Reduced glucocorticoid receptor α expression in mood disorder patients and first-degree relatives

Background: Individuals with mood disorders exhibit altered function of the hypothalamic-pituitiary-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 GR alpha and GR beta which have distinct biological activity, It has not been examined whether GR alpha messenger RNA (mMNA) and GR beta mRNA expressions are altered in peripheral blood cells of mood disorder patients. Methods: Using quantitative reverse transcription polymerase chain. reaction (RT-PCR), GR alpha mRNA and GRP 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 bipolar depressive (n = 17) and bipolar (n = 15) disorder patients. Results: Reduced expression of GR alpha mRNA was shown in both bipolar and major depressive disorderpatients in a current depressive state as well as in remission. First-degree relatives of bipolar disorderpatients also showed GR alpha mRNA reduction, Altered GR beta mRNA expression was not found in mood disorder patients. Conclusions: Our results suggest that reduced GR alpha mRNA expression might be trait-dependent and associated with the pathophysiology of mood disorders.