Mineralocorticoid receptor haplotypes sex-dependently moderate depression susceptibility following childhood maltreatment

C.H. Vinkers, M. Joels, Y. Milaneschi, L. Gerritsen, R. S. Kahn, B.W.J.H. Penninx, M.P.M. Boks

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66 Citations (Scopus)


The MR is an important regulator of the hypothalamic-pituitary-adrenal (HPA) axis and a prime target for corticosteroids. There is increasing evidence from both clinical and preclinical studies that the MR has different effects on behavior and mood in males and females. To investigate the hypothesis that the MR sex-dependently influences the relation between childhood maltreatment and depression, we investigated three common and functional MR haplotypes (GA, CA, and CG haplotype, based on rs5522 and rs2070951) in a population-based cohort (N=665) and an independent clinical cohort from the Netherlands Study of Depression and Anxiety (NESDA) (N=1639). The CA haplotype sex-dependently moderated the relation between childhood maltreatment and depressive symptoms both in the population-based sample (sex×maltreatment×haplotype: β=-4.07, P=0.029) and in the clinical sample (sex×maltreatment×haplotype, β=-2.40, P=0.011). Specifically, female individuals in the population-based sample were protected (β=-4.58, P=2.0e
Original languageEnglish
Pages (from-to)90-102
Number of pages13
Publication statusPublished - Apr 2015


  • Adolescent
  • Adult
  • Child Abuse
  • Depression/genetics
  • Disease Susceptibility
  • Female
  • Genetic Predisposition to Disease
  • Haplotypes
  • Humans
  • Male
  • Polymorphism, Single Nucleotide
  • Receptors, Mineralocorticoid/genetics
  • Sex Factors
  • Young Adult

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