Reduction of serotonin transporters of patients with chronic fatigue syndrome

Abstract:

To assess the involvement of serotonin in the symptoms of chronic fatigue syndrome, we investigated the serotonergic neurotransmitter system of chronic fatigue syndrome patients by the positron emission tomography (PET).

Here we show that the density of serotonin transporters (5-HTTs) in the brain, as determined by using a radiotracer, [C](+)McN5652, was significantly reduced in the rostral subdivision of the anterior cingulate as compared with that in normal volunteers. This subdivision is different from that in the dorsal anterior cingulate in which binding potential values of individual patient showed a weak negative correlation with self-reported pain score of the patients.

Therefore, an alteration of serotonergic system in the rostral anterior cingulate plays a key role in pathophysiology of chronic fatigue syndrome.

 

Source: Yamamoto S, Ouchi Y, Onoe H, Yoshikawa E, Tsukada H, Takahashi H, Iwase M, Yamaguti K, Kuratsune H, Watanabe Y. Reduction of serotonin transporters of patients with chronic fatigue syndrome. Neuroreport. 2004 Dec 3;15(17):2571-4. http://www.ncbi.nlm.nih.gov/pubmed/15570154

 

Observer independent analysis of cerebral glucose metabolism in patients with chronic fatigue syndrome

Abstract:

OBJECTIVES: To evaluate cerebral glucose metabolism, assessed by 18-fluorodeoxyglucose positron emission tomography (FDG-PET), in patients with chronic fatigue syndrome (CFS), using an observer independent analytical approach; and to characterise any observed alterations by correlating them with neuropsychological deficits.

METHODS: 26 patients (13 female, 13 male) were examined. They all fulfilled the CDC diagnostic criteria for CFS. Their ages ranged from 26 to 61 years (mean (SD) age, 43 (9.3) years). They underwent extensive psychometric testing including the hospital anxiety and depression scale (HADS) and the short form 36 item health questionnaire (SF-36). Brain FDG-PET was done in all the subjects. After stereotactic normalisation, single subject comparisons with an age and sex matched normal database (n = 18) and a group comparison between the patients and normal controls were undertaken, along with additional correlation analyses between brain metabolism and psychometric test scores.

RESULTS: 12 of the 26 patients showed no significant decrease in FDG uptake compared with the controls. Of the remaining 14, 12 showed hypometabolism bilaterally in the cingulate gyrus and the adjacent mesial cortical areas. Five of these 12 patients also had decreased metabolism in the orbitofrontal cortex. The two remaining patients had hypometabolism in the cuneus/praecuneus. Correlation analyses showed significant correlations between some test scores (anxiety, depression, health related quality of life) but not fatigue and regional reductions in glucose metabolism.

CONCLUSIONS: Although abnormalities in FDG-PET were only detectable in approximately half the CFS patients examined, and no specific pattern for CFS could be identified, PET may provide valuable information in helping to separate CFS patients into subpopulations with and without apparent alterations in the central nervous system.

 

Source: Siessmeier T, Nix WA, Hardt J, Schreckenberger M, Egle UT, Bartenstein P. Observer independent analysis of cerebral glucose metabolism in patients with chronic fatigue syndrome. J Neurol Neurosurg Psychiatry. 2003 Jul;74(7):922-8. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1738575/ (Full article)

 

 

Brain positron emission tomography (PET) in chronic fatigue syndrome: preliminary data

Abstract:

Chronic fatigue syndrome (CFS) has been widely studied by neuroimaging techniques in recent years with conflicting results. In particular, using single-photon emission computed tomography (SPECT) and perfusion tracers, hypoperfusion has been found in several brain regions, although the findings vary across research centers. The objective of this study was to investigate brain metabolism of patients affected by CFS, using [18F]fluorine-deoxyglucose (18FDG) positron emission tomography (PET).

We performed 18FDG PET in 18 patients who fulfilled the criteria of the working case definition of CFS. Twelve of the 18 patients were females; the mean age was 34 +/- 15 years (range, 15-68) and the median time from CFS diagnosis was 16 months (range, 9-138). Psychiatric diseases and anxiety/neurosis were excluded in all CFS patients.

