Brain-derived neurotrophic factor concentration may not be depressed in chronic fatigue syndrome

[Kati]

Brain-derived neurotrophic factor concentration may not be depressed in chronic fatigue syndrome

David M. Patrick, Ruth R. Miller, Theodore Steiner, Jennifer L. Gardy, Shoshana M. Parker and Patrick Tang (Vancouver, Canada))

Abstract:

Due to its effect on the central nervous system, brain-derived neurotrophic factor (BDNF) has been hypothesized to be involved in a number of neurodegenerative and psychiatric disorders.

Recently, BDNF was also reported to be significantly lower in patients with chronic fatigue syndrome (CFS) and multiple sclerosis patients, than in healthy controls.

We tried to repeat this observation in 25 patients with CFS matched to 25 healthy controls and 11 patients with systemic lupus erythematosus.

Our study did not find significant differences in BDNF between groups. Furthermore, we investigated the relationship between BDNF levels and fatigue within CFS sufferers using the fatigue severity score and found no correlation between the two measures.

Our findings act as a caution that results should be replicated in independent laboratories for validation, and we would welcome more research in this area.

(Each sentence has been given a new paragraph to make reading easier)

 

[halcyon]

I've been wondering lately if increasing BDNF would help or hurt. I didn't realize there were findings that it was low.

Our findings act as a caution that results should be replicated in independent laboratories for validation, and we would welcome more research in this area.

I agree with the last part, but how do they know they're right and the other study was wrong?

 

[WillowJ]

how do they know they're right and the other study was wrong?

A previous study had only 15 ME/CFS patients
http://omicsonline.org/open-access/...ple-sclerosis-2155-9562-S12-013.php?aid=25722

25 doesn't meet current standards for "large enough", either.

 

[halcyon]

I wonder why the follow up study used SLE patients instead of MS patients like the first study.

 

[WillowJ]

I wonder why the follow up study used SLE patients instead of MS patients like the first study.

I don't know. SLE seems to have an association with changes in BDNF (seems high here), but maybe only in those with CNS involvement. Or are changed only in those with insufficient treatment. I think the study numbers may be too small to draw any conclusions--there were only 11 participants with SLE.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2646658/

Between 18% and 67% of patients with SLE exhibit central nervous system involvement, which is associated with inflammatory features in the brain. Neuropsychiatric syndromes of SLE (NPSLE) patients often reveal various psychiatric features such as delirium, cognitive blunting, psychosis, and affective disorder (ACR 1999). Recently, we had reported that serum BDNF levels were increased in the presence of severe psychiatric symptoms and organic changes in the brain (Ikenouchi et al 2006). In that case, serum BDNF levels were normalized in parallel with recovering organic brain changes and improving their associated psychotic symptoms.

http://www.medscape.com/medline/abstract/24942492

Plasma BDNF level is increased in SLE patients and this increase is independent of the occurrence of NP manifestations. In addition, plasma BDNF levels increased with control of SLE activity, which points to the potential use of BDNF as a biomarker of response to treatment

If high anyway, not sure why increase in response to treatment would be good; maybe they meant decrease

 

[Kati]

I wonder why the follow up study used SLE patients instead of MS patients like the first study.

The research group is comparing ME patients to Lyme patient (if they accrued enough according to criteria as patients with Lyme were reluctant to participate) to SLE patients to healthy control, The research was blood pathogen based, as far as I know. It has not yet published but it may come in the future. (No timeline)

They chose SLE over other disease as a comparison group with the autoimmunity in mind I suppose. We will find out more when the main paper publishes

 

[SOC]

@Kati, do you know the quality of their ME/CFS cohort? In other words, what was the criteria they used to select patients? I'm not comfortable with the results of any research that uses patients without PEM in the CFS cohort. Not that I have any thoughts either way about BDNF, I've just become pessimistic about research that may not actually apply to us, so I find it helps to know what their entry diagnosis/requirements were before I take any results seriously.

