1. Patients launch $1.27 million crowdfunding campaign for ME/CFS gut microbiome study.
    Check out the website, Facebook and Twitter. Join in donate and spread the word!
ME/CFS and the Magic of the Canine Factor
There's been plenty of research indicating that having pets is good for your health. I never really noticed any particular benefits to having cats, though that may have had more to do with my cats. They've been fairly indifferent to my presence and we've shared a live-and-let-live...
Discuss the article on the Forums.

Mitochondria in mental illness

Discussion in 'General ME/CFS News' started by Richie, Oct 26, 2013.

  1. Richie

    Richie

    Messages:
    45
    Likes:
    29
    I think pwME/CFS should be aware the role of mitochondria in mental illness is being increasingly investigated and emphasised as this has dangers and potential positives.
    Two links:-
    http://www.ncbi.nlm.nih.gov/pubmed/20691744

    Any attempt at monotherapy of undifferentiated CFS/ME cohorts with a-d's as the new CBT is thankfully probably unlikely due to recognised lack of success, but the affect of a-d's on mito function may be of interest. Esp interesting might be to try and determine whether the effect is direct and unrelated to a-d action (I think trimipramine has primary antiinflammatory effects), whether it is related to antimicrobial effects, or whether it is related to the a-d effect,esp through change in stress response.

    This link suggests differential approaches according to condition, which is sensible, of course.

    http://www.mitoaction.org/guide/fatigue-and-exercise-intolerance
    Wayne, SickOfSickness and rosie26 like this.
  2. anciendaze

    anciendaze Senior Member

    Messages:
    859
    Likes:
    882
    Virtually all psychotropic medication effective for almost any indication seems to have anti-inflammatory effects. This is the most consistent characteristic I've noticed. It is also at odds with common explanations of their actions.

    I've run across this repeatedly, but have never had the stamina to collect all the references in one place. Older anti-psychotic drugs sometimes caused serious immune problems like agranulocytosis, so perhaps you need to widen the definition beyond anti-inflammatory to include downregulation of immune response, and even damage to components of the immune system. Promising results with Rituximab come from its action of depleting a specific type of B-cell. This is one reason to look for autoantibodies in ME/CFS.

    On the other hand, various means of immune suppression have not been as useful as expected in known autoimmune diseases. This could be the result of suppressing immune functions which have been keeping undetected pathogens from replicating, in addition to harming host tissues. It is fairly common to find previously undetected infections in mental patients at higher rates of incidence than in the general population, so an hypothesis of immune impairment looks viable.

    This only addresses one aspect of your post. I'll leave the subject of effects on mitochondria to others.
    ukxmrv, rosie26, Wayne and 2 others like this.
  3. Richie

    Richie

    Messages:
    45
    Likes:
    29
    It's all quite confusing imo.
    It might be irrelevant to their action, whatever its mechanism.
    If it is clinically relevant it may be that addressing neuro-psychiatric circuitry indirectly relieves inflammation or it may be direct anti-inflammatoiry action.
    The fact that it occurs so widely across different classes of drug might suggest sth based on circuitry is going on. On the other hand many antibiotics are also anti-inflammatory, so it could be that just by chance a lot of different drugs have direct, unexpected anti-inflammatory effects, rlevant or not to their effect.
  4. Marco

    Marco Old blackguard

    Messages:
    1,237
    Likes:
    884
    Near Cognac, France
    I think they're slowly getting there.

    The serotonin hypothesis was always suspect given that serotonin reaches supposedly therapeutic levels within hours of starting AD meds while the therapeutic effects aren't seen for weeks.

    In contrast a single adminstration of ketamine gives almost instant relief an can last for a number of says.

    Rather than talk about "affective spectrum disorders" - they could more usefully talk about a spectrum of neuroinflammatory disorders which would include neurodegenerative ones and would also include a wide range of physiological effects not limited to affect.
    Sea, rosie26 and Wayne like this.
  5. anciendaze

    anciendaze Senior Member

    Messages:
    859
    Likes:
    882
    Hi, Marco, (Old blackguard).

    I am not simply talking about "affective spectrum disorders". This also applies to conditions deep in psychotic states. I've seen people hallucinating due to anaphylaxis from wasp stings. I'm willing to bet many here will report the chronic allergic rhinitis or sinusitis considered a predisposing factor. You might also consider that there has been some success in treating schizophrenia with minocycline, if done soon after onset. (I do not think waiting two years to treat possible infectious causes is appropriate.)

