The heterogeneity in cortisol concentrations may suggest clinical heterogeneity within the diagnostic grouping of CFS and emphasizes the impact of disparate and competing factors on GR function including current and previous stressors, the common use of antidepressants [20, 54] (even in those who have never met criteria for major depressive disorder) [20, 57], and the impact of a primary dysregulation of proinflammatory cytokines [58]. This evidence concerns the gene NR3C1 and myalgic encephalomeyelitis/chronic fatigue syndrome.