What causes chronic fatigue syndrome in adults?

Chronic fatigue syndrome in adults, also called myalgic encephalomyelitis, has no single established cause. The National Academy of Medicine formerly the Institute of Medicine concluded that ME/CFS is a serious, chronic, complex systemic disease and emphasized that multiple biological systems can be involved. Research increasingly treats the condition as multifactorial: an interplay of environmental triggers, immune and nervous system alterations, and individual vulnerability rather than a purely psychological disorder. Anthony L. Komaroff at Harvard Medical School has reviewed clinical evidence showing that many patients report an infectious illness or other physiologic stressor shortly before symptoms begin, which frames infection as a common trigger rather than the sole cause.

Biological mechanisms under study
Studies led by investigators at major institutions point to several overlapping pathways. William C. Reeves at the Centers for Disease Control and Prevention described immune abnormalities in subsets of patients including altered cytokine patterns and persistent immune activation. Avindra Nath at the National Institutes of Health has reported findings consistent with neuroinflammation and altered brain signaling in some people with ME/CFS, which may underlie cognitive symptoms and sensory hypersensitivity. Autonomic nervous system dysfunction, manifesting as orthostatic intolerance and abnormal heart rate or blood pressure responses, is documented in clinic series and by researchers at autonomic centers. Metabolic research reported by teams in academic centers indicates disturbances in cellular energy production and metabolic responses to exertion, which help explain the hallmark symptom post-exertional malaise where physical or mental activity leads to disproportionate and prolonged worsening.

Triggers, risk factors, and individual vulnerability
Commonly reported infectious triggers include Epstein-Barr virus, other viral and bacterial infections, and more recently a proportion of people developed persistent fatigue-like syndromes after SARS-CoV-2 infection. Genetic and epigenetic factors are under investigation as modifiers of risk and disease course, and psychosocial stressors may influence onset or exacerbation without being primary causes. The Centers for Disease Control and Prevention emphasizes that no single test identifies ME/CFS, and diagnosis relies on clinical criteria that capture the pattern of debilitating fatigue, unrefreshing sleep, cognitive impairment, and post-exertional symptom exacerbation.

Social, cultural, and territorial consequences
Consequences extend beyond biology. The National Academy of Medicine highlighted substantial reductions in work, education, and social participation among affected adults. Cultural attitudes toward unexplained illness and territorial differences in healthcare systems shape recognition, diagnostic practices, and access to symptom management. In some regions limited awareness and skepticism have delayed diagnosis and disabled access to supportive services, while other health systems such as the United Kingdom’s National Health Service have developed structured pathways for assessment and rehabilitation support. Stigma and disbelief exacerbate psychological distress for many patients and can impede appropriate care.

Given the current evidence base, leading experts and institutions stress the need for continued multidisciplinary research to clarify causal pathways, identify biomarkers, and develop targeted treatments. Clinicians are advised by public health authorities to validate patients’ experiences, manage symptoms, and coordinate care while research efforts refine our understanding of the complex causes behind chronic fatigue syndrome.