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Title: Child Abuse, Depression, and Methylation in Genes Involved With Stress, Neural Plasticity, and Brain Circuitry
Authors: Weder, Natalie
Zhang, Huiping
Jensen, Kevin
Yang, Bao Zhu
Simen, Arthur
Jackowski, Andrea [UNIFESP]
Lipschitz, Deborah
Douglas-Palumberi, Heather
Ge, Margrat
Perepletchikova, Francheska
O'Loughlin, Kerry
Hudziak, James J.
Gelernter, Joel
Kaufman, Joan
Yale Univ
Universidade Federal de São Paulo (UNIFESP)
Univ Vermont
Keywords: child abuse
Issue Date: 1-Apr-2014
Publisher: Elsevier B.V.
Citation: Journal of the American Academy of Child and Adolescent Psychiatry. Amsterdam: Elsevier B.V., v. 53, n. 4, p. 417-424, 2014.
Abstract: Objectives: To determine whether epigenetic markers predict dimensional ratings of depression in maltreated children. Method: A genome-wide methylation study was completed using the Iliumina 450K BeadChip array in 94 maltreated and 96 healthy nontraumatized children with saliva-derived DNA. the 450K BeadChip does not include any methylation sites in the exact location as sites in candidate genes previously examined in the literature, so a test for replication of prior research findings was not feasible. Results: Methylation in 3 genes emerged as genome-wide-significant predictors of depression: DNA-Binding Protein Inhibitor ID-3 (ID3); Glutamate Receptor, Ionotropic N-methy1-D-aspartate (NMDA) 1 (GRIM); and Tubulin Polymerization Promoting Protein (TPPP) (p <5.0 x 10(-7), all analyses). These genes are all biologically relevant with ID3 involved in the stress response, GRIM involved in neural plasticity, and TPPP involved in neural circuitry development. Methylation in CpG sites in candidate genes were not predictors of depression at significance levels corrected for whole genome testing, but maltreated and control children did have significantly different 13 values after Bonferroni correction at multiple methylation sites in these candidate genes (e.g., BDNF, NR3C1, FKBP5). Conclusions: This study suggests that epigenetic changes in ID3, GRIN1, and TPPP genes, in combination with experiences of maltreatment, may confer risk for depression in children. the study adds to a growing body of literature supporting a role for epigenetic mechanisms in the pathophysiology of stress-related psychiatric disorders. Although epigenetic changes are frequently long lasting, they are not necessarily permanent. Consequently, interventions to reverse the negative biological and behavioral sequelae associated with child maltreatment are briefly discussed.
ISSN: 0890-8567
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