Influence of Antidepressant Drugs on DNA Methylation of Ion Channels Genes in Blood Cells of Psychiatric Patients

Abstract

Aim: This study investigated the influence of antidepressant drugs on methylation status of KCNE1, KCNH2 and SCN5A promoters and ECG parameters in adult psychiatric patients. Materials & methods: Electrocardiographic evaluation (24 h) and blood samples were obtained from 34 psychiatric patients before and after 30 days of antidepressant therapy. Methylation of promoter CpG sites of KCNE1, KCNH2 and SCN5A was analyzed by pyrosequencing. Results: Three CpG and four CpG sites of KCNE1 and SCN5A, respectively, had increased % methylation after treatment. Principal component analysis showed correlations of the methylation status with electrocardiographic variables, antidepressant doses and patient age. Conclusion: Short-term treatment with antidepressant drugs increase DNA methylation in KCNE1 and SCN5A promoters, which may induce ECG alterations in psychiatric patients.

Graphical abstract

Keywords::

• antidepressant drugs
• cardiac arrhythmias
• DNA methylation
• pharmacoepigenetics
• pyrosequencing

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/epi-2022-0089

Author contributions

LV Nascimento: patient selection and data collection, execution of experimental procedures, manuscript writing. F Lotufo Neto: psychiatry clinic coordinator, support in patient selection. DA Ribeiro Moreira and V Braga Cerutti: Holter and electrocardiographic analyses. H Thurow: patient selection and data collection. G Medeiros Bastos: scientific and technical support in the development of the project. E Batista Ferreira: statistical analyses, figure preparation. RD Crespo Hirata: critical revision of the manuscript, figure preparation. M Hiroyuki Hirata: conception and design of the project, critical revision of the manuscript.

Acknowledgments

The authors thank Leda Leme Talib for technical support in measurements of plasma concentration of psychotropic drugs.

Financial & competing interests disclosure

This work was supported by grants from FAPESP (#2016/12899-6), CNPq (#302733/2016-7) and CAPES (#Code 001). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The study protocol was approved by the ethics committees of the School of Pharmaceutical Sciences of the University of Sao Paulo (CAAE 60179516.1.3002.0067), School of Medicine of the University of Sao Paulo (CAAE 60179516.1.0000.0068), and Institute Dante Pazzanese of Cardiology (CAAE 60179516.1.3001.5462), Sao Paulo, Brazil. All subjects signed an approved written informed consent before enrollment.

Additional information

Funding

This work was supported by grants from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) (#2016/12899-6), Conselho Nacional de Desenvolvimento Cient�fico e Tecnol�gico (CNPq) (#302733/2016-7) and Committee on the Academic and Professional Evaluation of Students (CAPES) (#Code 001). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.