van der Meer, J W · Nederlands tijdschrift voor geneeskunde · 1997
This review examines different theories about what causes ME/CFS, ranging from persistent infections and metabolic problems to psychiatric factors. While many potential causes have been proposed—including lingering infections, toxins, immune system problems, nervous system dysfunction, and hormone imbalances—none have been definitively proven. The authors note that psychological factors play an important role in how the illness develops and can be helpful in treating patients.
This review is historically significant because it documents the state of ME/CFS science in the 1990s and highlights the persistent challenge of identifying biomarkers or definitive causative mechanisms. It demonstrates that even after years of investigation, multiple competing hypotheses remained unresolved, underscoring the need for rigorous, mechanistic research—a challenge that continues today.
This review does not establish the validity or invalidity of any specific proposed mechanism, nor does it prove that ME/CFS is primarily psychiatric. The absence of substantiation at the time does not mean causes don't exist; it reflects the limitations of available research methodology and technology in 1997. This is a narrative review summarizing existing literature rather than presenting new empirical evidence.
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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