Moss-Morris, Rona, Deary, Vincent, Castell, Bronwyn · Handbook of clinical neurology · 2013 · DOI
ME/CFS is a complex illness where extreme tiredness lasts at least 6 months and can severely limit daily activities. Rather than having one single cause, the condition likely develops from a combination of factors: some people may be triggered by viral infections or stressful life events, while others have genetic traits or personality patterns that increase risk. The condition is then maintained by a cycle involving sleep problems, reduced activity, worry about the illness, and uncertainty from doctors. Treatments like cognitive behavioral therapy and graded exercise have shown promise in helping reduce fatigue and improve function.
This review provides a conceptual framework integrating biological and psychological perspectives on ME/CFS aetiology, validating the complexity of the condition and moving beyond single-cause explanations. The evidence-based treatment recommendations (CBT and GET) offer patients and clinicians concrete intervention options supported by trial data, addressing the clinical uncertainty that often accompanies diagnosis.
This review does not establish causation—it synthesizes existing evidence and proposes a theoretical model without new experimental data. The model cannot definitively prove which aetiological factors are primary versus secondary, or explain why some individuals exposed to similar triggers develop ME/CFS while others do not. The effectiveness claims for CBT and GET are based on cited trials and do not address individual treatment variability or adverse response cases.
About the PEM badge: “PEM required” means post-exertional malaise was an explicit required diagnostic criterion for participant inclusion in this study — not that PEM was studied, observed, or discussed. Studies using criteria that do not require PEM (e.g. Fukuda, Oxford) are tagged “PEM not required”. How the atlas works →
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