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 TthIIII+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.