Associations of CYP3A4*22 and CYP3A5*3 with the effectiveness and safety of therapy for conduct disorder in children

Introduction . Polymorphisms of CYP3A4 and CYP3A5 genes are currently poorly understood as biomarkers of antipsychotic efficacy and safety. There are no studies of these factors in children taking antipsychotics for conduct disorder. Aim . To identify associations of CYP3A4*22 , CYP3A5*3 carriers with the effectiveness and safety of antipsychotics in children with conduct disorder Materials and methods . Eighty-four children aged 7–12 years hospitalised for conduct disorders were included in the study. All patients received antipsychotics for correction of conduct disorder. Observation was carried out for 14 days, the efficacy of pharmacotherapy was assessed using CGAS, CGI-S, CGI-I scales; safety was evaluated using the UKU SERS scale. All patients were genotyped for CYP3A4*22 (rs35599367) and CYP3A5*3 (rs776746) polymorphisms. Results . Carriers of the CYP3A5*1 (GA + AA) allele differed in lower severity of oppositional defiant behaviour on the CGI-S scale (3 [3; 4] vs. 4 [3; 4] points; p = 0.040) at the time of inclusion in the study. Also, CYP3A5*1 (GA + AA) was associated with less improvement on the CGI-I scale on day 5 (4 [3; 4] vs. 3 [3; 4] points; p = 0.026). CYP3A4*22 carriers reported a greater score on the UKU Mental Disorders subscale at day 5 (1 [0.25; 2] vs. 0 [0; 1], p = 0.026). Also, CYP3A4*22 carriers had higher scores on the UKU ‘Other HP’ subscale at 14 days (0 [0; 1] vs 0 [0; 0], p = 0.023). In carriers of the active CYP3A5*1 allele (genotypes GA + AA), the SAS scale score on day 5 was on average significantly higher compared to CYP3A5*3 GG carriers (0 [0; 1] vs 0 [0; 0] respectively, p = 0.019). Conclusion . It was found that carriers of the ‘wild’ allele of CYP3A5*1 responded worse to pharmacotherapy of conduct disorders after 5 days. Significant associations of CYP3A4*22 carriers with worse tolerability of pharmacotherapy were found.