Reduced Glucocorticoid Receptor α Expression in Mood Disorder Patients and First-Degree Relatives

Background Individuals with mood disorders exhibit altered function of the hypothalamic-pituitary-adrenal (HPA) axis in response to stress. The glucocorticoid receptor (GR) plays an important role in the negative feedback regulation of the HPA axis. There are two protein isoforms of GR, GRα and GRβ, which have distinct biological activity. It has not been examined whether GRα messenger RNA (mRNA) and GRβ mRNA expressions are altered in peripheral blood cells of mood disorder patients. Methods Using quantitative reverse transcription polymerase chain reaction (RT-PCR), GRα mRNA and GRβ mRNA were measured in peripheral blood cells of major depressive disorder patients (depressive n = 18; remissive n = 38), bipolar disorder patients (depressive n = 13; remissive n = 35), normal control subjects (n = 31), and first-degree relatives of major depressive (n = 17) and bipolar (n = 15) disorder patients. Results Reduced expression of GRα mRNA was shown in both bipolar and major depressive disorder patients in a current depressive state as well as in remission. First-degree relatives of bipolar disorder patients also showed GRα mRNA reduction. Altered GRβ mRNA expression was not found in mood disorder patients. Conclusions Our results suggest that reduced GRα mRNA expression might be trait-dependent and associated with the pathophysiology of mood disorders.