Plain language summary
Chronic fatigue syndrome /myalgic encephalomyelitis (CFS/ME) is complex and probably triggered by several interconnected factors and the identification of these is essential to develop better treatments and preventative measures. This systematic scoping review of 1161 studies aimed to discuss potential causal factors of CFS/ME. The results showed that there were several main causal factors that were investigated in the literature and no single factor dominated the research; immunological, psychological/psychosocial/socioeconomic, infectious, and neuroendocrinal/hormonal/metabolic. Studies varied in their design and methods. Interestingly research in this area was at its highest before 1995 and from 2015-2019, studies have markedly decreased. It was concluded that large variations in methods and design of studies of causal factor studies, is problematic. More large, well designed studies are required especially as research has declined recently and considering post covid-19 fatigue. This study could be used by healthcare professionals to understand where there are gaps in the research to design more robust studies in the future.
BACKGROUND Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is understood as a complex condition, likely triggered and sustained by an interplay of biological, psychological, and social factors. Little oversight exists of the field of causal research. This systematic scoping review explores potential causal factors of CFS/ME as researched by primary studies. METHODS We searched eight databases for primary studies that examined potential causal factors of CFS/ME. Based on title/abstract review, two researchers independently sorted each study's factors into nine main categories and 71 subordinate categories, using a system developed with input given during a 2018 ME conference, specialists and representatives from a ME patient advocacy group, and using BMJ Best Practice's description of CFS/ME etiology. We also extracted data related to study design, size, diagnostic criteria and comparison groups. RESULTS We included 1161 primary studies published between January 1979 and June 2019. Based on title/abstract analysis, no single causal factor dominated in these studies, and studies reported a mean of 2.73 factors. The four most common factors were: immunological (297 studies), psychological (243), infections (198), and neuroendocrinal (198). The most frequent study designs were case-control studies (894 studies) comparing CFS/ME patients with healthy participants. More than half of the studies (that reported study size in the title/abstract) included 100 or fewer participants. CONCLUSION The field of causal hypotheses of CFS/ME is diverse, and we found that the studies examined all the main categories of possible factors that we had defined a priori. Most studies were not designed to adequately explore causality, rather to establish hypotheses. We need larger studies with stronger study designs to gain better knowledge of causal factors of CFS/ME.