Multimodal and Simultaneous Assessments of Brain and Spinal Fluid Abnormalities in CFS,... Effects of Psychiatric Comorbidity, 2017, Natelson et al

[Hutan]

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5393352/

Abstract
The purpose of this study was to investigate whether CFS patients without comorbid psychiatric diagnoses differ from CFS patients with comorbid psychiatric diagnoses and healthy control subjects in neuropsychological performance, the proportion with elevated spinal fluid protein or white cell counts, cerebral blood flow (CBF), brain ventricular lactate and cortical glutathione (GSH).

The results of the study did not show any differences in any of the outcome measures between CFS patients with and without psychiatric comorbidity, thus indicating that psychiatric status may not be an exacerbating factor in CFS. Importantly, significant differences were found between the pooled samples of CFS compared to controls. These included lower GSH and CBF and higher ventricular lactate and rates of spinal fluid abnormalities in CFS patients compared to healthy controls. Thirteen of 26 patients had abnormal values on two or more of these 4 brain-related variables.

These findings, which replicate the results of several of our prior studies, support the presence of a number of neurobiological and spinal fluid abnormalities in CFS. These results will lead to further investigation into objective biomarkers of the disorder to advance the understanding of CFS.

 

[Hutan]

Participants for this study, which was conducted from January 2012 through February 2015, consisted of 44 patients fulfilling the 1994 case definition for CFS5 and 17 healthy controls who did not exercise more than once a week – i.e., sedentary,

Fukuda criteria

The presence of lifetime and current psychiatric diagnosis was assessed with the SCID6 administered by telephone. Current psychiatric diagnostic status was used to separate patients into two groups: CFS with current psychiatric diagnosis (CFS-P) and CFS without current psychiatric diagnosis (CFS-NP). All subjects underwent a battery of neuropsychological tests, which included the b Adult Reading Test, a measure used to estimate overall intellectual ability prior to illness onset7; the Gordon Vigilance and Distractibility Test, computer administered measures to evaluate sustained and focused attention as well as processing speed8; the WAIS IV Digit Span forward and backward, assessments of simple attention and working memory9; and the Rey-Osterrieth complex figure test, a measure of visuo-constructional ability and visual memory10. Additional mental and physical health and disability information was obtained using the Short Form Health Survey (SF-36)11, Profile of Mood States (POMS)12, Fatigue Severity Scale (FSS)13 and Center for Epidemiologic Studies Depression Scale (CES-D)

Some days after this intake process, proton magnetic resonance spectroscopy (1H MRS) was performed to measure ventricular lactate and glutathione and arterial spin labeling MRI to derive cerebral blood flow as fully described elsewhere15.
...
Regional cerebral blood flow in 39 a priori defined bilateral regions of interest was compared between groups

One patient completed only the symptom and mood measures and did not take part in any other procedures. As a result, this individual was excluded from all analyses which then reduced the final sample to 60 individuals (CFS: 43, Controls: 17). Due to incomplete participation in all testing sessions, the final samples for the neuroimaging (CFS: 35, Controls: 17) and spinal fluid analyses (CFS: 35, Controls: 13) were further reduced. There were no significant differences in age, gender breakdown or body mass index between patients and controls (Table 1). In addition, those individuals not included in either the neuroimaging or spinal fluid analyses due to missing data did not significantly differ from their peers on any of the demographic, symptom, or mood variables.

 

[SNT Gatchaman]

These results will lead to further investigation into objective biomarkers of the disorder to advance the understanding of CFS.

Not yet. Sadly the cited-bys are reviews and "may help withs".

 

[Hutan]

Sixteen of the 43 CFS patients (37.2%) were found to have current psychiatric diagnoses consisting of major depressive disorder, depression not otherwise specified, general anxiety disorder, post traumatic stress disorder, anxiety not otherwise specified, or phobia. Seven patients had an anxiety disorder diagnosis; 8 a depressive disorder; and 1 patient had both anxiety and depressive disorders.

Cognitive tests

There were no differences between controls and patients or between CFS-P and CFS-NP in any of the neuropsychological variables (p > 0.05). [these being the cognitive function tests]

Spinal fluid

Spinal fluid abnormalities were found in 9 of 35 patients (4 with elevated white cell counts, 4 with elevated protein concentrations, and 1 with both; Chi square = 4.11; p = 0.04) and in none of the 13 healthy controls. Presence or absence of psychiatric diagnosis did not affect results. There were no significant differences in peripherally obtained spinal fluid lactate levels among groups, and spinal fluid lactate did not correlate with ventricular lactate levels (r = 0.21, p = 0.17).

Neuroimaging

Pooled CFS patients, .. had significantly higher ventricular lactate and significantly lower occipital lobe glutathione than healthy controls (Figures 1 & 2).

some overlap but interesting

Cerebral blood flow, assessed in 39 regions bilaterally, was found to be significantly lower in CFS than in controls in only 3 regions: the frontal medial orbital, frontal superior medial and rectus gyri (Table 4); these CBF differences did not survive correction for multiple comparisons.

underwhelming result, given these three regions were the most different out of 39 regions.

 

[Joan Crawford]

This is the neuropsychological testing used:

"All subjects underwent a battery of neuropsychological tests, which included the b Adult Reading Test, a measure used to estimate overall intellectual ability prior to illness onset7; the Gordon Vigilance and Distractibility Test, computer administered measures to evaluate sustained and focused attention as well as processing speed8; the WAIS IV Digit Span forward and backward, assessments of simple attention and working memory9; and the Rey-Osterrieth complex figure test, a measure of visuo-constructional ability and visual memory10."

