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

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, N363S, BclI, and 9β 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 BclI haplotype and the T. thIIII. +. 9β 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.

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