@ duncan -- here's what I've learned so far.
1) The researchers used voxel-based regressions. This is a very subtle, sensitive way of gauging differences in brain anatomy using scans + statistics. Read the introduction in
this Wikipedia article for more.
2) In addition to voxel-based morphometry, they did T1 and T2-weighed spin echoes.
- T1w shows changes in levels of myelin.
- T2w shows blood volume in that region
3) They used 25 subjects who met BOTH Fukuda and CCC definitions, ages 19-47. They discontinued meds for the purposes of the study. Those who were too ill to stop their meds were excluded. Therefore it's viable to assume that,
like the vast majority of ME/CFS studies, this one only ended up testing people who have minor-moderate form of the illness.
Study period was delayed if the patient was too ill to get the scan, and then resumed once they were well enough to continue -- I think that's good practice, really, or you could lose a lot of subjects in a patient pop like this.
There were 25 age-, gender- and even weight-matched, non-related controls. They were not on meds and had no major illnesses.
4) Three CFS severity scores were used:
- Bell's CFS disability scale
- Somatic Symptom Score
- Fatigue
- Change in sleep pattern
- Dizziness on standing
- Muscle pain
- stomach symptoms
- overall level of function
- Neurological Symptom Score
- change in concentration
- change in short-term memory
- headaches
- emotional swings
(For these, low scores = higher severity)
They also carried out a Hospital Anxiety and Depression Scale (HADS) questionnaire.
5)
@duncan , these MR images were acquired on a Philips
1.5-T scanner.
6) They DID correct for multiple regressions (bless them).
7) Correlations were found between:
- CFS disability and somatic SS ; CFS disability and neuro SS; CFS disability and depression
- Somatic SS and Neuro SS; Somatic SS and depression
- Anxiety and depression (que surprise!)
There was no correlation between CFS disability and anxiety, or somatic symptoms and anxiety.
8) Nerve conduction through the midbrain appears to be impaired in CFS. This was shown through an increase in prefrontal myelination (via T1w) in sickest patients, and volume loss in midbrain white matter (via T2w).
9) CFS severity effects are not directly related to depression or anxiety (even though depression is correlated, it's not causative.) Anxiety and depression were included as 'nuisance' covariates in order to remove any apparent contribution to severity correlations.
If this appeared to weaken the correlation of damage to that part of the brain with CFS severity, one could feel more confident in saying that depression is at least a strong part of what drives CFS symptom severity; that is, it is a somatoform disorder.
Instead, both T1w imaging and T2w imaging with depression and anxiety 'removed' from the picture showed a stronger correlation to CFS severity rather than a weaker one. In other words, if you removed the 'white noise' caused by depression/anxiety, it strengthened the association between brain abnormalities and CFS severity.
Thus,
...depression is a statistical 'confounder'... Adjusting out the depression-related variance... results in a stronger statistical inference.... All MRI regressions with depression itself yielded only one cluster which was located in the same prefrontal WM in which the depression-independent T1w versus CFS severity regression was detected. That is, MRI signals in no other brain locations (which might influence CFS severity) correlated with depression, and therefore a depression-driven hypothesis for CFS was not supported here.
10) Volume loss might be due to astrocyte shrinkage; it's definitely not due to oligodendrocytes.
Overall conclusions:
Elevation of myelination is severity-dependent. There are midbrain nerve conduction issues in CFS, as defined by CCC, with midbrain volume loss and midbrain neuroinflammation. This might help explain autonomic and cognitive issues experienced by PWME. Despite the fact that severity of the illness correlates to depression, the neuroimaging studies don't support that CFS is caused by depression; in fact, when depression is eliminated as a 'possibility', the correlation between midbrain damage and CFS severity increases rather than disappears. CFS is therefore a distinct disorder rather than a form of depression.
Guys, please read this study for yourself. I am an absolute novice at both statistics and MRI, and, er...
That was the two topics. So.
-J