Genes involved in glucocorticoid receptor signalling affect susceptibility to mood disorders

Objectives: In mood disorders chronic stress contributes to decreased glucocorticoid receptor signalling in the brain and resistance in the periphery. We hypothesised that aberrant glucocorticoid receptor function may result from genetic predisposition and that decreased GR signalling in the brain correlates with the expression of genes regulating GR complex formation. Methods: We performed the association analysis of 698 patients: 490 patients with bipolar disorder and 208 patients with major depressive disorder and 564 control subjects. We genotyped 11 variants using TaqMan assays. Gene expression in the brain tissue was done in male Wistar rats after chronic mild stress protocol. The SRSF5 serum concentration was performed using ELISA. Data were analysed in Statistica and GraphPad. Results: We found an association of STIP1 and SRSF5 variants with major depressive disorder and BAG1 variant with bipolar disorder. Gene expression analysis in a rat model of depression confirmed significant changes in the expression of SRSF5, BAG1, and FKBP4 in the brain. For SRSF5, we observed significantly increased expression in the serum of depressed females and male rats exposed to chronic stress. Conclusions: Our results indicate the involvement of genes associated with GR function, SRSF5, BAG1, and FKBP4 with susceptibility to mood disorders.