 

[Kati]

I am quite sure that their cohort is solid and met the Canadian Consensus Criteria which included PEM. The patients were referred from local 'specialists' which included Dr Carruthers.

However we still need to remember that we are a heterogenous population and we have not yet been able to separate subsets. i am not sure what composition this group was, whether they were mostly long-timers and whether it mattered. Can we truly compare cohorts? In my opinion, unless they have been picked by the same doctors, I don't think so. also, until we have cohort sizes of 250 and more, until we can replicate results across groups and nations, results will remain sketchy.

i have not read the full paper for this, and quite honestly, I cannot even make sense of the abstract, and what it means.

At this point, I am just taking a laid back, wait and see approach. i am thankful that a new group, especially a local group is engaging in sound research, because this is exactly what needs to happen.

 

[SOC]

I am quite sure that their cohort is solid and met the Canadian Consensus Criteria which included PEM. The patients were referred from local 'specialists' which included Dr Carruthers.

Excellent! If they all met the CCC including PEM, I'm satisfied.

However we still need to remember that we are a heterogenous population and we have not yet been able to separate subsets. i am not sure what composition this group was, whether they were mostly long-timers and whether it mattered. Can we truly compare cohorts? In my opinion, unless they have been picked by the same doctors, I don't think so. also, until we have cohort sizes of 250 and more, until we can replicate results across groups and nations, results will remain sketchy.

Of course. At this point I don't see that we can subset further until we have a lot more scientific data. Our cohorts are going to continue to be mixed and possibly confusing. Are recent patients' results going to look different from long-term patients'? Are viral onset patients going to look different from patients with other onset patterns? Do mild patients have different cytokine/pathogen/genetic/whatever patterns from severe patients? We just don't know at this time. What I'm most concerned about today is that we stop including chronic fatigue and primary psych patients in our research cohorts. For me (at this time), PEM has to be a part of the illness of any patient in an ME/CFS/SEID research cohort. That is where my good/bad cohort line is drawn. Other people are likely to have different views on the matter.

 

[Simon]

Once is never enough...​

Recently, BDNF was also reported to be significantly lower in patients with chronic fatigue syndrome (CFS) and multiple sclerosis patients, than in healthy controls.

We tried to repeat this observation in 25 patients with CFS matched to 25 healthy controls and 11 patients with systemic lupus erythematosus.

Our study did not find significant differences in BDNF between groups. Furthermore, we investigated the relationship between BDNF levels and fatigue within CFS sufferers using the fatigue severity score and found no correlation between the two measures.

Our findings act as a caution that results should be replicated in independent laboratories for validation, and we would welcome more research in this area.

That's true across all of mecfs research (and for science in general - replication is the gold standard). Mecfs is awash with small unreplicated findings that may well not be real - meanwhile anyone is free to pick and choose findings to their liking from the vast body of minor research, which doens't really get us anywhere.

My very first blog was Once Is Not Enough and not much has changed since then, though at least we are now seeing much bigger studies (sometimes) and a few replications, such as this one.

I agree with the last part, but how do they know they're right and the other study was wrong?

A previous study had only 15 ME/CFS patients
http://omicsonline.org/open-access/...ple-sclerosis-2155-9562-S12-013.php?aid=25722
25 doesn't meet current standards for "large enough", either.

We are still in the dark - BDNF may or may not be associated with mecfs. Much bigger studies are needed. But in the meantime it makes sense to be cautious about findings on a few dozen or fewer patients (which covers most findings about this illness).

 

[leokitten]

FYI for people wondering how they determine BDNF levels in brain without taking CSF:
Blood BDNF concentrations reflect brain-tissue BDNF levels across species

 

[Sea]

I agree with the last part, but how do they know they're right and the other study was wrong?

I don't think they do know, that would be why they chose a conservative title that says BDNF MAY not be associated. Also why they say they would welcome more research into this area.