title: Oxytocin Receptor Genetic and Epigenetic Variations: Association With Child Abuse and Adult Psychiatric Symptoms.
abstract: Childhood abuse can alter biological systems and increase risk for adult psychopathology. Epigenetic mechanisms, alterations in DNA structure that regulate the gene expression, are a potential mechanism underlying this risk. While abuse associates with methylation of certain genes, particularly those in the stress response system, no study to date has evaluated abuse and methylation of the oxytocin receptor (OXTR). However, studies support a role for OXTR in the link between abuse and adverse adult outcomes, showing that abuse can confer greater risk for psychiatric symptoms in those with specific OXTR genotypes. This study therefore sought to (a) assess the role of epigenetics in the link between abuse and psychopathology and (b) begin to integrate the genetic and epigenetic literature by exploring associations between OXTR genotypes and DNA CpG methylation. Data on 18 OXTR CpG sites, 44 single nucleotide polymorphisms, childhood abuse, and adult depression and anxiety symptoms were assessed in 393 African American adults (age = 41 ± 12.8 years). Overall, 68% of genotypes were associated with methylation of nearby CpG sites, with a subset surviving multiple test correction. Child abuse associated with higher methylation of two CpG sites yet did not survive correction or serve as a mediator of psychopathology. However, abuse interacted with CpG methylation to predict psychopathology. These findings suggest a role for OXTR in understanding the influence of early environments on adult psychiatric symptoms.
authors.affiliation: Emory University.
authors.forename: Erica L
authors.initials: EL
authors.lastname: Smearman
authors.affiliation: Emory University School of Medicine.
authors.forename: Lynn M
authors.initials: LM
authors.lastname: Almli
authors.affiliation: Emory University School of Medicine.
authors.forename: Karen N
authors.initials: KN
authors.lastname: Conneely
authors.affiliation: Emory University.|University of Georgia.
authors.forename: Gene H
authors.initials: GH
authors.lastname: Brody
authors.affiliation: Emory University.|University of Georgia.
authors.forename: Jessica M
authors.initials: JM
authors.lastname: Sales
authors.affiliation: Emory University School of Medicine.|Department of Veterans Affairs Medical Center.
authors.forename: Bekh
authors.initials: B
authors.lastname: Bradley
authors.affiliation: Emory University.|McLean Hospital, Harvard Medical School.
authors.forename: Kerry J
authors.initials: KJ
authors.lastname: Ressler
authors.affiliation: Emory University School of Medicine.
authors.forename: Alicia K
authors.initials: AK
authors.lastname: Smith
mesh_terms: D000293:Adolescent; D000328:Adult; D054523:Adult Survivors of Child Abuse; D001741:Black or African American / Q000235:genetics / Q000523:psychology*; D000368:Aged; D001007:Anxiety / Q000209:etiology* / Q000235:genetics; D018899:CpG Islands; D019175:DNA Methylation / Q000235:genetics*; D003863:Depression / Q000209:etiology* / Q000235:genetics; D044127:Epigenesis, Genetic / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D018045:Receptors, Oxytocin / Q000235:genetics*; D055815:Young Adult
chemical_list: C569600:OXTR protein, human; D018045:Receptors, Oxytocin
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