This page was translated automatically from Turkish. Read the original

This page is an AI-assisted Turkish summary of the study presented at the 26th World Congress of Psychiatry. The study belongs to the presenting authors; please refer to the original source when citing it.

SO423

Uncovering genetic risk: the role of DRD3 and ABCB1 polymorphisms in clozapine-induced seizures in Asian Indian patients with treatment-resistant schizophrenia

UNCOVERING GENETIC RISK: ROLE OF DRD3 AND ABCB1 POLYMORPHISMS IN CLOZAPINE-INDUCED SEIZURES IN ASIAN INDIAN TREATMENT RESISTANT SCHIZOPHRENIA PATIENTS

The ABCB1 (rs1045462) polymorphism was not associated with the risk of clozapine-induced seizures, whereas the DRD3 (rs6280) polymorphism was significantly associated with seizures.

The aim was to investigate the role of ABCB1 (rs1045462) and DRD3 (rs6280) polymorphisms in seizure susceptibility among patients taking clozapine; information on risk factors for clozapine-induced seizures other than high doses is limited. The clinical records of 200 patients with treatment-resistant schizophrenia (TRS) receiving clozapine who had been genotyped for ABCB1 and DRD3 variants as part of another pharmacogenetic study were retrospectively reviewed for new-onset seizures following clozapine initiation. After excluding patients with pre-existing seizures, 187 patients were included in the analysis; Pearson's chi-square test and Cramér's V were used. According to the poster results, 3.7% of patients (7/187) developed clozapine-associated seizures (the conference abstract reported this number as 12; the poster tables show 7 patients). No significant association was found between ABCB1 genotype and seizures (wild-type CC 3/68, heterozygous CT 1/85, homozygous TT 3/34; chi-square = 4.074, df = 2, p = 0.130; Cramér's V = 0.148). In contrast, the DRD3 polymorphism was significantly associated with seizures (wild-type AA 5/49, heterozygous AG 2/122, homozygous GG 0/16; chi-square = 7.798, df = 2, p = 0.020; Cramér's V = 0.204). This effect size suggests a small-to-moderate genetic contribution, and the seizure burden was concentrated in the DRD3 wild-type and ABCB1 wild-type/homozygous groups. In the main study, 86.5% of patients (173/200) responded to treatment, ABCB1 and DRD3 genotype frequencies differed significantly between responders and nonresponders (p = 0.02 and 0.018), responders required a lower mean clozapine dose (232 versus 291 mg/day), and these factors explained up to 27% of the variability in clozapine dose. In conclusion, DRD3 emerges as a potential pharmacogenetic marker for predicting clozapine-induced seizures, suggesting that dopaminergic mechanisms may be more influential than drug transport mechanisms. However, because seizures occurred in only 7 patients, the findings are preliminary and require validation in larger samples.

All WCP 2026 summaries