    On the subject of mitochondria and metabolism, I want to remind people that this is intimately connected with parts of immune response. One problem cells have to deal with is disposing of dysfunctional proteins which are either foreign or misfolded. There are ligands which attach ATP to these molecules, not just once, but repeatedly. These not only serve to tag molecules which might harm the cell, they also serve to power the cellular machinery which destroys them (proteasomes). If this is not possible, the cell may commit suicide (programmed cell death) to protect other cells carrying the same genes from infection.

    Researchers looking for SNPs which might explain diseases with unknown etiology, like MS, have found, more than once, that those SNPs correlating with the disease are in the genes coding for some of those ligands or receptors. This is not where they expected to find them, in genes coding for the nervous system. Here's an example in antiviral immunity. Here's an example in relation to TB. And, here's an example related to affective disorders. This also shows up in chronic lymphocytic leukemia. (I now realize my search picked up references to ligand-gated ion channels as well as the ligands I was originally discussing. I've decided to leave these in because the associations are very suggestive of a link between ATP, immune function and a variety of diseases which concern us.)

    The narrow view of "antioxidants" as good, and "oxidants", even superoxides, as bad, totally misses this function of metabolic attack on foreign proteins or pathogens, or on cells which are hopelessly compromised by them.
    Sea and Wayne like this.
  6. lansbergen

    lansbergen Senior Member

    Messages:
    1,027
    Likes:
    489
    I agree
  7. Marco

    Marco Old blackguard

    Messages:
    1,237
    Likes:
    884
    Near Cognac, France
    I appreciate that AD. I was quoting the terminology used in the first paper Richie linked to. I also appreciate that researchers are loathe to speculate beyond the data (no-one wants the sack after all) but the constant lack of breadth in science is a constant frustration to me (maybe due to too much exposure to James Burke's Connections series in the 1970's).

    How about hyperekplexia following an insect bite?

    http://jnnp.bmj.com/content/65/1/122.full
  8. Ecoclimber

    Ecoclimber Senior Member

    Messages:
    612
    Likes:
    987
    Mercer Island Wa
    What the researchers are attempting to do is define the symptoms of the CFS, Fibromyalgia and the CMI patient communities as mental illness issue rather than a medical issues using ill define cohorts of patients who have never been categorized under the CCC patient critieria but are grouped together with patients who have a depressive disorder...the old smoke and mirror tatics. Thier research is a theory based on a speculation and hypothesis and is not definitely answered in their research.
    Wayne likes this.
  9. Ecoclimber

    Ecoclimber Senior Member

    Messages:
    612
    Likes:
    987
    Mercer Island Wa
    As one prominent researcher aske me, who is ancientdaze as his analysis is quite flawed. MS, CLL, TB are not in any way shape or form associated with major depressive disorders. You tend to lean toward a psychiatric explanations for illnesses such as ME/CFS, Fibromyalgia and CMI based on your own personal situation and experiences.
  10. Wayne

    Wayne Senior Member

    Messages:
    2,189
    Likes:
    1,261
    Ashland, Oregon
    I had an aunt who had schizophrenia (and died at the early age of 40), so I'm always interested in anything having to do with this disorder. My aunt was one of the sweetest people, and I've never been able to understand (perhaps from a spiritual perspective) why she ended up dealing with such a devastating disorder. She apparently asked her brother (my uncle) a few months before her "first episode", whether he ever felt like he was losing his mind (which is apparently what she was experiencing at the time).

    Over the years, I've learned that in one particular study, various kinds of nutritional interventions allowed 90% of institutionalized schizophrenics to live independently on their own. My partner (a therapist) recently started working with a client who is schizophrenic. Turns out the "trigger" for his first schizophrenic episode was fasting (another hint at nutritional aspects). Without going into detail, I've also learned there's a variety of evidence indicating a pathogenic element to it as well, and a lot of evidence indicating gut issues are also a huge factor.

