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

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Title: Polygenetic risk scores and phenotypic constellations of obsessive–compulsive disorder in clozapine-treated schizophrenia.
Authors: Morgenroth, Carla Lou (AUTHOR), Kleymann, Philipp (AUTHOR), Ripke, Stephan (AUTHOR), Awasthi, Swapnil (AUTHOR), Wagner, Elias (AUTHOR), Oviedo-Salcedo, Tatiana (AUTHOR), Okhuijsen-Pfeifer, Cynthia (AUTHOR), Luykx, Jurjen J. (AUTHOR), van der Horst, Marte Z. (AUTHOR), Hasan, Alkomiet (AUTHOR), Bermpohl, Felix (AUTHOR), Gutwinski, Stefan (AUTHOR), Schreiter, Stefanie (AUTHOR)
Source: European Archives of Psychiatry & Clinical Neuroscience. Feb2024, Vol. 274 Issue 1, p181-193. 13p.
Subjects: Disease risk factors, Obsessive-compulsive disorder, Pathological psychology, Phenotypes, Schizophrenia
Abstract: Obsessive–compulsive symptoms (OCS) are frequently observed in individuals with schizophrenia (SCZ) treated with clozapine (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 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 (r = 0.28; p = 0.008) and the PANSS general psychopathology subscale score (r = 0.23; p = 0.028). 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. [ABSTRACT FROM AUTHOR]
Copyright of European Archives of Psychiatry & Clinical Neuroscience is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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  Data: Polygenetic risk scores and phenotypic constellations of obsessive–compulsive disorder in clozapine-treated schizophrenia.
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  Data: <searchLink fieldCode="AR" term="%22Morgenroth%2C+Carla+Lou%22">Morgenroth, Carla Lou</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Kleymann%2C+Philipp%22">Kleymann, Philipp</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Ripke%2C+Stephan%22">Ripke, Stephan</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Awasthi%2C+Swapnil%22">Awasthi, Swapnil</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Wagner%2C+Elias%22">Wagner, Elias</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Oviedo-Salcedo%2C+Tatiana%22">Oviedo-Salcedo, Tatiana</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Okhuijsen-Pfeifer%2C+Cynthia%22">Okhuijsen-Pfeifer, Cynthia</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Luykx%2C+Jurjen+J%2E%22">Luykx, Jurjen J.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22van+der+Horst%2C+Marte+Z%2E%22">van der Horst, Marte Z.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Hasan%2C+Alkomiet%22">Hasan, Alkomiet</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Bermpohl%2C+Felix%22">Bermpohl, Felix</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Gutwinski%2C+Stefan%22">Gutwinski, Stefan</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Schreiter%2C+Stefanie%22">Schreiter, Stefanie</searchLink> (AUTHOR)
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  Data: <searchLink fieldCode="JN" term="%22European+Archives+of+Psychiatry+%26+Clinical+Neuroscience%22">European Archives of Psychiatry & Clinical Neuroscience</searchLink>. Feb2024, Vol. 274 Issue 1, p181-193. 13p.
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  Data: Obsessive–compulsive symptoms (OCS) are frequently observed in individuals with schizophrenia (SCZ) treated with clozapine (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 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 (r = 0.28; p = 0.008) and the PANSS general psychopathology subscale score (r = 0.23; p = 0.028). 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. [ABSTRACT FROM AUTHOR]
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  Data: <i>Copyright of European Archives of Psychiatry & Clinical Neuroscience is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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              Text: Feb2024
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