HTR2A rs6313 polymorphic variant is associated with adverse effects to antipsychotics in adolescents with an acute psychotic episode

Background. Personalized prescription of antipsychotics is being actively studied today. But pharmacodynamic genetic factors have been studied to a lesser extent. Previously, a significant association of the HTR2A rs6313 polymorphic variant with the parameters of the efficacy and safety of antipsychotics in adult patients was established. Further research on this biomarker in adolescents who need to take antipsychotics for an acute psychotic episode is required. Methods. The study included 101 adolescents with an established diagnosis of acute polymorphic psychotic disorder at admission (F23.0-9 according to ICD-10). All patients received an antipsychotic medication as their primary therapy. The patients were followed-up for 14 days. The effectiveness of antipsychotics was assessed using the CGAS, PANSS, CGI-S, and CGI-I scales. The safety of pharmacotherapy was assessed using the UKU SERS, SAS, BARS scales. A scraping of the buccal epithelium was obtained from each patient, from which DNA was extracted by the sorbent method, and the carriage of the HTR2A rs6313 polymorphic variant (T102C) was detected by real-time polymerase chain reaction. Statistical analysis was carried out using the SPSS Statistics 21.0 software. Results. Patients with CC+CT genotypes more often complained of increased sleep duration (24.4% versus 0%; p=0.006) and tremor (35.9% versus 4.3%; p=0.003). Patients with CC+CT genotypes had significantly less severity of akathisia according to the BARS scale. Compared with TT homozygotes, the objective subscale BARS score (0 [0; 0] versus 0 [0; 1]; p=0.029) and the overall akathisia score (1 [1; 1] versus 1 [1; 2]; p=0.023) were lower. Analysis of the effectiveness of therapy depending on the HTR2A rs6313 carriage did not establish statistically significant differences. Carriers of CC+CT genotypes showed a lower PANSS “General symptoms" subscale score at the level of tendency to significance compared to TT homozygotes (28.37+7.64 versus 31.39+7.1; p=0.051). Conclusion. Carriers of the C allele HTR2A rs6313 were less likely to be associated with symptoms of akathisia. Carriers of the TT genotype were less likely to experience side effects that patients feel subjectively - tremor and increased sleep duration. There were no significant associations between HTR2A rs6313 and antipsychotic efficacy parameters.

HTR2A, pharmacogenetics, antipsychotics, HTR2A, acute psychotic episode, safety, efficacy