Altered DNA methylation status of human brain derived neurotrophis factor gene could be useful as biomarker of depression

Abstract

Brain-derived neurotrophic factor (BDNF) is involved in the survival, development, and synaptic plasticity of neurons. BDNF is believed to be associated with the pathophysiology of psychiatric disorders. Several studies have suggested the relevance of DNA methylation in its promoter region with depression. Here, we report different methylation statuses in groups with different depressive scores or undergoing different levels of job-stress. DNA samples were extracted from the saliva of 774 Japanese workers, and the methylation status was determined using the Illumina HumanMethylation 450 K Microarray. Depressive symptoms were measured using the Kessler's K6 questionnaire. Job-stress scales were assessed via a self-administered questionnaire. Independent DNA pools were formed based on K6 and job-strain scores, and the methylation levels were compared among these pools. The average DNA methylation rate was significantly decreased in the highest K6 score group compared to the lowest group (methylated signals, 14.2% vs. 16.5%, P = 2 · 16 × 10−198). This difference remained for the CpG island in the promoter region (10.4% vs. 5.8%, P = 3 · 67 × 10−133). Regarding the job-strain score, there was a slight increase in the methylation level of the whole gene in the group with the highest score compared to that with the lowest score; however, these groups showed no difference in the promoter region. Our results revealed significant changes in the DNA methylation status of the complete human BDNF gene in persons with depression compared to normal individuals, especially in the promoter region of exon 1. This indicates that DNA methylation in this gene is a promising biomarker for diagnosing depression. © 2014 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Published by Wiley Periodicals, Inc.

Peripheral leukocyte expression of the potential biomarker proteins Bdnf, Sirt1, and Psen1 is not regulated by promoter methylation in Alzheimer's disease patients

“…Increased DNA methylation at Bdnf gene promoter was observed in DNA from peripheral blood mononuclear cells of patients affected with major Page 10 of 20 A c c e p t e d M a n u s c r i p t 9 depression as compared to control subjects [34,35]. However, lower methylation levels in saliva DNA were associated with symptoms of depression in Japanese workers [36]. Bdnf promoter hypermethylation in blood DNA was found in bipolar disorder type II patients in comparison with controls and with bipolar disorder type I cases [37].…”

Promoter Methylation and <b><i>BDNF</i></b> and <b><i>DAT1</i></b> Gene Expression Profiles in Patients with Drug Addiction

“…Studies of the DNA methylation profiles of the CpG island of the BDNF gene have shown that this gene could be useful as a biomarker of major depression [13,28]. The BDNF gene has been implicated as a susceptible locus for addiction to multiple drugs of abuse, such as alcohol.…”

Epigenetic Changes Caused by Occupational Stress in Humans Revealed through Noninvasive Assessment of DNA Methylation of the Tyrosine Hydroxylase Gene

“…J-HOPE is a national level, large-scale occupational cohort study on social class and health in Japanese workers involving more than ten thousand employees representing a number of different industries [16][17][18][19]; the study was initiated in 2009 and designed as a 5-year follow-up survey. For the current study, workers of a major manufacturing company with offices spread all over Japan were recruited.…”

“…We previously investigated human mental health and its contributing factors in a large occupational cohort study (Japanese Study of Health, Occupation, and Psychosocial Factors Related Equity; J-HOPE) [16][17][18][19]. Since there is little evidence about epigenetic changes in the human TH gene in response to stress, we aimed to elucidate the DNA methylation state of the human TH gene in a non-invasive manner by referring to occupational cohort data that includes information on both validated stress markers [20][21][22] and a depression score [23,24].…”