Akademik Veri Yönetim Sistemi
37th ECNP Congress 2024, Milan, İtalya, 21 - 24 Eylül 2024, ss.1
Background: The presence of obsessive-compulsive symptoms (OCS) in schizophrenia has long been recognised [1]. The fact that these symptoms are particularly common in schizophrenia patients treated with clozapine suggests a link between treatment-resistant schizophrenia and OCD [2]. Evidence from genetic studies of clozapine-associated OCD and treatment resistance suggests that polymorphisms in certain protein and receptor genes, such as BDNF, COMT, HTR2A, SLC6A4, GRIN2B and SLC1A1, may confer susceptibility to clozapine-induced OCD [3, 4, 5]. However, the genetic factors underlying this apparent non-random association remain unclear.
Objective: The aim of this study was to investigate the role of polymorphisms related to the BDNF, COMT, HTR2A and SLC6A4 genes, which have been found to confer susceptibility to the development of OCD and may be associated with treatment resistance or clozapine use in schizophrenia.
Methods: The study included 70 volunteers, from our clinic, aged 18-65 years who had been diagnosed with schizophrenia and were starting or planning to start clozapine treatment, had at least five years of education, and were of clinically normal intelligence. All participants were administered the Positive and Negative Syndrome Scale (PANSS) to assess the severity of schizophrenia symptoms, the Clinical Global Impression-Schizophrenia Scale (CGI-SS) to assess the patients' response to treatment, and the Yale-Brown Obsession-Compulsion Scale (YB-OCS) to assess the patients' obsessive-compulsive symptoms. Subsequently, 5 cc peripheral blood samples were collected from all participants for genetic analysis, and genetic analyses were performed to evaluate BDNF rs6265, COMT rs4680, SLC6A4 5-HTTLPR and rs25531, and HTR2A rs6313 single nucleotide polymorphisms, which are thought to be associated with OCS.
Results: No significant difference was found between participants with and without OCD symptoms in terms of sociodemographic characteristics and schizophrenia symptom severity. Upon analysis of genetic variations associated with obsessive-compulsive symptoms, it was found that carriers of the L allele for the SLC6A4 rs25531 polymorphism had lower YB-OCS scores than those who did not carry the L allele. Additionally, when the YB-OCS scores for the HTR2A gene rs6313 polymorphism were examined, it was observed that participants with the wild-type genotype had higher scores than those with the heterozygous and mutant genotypes; however, these results did not reach statistical significance (p>0. 05). The genotype and allele frequencies of BDNF rs6265, COMT rs4680 single nucleotide polymorphisms and SLC6A4 HTTLPR polymorphisms did not show a significant difference between participants with and without OCS, and the YB-OCS scores were similar between the polymorphism groups of these genes (p>0.05).
Conclusions: No association was found between OCS and the COMT rs4680, BDNF rs6265, SLC6A4 5-HTTLPR and rs25531 and HTR2A rs6313 polymorphisms observed in treatment-resistant schizophrenia patients. In order to clarify the relationship between treatment resistance and OCD in schizophrenia, larger prospective studies are needed in which the relationship between clozapine treatment and the onset of OCD can be evaluated in detail. Future studies with larger samples focusing on polymorphisms related to glutamatergic system genes such as GRIN2B and SLC1A1 will provide important information about the relationship between these disorders.
References
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No conflict of interest