Curr Opin Psychiatry 22(1) (2009): 75-83. PMID: 19127706

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  IO & NS pathways is the key phenomenon underpinning chronic fatigue syndrome (CFS): intracellular inflammation, with an increased production of nuclear factor kappa beta (NF-kappabeta), cyclo-oxygenase-2 (COX-2) and inducible NO synthase (iNOS); and damage caused by IO & 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 IO & 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.