by Michael Maes
January 9, 2009
[Note: oxidative and nitrosative stress pathways refer to complex series of biochemical reactions leading to harmful free radical and nitric oxide effects at the cellular level. LPS (lipopolysaccharide) is a component of certain bacteria normally confined to the intestine that may leak out due to infection.]
Purpose of Review The aim of this paper is to review recent findings on inflammatory and oxidative and nitrosative stress (IO&NS) pathways in chronic fatigue and somatization disorder.
Recent Findings
• Activation of oxidative and nitrosative stress (IO&NS) pathways is the key phenomenon underpinning chronic fatigue syndrome (CFS):
- Intracellular inflammation, with an increased production of nuclear factor kappa beta (NFkappabeta), cyclo-oxygenase-2 (COX-2) and inducible NO synthase (iNOS);
- And damage caused by O&NS to membrane fatty acids and functional proteins.
• These IO&NS pathways are induced by a number of trigger factors, for example: Psychological stress, strenuous exercise, viral infections, and an increased translocation of LPS from gram-bacteria (leaky gut).
• The 'psychosomatic' symptoms experienced by CFS patients are caused by:
- Intracellular inflammation (aches and pain, muscular tension, fatigue, irritability, sadness, and the subjective feeling of infection);
- Damage caused by O&NS (aches and pain, muscular tension and fatigue);
- And gut-derived inflammation (complaints of irritable bowel).
• Inflammatory pathways (monocytic activation) are also detected in somatizing disorder.
Summary:
• 'Functional' symptoms, as occurring in CFS and somatization, have a genuine organic cause, that is activation of peripheral and central IO&NS pathways and gut-derived inflammation.
• The development of new drugs, aimed at treating those disorders, should target these IO&NS pathways.
Source: Current Opinion in Psychiatry, Jan 2009;22(1):75-83. PMID: 19127706, by Maes M. Clinical Research Centre of Mental Health (CRC-MH), Antwerp, Belgium. [E-mail: crc.mh@telenet.be]
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