title: The aetiopathogenesis of fatigue: unpredictable, complex and persistent.
abstract: BACKGROUND
  Chronic fatigue syndrome is a common condition characterized by severe fatigue with post-exertional malaise, impaired cognitive ability, poor sleep quality, muscle pain, multi-joint pain, tender lymph nodes, sore throat or headache. Its defining symptom, fatigue is common to several diseases.
  
  
  RESULTS
  Research has established a broad picture of impairment across autonomic, endocrine and inflammatory systems though progress seems to have reached an impasse.
  
  
  RESULTS
  The absence of a clear consensus view of the pathophysiology of fatigue suggests the need to switch from a focus on abnormalities in one system to an experimental and clinical approach which integrates findings across multiple systems and their constituent parts and to consider multiple environmental factors.
  
  
  CONCLUSIONS
  We discuss this with reference to three key factors, non-determinism, non-reductionism and self-organization and suggest that an approach based on these principles may afford a coherent explanatory framework for much of the observed phenomena in fatigue and offers promising avenues for future research.
  
  
  CONCLUSIONS
  By adopting this approach, the field can examine issues regarding aetiopathogenesis and treatment, with relevance for future research and clinical practice.
authors.affiliation: Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: James E
authors.initials: JE
authors.lastname: Clark
authors.affiliation: Faculty of Medical Sciences, Institute of Cellular Medicine, Newcastle University, Clinical Academic Office, 3rd Floor, William Leech Building, Newcastle upon Tyne NE2 4HH, UK.
authors.forename: W
authors.initials: W
authors.lastname: Fai Ng
authors.affiliation: Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Stuart
authors.initials: S
authors.lastname: Watson
authors.affiliation: Faculty of Medical Sciences, Institute of Cellular Medicine, Newcastle University, Clinical Academic Office, 3rd Floor, William Leech Building, Newcastle upon Tyne NE2 4HH, UK Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK julia.newton@newcastle.ac.uk julia.newton@ncl.ac.uk.
authors.forename: Julia L
authors.initials: JL
authors.lastname: Newton
mesh_terms: D004781:Environmental Exposure / Q000009:adverse effects; D005221:Fatigue / Q000209:etiology* / Q000503:physiopathology / Q000628:therapy; D015673:Fatigue Syndrome, Chronic / Q000209:etiology* / Q000503:physiopathology / Q000628:therapy; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D008954:Models, Biological
keywords: chronic fatigue syndrome; complexity; fatigue