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Glucocorticoid receptor gene polymorphisms and childhood adversity are associated with depression: New evidence for a gene–environment interaction
Author(s) -
Bet Pierre M.,
Penninx Brenda W.J.H.,
Bochdanovits Zoltan,
Uitterlinden André G.,
Beekman Aartjan T.F.,
van Schoor Natasja M.,
Deeg Dorly J.H.,
Hoogendijk Witte J.G.
Publication year - 2009
Publication title -
american journal of medical genetics part b: neuropsychiatric genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.393
H-Index - 126
eISSN - 1552-485X
pISSN - 1552-4841
DOI - 10.1002/ajmg.b.30886
Subject(s) - glucocorticoid receptor , depression (economics) , pathogenesis , glucocorticoid , population , major depressive disorder , medicine , psychology , endocrinology , clinical psychology , environmental health , amygdala , economics , macroeconomics
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 × 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 × E interaction also influenced HPA‐axis markers providing support for the involvement of the HPA‐axis in both stress regulation and the pathogenesis of depression. © 2008 Wiley‐Liss, Inc.