Global disruptions to cortisol signaling  Hypothalamic–pituitary–adrenal (HPA) hyperactivation and increased stress reactivity  Disrupted glucocorticoid receptor (GR) expression in brain tissue  Mutations in GR cochaperone associated with serum cortisol and social anxiety  Cortisol awakening response, evening cortisol and signaling between the HPA and autonomic nervous system correlated with psychopathology, anxiety, depression and suicidal ideation. This evidence concerns the gene NR3C1 and major depressive disorder.