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).