An increasing amount of neuroimaging evidence supports the hypothesis that chronic fatigue syndrome patients have structural or functional abnormalities within the brain. Moreover, some neurotrophic factors, neurotransmitters and cytokines have also been evaluated in order to elucidate the mechanism of abnormal neuropsychic findings in chronic fatigue syndrome. In this review, we suggest that the focal point of chronic fatigue syndrome research should be transferred to the central nervous system.
FukudaKStrausSEHickieI: The International Chronic Fatigue Syndrome Study Group. The chronic fatigue syndrome: A comprehensive approach to its definition and study. Ann Intern Med1994; 121: 953–959.
2.
LangeGWangSDeLucaJ: Neuroimaging in chronic fatigue syndrome. Am J Med1998; 105: 50S–53S.
3.
YamamotoSOuchiYOnoeH: Reduction of serotonin transporters of patients with chronic fatigue syndrome. Neuroreport2004; 15: 2571–2574.
4.
IchiseMSalitIEAbbeySE: Assessment of regional cerebral perfusion by 99Tcm-HMPAO SPECT in chronic fatigue syndrome. Nucl Med Commun1992; 13: 767–772.
5.
CostaDCTannockCBrostoffJ: Brainstem perfusion is impaired in chronic fatigue syndrome. QJM1995; 88: 767–773.
6.
TirelliUChierichettiFTavioM: Brain positron emission tomography (PET) in chronic fatigue syndrome: Preliminary data. Am J Med1998; 105: 54S–58S.
7.
LangeGDeLucaJMaldjianJA: Brain MRI abnormalities exist in a subset of patients with chronic fatigue syndrome. J Neurol Sci1999; 171: 3–7.
8.
BrooksJCRobertsNWhitehouseG: Proton magnetic resonance spectroscopy and morphometry of the hippocampus in chronic fatigue syndrome. Br J Radiol2000; 73: 1206–1208.
9.
SchmalingKBLewisDHFiedelakJI: Single-photon emission computerized tomography and neurocognitive function in patients with chronic fatigue syndrome. Psychosom Med2003; 65: 129–136.
10.
OkadaTTanakaMKuratsuneH: Mechanisms underlying fatigue: A voxel-based morphometric study of chronic fatigue syndrome. BMC Neurol2004; 4: 14.
11.
CleareAJMessaCRabinerEA: Brain 5-HT1A receptor binding in chronic fatigue syndrome measured using positron emission tomography and [11C]WAY-100635. Biol Psychiatry2005; 57: 239–246.
12.
de LangeFPKalkmanJSBleijenbergG: Gray matter volume reduction in the chronic fatigue syndrome. Neuroimage2005; 26: 777–781.
13.
YoshiuchiKFarkasJNatelsonBH: Patients with chronic fatigue syndrome have reduced absolute cortical blood flow. Clin Physiol Funct Imaging2006; 26: 83–86.
14.
CookDBO'ConnorPJLangeG: Functional neuroimaging correlates of mental fatigue induced by cognition among chronic fatigue syndrome patients and controls. Neuroimage2007; 36: 108–122.
15.
SchwartzRBGaradaBMKomaroffAL: Detection of intracranial abnormalities in patients with chronic fatigue syndrome: Comparison of MR imaging and SPECT. AJR Am J Roentgenol1994; 162: 935–941.
NatelsonBHCohenJMBrassloffI: A controlled study of brain magnetic resonance imaging in patients with the chronic fatigue syndrome. J Neurol Sci1993; 120: 213–217.
18.
PoteliakhoffA: Adrenocortical activity and some clinical findings in acute and chronic fatigue. J Psychosom Res1981; 25: 91–95.
19.
JerjesWKTaylorNFWoodPJ: Enhanced feedback sensitivity to prednisolone in chronic fatigue syndrome. Psychoneuroendocrinology2007; 32: 192–198.
20.
JerjesWKTaylorNFPetersTJ: Urinary cortisol and cortisol metabolite excretion in chronic fatigue syndrome. Psychosom Med2006; 68: 578–582.
21.
CleareAJ: The HPA axis and the genesis of chronic fatigue syndrome. Trends Endocrinol Metab2004; 15: 55–59.
22.
BardeYAEdgarDThoenenH: Purification of a new neurotrophic factor from mammalian brain. EMBO J1982; 1: 549–553.
23.
ChenRMoriyaJYamakawaJI: Brain atrophy in a murine model of chronic fatigue syndrome and beneficial effect of hochu-ekki-to (TJ-41). Neurochem Res2008 Mar 4; doi 10.1007/s11064–008–9620–1.
