A Comparison of Neuroimaging Abnormalities in Multiple Sclerosis, Major Depression and Chronic Fatigue Syndrome (Myalgic Encephalomyelitis): is There a Common Cause?
A Comparison of Neuroimaging Abnormalities in Multiple Sclerosis, Major Depression and Chronic Fatigue Syndrome (Myalgic Encephalomyelitis): is There a Common Cause?
Gerwyn Morris 0 1 2 3 4 5
Michael Berk 0 1 2 3 4 5
Basant K. Puri 0 1 2 3 4 5
0 The Centre for Molecular and Medical Research, School of Medicine, Deakin University , P.O. Box 291, Geelong 3220 , Australia
1 Tir Na Nog , Bryn Road Seaside 87, Llanelli, Wales SA15 2LW , UK
2 Department of Medicine, Imperial College London, Hammersmith Hospital , London, England W12 0HS , UK
3 Orygen Youth Health Research Centre and the Centre of Youth Mental Health, The Florey Institute for Neuroscience and Mental Health and the Department of Psychiatry, University of Melbourne , Parkville 3052 , Australia
4 IMPACT Strategic Research Centre, School of Medicine, Deakin University , P.O. Box 291, Geelong 3220 , Australia
5 Department of Clinical Medicine and Translational Psychiatry Research Group, Faculty of Medicine, Federal University of Ceará , Fortaleza, CE 60430-040 , Brazil
There is copious evidence of abnormalities in resting-state functional network connectivity states, grey and white matter pathology and impaired cerebral perfusion in patients afforded a diagnosis of multiple sclerosis, major depression or chronic fatigue syndrome (CFS) (myalgic encephalomyelitis). Systemic inflammation may well be a major element explaining such findings. Inter-patient and inter-illness variations in neuroimaging findings may arise at least in part from regional genetic, epigenetic and environmental variations in the functions of microglia and astrocytes. Regional differences in neuronal resistance to oxidative and inflammatory insults and in the performance of antioxidant defences in the central nervous system may also play a role. Importantly, replicated experimental findings suggest that the use of highresolution SPECT imaging may have the capacity to differentiate patients afforded a diagnosis of CFS from those with a diagnosis of depression. Further research involving this form of neuroimaging appears warranted in an attempt to overcome the problem of aetiologically heterogeneous cohorts which probably explain conflicting findings produced by investigative teams active in this field. However, the ionising radiation and relative lack of sensitivity involved probably preclude its use as a routine diagnostic tool.
Chronic fatigue syndrome; Depression; Inflammation; Multiple sclerosis; Neuroimaging
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M a n y p a t i e n t s w i t h m u l t i p l e s c l e r o s i s ( M S ) , a
neuroinflammatory illness, major depressive disorder
(MDD), a neuroprogressive condition and chronic fatigue
syndrome (CFS) (myalgic encephalomyelitis), a phenotype
of no fixed aetiology, share a range of underlying
abnormalities [1, 2]. These include mitochondrial dysfunction; systemic
inflammation; oxidative stress; a range of autoimmune
phenomena; hypothalamic-pituitary axis dysfunction and
evidence of structural and functional brain change obtained by
neuroimaging using magnetic resonance imaging (MRI),
functional MRI (fMRI), magnetic resonance spectroscopy
(MRS), positron emission tomography (PET) and
singlephoton emission computerised tomography (SPECT) (also
known as single-photon emission tomography (SPET)) and
cognitive symptoms [1–3]. Neuroimaging abnormalities in
MS are well recognised, and there are numerous excellent
reviews on the subject [4–6]. There are also many excellent
reviews of neuroimaging abnormalities in MDD utilising
voxel-based morphometry (VBM) which is widely used
within neuropsychiatry [7–11]. Such neuroimaging abnormalities
are routinely seen in many patients afforded a diagnosis of
CFS according to international consensus criteria [3]. Such
abnormalities have been discerned via MRI [12–14], fMRI
[15–17], MRS [17–19] and PET [20].
Despite the existence of such data, however, there would
appear to be no comprehensive review of neuroimaging
abnormalities in patients afforded such a diagnosis which
includes the most recent evidence obtained via VBM analysis.
There have been few attempts to compare the transdiagnostic
neuroimaging data obtained for patients with MS and MDD
[2] although there have been several studies comparing
neuroimaging abnormalities seen in MS patients with or without
co-morbid depressive symptoms which appear to demonstrate
changes in global and regional patterns of white and grey
matter reduction [21–23]. Similarly, there have been few
attempts to compare neuroimaging data in MS, MDD and CFS
[2, 3]. We aim to remedy this by engaging in such an in-depth
review. We have chosen to focus on data examining
restingstate functional connectivity, white and grey matter structure
and volume and cerebral perfusion for two main reasons. First,
this renders the analysis manageable in terms of length.
Second, and perhaps more importantly, these parameters are
strongly influenced by the presence of systemic inflammation
[24–31]. Hence, by comparing and c (...truncated)