Pharmacotherapeutic and pharmacogenetic features of patients with affective and schizophrenia spectrum disorders with non-suicidal self-injury
Abstract
Background . Nonsuicidal self-injury (NSSI) is a transdiagnostic clinical factor that may influence the choice of psychopharmacotherapy (PT) and patterns of treatment response. However, evidence on the association between NSSI and PT characteristics using real-world data (RWD) remains limited. The potential modifying role of genetic factors has also been insufficiently explored. Aim . To assess the impact of NSSI as a transdiagnostic phenomenon on PT features in patients with schizophrenia spectrum disorders (F2) and affective disorders (F3), and to analyze associations with polymorphisms in CYP2D6, CYP3A4, CYP3A5 and OPRM1. Methods . The study included 61 patients (median (Q1-Q3) age 21 (19–24) years; 54,5% female; 49,2% with F2; 75,4% reported lifetime NSSI). PT parameters were assessed based on medical records and clinical interviews. Current clinical status was evaluated using PANSS, CDSS, MADRS, UKU, and MARS. Pharmacogenetic testing was performed (genotyping of CYP2D6, CYP3A4, CYP3A5 polymorphisms) along with genotyping of OPRM1 rs1799971. Between-group comparisons were conducted using the Mann–Whitney U test and Pearson’s χ² test; general linear models (GLM) were applied to jointly evaluate the effects of NSSI and diagnostic group. Results . NSSI was associated with an earlier age at onset of the index disorder (p=0,002) and with longer mood stabilizer treatment (p=0,020 and p=0,013); GLM results supported the transdiagnostic nature of these associations. No between-group differences were observed in genotype frequencies for OPRM1/CYP2D6/CYP3A4/CYP3A5 or in CYP2D6 metabolic phenotype. Within the NSSI group, the minor allele of OPRM1 rs1799971 was associated with a shorter duration of antidepressant treatment (p=0,029), whereas the minor allele of CYP2D6 rs16947 (*2) — with a longer duration (p=0,039). Conclusion . According to RWD NSSI is associated with longer mood stabilizer treatment irrespective of diagnostic group. OPRM1 and CYP2D6 polymorphisms may be related to antidepressant treatment patterns in patients with NSSI.