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Title		Authors	PubMed ID
1	Empathy, Defending, and Functional Connectivity While Witnessing Social Exclusion	McIver TA; Craig W; Bosma RL; Chiarella J; Klassen J; Sandra A; Goegan S; Booij L;	35659207 PSYCHOLOGY
2	DNA methylation differences in stress-related genes, functional connectivity and gray matter volume in depressed and healthy adolescents.	Chiarella J, Schumann L, Pomares FB, Frodl T, Tozzi L, Nemoda Z, Yu P, Szyf M, Khalid-Khan S, Booij L	32479312 PSYCHOLOGY
3	The Neuroscience of Sadness: A Multidisciplinary Synthesis and Collaborative Review for the Human Affectome Project.	Arias JA, Williams C, Raghvani R, Aghajani M, Baez S, Belzung C, Booij L, Busatto G, Chiarella J, Fu CH, Ibanez A, Liddell BJ, Lowe L, Penninx BWJH, Rosa P, Kemp AH	32001274 PSYCHOLOGY
4	Epigenetic Changes of FKBP5 as a Link Connecting Genetic and Environmental Risk Factors with Structural and Functional Brain Changes in Major Depression.	Tozzi L, Farrell C, Booij L, Doolin K, Nemoda Z, Szyf M, Pomares FB, Chiarella J, O'Keane V, Frodl T	29182159 PSYCHOLOGY
5	Functional connectivity across social inclusion and exclusion is related to peer victimization and depressive symptoms in young adults.	McIver TA, Bosma RL, Goegan S, Sandre A, Klassen J, Chiarella J, Booij L, Craig W	31078837 PSYCHOLOGY

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
Publication:	Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
Keywords:
PMID:	29182159	Category:	Neuropsychopharmacology	Date Added:	2019-06-20
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]

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