A preliminary evaluation of leukocyte phospho-glucocorticoid receptor as a potential biomarker of depressogenic vulnerability in healthy adults

The mechanism of maladaptive chronic stress response involves altered phosphorylation of the glucocorticoid receptor (GR). In this study, we investigated if important depressogenic vulnerability factors, such as neuroticism and self-reports of negative affective states, may be associated with alterations in levels of the GR and GR phosphoisoforms in peripheral blood mononuclear cells (PBMC) of healthy adults. In 21 women and 16 men we evaluated PMBC levels of total GR (tGR), GR phosphorylated at serine 211 (pGR-S211) and serine 226 (pGR-S226) and correlated these data with personality traits and current reports of stress, anxiety and depression. Also, we assessed plasma cortisol levels in all tested subjects. Our results showed that in women nuclear pGR-S226 was positively correlated with neuroticism and current reports of depression, anxiety and stress, while the ratio of nuclear pGR-S211/pGR-S226 was negatively correlated with reports of depression. None of the aforementioned correlations were significant in men. No significant relations between cortisol levels and any of GR parameters were observed. These preliminary findings highlight the value of GR phosphorylation-related research in identifying molecular biomarkers of depressogenic vulnerability, at least in women.