Pronounced and sustained central hypernoradrenergic function in major depression with melancholic features: relation to hypercortisolism and corticotropin-releasing hormone
by
Wong ML, Kling MA, Munson PJ, Listwak S, Licinio J,
Prolo P, Karp B, McCutcheon IE, Geracioti TD Jr,
DeBellis MD, Rice KC, Goldstein DS, Veldhuis JD,
Chrousos GP, Oldfield EH, McCann SM, Gold PW.
Clinical Neuroendocrinology Branch,
National Institute of Mental Health,
National Institutes of Health,
Bethesda, MD 20892, USA.
Proc Natl Acad Sci U S A. 2000 Jan 4;97(1):325-30.


ABSTRACT

Both stress-system activation and melancholic depression are characterized by fear, constricted affect, stereotyped thinking, and similar changes in autonomic and neuroendocrine function. Because norepinephrine (NE) and corticotropin-releasing hormone (CRH) can produce these physiological and behavioral changes, we measured the cerebrospinal fluid (CSF) levels each hour for 30 consecutive hours in controls and in patients with melancholic depression. Plasma adrenocorticotropic hormone (ACTH) and cortisol levels were obtained every 30 min. Depressed patients had significantly higher CSF NE and plasma cortisol levels that were increased around the clock. Diurnal variations in CSF NE and plasma cortisol levels were virtually superimposable and positively correlated with each other in both patients and controls. Despite their hypercortisolism, depressed patients had normal levels of plasma ACTH and CSF CRH. However, plasma ACTH and CSF CRH levels in depressed patients were inappropriately high, considering the degree of their hypercortisolism. In contrast to the significant negative correlation between plasma cortisol and CSF CRH levels seen in controls, patients with depression showed no statistical relationship between these parameters. These data indicate that persistent stress-system dysfunction in melancholic depression is independent of the conscious stress of the disorder. These data also suggest mutually reinforcing bidirectional links between a central hypernoradrenergic state and the hyperfunctioning of specific central CRH pathways that each are driven and sustained by hypercortisolism. We postulate that alpha-noradrenergic blockade, CRH antagonists, and treatment with antiglucocorticoids may act at different loci, alone or in combination, in the treatment of major depression with melancholic features.
CRF
LHPA
Stress
Metyrapone
Ketoconazole
Cortisol blues
Stressed tree shrews
Learned helpless rats
Glucocorticoids and mood
Hippocampal remodelling
Stress, depression and the rat
Corticosteroids and depression
Hormones, the brain and stress
Glucocorticoids and antidepressants
Are antidepressants neuroprotective?
Antiglucocorticoids as antidepressants
A neurotrophic model for stress-related mood disorders
Stress, dynorphin, dysphoria and the kappa opioid system
Regulation of 5-HT1a, glucocorticoid, and mineralocorticoid receptors


Refs
and further reading

HOME
HedWeb
Nootropics
cocaine.wiki
Future Opioids
BLTC Research
MDMA/Ecstasy
Superhapiness?
Utopian Surgery?
The Abolitionist Project
The Hedonistic Imperative
The Reproductive Revolution
Critique of Huxley's Brave New World

The Good Drug Guide
The Good Drug Guide

The Responsible Parent's Guide
To Healthy Mood Boosters For All The Family