Chronic fatigue syndrome: Harvey and Wessely's (bio)psychosocial model versus a bio(psychosocial) model based on inflammatory and oxidative and nitrosative stress pathways.

Observed Findings

• Research literature documents abnormalities in inflammatory, immune, oxidative, and nitrosative stress pathways in ME/CFS patients
• Both ME/CFS and major depression involve shared IO&NS pathway activation but can be distinguished by specific symptom profiles and non-overlapping biological markers
• Viral and bacterial infections, physical stressors, and psychosocial stressors are known to activate IO&NS pathways
• IO&NS pathway activation is associated with induction of fatigue and somatic symptoms
• Harvey and Wessely's biopsychosocial model does not account for documented IO&NS pathophysiological abnormalities

Inferred Conclusions

• A biological model based on IO&NS pathways provides a more complete and accurate explanation of ME/CFS pathophysiology than purely biopsychosocial models
• Behaviorally-oriented interventions like CBT and GET may be potentially harmful for many ME/CFS patients because physical stressors can intensify underlying IO&NS abnormalities
• Clinical practice should include laboratory testing to assess IO&NS pathways rather than relying solely on behavioral interventions
• ME/CFS should be understood as a disorder with distinct biological mechanisms that differentiate it from depression despite some shared inflammatory pathways

Remaining Questions