Glucocorticoid and mineralocorticoid receptor polymorphisms and clinical characteristics in bipolar disorder patients

AT Spijker, EJ Giltay, Liesbeth van Rossum, Laura Manenschijn, RH DeRijk, J Haffmans, FG Zitman, E Hoencamp

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Introduction: The hypothalamus-pituitary-adrenal (HPA)-axis is often found to be dysregulated in bipolar disorder (BD) while stress and changes in day-night rhythms can trigger a new mood episode. Genetic variants of the glucocorticoid receptor (GR)- and mineralocorticoid receptor (MR)-gene influence both the reactivity of the stress-response and associate with changes in mood. In this study we tested the hypothesis that these polymorphisms associate with different clinical characteristics of BD. Methods: We studied 326 outpatients with BD and performed GR genotyping of the TthIIII, ER22/23EK, N3635, Bc1I, and 9 beta polymorphisms, as well as MR genotyping of the 2G/C and I180V variants. All patients were interviewed for clinical characteristics. Results: Seasonal patterns of hypomania are related to the Bc1I haplotype and the TthIIII + 9 beta haplotype of the GR gene (respectively, crude p = .007 and crude p = .005). Carriers of the ER22/23EK polymorphism had an almost 8 years earlier onset of their first (hypo)manic episode than non-carriers (crude p = .004, after adjustment p = .016). No evidence for a role of the MR in modifying clinical manifestations was found. Conclusion: Polymorphisms of the GR-gene are factors which influence some clinical manifestations of BD, with respect to seasonal pattern of (hypo)mania and age of onset. (C) 2011 Elsevier Ltd. All rights reserved.
Original languageUndefined/Unknown
Pages (from-to)1460-1469
Number of pages10
Issue number10
Publication statusPublished - 2011

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  • EMC MM-01-39-01

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