CRH and major depressive disorder: Corresponding to the increasing evidence of the relationship between CRF and sleep, a pathophysiological model of CRF focuses on the interaction of chronic inflammation, sleep disorder, disrupted rhythm, neuroendocrine disturbances such as cortisol rhythm flattening or reduced responsiveness of cortisol to stress and consecutive central nervous system dysregulations such as elevated corticotropin-releasing hormone, reduced growth factor or 5-Hydroxytryptamin on CRF, cognitive dysfunction, impaired sleep or depression [43].