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Epigenetic Changes of FKBP5 as a Link Connecting Genetic and Environmental Risk Factors with Structural and Functional Brain Changes in Major Depression.

Author(s): Tozzi L, Farrell C, Booij L, Doolin K, Nemoda Z, Szyf M, Pomares FB, Chiarella J, O'Keane V, Frodl T

Neuropsychopharmacology. 2018 04;43(5):1138-1145 Authors: Tozzi L, Farrell C, Booij L, Doolin K, Nemoda Z, Szyf M, Pomares FB, Chiarella J, O'Keane V, Frodl T

Article GUID: 29182159
DNA methylation differences at the glucocorticoid receptor gene in depression are related to functional alterations in hypothalamic-pituitary-adrenal axis activity and to early life emotional abuse.

Author(s): Farrell C, Doolin K, O' Leary N, Jairaj C, Roddy D, Tozzi L, Morris D, Harkin A, Frodl T, Nemoda Z, Szyf M, Booij L, O'Keane V

Psychiatry Res. 2018 07;265:341-348 Authors: Farrell C, Doolin K, O' Leary N, Jairaj C, Roddy D, Tozzi L, Morris D, Harkin A, Frodl T, Nemoda Z, Szyf M, Booij L, O'Keane V

Article GUID: 29793048
Title:Epigenetic Changes of FKBP5 as a Link Connecting Genetic and Environmental Risk Factors with Structural and Functional Brain Changes in Major Depression.
Authors:Tozzi L,  Farrell C,  Booij L,  Doolin K,  Nemoda Z,  Szyf M,  Pomares FB,  Chiarella J,  O'Keane V,  Frodl T
Link:https://www.ncbi.nlm.nih.gov/pubmed/29182159?dopt=Abstract
DOI:10.1038/npp.2017.290
Category:Neuropsychopharmacology
PMID:29182159
Dept Affiliation: PSYCHOLOGY
1 Department of Psychiatry, Trinity College School of Medicine and Trinity College Institute of Neuroscience, Dublin, Ireland.
2 Department of Psychiatry, Otto von Guericke University Magdeburg, Magdeburg, Germany.
3 Department of Psychology, Concordia University, Montreal, Canada.
4 CHU Sainte-Justine Hospital Research Centre, University of Montreal, Montreal, Canada.
5 Department of Pharmacology and Therapeutics, McGill University, Montreal, Canada.

Description:

Epigenetic Changes of FKBP5 as a Link Connecting Genetic and Environmental Risk Factors with Structural and Functional Brain Changes in Major Depression.

Neuropsychopharmacology. 2018 04;43(5):1138-1145

Authors: Tozzi L, Farrell C, Booij L, Doolin K, Nemoda Z, Szyf M, Pomares FB, Chiarella J, O'Keane V, Frodl T

Abstract

The gene for the glucocorticoid receptor regulator FK506 binding protein 5 (FKBP5) plays a role for risk, response to treatment, and changes in brain areas in major depressive disorder (MDD). Chronic stress is associated with lower methylation of FKBP5. Our aim was to investigate whether methylation of FKBP5 reflected exposure to childhood adversity in MDD and controls and whether it was associated with structure and function of emotional processing regions. FKBP5 intron 7 GR response element region methylation and rs1360780 allelic status were assessed from whole blood in 56 MDD adults and 50 controls. Using magnetic resonance imaging, we assessed gray matter concentration of selected areas and their function during valence recognition of emotional images. Childhood adversity was investigated using the Childhood Trauma Questionnaire. In MDD patients carrying the high-risk T allele of rs1360780, lower methylation of FKBP5 was predicted by childhood adversity (F=4.95, p=0.04). In all participants, lower FKBP5 intron methylation levels were associated with reduced gray matter concentration in the inferior frontal orbital gyrus bilaterally (Wald chi-square=11.93, pFDR<0.01) and, in MDD, with its bilaterally higher activation during valence recognition (Wald chi-square=5.58, p=0.02). Activation of this region, regardless of side, was found to be lower in MDD compared to controls (Wald chi-square=3.88, p=0.049) and to be inversely correlated with depression severity (Wald chi-square=4.65, p=0.03). Our findings support the hypothesis that, in genetically predisposed individuals carrying a high-risk variant of the gene, childhood maltreatment might induce demethylation of FKBP5. This is in turn associated with structural and functional changes in the inferior frontal orbital gyrus, a relevant area for the clinical symptoms of MDD.

PMID: 29182159 [PubMed - indexed for MEDLINE]