BDNF methylation and mRNA expression in brain and blood of completed suicides in Slovenia

BACKGROUND: Suicide is a major public health problem. Worldwide, around 800000 people die by suicide every year. Suicide is a multifactorial disorder, with numerous environmental and genetic risk factors involved. Among the candidate genes, changes in the BDNF locus at the gene, epigenetic, mRNA, and protein expression levels have been implicated in psychiatric disorders, including suicidal behavior and completed suicides. AIM: To investigate changes in BDNF methylation and expression of four alternative BDNF transcripts for association with completed suicide. METHODS: This case-control study included 42 unrelated male Caucasian subjects, where 20 were control subjects who died following acute cardiac arrest, and 22 were suicide victims who died by hanging. DNA and RNA were extracted from brain tissue (Brodmann area 9 and hippocampus) and from blood. DNA methylation and mRNA expression levels were determined by targeted bisulfite next-generation sequencing and reverse-transcription quantitative PCR. Statistical analysis was done by use of two-tailed Student’s t tests for two independent samples, and the Benjamini-Hochberg procedure was implemented for correction for multiple comparisons. RESULTS: In DNA from brain tissue, there were no significant differences in BDNF methylation between the study groups. However, data showed significantly reduced DNA methylation of the BDNF region upstream of exon I in blood samples of suicide victims compared to the controls (5.67 ± 0.57 vs 6.83 ± 0.64, P(corr) = 0.01). In Brodmann area 9 of the brain of the suicide victims but not in their hippocampus, there was higher expression of BDNF transcript I-IX (NM_170731.4) compared to the controls (0.077 ± 0.024 vs 0.05 ± 0.013, P = 0.042). In blood, expression analysis for the BDNF transcripts was not feasible due to extensive RNA degradation. CONCLUSION: Despite the limitations of the study, the obtained data further support a role for BDNF in suicidality. However, it should be noted that suicidal behavior is a multifactorial disorder with numerous environmental and genetic risk factors involved.