Objectives: The aim of this study was to analyze the expression of 3 genes involved in the regulation of HPA axis: GR, HSP90 and FKBP5, in patients with major depressive disorder (MDD) before antidepressant treatment and after 8 weeks of pharmacotherapy. Additionally, we analyzed the level of glucocorticoid receptor isoforms before and after treatment.
Methods: The study included 30 female patients (aged 18-60 years), with major depres- sive disorder diagnosed on the basis of the Structured Clinical Interview for DSM-IV (SCID). Antidepressant treatment included use of sertraline or venlafaxine. The assessment of patients' mental state (severity of depression) was checked by the Hamilton Depression Rating Scale (HDRS). After 8 weeks of treatment, the same clinical and molecular tests were performed. All of the patients underwent dexamethasone suppression test (DST). MRNA was isolated from the peripheral blood to evaluate the expression of the studied genes using real-time PCR with TaqMan probes. The concentration of GR isoforms (α and β) in serum was also determined using ELISA. Statistical analysis was performed using Statistica v.12.0 software.
Results: The abnormal cortisol level was only seen in 20% of patients. Dysregulation on HPA axis was observed in 10% of patients. We observed significant clinical improvement after 8 weeks of pharmacotherapy in all patients. Almost the whole group of patients (except one patient) showed full remission of symptoms. We observed significant moderate correlation between cortisol level after DST before treatment and after 8 weeks of pharmacotherapy (r2 = 0.44). The results showed no significant difference in the expression of 3 analyzed genes compared before and after 8 weeks of therapy. The results of ELISA showed decreased level of α isoform after pharmacotherapy, independent of drug.
Conclusions: The results showed no significant changes in the expression of genes involved in the stress axis activity during antidepressant therapy.
Keywords: depression; dexamethasone suppression test; stress axis.