¹Laboratory of Biological Chemistry, University of Athens Medical School, 75 Mikras Asias Str, GR-115 27 Goudi, Athens, Greece

²Eginition Hospital, Department of Psychiatry, University of Athens Medical School, 74 Vas Sofias Ave, Athens, Greece

³Institute of Biological Research and Biotechnology, National Hellenic Research Foundation, 48 Vas Constantinou Avenue, GR-116 35 Athens, Greece

Correspondence to: P Moutsatsou, University of Athens Medical School, Department of Biological Chemistry, 75 Mikras Asias Str, GR-115 27 Athens, Greece. E-mail: biolchem@ath.forthnet.gr

The periodically hyperactive hypothalamic-pituitary-adrenal (HPA) axis in bipolar affective disorders, as well as the reported changes in the binding characteristics of the glucocorticoid receptor (GR), suggest the possible involvement of the GR in the aetiopathology of this disease. This was investigated by screening the coding sequences of both GR isoforms, GR and GR, for the presence of mutations. As a genetic predisposition has been implicated, we included in this study bipolar patients who were siblings. By RT-PCR of peripheral blood mononuclear cells from patients suffering from bipolar illness, using primers spanning the whole length of the GR and GR coding region and subsequent agarose gel electrophoresis, heteroduplex and sequence analyses, no GR mutations could be detected. Since glucocorticoid receptor activity can be modulated by agents other than the respective ligand (eg by growth factors, cytokines and stress signals), our results favor derangements in the modulation of GR activity by such agents and not in the primary structure of the receptor as aetiopathologic factors of bipolar disease. Molecular Psychiatry (2000) 5, 196-202.

receptor; mutation; affective disease; glucocorticoids; receptor isoforms