Glucocorticoid receptor alpha and beta isoforms are not mutated in bipolaraffective disorder

The periodically hyperactive hypothalamic-pituitary-adrenal (HPA) axis in b ipolar affective disorders, as well as the reported changes in the binding characteristics of the glucocorticoid receptor (GR), suggest the possible i nvolvement of the GR in the aetiopathology of this disease. This was invest igated by screening the coding sequences of both GR isoforms, GR alpha and GR beta, for the presence of mutations. As a genetic predisposition has bee n implicated, we included in this study bipolar patients who were siblings. By RT-PCR of peripheral blood mononuclear cells from patients suffering fr om bipolar illness, using primers spanning the whole length of the GR alpha and GR beta coding region and subsequent agarose gel electrophoresis, hete roduplex and sequence analyses, no GR mutations could be detected. Since gl ucocorticoid receptor activity can be modulated by agents other than the re spective ligand leg by growth factors, cytokines and stress signals), our r esults favor derangements in the modulation of GR activity by such agents a nd not in the primary structure of the receptor as aetiopathologic factors of bipolar disease.