Objective: We reviewed previous studies that have described an association between abnormal functioning of the hypothalamic-pituitary-adrenal axis and depression. In addition to melancholic depression, a spectrum of conditions may be associated with increased and prolonged activation of the hypothalamic-pituitary-adrenal axis. In contrast another group of states is characterized by hypoactivation of the stress system, rather than sustained activation, in which chronically reduced secretion of corticotropin releasing factor may result in pathological hypoarousal and an enhanced hypothalamic-pituitary-adrenal negative feedback. Patients with atypical depression, seasonal affective disorder and chronic fatigue syndrome fall in this category.
Method: The literature data on the overlap between the key-words were reviewed, summarized and discussed.
Results: Many studies suggest that these conditions themselves overlap biologically, showing hypofunction of central corticotropin releasing factor neuronal systems.
Conclusions: Therefore, in the real world of clinical practice, patients often present in a grey area between classical idiopathic fatigue and early chronic atypical depression and/or seasonal depression. This underscores the potential common biological links underpinning common symptom clusters not only between depression (atypical and seasonal) and chronic fatigue syndrome, but also other conditions characterized by the hypothalamic-pituitary-adrenal axis mainly diminished the corticotropin realising factor activity.