title: Increased DNA methylation in the suicide brain.
abstract: Clinical studies find that childhood adversity and stressful life events in adulthood increase the risk for major depression and for suicide. The predispositions to either major depression or suicide are thought to depend on genetic risk factors or epigenetic effects. We investigated DNA methylation signatures postmortem in brains of suicides with diagnosis of major depressive disorder. DNA methylation levels were determined at single C-phosphate-G (CpG) resolution sites within ventral prefrontal cortex of 53 suicides and nonpsychiatric controls, aged 16 to 89 years. We found that DNA methylation increases throughout the lifespan. Suicides showed an 8-fold greater number of methylated CpG sites relative to controls (P < 2.2 x 10(-16)), with greater DNA methylation changes over and above the increased methylation observed in normal aging. This increased DNA methylation may be a significant contributor to the neuropathology and psychopathology underlying the risk of suicide in depression.
authors.affiliation: James J. Peters Veterans Affairs Medical Center; Fishberg Department of Neuroscience, Mount Sinai School of Medicine; Department of Psychiatry, Division of Molecular Imaging and Neuropathology, New York State Psychiatric Institute, Columbia University; New York, USA.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Haghighi
authors.affiliation: Department of Psychiatry, Division of Molecular Imaging and Neuropathology, New York State Psychiatric Institute, Columbia University; New York, USA.
authors.forename: Yurong
authors.initials: Y
authors.lastname: Xin
authors.affiliation: Department of Psychiatry, Division of Molecular Imaging and Neuropathology, New York State Psychiatric Institute, Columbia University; New York, USA.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Chanrion
authors.affiliation: Department of Psychiatry, Division of Molecular Imaging and Neuropathology, New York State Psychiatric Institute, Columbia University; New York, USA.
authors.forename: Anne H
authors.initials: AH
authors.lastname: O'Donnell
authors.affiliation: Department of Neurology, Icahn School of Medicine at Mount Sinai; New York, USA.
authors.forename: Yongchao
authors.initials: Y
authors.lastname: Ge
authors.affiliation: Department of Psychiatry, Division of Molecular Imaging and Neuropathology, New York State Psychiatric Institute, Columbia University; New York, USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Dwork
authors.affiliation: Department of Psychiatry, Division of Molecular Imaging and Neuropathology, New York State Psychiatric Institute, Columbia University; New York, USA.
authors.forename: Victoria
authors.initials: V
authors.lastname: Arango
authors.affiliation: Department of Psychiatry, Division of Molecular Imaging and Neuropathology, New York State Psychiatric Institute, Columbia University; New York, USA.
authors.forename: J John
authors.initials: JJ
authors.lastname: Mann
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000375:Aging; D001921:Brain / Q000473:pathology / Q000503:physiopathology*; D019175:DNA Methylation / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D019964:Mood Disorders / Q000523:psychology*; D013405:Suicide; D055815:Young Adult
keywords: DNA methylation; aging; depression; epigenetics; mood disorder; suicide