Case Control Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Psychiatr. Dec 19, 2021; 11(12): 1301-1313
Published online Dec 19, 2021. doi: 10.5498/wjp.v11.i12.1301
BDNF methylation and mRNA expression in brain and blood of completed suicides in Slovenia
Sandra Ropret, Katarina Kouter, Tomaž Zupanc, Alja Videtic Paska
Sandra Ropret, Katarina Kouter, Alja Videtic Paska, Institute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, Ljubljana SI-1000, Slovenia
Tomaž Zupanc, Institute of Forensic Medicine, Faculty of Medicine, University of Ljubljana, Ljubljana SI-1000, Slovenia
Author contributions: Videtic Paska A and Ropret S designed the study and the experiments; Zupanc T collected patient data, brain tissue, and blood samples; Ropret S performed the majority of experiments, analyzed the data, and wrote the manuscript; Kouter K performed DNA extraction, bisulfite conversion of DNA, and helped with RNA extraction; Videtic Paska A corrected the manuscript; all the authors approved the final version of the manuscript.
Supported by Slovenian Research Agency, No. P1-0390, and No. J3-7132.
Institutional review board statement: The study was reviewed and approved by the Medicinal Ethics Committee of the Republic of Slovenia, No. 47/12/12.
Informed consent statement: The samples included in the study are post mortem samples collected during the course of autopsy at the Institute of Forensic Medicine, University of Ljubljana. The collected samples were used for routine analyses associated with the autopsy as well as for the molecular-genetic analyses. In Slovenia use of post mortem samples does not include use of informed consent, but the collection and use of the samples has to be approved by the Medicinal Ethics Committee of the Republic of Slovenia. For the collected samples the approval of the Medicinal Ethics Committee is attached.
Conflict-of-interest statement: None to declare.
Data sharing statement: No additional data are available.
STROBE statement: The authors have read the STROBE Statement—checklist of items, and the manuscript was prepared and revised according to the STROBE Statement—checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Alja Videtic Paska, PhD, Associate Professor, Institute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, Vrazov trg 2, Ljubljana SI-1000, Slovenia. alja.videtic@mf.uni-lj.si
Received: March 16, 2021
Peer-review started: March 16, 2021
First decision: May 5, 2021
Revised: May 25, 2021
Accepted: September 16, 2021
Article in press: September 16, 2021
Published online: December 19, 2021
Processing time: 273 Days and 13.3 Hours
ARTICLE HIGHLIGHTS
Research background

Suicidal behavior is a complex behavior with multifactorial etiology. Despite the large body of work, the full mechanism of suicidal behavior is not known. There are however strong indicators that changes in epigenetic mechanisms, specifically DNA methylation, can be an important factor.

Research motivation

Brain derived neurotrophic factor, BDNF, plays an important role in brain plasticity, and therefore it could be involved in modulation of suicidal behavior. Molecular-genetic data from a population with a high suicide rate could contribute to deeper understanding of the biological background of suicide.

Research objectives

The objective of our study was to investigate BDNF at two levels: DNA methylation and gene expression. As DNA methylation and gene expression can be highly tissue specific, we included two different brain regions and also blood as a peripheral tissue that is more easily accessible.

Research methods

Altogether, 42 subjects were included in the study (20 control subjects and 22 suicide victims). Samples of brain (hippocampus and Brodmann area 9) and blood were obtained during routine autopsy. We used targeted bisulfite sequencing to assess the DNA methylation level of five BDNF regions of interest (I1, I2, II, IV, and VI), and quantitative PCR to determine gene expression of four BDNF transcripts.

Research results

When comparing suicide victims and control group, we observed no significant changes in BDNF DNA methylation level in the brain. Changes were observed in blood, where suicide victims exhibited lower mean DNA methylation level of BDNF region I2 compared to the control group. In gene expression analysis, one BDNF transcript (NM_170731.4.) was upregulated in Brodmann area 9 of suicide victims compared to the control group.

Research conclusions

Due to tissue associated limitation, a complete insight into BDNF changes was not possible, namely inspection of blood BDNF expression level. Still, we observed changes both in DNA methylation level in blood and gene expression in brain, indicating the possible association of BDNF with suicidal behavior.

Research perspectives

Data from this study was obtained from a Slovenian population, which has a high suicide risk. The findings are thus an important contribution to a better understanding of the biological basis of suicidal behavior and the involvement of neurotrophic factors such as BDNF.