PMID- 37020043
OWN - NLM
STAT- MEDLINE
DCOM- 20240115
LR  - 20240115
IS  - 1433-8491 (Electronic)
IS  - 0940-1334 (Print)
IS  - 0940-1334 (Linking)
VI  - 274
IP  - 1
DP  - 2024 Feb
TI  - Polygenetic risk scores and phenotypic constellations of obsessive-compulsive 
      disorder in clozapine-treated schizophrenia.
PG  - 181-193
LID - 10.1007/s00406-023-01593-y [doi]
AB  - 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.
CI  - (c) 2023. The Author(s).
FAU - Morgenroth, Carla Lou
AU  - Morgenroth CL
AUID- ORCID: 0000-0001-9048-5264
AD  - Department of Psychiatry and Neurosciences, Charite - Universitatsmedizin Berlin, 
      Corporate Member of Freie Universitat Berlin and Humboldt-Universitat Zu Berlin, 
      Berlin, Germany. carla-lou.morgenroth@charite.de.
FAU - Kleymann, Philipp
AU  - Kleymann P
AD  - Department of Psychiatry and Neurosciences, Charite - Universitatsmedizin Berlin, 
      Corporate Member of Freie Universitat Berlin and Humboldt-Universitat Zu Berlin, 
      Berlin, Germany.
FAU - Ripke, Stephan
AU  - Ripke S
AUID- ORCID: 0000-0003-3622-835X
AD  - Department of Psychiatry and Neurosciences, Charite - Universitatsmedizin Berlin, 
      Corporate Member of Freie Universitat Berlin and Humboldt-Universitat Zu Berlin, 
      Berlin, Germany.
FAU - Awasthi, Swapnil
AU  - Awasthi S
AUID- ORCID: 0000-0002-9692-8123
AD  - Department of Psychiatry and Neurosciences, Charite - Universitatsmedizin Berlin, 
      Corporate Member of Freie Universitat Berlin and Humboldt-Universitat Zu Berlin, 
      Berlin, Germany.
FAU - Wagner, Elias
AU  - Wagner E
AUID- ORCID: 0000-0002-7147-6167
AD  - Department of Psychiatry and Psychotherapy, University Hospital-LMU Munich, 
      Munich, Germany.
FAU - Oviedo-Salcedo, Tatiana
AU  - Oviedo-Salcedo T
AD  - Department of Psychiatry and Psychotherapy, University Hospital-LMU Munich, 
      Munich, Germany.
FAU - Okhuijsen-Pfeifer, Cynthia
AU  - Okhuijsen-Pfeifer C
AD  - Department of Psychiatry, University Medical Center Utrecht, Utrecht University, 
      Utrecht, The Netherlands.
FAU - Luykx, Jurjen J
AU  - Luykx JJ
AUID- ORCID: 0000-0002-6439-2774
AD  - Department of Psychiatry, University Medical Center Utrecht, Utrecht University, 
      Utrecht, The Netherlands.
AD  - Brain Center Rudolf Magnus, Department of Translational Neuroscience, University 
      Medical Center Utrecht, Utrecht, The Netherlands.
AD  - GGNet Mental Health, Warnsveld, The Netherlands.
FAU - van der Horst, Marte Z
AU  - van der Horst MZ
AD  - Department of Psychiatry, University Medical Center Utrecht, Utrecht University, 
      Utrecht, The Netherlands.
AD  - GGNet Mental Health, Warnsveld, The Netherlands.
FAU - Hasan, Alkomiet
AU  - Hasan A
AD  - Department of Psychiatry, Psychotherapy and Psychosomatics, Medical Faculty, 
      University of Augsburg, Bezirkskrankenhaus Augsburg, Augsburg, Germany.
FAU - Bermpohl, Felix
AU  - Bermpohl F
AD  - Department of Psychiatry and Neurosciences, Charite - Universitatsmedizin Berlin, 
      Corporate Member of Freie Universitat Berlin and Humboldt-Universitat Zu Berlin, 
      Berlin, Germany.
FAU - Gutwinski, Stefan
AU  - Gutwinski S
AD  - Department of Psychiatry and Neurosciences, Charite - Universitatsmedizin Berlin, 
      Corporate Member of Freie Universitat Berlin and Humboldt-Universitat Zu Berlin, 
      Berlin, Germany.
AD  - Department of Psychiatry, St. Hedwig-Krankenhaus, Charite-Universitatsmedizin, 
      Berlin, Germany.
FAU - Schreiter, Stefanie
AU  - Schreiter S
AUID- ORCID: 0000-0001-9598-0029
AD  - Department of Psychiatry and Neurosciences, Charite - Universitatsmedizin Berlin, 
      Corporate Member of Freie Universitat Berlin and Humboldt-Universitat Zu Berlin, 
      Berlin, Germany.
LA  - eng
PT  - Journal Article
PT  - Multicenter Study
DEP - 20230405
PL  - Germany
TA  - Eur Arch Psychiatry Clin Neurosci
JT  - European archives of psychiatry and clinical neuroscience
JID - 9103030
RN  - J60AR2IKIC (Clozapine)
SB  - IM
MH  - Humans
MH  - *Schizophrenia/drug therapy/genetics/diagnosis
MH  - *Clozapine/therapeutic use
MH  - Schizophrenic Psychology
MH  - *Obsessive-Compulsive Disorder/drug therapy/epidemiology/genetics
MH  - Comorbidity
MH  - Genetic Risk Score
MH  - Phenotype
PMC - PMC10786740
OTO - NOTNLM
OT  - Clozapine
OT  - OCD
OT  - PRS
OT  - Schizophrenia
COIS- The authors declare that they have no conflict of interest with regard to the 
      content of this report. 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.
EDAT- 2023/04/06 06:00
MHDA- 2024/01/15 12:42
PMCR- 2023/04/05
CRDT- 2023/04/05 23:22
PHST- 2022/11/03 00:00 [received]
PHST- 2023/03/14 00:00 [accepted]
PHST- 2024/01/15 12:42 [medline]
PHST- 2023/04/06 06:00 [pubmed]
PHST- 2023/04/05 23:22 [entrez]
PHST- 2023/04/05 00:00 [pmc-release]
AID - 10.1007/s00406-023-01593-y [pii]
AID - 1593 [pii]
AID - 10.1007/s00406-023-01593-y [doi]
PST - ppublish
SO  - Eur Arch Psychiatry Clin Neurosci. 2024 Feb;274(1):181-193. doi: 
      10.1007/s00406-023-01593-y. Epub 2023 Apr 5.