The polymorphic variants DRD2, DRD3, and DRD4 are associated with early efficacy and safety of antipsychotics in adolescents with an acute psychotic episode

Ivaschenko D.V.: Russian Medical Academy of Continuing Professional Education, Penza Institute for Continuing Medical Education - Affiliate of the Russian Medical Academy of Continuing Professional Education

Fedina L.V.: Russian Medical Academy of Continuing Professional Education

Yudelievich D.A.: Sechenov First Moscow State Medical University

Buromskaya N.I.: Sukhareva Scientific and Practical Center for Mental Health of Children and Adolescents

Shimanov P.V.: Sukhareva Scientific and Practical Center for Mental Health of Children and Adolescents

Deitsch R.V.: Sukhareva Scientific and Practical Center for Mental Health of Children and Adolescents

Dorina I.V.: Sukhareva Scientific and Practical Center for Mental Health of Children and Adolescents

Akmalova K.A.: Russian Medical Academy of Continuing Professional Education

Kachanova A.A.: Russian Medical Academy of Continuing Professional Education

Grishina E.A.: Russian Medical Academy of Continuing Professional Education

Savchenko L.M.: Russian Medical Academy of Continuing Professional Education

Shevchenko Y.S.: Russian Medical Academy of Continuing Professional Education

Sychev D.A.: Russian Medical Academy of Continuing Professional Education

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Summary

Aim

To study associations of polymorphic variants of dopamine receptor genes with efficacy and safety parameters of antipsychotics in adolescents with an acute psychotic episode.

Material and methods

The prospective observational study included 101 adolescents diagnosed with acute polymorphic psychotic disorder at the time of admission. Patients were followed up for 14 days. All patients received an antipsychotic as their main therapy. The following scales were used to assess the efficacy and safety of therapy on day 14: CGAS, PANSS, CGI-S, CGI-I, UKU SERS, SAS, BARS. The determination of polymorphic variants of DRD2 (rs1800497, C>T), DRD3 (rs6280, C>T), DRD3 (rs324026, C>T), and DRD4 (rs1800955, C>T) genes was performed by real-time polymerase chain reaction (PCR).

Results

Carriers of the TT homozygote of the DRD3 rs6280 polymorphic variant had no significant change in the PANSS “Negative Symptoms” subscale score during treatment. Carriage of DRD2 rs1800497 CT+TT was associated with a more pronounced reduction in the PANSS subscale score “productive symptomatology” on day 14 compared with carriers of the CC genotype (-7.00 [-9; -5.75] vs. -6.00 [-8; -2]; p=0.008). Carriers of the TT DRD3 rs6280 homozygote had less intense dreams and subjective severity of adverse drug effects compared to carriers of the “wild” allele C. Carriers of the CT+TT DRD2 rs1800497 genotype had a higher mean SAS score relative to the CC genotype (2.00 [1; 3.25] vs. 1.00 [0; 2]; p=0.016). Haplotype analysis of the DRD3 polymorphic variants rs324026 and rs6280 showed no statistically significant associations with the efficacy and safety of treatment.

Conclusion

The DRD2 rs1800497 and DRD3 rs6280 polymorphic variants were significantly associated with the efficacy and safety of antipsychotics in adolescents with an acute psychotic episode.

Key words

Pharmacogenetics, antipsychotics, adoles- cents, DRD2, DRD3.