Polygenetic risk scores and phenotypic constellations of obsessive–compulsive disorder in clozapine-treated schizophrenia

  • Obsessive–compulsive symptoms (OCS) are frequently observed in individuals with schizophrenia (SCZ) treated with clo- zapine (CLZ). This study aimed to analyze prevalence of OCS and obsessive–compulsive 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–Brown Obsessive–Compulsive 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 theObsessive–compulsive symptoms (OCS) are frequently observed in individuals with schizophrenia (SCZ) treated with clo- zapine (CLZ). This study aimed to analyze prevalence of OCS and obsessive–compulsive 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–Brown Obsessive–Compulsive 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 metabo- lism. 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 (r = 0.28; p = 0.008) and the PANSS general psychopathology subscale score (r = 0.23; p = 0.028). A significant cor- relation 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 dura- tion 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.show moreshow less

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Metadaten
Author:Carla Lou Morgenroth, Philipp Kleymann, Stephan Ripke, Swapnil Awasthi, Elias WagnerGND, Tatiana Oviedo-Salcedo, Cynthia Okhuijsen-Pfeifer, Jurjen J. Luykx, Marte Z. van der Horst, Alkomiet HasanORCiDGND, Felix Bermpohl, Stefan Gutwinski, Stefanie Schreiter
URN:urn:nbn:de:bvb:384-opus4-1045971
Frontdoor URLhttps://opus.bibliothek.uni-augsburg.de/opus4/104597
ISSN:0940-1334OPAC
ISSN:1433-8491OPAC
Parent Title (English):European Archives of Psychiatry and Clinical Neuroscience
Publisher:Springer Science and Business Media LLC
Place of publication:Berlin
Type:Article
Language:English
Year of first Publication:2024
Publishing Institution:Universität Augsburg
Release Date:2023/05/25
Tag:Pharmacology (medical); Biological Psychiatry; Psychiatry and Mental health; General Medicine
Volume:274
First Page:181
Last Page:193
DOI:https://doi.org/10.1007/s00406-023-01593-y
Institutes:Medizinische Fakultät
Medizinische Fakultät / Lehrstuhl für Psychiatrie und Psychotherapie
Medizinische Fakultät / Professur für Evidenzbasierte Psychiatrie und Psychotherapie
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):CC-BY 4.0: Creative Commons: Namensnennung (mit Print on Demand)