DNA Methylation Profiles of the Brain-Derived Neurotrophic Factor (BDNF) Gene as a Potent Diagnostic Biomarker in Major Depression

• Published in: PloS one Vol. 6; no. 8; p. e23881
• Main Authors: Fuchikami, Manabu, Morinobu, Shigeru, Segawa, Masahiro, Okamoto, Yasumasa, Yamawaki, Shigeto, Ozaki, Norio, Inoue, Takeshi, Kusumi, Ichiro, Koyama, Tsukasa, Tsuchiyama, Kounosuke, Terao, Takeshi
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 2011; Public Library of Science (PLoS)
• Subjects: Adult; Analysis; Biology; Biomarkers; Biomarkers - metabolism; Brain; Brain-derived neurotrophic factor; Brain-Derived Neurotrophic Factor - genetics; Case-Control Studies; Classification; Cluster analysis; Clustering; CpG islands; CpG Islands - genetics; Deoxyribonucleic acid; Depressive Disorder, Major - diagnosis; Depressive Disorder, Major - genetics; Diagnosis; Diagnostic systems; DNA; DNA Methylation; Epigenesis, Genetic - genetics; Epigenetic inheritance; Exons - genetics; Female; Genes; Humans; Major depressive disorder; Male; Medical diagnosis; Medical schools; Medicine; Mental depression; Methylation; Middle Aged; Patients; Peripheral blood; Promoter Regions, Genetic - genetics; Psychotropic drugs; Two dimensional analysis; Japan
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0023881

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.