title: DNA methylation profiles of the brain-derived neurotrophic factor (BDNF) gene as a potent diagnostic biomarker in major depression.
abstract: Major depression, because of its recurring and life-threatening nature, is one of the top 10 diseases for global disease burden. Major depression is still diagnosed on the basis of clinical symptoms in patients. The search for specific biological markers is of great importance to advance the method of diagnosis for depression. We examined the methylation profile of 2 CpG islands (I and IV) at the promoters of the brain-derived neurotrophic factor (BDNF) gene, which is well known to be involved in the pathophysiology of depression. We analyzed genomic DNA from peripheral blood of 20 Japanese patients with major depression and 18 healthy controls to identify an appropriate epigenetic biomarker to aid in the establishment of an objective system for the diagnosis of depression. Methylation rates at each CpG unit was measured using a MassArray® system (SEQUENOM), and 2-dimensional hierarchical clustering analyses were undertaken to determine the validity of these methylation profiles as a diagnostic biomarker. Analyses of the dendrogram from methylation profiles of CpG I, but not IV, demonstrated that classification of healthy controls and patients at the first branch completely matched the clinical diagnosis. Despite the small number of subjects, our results indicate that classification based on the DNA methylation profiles of CpG I of the BDNF gene may be a valuable diagnostic biomarker for major depression.
authors.affiliation: Division of Frontier Medicine, Department of Psychiatry and Neurosciences, Graduate School of Medical Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Fuchikami
authors.forename: Shigeru
authors.initials: S
authors.lastname: Morinobu
authors.forename: Masahiro
authors.initials: M
authors.lastname: Segawa
authors.forename: Yasumasa
authors.initials: Y
authors.lastname: Okamoto
authors.forename: Shigeto
authors.initials: S
authors.lastname: Yamawaki
authors.forename: Norio
authors.initials: N
authors.lastname: Ozaki
authors.forename: Takeshi
authors.initials: T
authors.lastname: Inoue
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kusumi
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Koyama
authors.forename: Kounosuke
authors.initials: K
authors.lastname: Tsuchiyama
authors.forename: Takeshi
authors.initials: T
authors.lastname: Terao
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D016022:Case-Control Studies; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D003865:Major Depressive Disorder / Q000175:diagnosis* / Q000235:genetics*; D044127:Epigenesis, Genetic / Q000235:genetics; D005091:Exons / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic / Q000235:genetics
chemical_list: D015415:Biomarkers; D019208:Brain-Derived Neurotrophic Factor