Evidence in chronic fatigue syndrome for severity‐dependent upregulation of prefrontal myelination that is independent of anxiety and depression

Abstract

White matter (WM) involvement in chronic fatigue syndrome (CFS) was assessed using voxel-based regressions of brain MRI against CFS severity scores and CFS duration in 25 subjects with CFS and 25 normal controls (NCs). As well as voxel-based morphometry, a novel voxel-based quantitative analysis of T1- and T2-weighted spin-echo (T1w and T2w) MRI signal level was performed. Severity scores included the Bell CFS disability scale and scores based on the 10 most common CFS symptoms. Hospital Anxiety and Depression Scale (HADS) depression and anxiety scores were included as nuisance covariates. By relaxing the threshold for cluster formation, we showed that the T1w signal is elevated with increasing CFS severity in the ventrolateral thalamus, internal capsule and prefrontal WM. Earlier reports of WM volume losses and neuroinflammation in the midbrain, together with the upregulated prefrontal myelination suggested here, are consistent with the midbrain changes being associated with impaired nerve conduction which stimulates a plastic response on the cortical side of the thalamic relay in the same circuits. The T2w signal versus CFS duration and comparison of T2w signal in the CFS group with the NC group revealed changes in the right middle temporal lobe WM, where impaired communication can affect cognitive function. Adjustment for depression markedly strengthened cluster statistics and increased cluster size in both T1w severity regressions, but adjustment for anxiety less so. Thus, depression and anxiety are statistical confounders here, meaning that they contribute variance to the T1w signal in prefrontal WM but this does not correlate with the co-located variance from CFS severity. MRI regressions with depression itself only detected associations with WM volume, also located in prefrontal WM. We propose that impaired reciprocal brain–body and brain–brain communication through the midbrain provokes peripheral and central responses which contribute to CFS symptoms. Although anxiety, depression and CFS may share biological features, the present evidence indicates that CFS is a distinct disorder. © 2015 The Authors. NMR in Biomedicine published by John Wiley & Sons, Ltd.

Progressive brain changes in patients with chronic fatigue syndrome: A longitudinal MRI study

“…Although most VBM processing and analysis is automated in SPM, several methodological options remain for user specification,19 especially in analysis of longitudinal image data. Inconsistent VBM findings in CFS patients in previous studies6, 7, 12, 14 motivated us here to validate segmentation and optimize VBM methodology. The VBM atrophy simulation experiment demonstrated (1) that normalization to a study specific template performs better than direct normalization to the default template provided in SPM12; (2) when the sample size is small, a random effects one‐sample t‐test of longitudinal difference images, either by means of the Jacobian difference method or the direct difference between different time points, has higher sensitivity than a paired t‐test of images from two time points; (3) that creation of a single image representative of the two time points (within‐subject template) for the purpose of the shared final spatial normalization should involve similar normalizations of both raw images and the same processing steps.…”

“…CFS severity was measured by three scores: the Bell CFS disability score,15 a somatic symptom score (Somatic SS), and a neurological symptom score (Neuro SS) 14. The Somatic and Neuro SS were derived from self‐scores of the 10 most significant symptoms 16.…”

Small-World Network Analysis of Cortical Connectivity in Chronic Fatigue Syndrome Using Quantitative EEG

“…For example, system-dependent coupling of oscillations has fundamental importance to CNS function and may be strongly influenced by delays in conduction velocity and myelin plasticity. Changes to white matter have been reported in CFS (Puri et al, 2012), also associated with clinical measures (Barnden et al, 2011), and a severity-dependent increase in myelination has also been found (Barnden, Crouch, Kwiatek, Burnet, & Del Fante, 2015). Disruption to white matter could explain the relationship between abnormal eLORETA coherence patterns over largescale complex systems in CFS.…”

Mortality in patients with myalgic encephalomyelitis and chronic fatigue syndrome

“…Compared to patients with depression, patients with ME and CFS have shown significantly lower scores on the SF-36, a different degree of disability and pattern of impairment [54]; different reporting of widespread body pain [55]; distinct brain physiology [56]; and differences in white matter volume [57]. These differences suggest that, although some patients also suffer from depression, as do some patients with other serious illnesses, ME and CFS are different from solely psychiatric illnesses such as major depressive disorder [58].…”