title: Childhood maltreatment and methylation of FK506 binding protein 5 gene (FKBP5).
abstract: A growing body of evidence suggests that alterations of the stress response system may be a mechanism by which childhood maltreatment alters risk for psychopathology. FK506 binding protein 51 (FKBP5) binds to the glucocorticoid receptor and alters its ability to respond to stress signaling. The aim of the present study was to examine methylation of the FKBP5 gene (FKBP5), and the role of an FKBP5 genetic variant, in relation to childhood maltreatment in a sample of impoverished preschool-aged children. One hundred seventy-four families participated in this study, including 69 with child welfare documentation of moderate to severe maltreatment in the past 6 months. The children, who ranged in age from 3 to 5 years, were racially and ethnically diverse. Structured record review and interviews in the home were used to assess a history of maltreatment, other traumas, and contextual life stressors; and a composite variable assessed the number exposures to these adversities. Methylation of two sites in intron 7 of FKBP5 was measured via sodium bisulfite pyrosequencing. Maltreated children had significantly lower levels of methylation at both CpG sites (p < .05). Lifetime contextual stress exposure showed a trend for lower levels of methylation at one of the sites, and a trend for an interaction with the FKBP5 polymorphism. A composite adversity variable was associated with lower levels of methylation at one of the sites as well (p < .05). FKBP5 alters glucocorticoid receptor responsiveness, and FKBP5 gene methylation may be a mechanism of the biobehavioral effects of adverse exposures in young children.
authors.affiliation: Butler Hospital.
authors.forename: Audrey R
authors.initials: AR
authors.lastname: Tyrka
authors.affiliation: Butler Hospital.
authors.forename: Kathryn K
authors.initials: KK
authors.lastname: Ridout
authors.affiliation: Brown University Alpert Medical School.
authors.forename: Stephanie H
authors.initials: SH
authors.lastname: Parade
authors.affiliation: Dartmouth College Geisel School of Medicine.
authors.forename: Alison
authors.initials: A
authors.lastname: Paquette
authors.affiliation: Dartmouth College Geisel School of Medicine.
authors.forename: Carmen J
authors.initials: CJ
authors.lastname: Marsit
authors.affiliation: Brown University Alpert Medical School.
authors.forename: Ronald
authors.initials: R
authors.lastname: Seifer
mesh_terms: D002649:Child Abuse / Q000523:psychology*; D002675:Child, Preschool; D019175:DNA Methylation / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; D011203:Poverty / Q000523:psychology*; D012306:Risk; D013315:Stress, Psychological / Q000378:metabolism*; D022021:Tacrolimus Binding Proteins / Q000235:genetics*; D000099159:Tacrolimus Binding Protein 5
chemical_list: D022021:Tacrolimus Binding Proteins; D000099159:Tacrolimus Binding Protein 5