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Table 1 Characteristics of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and sickness behavior

From: A narrative review on the similarities and dissimilarities between myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and sickness behavior

Category ME/CFS Sickness behavior
Physiosomatic symptoms Disabling fatigue Fatigue, lethargy, behavioral inhibition
  Mental fatigue Reduction of exploration
  'Pacing' as an energy-conservation strategy Reduced locomotor activity
  Post-exertion malaise following mental/physical activities Fatigability
  A flu-like malaise Malaise, flu-like symptoms
  Hyperalgesia Hyperalgesia
  Muscle tension and pain Muscle pain
  Sleep disorders Sleepiness
  High incidence of autonomic symptoms Probably yes, but not well documented
  Failure to concentrate Failure to concentrate
  Memory disturbances Memory disturbances
  Gastrointestinal symptoms -
Depressive symptoms May occur when comorbid depression is present Disinterest in social interactions
  Anhedonia may occur when depression co-occurs Anhedonia, or reduced intake of sweetened milk in rodent models
  Sadness Sadness
Anorexia/weight loss May occur when comorbid depression is present Anorexia and weight loss
Pyrexia Slightly increased body temperature in a few patients Pyrexia
Onset Acute onset or insidious Acute onset
Course Waxing and waning or progressive course Acute adaptive response
  Chronic course (>6 months) Maximal 19 to 43 days
Energy metabolism Mitochondrial dysfunction, lowered ATP, abnormally high lactate levels Is an adaptive behavioral response aiming to conserve energy and to redirect energy to immune cells to combat the pathogens
   Is an adaptive response to counteract negative energy balance
  Impaired oxidative phosphorylation Sickness behavior plays a key role in the resolution of acute inflammation
   When the energy stores are depleted and the acute inflammation is not resolved, chronic inflammation ensues
  Structural mitochondrial abnormalities  
  Accelerated glycolysis; decreased phosphocreatine synthesis rates following exercise  
Pathways (Sub)chronic inflammation with increased proinflammatory cytokines Acute inflammation with increased proinflammatory cytokines
  Cell-mediated immune (CMI) activation Probably activated
  Simultaneous T helper (Th)1 and Th2 responses -
  Multiple immune dysfunctions -
  Lowered antioxidant levels -
  Reactive oxygen species (ROS)/reactive nitrogen species (RNS) Probably yes
  Damage by oxidative and nitrosative stress (O&NS) to lipids, DNA, proteins -
  Autoimmune responses to O&NS modified neoepitopes -
  Autoimmunity -
  Reduced hypothalamic-pituitary-adrenal (HPA) axis function in some patients Enhanced HPA axis activity (part of compensatory (anti)-inflammatory reflex system (CIRS))
Triggers Multiple, not well defined Acute, highly defined
  Long-term effects of acute infection Acute pathogens and tissue injury
  Disease exacerbated by infections -
  Disease exacerbated by psychological stress -
  Chronic medical inflammatory illness -
  Chronic neuroinflammatory disorders -
  Autoimmune disorders -
  Sometimes no trigger factor is observed Is always a response to a defined trigger
Risk factors IgG, IgG1 and IgG3 deficiencies -
  Immune gene polymorphisms -
  Reduced ω3/ω6 ratio -
General Inflammation, O&NS and mitochondrial-related chronic progressive disorder Inflammation-induced adaptive behavioral and CIRS response that is conserved through evolution
Janus face Bad 'chronic' side: a chronic disorder with positive feedback loops between inflammatory responses and autoimmune processes Beneficial 'acute' side: supports inflammation, redirects energy to immune cells, conserves energy and prevents negative energy balance, helps eradicating the trigger, and has anti-inflammatory effects