The endocrinology of melancholic and atypical depression: relation to neurocircuitry and somatic consequences
by
Gold PW, Chrousos GP
National Institute of Mental Health,
National Institutes of Health,
Bethesda, MD 20892-1284, USA.
Proc Assoc Am Physicians 1999 Jan-Feb; 111(1):22-34

ABSTRACT

The cardinal clinical manifestations of major depression with melancholic features include sustained anxiety and dread for the future as well as evidence of physiological hyperarousal (e.g., sustained hyperactivity of the two principal effectors of the stress response, the corticotropin-releasing-hormone, or CRH, system, and the locus ceruleus-norepinephrine, or LC-NE, system). Sustained stress system activation in melancholic depression is thought to confer both behavioral arousal as well as the hypercortisolism, sympathetic nervous system activation, and inhibition of programs for growth and reproduction that consistently occur in this disorder. Data also suggest that activation of the CRH and LC systems in melancholia are involved in the long-term medical consequences of depression such as premature coronary artery disease and osteoporosis, the two-three-fold preponderance of females in the incidence of major depression, and the mechanism of action of antidepressant drugs. In addition, recent data reveal important bidirectional interactions between stress-system hormonal factors in depression and neural substrates implicated in many discrete behavioral alterations in depression (e.g., the medial prefrontal cortex, important in shifting affect based on internal and external cues, the mesolimbic dopaminergic reward system, and the amygdala fear system). We have also advanced data indicating that the hypersomnia, hyperphagia, lethargy, fatigue, and relative apathy of the syndrome of atypical depression are associated with concomitant hypofunctioning of the CRH and LC-NE systems. These data indicate the need for an entirely different therapeutic strategy than that used in melancholia for the treatment of atypical depression, and they suggest that this subtype of major depression will be associated with its own unique repertoire of long-term medical consequences.

CRF
Options
Dysthymia
Anhedonia
Noradrenaline
Undertreatment
Chronic depression
New antidepresants
Psychotic depression
Melancholia and SSRIs
The depressive spectrum
Genius and psychopathology
Melancholia and bipolar depression
ECT, melancholia and hippocampal neogenesis