Neurological Brain imaging, comparing adolescents with<unk>  and healthy controls showing abnormal network activity in regions of the brain.A range of neurological structural and functional abnormalities is found in people with<unk> , including lowered metabolism at the brain stem, and reduced blood flow to areas of the brain; these differences are consistent with neurological illness, but not depression or psychological illness. The World Health Organization classes<unk>  as a central nervous system disease. Some neuroimaging studies have observed prefrontal and brainstem hypometabolism; however, sample size was limited. Neuroimaging studies in persons with<unk>  have identified changes in brain structure, and correlations with various symptoms. Results were not consistent across the neuroimaging brain structure studies, and more research is needed to resolve the discrepancies found between the disparate studies. Tentative evidence suggests a relationship between autonomic nervous system dysfunction and diseases such as<unk> , fibromyalgia, irritable bowel<unk> , and interstitial cystitis. However, it is unknown if this relationship is causative. Reviews of<unk>  literature have found autonomic abnormalities such as decreased sleep efficiency, increased sleep latency, decreased slow wave sleep, and abnormal heart rate response to tilt table tests suggesting a role of the autonomic nervous system in<unk> . However, these results were limited by inconsistency. Immunological Immunological abnormalities are frequently observed in those with<unk> . Decreased NK cell activity is found more often in people with<unk>  and this correlates with severity of symptoms. People with<unk>  have an abnormal response to exercise, including increased production of complement products, increased oxidative stress combined with decreased antioxidant response, and increased Interleukin 10, and TLR4, some of which correlates with symptom severity. Increased levels of cytokines have been proposed to account for the decreased ATP production and increased lactate during exercise; however, the elevations of cytokine levels are inconsistent in specific cytokine, albeit frequently found. Similarities have been drawn between cancer and<unk>  with regard to abnormal intracellular immunological signaling. Abnormalities observed include hyperactivity of Ribonuclease L, a protein activated by IFN, and hyperactivity of NF-κB. Endocrine Evidence points to abnormalities in the hypothalamic-pituitary-adrenal axis (HPA axis) in some, but not all, persons with<unk> , which may include slightly low cortisol levels, a decrease in the variation of cortisol levels throughout the day, decreased responsiveness of the HPA axis, and a high serotonergic state, which can be considered to be a "HPA axis phenotype" that is also present in some other conditions, including post-traumatic stress disorder and some autoimmune conditions. It is unclear whether or not decreased cortisol levels of the HPA axis plays a primary role as a cause of<unk> , or has a secondary role in the continuation or worsening of symptoms later in the illness. In most healthy adults, the cortisol awakening response shows an increase in cortisol levels averaging 50% in the first half-hour after waking. In people with<unk> , this increase apparently is significantly less, but methods of measuring cortisol levels vary, so this is not certain. Autoimmunity Autoimmunity has been proposed to be a factor in<unk> , but there are only a few relevant findings so far. There are a subset of patients with increased B cell activity and autoantibodies, possibly as a result of decreased NK cell regulation or viral mimicry. In 2015, a large German study found 29% of ME/CFS patients had elevated autoantibodies to M3 and M4 muscarinic acetylcholine receptors as well as to ß2 adrenergic receptors. A 2016 Australian study found that ME/CFS patients had significantly greater numbers of single nucleotide polymorphisms associated with the gene encoding for M3 muscarinic acetylcholine receptors. Energy metabolism Studies have observed mitochondrial abnormalities in cellular energy production, but recent focus has concentrated on secondary effects that may result in aberrant mitochondrial function because inherent problems with the mitochondria structure or genetics have not been replicated.
Chronic fatigue syndrome
Hypothyroidism
Cancer-related fatigue
Idiopathic chronic fatigue
Da Costa's syndrome  Da Costa's syndrome  1
Exercise addiction
Medication phobia
Generalized anxiety disorder