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Increased Ventricular Lactate In CFS

Discussion in 'Latest ME/CFS Research' started by shannah, Jul 29, 2010.

  1. shannah

    shannah Senior Member

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    Increased ventricular lactate in chronic fatigue syndrome measured by (1)H MRS imaging at 3.0 T. II: comparison with major depressive disorder.
    by: James W. Murrough, Xiangling Mao, Katherine A. Collins, Chris Kelly, Gizely Andrade, Paul Nestadt, Susan M. Levine, Sanjay J. Mathew, Dikoma C. Shungu

    http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=20661876
    --------------------------------------------------------------------------------


    NMR in biomedicine, Vol. 23, No. 6. (July 2010), pp. 643-650.

    Abstract
    Chronic fatigue syndrome (CFS), a complex illness characterized by fatigue, impaired concentration, and musculoskeletal pain, is often misdiagnosed as a psychiatric illness due to the overlap of its symptoms with mood and anxiety disorders. Using proton magnetic resonance spectroscopic imaging ((1)H MRSI), we previously measured levels of the major brain metabolites in CFS, in generalized anxiety disorder (GAD), and in healthy control subjects, and found significantly higher levels of ventricular cerebrospinal fluid (CSF) lactate in CFS compared to the other two groups. In the present study, we sought to assess the specificity of this observation for CFS by comparing ventricular lactate levels in a new cohort of 17 CFS subjects with those in 19 healthy volunteers and in 21 subjects with major depressive disorder (MDD), which, like GAD, is a neuropsychiatric disorder that has significant symptom overlap with CFS. Ventricular CSF lactate was significantly elevated in CFS compared to healthy volunteers, replicating the major result of our previous study. Ventricular lactate measures in MDD did not differ from those in either CFS or healthy volunteers. We found a significant correlation between ventricular CSF lactate and severity of mental fatigue that was specific to the CFS group. In an exploratory analysis, we did not find evidence for altered levels of the amino acid neurotransmitters, gamma-aminobutyric acid (GABA) and glutamate + glutamine ('Glx'), in CFS compared to MDD or healthy controls. Future (1)H MRS studies with larger sample sizes and well-characterized populations will be necessary to further clarify the sensitivity and specificity of neurometabolic abnormalities in CFS and MDD. Copyright (c) 2010 John Wiley & Sons, Ltd.
  2. Dolphin

    Dolphin Senior Member

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    Edited: I was going to suggest delete this thread given the other thread http://www.forums.aboutmecfs.org/showthread.php?6553-neurometabolic-abnormalities-in-CFS-GAD-and-MDD but this one has the more accurate title so think it might be better to keep this one and delete the other one?
  3. Dolphin

    Dolphin Senior Member

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    This explains the paradoxical findings i.e. how MDD is not statistically different with either the CFS or control group. They actually tested 10 more MDD patients but couldn't use their data which reduced the power of the study:
    This is good - it suggests the mechanism isn't aging in CFS but something else
    MERUK/Dundee/Vance Spence studies on oxidative stress and Martin Pall papers are quoted a few times in discussion.

    Here is an extract:
    I'm not sure how relevant their talk of treatment-resistant MDD is to CFS. The treatments are likely to be different.
  4. Dolphin

    Dolphin Senior Member

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    A thread on an earlier study by the same group using the same methods is at: http://www.forums.aboutmecfs.org/showthread.php?3339-We-Got-Lactate-on-our-Brains!&highlight=Shungu

    The numbers from that study were:
    .
  5. Alesh

    Alesh Senior Member

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    Czech Republic, EU
    "...Insofar as cerebral hypoperfusion is known to
    increase brain lactate..."

    "... leading to increased levels of nitric oxide (NO)..."

    Isn't this an invalid reasoning? As far as I understand the mechanism of headaches from nitroglycerine use nitric oxide increases cerebral perfusion.

    My, totally naive and unimportant, hunch is that XMRV somehow disrupts or damages the cerebrovascular endothelium.
  6. Alesh

    Alesh Senior Member

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    I would have an idea to move to some high altitude place and see the effects of hypoxia: erythropoietin mediated neuroregeneration?, vascular endothelial growth factor mediated endothelial regeneration?
  7. Hope123

    Hope123 Senior Member

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    Haven't read the paper yet but when I was skimming the abstract, this also was interesting to me. Nitric oxide is a vasodilator -- e.g. makes blood vessels expand in circumference - and vasodilation/ blood vessels spasms have been been postulated to be a mechanism behind migraine headaches.

    One thing, perfusion in the brain operates differently from the rest of the body. Because it is so important for the brain to maintain blood flow, there are mechanisms within it (it's been a long time since I studied this) to maintain blood flow that other parts of the body do not have.

    It is a good question to ask the researchers though.
  8. cobollives

    cobollives

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    Lower Alabama
    This research leaves the question as to why both CFS patients and MDD patients have elevated levels of ventricular cerebrospinal fluid lactate in each patient group. Conducting research by adding the factor of exercise might provide some clues. Since MDD patients respond well to aerobic activity and the fact that aerobic activity causes the severity of symptoms to increase with CFS patients, it stands to reason that if there should be correlation between increased ventricular cerebrospinal fluid lactate levels and degree of severity of CFS symptoms, it follows that increased levels of aerobic activity would increase ventricular cerebrospinal fluid lactate levels in CFS patients. On the other hand, ventricular cerebrospinal fluid lactate levels should drop with MDD patients experiencing reduced symptoms. Furthermore, the results from both experiments suggests that the researchers may have stumbled over a possible link between GAD and MDD and further research into this phenomenon may lead to a better overall understanding of the origin of these illnesses.

    For CFS patients, my feeling that the origin of increased ventricular cerebrospinal fluid lactate levels is due to corruption of aerobic respiration process in the mitochondria [see Int J Clin Exp Med (2009) 2, 1-16 16]. It would be interesting to take it one step further to determine if CFS patients have corrupted DNA sequencing and if so there is incorporation XMRV retrovirus replicated DNA in CFS patients mitochondrial DNA.
  9. richvank

    richvank Senior Member

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    Hi, cobollives.

    I think you are correct about this. There is abundant evidence for mito dysfunction in CFS. In the GD--MCB hypothesis, the initial cause of the mito dysfunction is depletion of glutathione, which allows the rise in concentration of reactive oxygen species, which in turn react with aconitase in the Krebs cycle and other enzymes, partially blocking the oxidative metabolism. With the mito function partially blocked, the cells in the brain are forced to rely more on glycolysis for their ATP production, and since the pyruvate cannot be processed readily by the mitochondria, it converts to lactate, giving the elevated lactate results that are observed by MRS. If you would like to read more about this hypothesis, information can be found at www.cfsresearch.org by clicking on CFS/M.E. and then on my name.

    Best regards,

    Rich

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