The brain mineralocorticoid receptor: A resilience factor for psychopathology?

After stress, the brain is exposed to waves of stress hormones, including (nor)adrenaline and corticosteroids. Corticosteroids act through mineralocorticoid (MR) and glucocorticoid receptors. Brain MRs are important for the stress response onset: they are critically involved in hypothalamus-pituitary-adrenal axis tone and threshold and, through rapid and delayed cellular effects, mediate increased attention and vigilance in anticipation of upcoming events, appraisal of novel information, and retrieval of previously acquired behavioral responses. MR functionality depends on genetic variations, moderated by (early) life environment. MRs can promote resilience in the face of adversity. Importantly, boosting MR function in healthy individuals may preserve health, yet inappropriately high MR activity during persistent adversity would demand treatment with MR antagonists as a lifesaver. MR actions cannot be seen in isolation from glucocorticoid receptor function, as the activity of both receptor types needs to be in balance to preserve homeostasis, resilience, and health.