    Gut issues, nutritional status, immune system dysfunction, mitochondrial dysfunction, etc., all seem to be important and significant factors in most if not all brain/neurological disorders, including ME/CFS. I've come to believe unaddressed (and significant) structural issues of many different kinds in the spine and skull also play important roles. I rarely think these days in terms of "mental illness". I think more in terms of Central Nervous System dysfunction, and all the many elements that combine to create such difficult health conditions.
    PNR2008 and rosie26 like this.
  11. Marco

    Marco Old blackguard

    Messages:
    1,237
    Likes:
    884
    Near Cognac, France
    I'm sure Anciendaze is more than willing to respond for himself but everything I've read of his merits the opposite interpretation - that so called 'mental' illnesses will be shown to have a physiological and potentially pathogen based etiology. I tend to agree with the former but don't see any exclusive need to invoke the latter.
    rosie26 likes this.
  12. anciendaze

    anciendaze Senior Member

    Messages:
    859
    Likes:
    882
    I'm replying to the unnamed source.
    This appears to be a social construct of medicine rather than a feature of biological reality.

    Does he/she want a list of publications on depression in MS? Has he talked to Dr. Michael Snyderman about misdiagnoses of CLL? (As both an oncologist and patient.) Does he know that antidepressants were discovered in research on TB? Does he want a more recent reference to a patient who died because miliary TB was mistaken for MDD? How about studies which consistently show that the physical health of mental patients is poorer than those without mental illness? All are available, and are regularly ignored.

    The main aid to diagnosis of "real" physical disease is the fact that patients with progressive disease will die if you wait long enough, or develop convenient prominent signs. Chronic disease is consistently overlooked.

    Is it possible a large part of the medical profession regularly gets things in the wrong diagnostic category because they can't tell s*** from shinola? With this as input to research is it any wonder research on mental illness has gone approximately nowhere in terms of etiology, prevention and cures?
    Sea, merylg, rosie26 and 1 other person like this.
  13. anciendaze

    anciendaze Senior Member

    Messages:
    859
    Likes:
    882
    My back was bothering me when I wrote the above, and I posted before toning it down.

    The more moderate reply would be that the examples were deliberately chosen to emphasize differences. The main features in common are depression, fatigue, cognitive impairment and immune dysfunction. Isn't it time somebody took this seriously?
  14. anciendaze

    anciendaze Senior Member

    Messages:
    859
    Likes:
    882
    By sheer coincidence, I see that an article concerning the detection of pathogens in acute CNS infection has been published. From the abstract:
    Please note that these are recognized progressive CNS infections, which often lead to death. Among the minority of cases with identified pathogens we find: EBV, VZV, CMV, HHV1, HHV2. (Common herpes viruses.) We also find bacteria: Escherichia coli, Mycobacterium tuberculosis. Two enteroviruses were also identified. This is obviously not an exhaustive list, as in most cases they failed to identify a pathogen even though life-threatening infection was clearly present.

    What about chronic infections, where such methods are scarcely ever applied? Not only is it possible to miss well-known pathogens, it happens all the time. Yes, most of those millions with TB that is undiagnosed and untreated are outside the U.S. The number inside the U.S. is hard to estimate, but may well be in the thousands. We tend to catch those epidemics resulting from the most virulent strains, but have little idea about those that can persist for long periods. Compounding the problem, immune systems may not respond as expected to tests based on tuberculin when infection is chronic. This is only one non-controversial classic pathogen. (If you want controversy consider spirochetes, and the problem of detecting one for which you don't have an official test. This just might have some effect on reported incidence.)

    Other chronic infections are definitely present in the general population, but are not considered dangerous. When a patient shows up with shingles, how often do we trace this to an outbreak of chickenpox 20, 30 or 40 years in the past? How much time do we spend thinking about the effect on the ganglia where this infection lay latent for all that time? How often do we identify the reason the infection became active again? Less benign pathogens like HTLV may also remain latent for similar periods. These are merely pathogens we already know about.