24.
TangSWChuEHuiT: Influence of exercise on serum brain-derived neurotrophic factor concentrations in healthy human subjects. Neurosci Lett2008; 431: 62–65.
25.
BerchtoldNCChinnGChouM: Exercise primes a molecular memory for brain-derived neurotrophic factor protein induction in the rat hippocampus. Neuroscience2005; 133: 853–861.
26.
MartinowichKManjiHLuB: New insights into BDNF function in depression and anxiety. Nat Neurosci2007; 10: 1089–1093.
27.
WuAMolteniRYingZ: A saturated-fat diet aggravates the outcome of traumatic brain injury on hippocampal plasticity and cognitive function by reducing brain-derived neurotrophic factor. Neuroscience2003; 119: 365–375.
28.
PangPTTengHKZaitsevE: Cleavage of proBDNF by tPA/plasmin is essential for long-term hippocampal plasticity. Science2004; 306: 487–491.
29.
Guzman-MarinRYingZSuntsovaN: Suppression of hippocampal plasticity-related gene expression by sleep deprivation in rats. J Physiol2006; 575: 807–819.
30.
HuangEJReichardtLF: Trk receptors: Roles in neuronal signal transduction. Annu Rev Biochem2003; 72: 609–642.
31.
ChenMJNguyenTVPikeCJ: Norepinephrine induces BDNF and activates the PI-3K and MAPK cascades in embryonic hippocampal neurons. Cell Signal2007; 19: 114–128.
32.
KoharaKKitamuraAMorishimaM: Activity-dependent transfer of brain-derived neurotrophic factor to postsynaptic neurons. Science2001; 291: 2419–2423.
33.
VaynmanSYingZGomez-PinillaF: Interplay between brain-derived neurotrophic factor and signal transduction modulators in the regulation of the effects of exercise on synaptic-plasticity. Neuroscience2003; 122: 647–657.
34.
ChenMJRusso-NeustadtAA: Exercise activates the phosphatidylinositol 3-kinase pathway. Brain Res Mol Brain Res2005; 135: 181–193.
35.
VasutaCCauntCJamesR: Effects of exercise on NMDA receptor subunit contributions to bidirectional synaptic plasticity in the mouse dentate gyrus. Hippocampus2007; 17: 1201–1208.
36.
GuanZPengXFangJ: Sleep deprivation impairs spatial memory and decreases extracellular signal-regulated kinase phosphorylation in the hippocampus. Brain Res2004; 1018: 38–47.
37.
CzarneckiABirtoliBUlrichD: Cellular mechanisms of burst firing-mediated long-term depression in rat neocortical pyramidal cells. J Physiol2007; 578: 471–479.
38.
NaritaMNishigamiNNaritaN: Association between serotonin transporter gene polymorphism and chronic fatigue syndrome. Biochem Biophys Res Commun2003; 311: 264–266.
39.
KatafuchiTKondoTTakeS: Brain cytokines and the 5-HT system during poly I:C-induced fatigue. Ann N Y Acad Sci2006; 1088: 230–237.
40.
LeonardBE: HPA and immune axes in stress: Involvement of the serotonergic system. Neuroimmunomodulation2006; 13: 268–276.
41.
PrinsJBvan der MeerJWBleijenbergG: Chronic fatigue syndrome. Lancet2006; 367: 346–355.
42.
DantzerRO'ConnorJCFreundGG: From inflammation to sickness and depression: When the immune system subjugates the brain. Nat Rev Neurosci2008; 9: 46–56.
43.
RostèneWKitabgiPParsadaniantzSM: Chemokines: A new class of neuromodulator?Nat Rev Neurosci2007; 8: 895–903.
44.
NatelsonBHWeaverSATsengCL: Spinal fluid abnormalities in patients with chronic fatigue syndrome. Clin Diagn Lab Immunol2005; 12: 52–55.
45.
MatsumuraSShibakusaTFujikawaT: Increase in transforming growth factor-beta in the brain during infection is related to fever, not depression of spontaneous motor activity. Neuroscience2007; 144: 1133–1140.
46.
AnismanHMeraliZPoulterMO: Cytokines as a precipitant of depressive illness: Animal and human studies. Curr Pharm Des2005; 11: 963–972.
47.
VgontzasANChrousosGP: Sleep, the hypothalamic-pituitary-adrenal axis, and cytokines: Multiple interactions and disturbances in sleep disorders. Endocrinol Metab Clin North Am2002; 31: 15–36.
