title: Childhood maltreatment and methylation of the glucocorticoid receptor gene NR3C1 in bipolar disorder.
abstract: BACKGROUND
  Early-life adversities represent risk factors for the development of bipolar affective disorder and are associated with higher severity of the disorder. This may be the consequence of a sustained alteration of the hypothalamic-pituitary-adrenal (HPA) axis resulting from epigenetic modifications of the gene coding for the glucocorticoid receptor (NR3C1).
  
  
  OBJECTIVE
  To investigate whether severity of childhood maltreatment is associated with increased methylation of the exon 1F NR3C1 promoter in bipolar disorder.
  
  
  METHODS
  A sample of people with bipolar disorder (n = 99) were assessed for childhood traumatic experiences. The percentage of NR3C1 methylation was measured for each participant.
  
  
  RESULTS
  The higher the number of trauma events, the higher was the percentage of NR3C1 methylation (β = 0.52, 95% CI 0.46-0.59, P<<0.0001). The severity of each type of maltreatment (sexual, physical and emotional) was also associated with NR3C1 methylation status.
  
  
  CONCLUSIONS
  Early-life adversities have a sustained effect on the HPA axis through epigenetic processes and this effect may be measured in peripheral blood. This enduring biological impact of early trauma may alter the development of the brain and lead to adult psychopathological disorder.
authors.affiliation: Nader Perroud, MD, Department of Mental Health and Psychiatry, Service of Psychiatric Specialties, University Hospitals of Geneva, and Department of Psychiatry, University of Geneva; Alexandre Dayer, MD, Department of Mental Health and Psychiatry, Service of Psychiatric Specialties, University Hospitals of Geneva, and Departments of Basic Neuroscience and of Psychiatry, University of Geneva; Camille Piguet, MD, Department of Neuroscience, Faculty of Medicine, University of Geneva; Audrey Nallet, MSc, Sophie Favre, PhD, Department of Psychiatry, University of Geneva; Alain Malafosse, MD, PhD, Department of Psychiatry, University of Geneva, and Department of Genetic Medicine and Laboratories, Psychiatric Genetic Unit, University Hospitals of Geneva; Jean-Michel Aubry, MD, Department of Mental Health and Psychiatry, Bipolar Programme, Service of Psychiatric Specialties, University Hospitals of Geneva, Switzerland.
authors.forename: Nader
authors.initials: N
authors.lastname: Perroud
authors.forename: Alexandre
authors.initials: A
authors.lastname: Dayer
authors.forename: Camille
authors.initials: C
authors.lastname: Piguet
authors.forename: Audrey
authors.initials: A
authors.lastname: Nallet
authors.forename: Sophie
authors.initials: S
authors.lastname: Favre
authors.forename: Alain
authors.initials: A
authors.lastname: Malafosse
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Aubry