Aberrant alternative splicing of HTR2A exon II in peripheral blood lymphocytes of drug-naïve schizophrenic patients

Maria N Grunina; Mariia A Belinskaia; Alexander S Zhuravlev; Regina F Nasyrova; Evgeny M Krupitsky; Anastasiya E Taraskina; Anna M Zabotina

doi:10.1016/j.heliyon.2020.e05809

Aberrant alternative splicing of HTR2A exon II in peripheral blood lymphocytes of drug-naïve schizophrenic patients

Heliyon. 2020 Dec 24;6(12):e05809. doi: 10.1016/j.heliyon.2020.e05809. eCollection 2020 Dec.

Authors

Maria N Grunina¹, Mariia A Belinskaia¹, Alexander S Zhuravlev¹, Regina F Nasyrova², Evgeny M Krupitsky^{3

2}, Anastasiya E Taraskina^{1

3

2}, Anna M Zabotina^{1

3}

Affiliations

¹ Laboratory of Molecular Human Genetics, Petersburg Nuclear Physics Institute Named by B.P.Konstantinov of National Research Centre "Kurchatov Institute", 1 Microdistrict Orlova roshcha, Leningradskaya Oblast, Gatchina, 188300, Russia.
² Department of Personalized Psychiatry and Neurology and Department of Addiction, V.M. Bekhterev National Medical Research Center Psychiatry and Neurology, ul. Bekhterev 3, Saint Petersburg, 192019, Russia.
³ Department of Molecular Genetics and Nanobiological Technologies, Pavlov First Saint Petersburg State Medical University, L`va Tolstogo str. 6/8, Saint Petersburg, 197022, Russia.

Abstract

The aim of the study was to characterize the pattern of transcript isoforms of HTR2A exon II in lymphocytes of the blood as peripheral biomarkers of schizophrenia development and the effectiveness of antipsychotic therapy. We primarily observed an increase in mRNA levels and elevation of alternative variants in a sample of drug-naïve schizophrenic patients compared to the control group. There was no association of the expression level of HTR2A transcript isoforms with the effectiveness of the antipsychotic therapy. Antipsychotic-induced akathisia was associated with a significant reduction in the mRNA levels of the studied isoforms. In summary, our results suggest that levels of HTR2A exon II transcript isoforms are upregulated in patients with schizophrenia, but at the same time, elevated expression level of the studied HTR2A transcripts is associated with fewer side effects of the therapy.

Keywords: Alternative splicing; Antipsychotic drugs; HTR2A; Peripheral blood lymphocytes; Schizophrenia; Transcript isoforms.