I've not seen the Gordon testing being used before in pwME. Seems an odd choice to use something new. It is used for ADHD assessment mainly. Digit Span is commonly OK ish in pwME. And the R-O doesn't necessarily get at the cognitive issues pwME face. Far better tests exist (for example PASAT - auditory information processing, working memory, time pressure etc) and it's a mystery why they were not used here.....

 

[SNT Gatchaman]

Cerebral blood flow, assessed in 39 regions bilaterally, was found to be significantly lower in CFS than in controls in only 3 regions

underwhelming result

Except the patients were scanned supine. The result might be quite different and stronger if they were in an upright MRI. This is one of the things we've been missing up until now -> #alltestsarenormal.

arterial spin labeling MRI to derive cerebral blood flow as fully described elsewhere[15]

[15] is Increased ventricular lactate in chronic fatigue syndrome. III. Relationships to cortical glutathione and clinical symptoms implicate oxidative stress in disorder pathophysiology (2012, NMR in Biomedicine) —

All neuroimaging studies were conducted on a research-dedicated, multinuclear, General Electric 3.0-T EXCITE MR system at Weill Cornell Medical College.

 

[Eddie]

Not yet. Sadly the cited-bys are reviews and "may help withs".

Jarred Younger presented some preliminary unpublished lactate data during the ME/CFS Research Roadmap series. It seemed to have a similar distribution to what they found in this paper; that there is overlap between HC and ME/CFS but a higher average and some patients with very clearly abnormal levels. This could reflect some patients being in PEM, as I'm pretty sure PEM was not specifically induced for either study. Not sure when it is planned to be published though.

 

[rvallee]

Sixteen of the 43 CFS patients (37.2%) were found to have current psychiatric diagnoses consisting of major depressive disorder, depression not otherwise specified, general anxiety disorder, post traumatic stress disorder, anxiety not otherwise specified, or phobia. Seven patients had an anxiety disorder diagnosis; 8 a depressive disorder; and 1 patient had both anxiety and depressive disorders.

All of those are routinely handed out to pwME, sometimes in alternative to, sometimes in addition to. So it's hard to say whether there is any validity to any of those. And the standard questionnaires for this mostly have overlapping questions so even if it's not just someone's opinion, there is no way to validate either way since the instrument is basically no better than a dowsing rod.

The DSM is often presented as a step forward, but frankly it has been a huge step backward for medicine because it sometimes works explicitly by taking the mere suspicion of something as a fact, when the medical standard is solid verifiable evidence most of the time. It's like twice-removed hearsay from an unverifiable source who commented anonymously counterbalancing anything but verified timestamped video. This is not the way to do things.

 

[Sean]

Sixteen of the 43 CFS patients (37.2%) were found to have current psychiatric diagnoses consisting of major depressive disorder, depression not otherwise specified, general anxiety disorder, post traumatic stress disorder, anxiety not otherwise specified, or phobia. Seven patients had an anxiety disorder diagnosis; 8 a depressive disorder; and 1 patient had both anxiety and depressive disorders.

All of which could easily be explained as the (secondary and contingent, i.e. unnecessary) consequences of having your life destroyed by a nasty disease, and even nastier neglect and mistreatment by the medical profession and society.

How often do you see those psychosocial factors being even mentioned by the psychosocial advocates, let alone robustly assessed and taken into account?

What is most interesting about those figures (and I would add in suicide rates) is that they are not a lot higher, given the extraordinary primary physical and secondary psychosocial (including economic) burden patients are having to endure.

What these figures really tell us is just how psychologically resilient patients are, under such extreme assaults.

There are psychosocial pathologies in play in this situation alright. But being unhappy about mistreatment and suffering, and speaking out about it and demanding it be fixed, is not one of them. What is indisputably a profound psychosocial and moral pathology is the abuse of power to prevent that situation being revealed and rectified.

 

[Eddie]

Stratifying patients by presence or absence of psychiatric comorbidity did not reveal significant subgroup differences in spinal fluid abnormalities, neuropsychological test results, ventricular lactate, cortical glutathione or cerebral blood flow. Thus, this study joins several prior others that found that the presence of psychiatric illness is not related to illness severity as reflected by illness course16,17, cognitive processing18, or physical function19. This result is very important because it indicates that neither the phenomenology of CFS nor its biology is driven by psychiatric diagnosis.

The study itself showed that these psychiatric diagnosis had no impact on the measured parameters. What is more interesting to me are the differences between the ME and control patients.

significant differences were found between pooled CFS patients and healthy controls that replicate the results of prior studies for higher rates of abnormal spinal fluid4, abnormally higher ventricular lactate15,20,21, lower cortical glutathione15, and lower regional cerebral blood flow3,22 in CFS.

 

[Joan Crawford]

What these figures really tell us is just how psychologically resilient patients are, under such extreme assaults.

Absolutely this.

 

[rvallee]

Absolutely this.

Hey we are Type A personalities after all! Well, some are. Not really statistically different than the whole population. And it doesn't affect outcomes. But it could! Imagine a world where it could. It would obviously explain why we all just give in to the "sick role". Well, we mostly don't, and those contradict one another, but it could be the case. Add an engine and some wings and you got a fully functioning airplane, you just have to meet a few conditions that aren't met and it's a perfect model of reality. It all makes sense if you don't think about it.

 

[Sean]

What these figures really tell us is just how psychologically resilient patients are, under such extreme assaults.

Extreme, and sustained.