The role of genetic variation in the Mineralocorticoid Receptor in stress response and psychopathology

Nienke van Leeuwen

Stress causes activation of the hypothalamic-pituitary-adrenal (HPA)-axis, resulting in secretion of corticosteroids which facilitate behavioural adaptation. These effects exerted by corticosteroids are mediated by two brain corticosteroid receptor types, i.e. the mineralocorticoid (MR), with a high affinity already occupied under basal conditions and the glucocorticoid receptor (GR), with a low affinity only activated during stress. The HPA-axis response to stressors is highly variable between individuals; and this variability is thought to underlie differences in susceptibility to psychopathology.
This project was designed to test if functional genetic polymorphisms in the coding region of the MR-gene underlie variability in stress-responsiveness and if this genetic variability is associated with psychopathology.
Up to now, two genetic polymorphisms in the MR are characterized, both are functional in in vitro assays and both modulate the cortisol awakening response after a low dose of the synthetic glucocorticoid dexamethasone and the response to a psychosocial stressor.