Glucocorticoid receptor gene polymorphisms and childhood adversity are associated with depression: New evidence for a gene-environment interaction

Pierre M. Bet, Brenda W.J.H. Penninx, Zoltan Bochdanovits, André G. Uitterlinden, Aartjan T.F. Beekman, Natasja M. Van Schoor, Dorly J.H. Deeg, Witte J.G. Hoogendijk

Research output: Contribution to journalArticleAcademicpeer-review

105 Citations (Scopus)

Abstract

The hypothalamic-pituitary-adrenal (HPA)-axis regulates the response to stressful events and is expected to be involved in the pathogenesis of depression. The glucocorticoid receptor (GR) regulates the activity of the HPA-axis. Both GR gene polymorphisms and childhood adversity are known to be associated with increased risk for depression. In the Longitudinal Aging Study Amsterdam, a large population based sample of older men and women, 906 subjects were genotyped. An association study was performed to determine the relationship between GR gene polymorphisms, childhood adversity, HPA-axis markers and depressive symptoms. A gene-environment interaction between the GR polymorphisms 22/23EK and 9beta and childhood adversity resulted in an increased risk of clinically relevant depressive symptoms. Without childhood adversity no increased risk was present. The 22/23EK variant was also associated with a lower Free Cortisol Index in the presence of childhood adversity. Persons that are heterozygous for the BclI variant, in contrast with wild-type and BclI-homozygotes, had lower serum levels of cortisol binding globulin and had no increased risk of recurrent depressive symptoms in the presence of childhood adversity. We found a gene-environment (G x E) interaction between common variants of the GR gene and childhood adversity, demonstrating a vulnerable phenotype for developing clinically relevant depressive symptoms at old age. This G x E interaction also influencedHPA-axismarkers providing support for the involvement of theHPA-axis in both stress regulation and the pathogenesis of depression.

Original languageEnglish
Pages (from-to)660-669
Number of pages10
JournalAmerican Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
Volume150 B
Issue number5
DOIs
Publication statusPublished - 5 Jul 2009

Fingerprint

Dive into the research topics of 'Glucocorticoid receptor gene polymorphisms and childhood adversity are associated with depression: New evidence for a gene-environment interaction'. Together they form a unique fingerprint.

Cite this