{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T12:37:15Z","timestamp":1791117435651,"version":"4.1.0"},"reference-count":56,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2008,12,2]],"date-time":"2008-12-02T00:00:00Z","timestamp":1228176000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt B"],"published-print":{"date-parts":[[2009,7,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The hypothalamic\u2010pituitary\u2010adrenal (HPA)\u2010axis 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\u2010axis. 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\u2010axis markers and depressive symptoms. A gene\u2013environment 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\u2010type and BclI\u2010homozygotes, 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\u2013environment (G\u2009\u00d7\u2009E) 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\u2009\u00d7\u2009E interaction also influenced HPA\u2010axis markers providing support for the involvement of the HPA\u2010axis in both stress regulation and the pathogenesis of depression. \u00a9 2008 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.b.30886","type":"journal-article","created":{"date-parts":[[2008,12,2]],"date-time":"2008-12-02T18:35:09Z","timestamp":1228242909000},"page":"660-669","source":"Crossref","is-referenced-by-count":111,"title":["Glucocorticoid receptor gene polymorphisms and childhood adversity are associated with depression: New evidence for a gene\u2013environment interaction"],"prefix":"10.1002","volume":"150B","author":[{"given":"Pierre M.","family":"Bet","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brenda W.J.H.","family":"Penninx","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zoltan","family":"Bochdanovits","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9 G.","family":"Uitterlinden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aartjan T.F.","family":"Beekman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natasja M.","family":"van Schoor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorly J.H.","family":"Deeg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Witte J.G.","family":"Hoogendijk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,6,15]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2005.09.008"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1210\/edrv-17-3-245"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bth457"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0033291796003510"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.59.7.605"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.mp.4001873"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2006.11.033"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1083968"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1126\/stke.2252004re5"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2007.01.012"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1683"},{"key":"e_1_2_6_13_1","first-page":"1","article-title":"Autonomy and well\u2010being in the aging population: Concepts and Design of the Longitudinal Aging Study Amsterdam. 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