Biological Underpinnings of the Commonalities in Depression, Somatization, and Chronic Fatigue Syndrome

Med Hypotheses. 2012 Jun;78(6):752-6. doi: 10.1016/j.mehy.2012.02.023. Epub 2012 Mar 23.


Background: Somatization is a multisomatoform disorder characterized by medically unexplained, functional or psychosomatic symptoms. Similar somatic symptoms are key components of depression and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).

Methods: This paper reviews the evidence that such symptoms are organically based. We use the term "physio-somatic" to describe these symptoms.

Results: Inflammation, cell-mediated immune (CMI) activation and alterations in the tryptophan catabolite (TRYCAT) pathway are associated with the physio-somatic symptoms of depression, ME/CFS and/or somatization. Proinflammatory cytokines, decreased tryptophan and aberrations in TRYCATs may cause physio-somatic symptoms, such as fatigue, autonomic symptoms, hyperalgesia and somatic presentations.

Conclusions: The data suggest co-ordinated and interacting biological pathways driving the occurrence of physio-somatic symptoms across these three disorders, giving a biologically validated "pathway phenotype". These data have far-reaching implications for DSM-IV diagnostic conceptualizations of somatization (and ME/CFS) suggesting the presence of an emerging organic explanation. Future research should focus on the role of immune regulation, and co-ordination, of neuronal activity and, through larger data sets, ultimately creating new, biologically validated classification rules. These data have implications for the development of novel therapies utilizing these insights, buttressing the role of psychotherapy in psychosomatic presentations.

Publication types

  • Comparative Study
  • Review

MeSH terms

  • Cytokines / metabolism
  • Depression / etiology
  • Depression / physiopathology*
  • Fatigue Syndrome, Chronic / etiology
  • Fatigue Syndrome, Chronic / physiopathology*
  • Humans
  • Immunity, Cellular / physiology*
  • Inflammation / complications*
  • Models, Biological*
  • Signal Transduction / physiology
  • Somatoform Disorders / etiology
  • Somatoform Disorders / physiopathology*
  • Tryptophan / metabolism*


  • Cytokines
  • Tryptophan