to OCS\/OCD. Limitations attributed to the small sample size or the inclusion of subjects on co-medication must be considered. If the association between OCD and PRS for CLZ metabolism can be replicated, it should be further evaluated if CYP1A2 alteration, respectively lower CLZ plasma level, is relevant for OCD development.<\/jats:p>","DOI":"10.1007\/s00406-023-01593-y","type":"journal-article","created":{"date-parts":[[2023,4,5]],"date-time":"2023-04-05T17:30:21Z","timestamp":1680715821000},"page":"181-193","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Polygenetic risk scores and phenotypic constellations of obsessive\u2013compulsive disorder in clozapine-treated schizophrenia"],"prefix":"10.1007","volume":"274","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9048-5264","authenticated-orcid":false,"given":"Carla Lou","family":"Morgenroth","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp","family":"Kleymann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3622-835X","authenticated-orcid":false,"given":"Stephan","family":"Ripke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9692-8123","authenticated-orcid":false,"given":"Swapnil","family":"Awasthi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7147-6167","authenticated-orcid":false,"given":"Elias","family":"Wagner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana","family":"Oviedo-Salcedo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia","family":"Okhuijsen-Pfeifer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6439-2774","authenticated-orcid":false,"given":"Jurjen J.","family":"Luykx","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marte Z.","family":"van der Horst","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alkomiet","family":"Hasan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix","family":"Bermpohl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Gutwinski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9598-0029","authenticated-orcid":false,"given":"Stefanie","family":"Schreiter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,4,5]]},"reference":[{"key":"1593_CR1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2014\/317980","volume":"2014","author":"M Zink","year":"2014","unstructured":"Zink M (2014) Comorbid obsessive\u2013compulsive symptoms in schizophrenia: insight into pathomechanisms facilitates treatment. 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A. Hasan has received paid speakerships from Janssen, Recordati, Otsuka, and Lundbeck. He was a member of Roche, Otsuka, Lundbeck, Recordati, Rovi, and Janssen advisory boards. He is editor of the WFSBP and the German AWMF-S3 schizophrenia guidelines.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interests"}},{"value":"Written informed consent was obtained from all individual participants included in the study.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"The study has been approved by the appropriate ethics committee and has therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. All persons gave their informed consent prior to their inclusion in the study. Approval was granted by the Ethics Committee of the University Hospital of Munich (LMU Munich) (Reference number 458-16) and the ethics committee of the University Medical Center Utrecht (Reference numbers 15-306\/15-312).","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical standards"}}]}}