title: Epigenetic modifications of the glucocorticoid receptor gene are associated with the vulnerability to psychopathology in childhood maltreatment.
abstract: Stress, particularly when experienced early in life, can have profound implications for mental health. Previous research covering various tissues such as the brain, suggests that the detrimental impact of early-life stress (ELS) on mental health is mediated via epigenetic modifications including DNA methylation. Genes of the hypothalamic-pituitary-adrenal axis--in particular, the glucocorticoid receptor (hGR) gene--stand out as key targets for ELS. Even though the link between hGR methylation and either ELS or psychopathology is fairly well established, the mutually dependent relationships between ELS, DNA methylation and psychopathology remain to be uncovered. The specific psychopathology an individual might develop in the aftermath of stressful events can be highly variable, however, most studies investigating hGR methylation and psychopathology suffer from being limited to a single symptom cluster of mental disorders. Here, we screened volunteers for childhood maltreatment and analyzed whether it associates with hGR methylation in lymphocytes and a range of measures of psychological ill-health. hGR methylation in lymphocytes most likely reflects methylation patterns found in the brain and thus provides valuable insights into the etiology of psychopathology. We find the interaction between childhood maltreatment and hGR methylation to be strongly correlated with an increased vulnerability to psychopathology providing evidence of epigenome × environment interactions. Furthermore, our results indicate an additive effect of childhood maltreatment and hGR methylation in predicting borderline personality disorder (BPD)-associated symptoms, suggesting that the combination of both ELS and DNA methylation that possibly represents unfavorable events experienced even earlier in life poses the risk for BPD.
authors.affiliation: 1] Clinical Psychology and Behavioral Neuroscience, Department of Psychology, University of Konstanz, Konstanz, Germany [2] Evolutionary Biology and Zoology, Department of Biology, University of Konstanz, Konstanz, Germany.
authors.forename: K M
authors.initials: KM
authors.lastname: Radtke
authors.affiliation: Clinical Psychology and Behavioral Neuroscience, Department of Psychology, University of Konstanz, Konstanz, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Schauer
authors.affiliation: Evolutionary Biology and Zoology, Department of Biology, University of Konstanz, Konstanz, Germany.
authors.forename: H M
authors.initials: HM
authors.lastname: Gunter
authors.affiliation: Clinical Psychology and Behavioral Neuroscience, Department of Psychology, University of Konstanz, Konstanz, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Ruf-Leuschner
authors.affiliation: Clinical Psychology and Behavioral Neuroscience, Department of Psychology, University of Konstanz, Konstanz, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Sill
authors.affiliation: Evolutionary Biology and Zoology, Department of Biology, University of Konstanz, Konstanz, Germany.
authors.forename: A
authors.identifier: 0000000208888193
authors.initials: A
authors.lastname: Meyer
authors.affiliation: Clinical Psychology and Behavioral Neuroscience, Department of Psychology, University of Konstanz, Konstanz, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Elbert
mesh_terms: D000293:Adolescent; D054523:Adult Survivors of Child Abuse / Q000523:psychology*; D001007:Anxiety / Q000235:genetics / Q000523:psychology; D019958:Attention Deficit and Disruptive Behavior Disorders / Q000235:genetics / Q000523:psychology; D001883:Borderline Personality Disorder / Q000235:genetics / Q000523:psychology; D002648:Child; D002649:Child Abuse / Q000523:psychology*; D015331:Cohort Studies; D019175:DNA Methylation; D003863:Depression / Q000235:genetics / Q000523:psychology; D044127:Epigenesis, Genetic; D005260:Female; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D001523:Mental Disorders / Q000235:genetics* / Q000523:psychology; D011965:Receptors, Glucocorticoid / Q000235:genetics*; D055815:Young Adult
chemical_list: D011965:Receptors, Glucocorticoid