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

Abstract

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, GRalpha and GRbeta, which have distinct biological activity. It has not been examined whether GRalpha messenger RNA (mRNA) and GRbeta mRNA expressions are altered in peripheral blood cells of mood disorder patients. Using quantitative reverse transcription polymerase chain reaction (RT-PCR), GRalpha mRNA and GRbeta 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. Reduced expression of GRalpha 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 GRalpha mRNA reduction. Altered GRbeta mRNA expression was not found in mood disorder patients. Our results suggest that reduced GRalpha mRNA expression might be trait-dependent and associated with the pathophysiology of mood disorders.