    Anyone still want to argue that all medically-unexplained problems are the result of mental illness?
    Ema, merylg and SOC like this.
  15. Marco

    Marco Old blackguard

    Messages:
    1,237
    Likes:
    884
    Near Cognac, France
    @anciendaze

    Just pointing out that minocycline is also a glial attenuator while common beta lactam antibiotics also reduce neuroinflammation by increasing the activity of the glutamate transporter EAAT2. Efficacy of these antiobiotics in 'mental illnesses' doesn't necessarily indicate any pathogenicity.
  16. alex3619

    alex3619 Senior Member

    Messages:
    7,017
    Likes:
    10,794
    Logan, Queensland, Australia
    Some metabolic paths absolutely require oxidative molecules, mitochondrial function always makes oxidative molecules (and we want them to be able to make even more) and it is correct that we may want more oxidative capacity in our immune cells. The antioxidants are mostly present to prevent collateral damage. They are the firemen and paramedics who accompany the SWAT teams. We have way too much collateral damage, but if we get rid of the SWAT teams we are in big trouble.
  17. anciendaze

    anciendaze Senior Member

    Messages:
    859
    Likes:
    882
    Agreed, and this is the standard interpretation among doctors, that "neuroprotective" and anti-inflammatory effects are responsible. The fact that professionals have seized on an explanation which doesn't require them to change much that they are now doing should not be taken as proof that no infectious agent is involved, any more than the labeling of fluoxetine as an antidepressant should rule out its powerful effect on some enteroviruses.

    What I was doing above was listing the variety of infectious agents already known to slip by under the radar. (Even then I stopped short of invoking parasites, yeasts and fungi.) I've also pointed out that even in cases where no agent is identified, there is little doubt in the case of acute disease that such agents exist. It is only in the case of chronic disease that the emphasis shifts to biopsychosocial explanations.

    My attempt to point out that diagnostic ambiguity regularly confuses rheumatological and neoplastic processes with mental illness may have fallen flat. I've even heard respectable medical people suggest that depression and fatigue can cause cancer, rather than vice versa, because these symptoms commonly precede clinical onset. They seem unaware that this puts them in the same camp with certain gurus who claim to cure cancer (or AIDS) by teaching people to think positive thoughts.
    Sidereal, merylg and SOC like this.
  18. Richie

    Richie

    Messages:
    45
    Likes:
    29
    Ancien
    I think "cause" is often sloppy expression and what they mean is "predispose", which it could be argued is a better term in many instances of real physical "causality" - does smoking "cause" or "predispose" to cancer?
    I think it is quite possible to entertain the thought that depression and fatigue may predispose to physical illness. Both are physical phenomena with a physiological impact/correlates on/in the body, even if the depression originates in circumstance or thought/emotional patterns. So why not?
    Allowing this also gives a reasonable alternative to "somatisation" as a vague concept easily equatable with "making it all up" or "any plausible placebo will do" - the latter imo is an at least partial assumption behind some of the CBT/GETTers (and in the case of hard core false illness belief theorists, GET can only be a placebo ruse - why exercise for a false illness belief unless exercise is a placebo?).
    Just looked up quinolinic acid which is defiinitely found as an alternative tryptophan product in infection. It turns out it is also found in primary depressives. Are they infected? Are they immune activated due to non biological stresses? Is psychological stress compromising the blood brain barrier allowing immune insults from the circulation in whihc case it would be stress related but certainly not somatisation? (Although it might be argued that any intervention, incl placebo, which attenuated stress might be beneficial)
    Imo the answers aren't there yet, or at least not widely known, and may be highly individual.
    Last edited: Oct 31, 2013
  19. lansbergen

    lansbergen Senior Member

    Messages:
    1,027
    Likes:
    489
    Good one.
  20. anciendaze

    anciendaze Senior Member

    Messages:
    859
    Likes:
    882
    Hi Richie,

    The point here is that there are definite thresholds for diagnostic criteria. Pathological processes can start long before they reach clinical diagnostic thresholds. Ignoring this, and assuming a person is healthy until they pass some clinical threshold, can not only cause you to overlook real chronic disease, it can also cause you to reverse cause and effect. When this happens don't be surprised if research goes nowhere for decades. Here's an example in the case of Alzheimer's.

    Now, beyond the question of physical exercise and ME/CFS, consider those reports which claim mental exercise can stave off Alzheimer's. Has anyone tested the hypothesis that they are merely distinguishing patients with slower pathological processes from those with faster pathological processes? While I encourage people to use whatever mental abilities they have, I can't say that this really changes the underlying pathology. It may only allow them to compensate better for cognitive impairment which continues unchecked. (I'm thinking that they may be finding ways to accomplish mental tasks using parts of the brain which happen to be less impaired.)

See more popular forum discussions.

Share This Page