CFS patients were compared with a group of 6 patients affected by depression (according to DSM IV-R) and 6 age-matched healthy controls. The CFS patients were not taking any medication at the time of PET, and depressed patients were drug-free for at least 1 week before the PET examination. The PET images examined 22 cortical and subcortical areas.

CFS patients showed a significant hypometabolism in right mediofrontal cortex (P = 0.010) and brainstem (P = 0.013) in comparison with the healthy controls. Moreover, comparing patients affected by CFS and depression, the latter group showed a significant and severe hypometabolism of the medial and upper frontal regions bilaterally (P = 0.037-0.001), whereas the metabolism of brain stem was normal.

Brain 18FDG PET showed specific metabolism abnormalities in patients with CFS in comparison with both healthy controls and depressed patients. The most relevant result of our study is the brain stem hypometabolism which, as reported in a perfusion SPECT study, seems to be a marker for the in vivo diagnosis of CFS.

 

Source: Tirelli U, Chierichetti F, Tavio M, Simonelli C, Bianchin G, Zanco P, Ferlin G. Brain positron emission tomography (PET) in chronic fatigue syndrome: preliminary data. Am J Med. 1998 Sep 28;105(3A):54S-58S. http://www.ncbi.nlm.nih.gov/pubmed/9790483

 

Neuroimaging in chronic fatigue syndrome

Abstract:

The diagnosis of chronic fatigue syndrome (CFS) is made difficult by the absence of specific biomedical markers, and depends primarily on determining whether subjective information provided by the patient meets the clinical case definition of this syndrome. Reported cognitive difficulties and/or complaints of headache may instigate referral for brain imaging.

This article will discuss the value of neuroimaging in evaluating CFS, specifically reviewing studies that (1) used static magnetic resonance imaging (MRI) to assess structural abnormalities; and (2) assessed regional cerebral blood flow (rCBF) via detection of Tc-99m hexamethylpropyl-eneamine oxime distribution by single-photon emission computed tomography (SPECT). Future research design considerations are explored including (1) the utilization of positron emission tomography (PET) and other emerging neuroimaging technologies; and (2) methodological concerns, i.e., the influence of psychopathology (such as depression) and neurologic disease (such as multiple sclerosis) as possible confounding factors.

 

Source: Lange G, Wang S, DeLuca J, Natelson BH. Neuroimaging in chronic fatigue syndrome. Am J Med. 1998 Sep 28;105(3A):50S-53S. http://www.ncbi.nlm.nih.gov/pubmed/9790482

 

Postviral fatigue syndrome

Comment on: Possible upregulation of hypothalamic 5-hydroxytryptamine receptors in patients with postviral fatigue syndrome. [BMJ. 1992]

 

EDITOR, -A M 0 Bakheit and colleagues recently reported’ a possible upregulation of hypothalamic 5-hydroxytryptamine receptors in patients with the postviral fatigue syndrome, giving some evidence for hypothalamic functional abnormalities in these patients, which are different from others with depression. There is a growing body of evidence which claims that this clinical condition is organic and cannot be simply perceived as a somatisation disorder in patients with predisposition to psychiatric disease.”

We reviewed and quantitatively analysed with Ceretec and single photon emission tomography the brain perfusion of 14 patients fulfilling the Oxford criteria for diagnosis of myalgic encephalomyelitis. They had all had disease for more than six months (more than half the time) manifested with generalised malaise and myalgia, as well as significant physical and intellectual disability. None had any medical condition known to produce fatigue or had recently or in the past had psychiatric disease. When compared with a group of 24 nondepressed age and sex matched controls (normal volunteers) there was significant reduction of the perfusion to several areas of the brain cortex but particularly the brain stem (table).

You can read the rest of this comment here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1882397/pdf/bmj00077-0053b.pdf

 

Source: Costa DC, Brostoff J, Douli V, Ell PJ. Postviral fatigue syndrome. BMJ. 1992 Jun 13;304(6841):1567. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1882397/