Glucocorticoid treatment
An interaction between GR and MR in humans is likely based on the widespread treatment with synthetic glucocorticoids, that are associated with pronounced psychopathology in a subset of users (Fardet, Petersen and Nazareth, 2012; Judd et al. , 2014; Laugesen et al. , 2021). In their review Judd et al (2012) put forward the hypothesis that an extreme imbalance between GRs and MRs is caused by exogenous glucocorticoids, based on preferential GR binding and suppression of the HPA axis, and that this may underlie cognitive impairment and disturbed emotions by many individuals during glucocorticoid therapy. Based on this hypothesis, it would be plausible to stimulate MR in parallel of very strong GR stimulation during treatment with steroids such as dexamethasone. Indeed, (Warris et al. , 2016) examined whether add-on hydrocortisone would ameliorate cognitive and emotional side effects of dexamethasone therapy as part of leukaemia treatment in children. As hypothesized, hydrocortisone attenuated the dexamethasone mental side effects in those individuals that suffered most strongly from mental side effects. This is compatible with the MR/GR balance concept of mental vulnerability to glucocorticoids (Meijer and de Kloet, 2017).