ABSTRACT
The symptomatic characterization of major depression includes low or depressed mood, loss of interest in most activities (anhedonia), and a decrease in energy level. There are several subtypes of major depression, each of which is distinguished by a specific pattern of symptoms. The melancholic subtype consists of qualitatively distinct symptoms that are comparable with those that occur during a state of overarousal. Though still controversial, accumulating evidence suggests that those with major depression with melancholic features have increased sympathetic nervous system and hypothalamo-pituitary-adrenal (HPA) activation. This hyperarousal state has recently been confirmed by indices of sustained activation of the HPA axis and norepinephrine (NE) system in a serial cerebrospinal fluid (CSF) sampling study. That study supports a dysregulation of the HPA axis and NE system in major depression with melancholic features because 1) hypercortisolemia detected in these patients was inefficacious in providing the appropriate feedback to the HPA axis and therefore unable to properly downregulate corticotropin-releasing hormone (CRH) and adrenocorticotropic hormone (ACTH) secretion and 2) sustained activation of NE in the CSF of these patients persisted throughout a 30-hour period, leading to the assumption that NE and CRH activate the central nervous system of melancholic patients regardless of their state of consciousness (asleep or awake). These findings are compatible with previous data on NE spillover in plasma and the apparent correlation between urinary-free cortisol and urinary NE outputs in major depression. They support the notion that central and peripheral NE systems are overactive, while the data caution against the generalization of central nervous system (CNS) deficiency of
NE postulated in the monoamine hypothesis for major depression. Thus, several lines of evidence suggest that major depression affects central as well as systemic systems.
