TY - JOUR
T1 - Glucocorticoid and mineralocorticoid receptor polymorphisms and clinical characteristics in bipolar disorder patients
AU - Spijker, AT
AU - Giltay, EJ
AU - van Rossum, Liesbeth
AU - Manenschijn, Laura
AU - DeRijk, RH
AU - Haffmans, J
AU - Zitman, FG
AU - Hoencamp, E
PY - 2011
Y1 - 2011
N2 - 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.
AB - 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.
U2 - 10.1016/j.psyneuen.2011.03.020
DO - 10.1016/j.psyneuen.2011.03.020
M3 - Article
SN - 0306-4530
VL - 36
SP - 1460
EP - 1469
JO - Psychoneuroendocrinology
JF - Psychoneuroendocrinology
IS - 10
ER -