Epigenetics in Suicide and Depression

  • Anita E. Autry
    Department of Psychiatry, The University of Texas Southwestern Medical Center, Dallas, Texas
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  • Lisa M. Monteggia
    Address correspondence to Lisa M. Monteggia, Ph.D., Department of Psychiatry, The University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9070
    Department of Psychiatry, The University of Texas Southwestern Medical Center, Dallas, Texas
    Search for articles by this author
      Underlying causes of major depressive disorder (MDD) remain an enigma. A major gain of uncovering mechanisms leading to this devastating disorder will be the prevention of suicide, the worst outcome of MDD. In the search to understand the neurobiology of MDD, several promising hypotheses have been formulated. These hypotheses are largely focused on alterations in monoaminergic neurotransmission, trophic factor signaling, neurogenesis, and glial development and transport. However, recent evidence may potentially bring together all of these hypotheses and offer a basis for understanding the complexity of MDD. This process involves epigenetic gene regulation and provides a nexus for gene/environment interaction, both of which are known to increase the risk for MDD. In addition, epigenetic mechanisms are accessible therapeutic targets that are already in development for many diverse diseases, including certain types of cancer and neurodegenerative disorders.
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        • Waddington C.H.
        The Strategy of Genes.
        Macillan, New York1957
        • Poulter M.O.
        • Du L.
        • Weaver I.C.
        • Palkovits M.
        • Faludi G.
        • Merali Z.
        • et al.
        GABAA receptor promoter hypermethylation in suicide brain: Implications for the involvement of epigenetic processes.
        Biol Psychiatry. 2008; 64: 645-652
        • Dwivedi Y.
        • Rizavi H.S.
        • Conley R.R.
        • Roberts R.C.
        • Tamminga C.A.
        • Pandey G.N.
        Altered gene expression of brain-derived neurotrophic factor and receptor tyrosine kinase B in postmortem brain of suicide subjects.
        Arch Gen Psychiatry. 2003; 60: 804-815
        • Karege F.
        • Perret G.
        • Bondolfi G.
        • Schwald M.
        • Bertschy G.
        • Aubry J.M.
        Decreased serum brain-derived neurotrophic factor levels in major depressed patients.
        Psychiatry Res. 2002; 109: 143-148
        • Ernst C.
        • Deleva V.
        • Deng X.
        • Sequeira A.
        • Pomarenski A.
        • Klempan T.
        • et al.
        Alternative splicing, methylation state, and expression profile of tropomyosin-related kinase B in the frontal cortex of suicide completers.
        Arch Gen Psychiatry. 2009; 66: 22-32
        • Fuchikami M.
        • Morinobu S.
        • Kurata A.
        • Yamamoto S.
        • Yamawaki S.
        Single immobilization stress differentially alters the expression profile of transcripts of the brain-derived neurotrophic factor (BDNF) gene and histone acetylation at its promoters in the rat hippocampus.
        Int J Neuropsychopharmacol. 2009; 12: 73-82
        • Tsankova N.M.
        • Berton O.
        • Renthal W.
        • Kumar A.
        • Neve R.L.
        • Nestler E.J.
        Sustained hippocampal chromatin regulation in a mouse model of depression and antidepressant action.
        Nat Neurosci. 2006; 9: 519-525
        • Mann J.J.
        The neurobiology of suicide.
        Nat Med. 1998; 4: 25-30
        • Du L.
        • Faludi G.
        • Palkovits M.
        • Demeter E.
        • Bakish D.
        • Lapierre Y.D.
        • et al.
        Frequency of long allele in serotonin transporter gene is increased in depressed suicide victims.
        Biol Psychiatry. 1999; 46: 196-201