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New Studies Show Borna Disease Virus Infection in Psychiatric Patients

Discussion in 'Other Health News and Research' started by Hip, Jan 25, 2017.

  1. Hip

    Hip Senior Member

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    New Studies Show Evidence of Borna Disease Virus Infection in Psychiatric Patients

    Borna disease virus (BDV) infects a wide array of species, including: humans, horses, foxes, cats, dogs, cows, sheep and birds. It can cause Borna disease, a neurological syndrome involving viral infection of the limbic system and the brain stem. 1

    Borna disease virus (BDV) has been associated with a range of human diseases, including ME/CFS, major depressive disorder, bipolar disorder, schizophrenia, anxiety disorder, multiple sclerosis, amyotrophic lateral sclerosis, dementia and glioblastoma multiforme. 1

    But in 2012, Ian Lipkin, Mady Hornig et al published a major study examining the prevalence of BDV antibodies and BDV RNA in the blood (although they did not check the cerebrospinal fluid) of 198 schizophrenia, bipolar disorder and major depressive disorder patients, and found no association with Borna disease virus infection. They concluded that: "our results argue strongly against a role for BDV in the pathogenesis of these psychiatric disorders".

    And back in 1999, a study by Lipkin et al found no evidence of Borna disease virus infection in Swedish patients with ME/CFS (although this 1997 Japanese study found BDV in 34% of ME/CFS patients).

    So does that put paid to the idea that Borna disease virus could be involved in psychiatric disorders, or involved in diseases with psychiatric and physical symptoms such as ME/CFS?



    Borna Disease Virus Circulating Immune Complexes (BDV CICs)

    Not quite, it seems, because in the last few years, a couple of new studies have provided fresh evidence of Borna disease virus infection in psychiatric patients using a novel means of BDV detection, namely by looking for Borna disease virus circulating immune complexes (BDV CICs) in the blood of these psychiatric patients.

    I'll get to these two new studies in a moment, but first we need to understand a bit about the nature of these BDV CICs.

    In Borna disease virus research, there was an apparent problem of erratic and inconsistent BDV detection, with various epidemiological studies showing contradictory results. But in 2001, a German study (full paper here) claimed that BDV CICs are responsible for this problem of erratic and inconsistent detectability of the virus. They found that BDV CICs interact with free BDV antibodies and BDV plasma antigens, making detection by normal viral antibodies haphazard. So this German study seemed to explain the inconsistent results in BDV detection.

    Furthermore, the German study found that high levels of BDV CICs in the blood correspond to a high presence of BDV antigens in the blood (antigenemia). So the authors suggest that finding Borna disease virus CICs is an easy and reliable way to detect BDV infection, more reliable than BDV antibody detection.

    Additionally, the study authors demonstrated an association between BDV CICs and some psychiatric disorders: they found that 28 patients with major depressive disorder or bipolar disorder hospitalized due to severe depressive crisis nearly all had high BDV CIC levels, as did a further 28 patients with the same disorders who were just moderately depressed. Whereas in healthy controls, only 32% had high BDV CICs.

    So BDV CICs are potentially a more reliable means of detecting BDV infection.



    Two New Studies on Borna Disease Virus and Psychiatric Disorders

    Two new studies used Borna disease virus CICs as a means to detect BDV, and discovered that BDV infections are more frequently found in psychiatric patients:

    Primary psychosis and Borna disease virus infection in Lithuania: a case control study (2016)

    This Lithuanian study looked at 106 patients with acute primary psychosis admitted to a mental hospital (these patients had no physical illnesses). They found BDV CICs in 40% of the psychosis patients (indicating a BDV infection), but only in 22% of the healthy controls.

    Interestingly, this finding of BDV CICs in 22% of healthy controls is one of the lowest figures reported in Europe (the authors point out that in the Czech Republic, the figure is 37%).

    This study also details how BDV CICs are formed:

    Borna disease virus (BDV) infection in psychiatric patients and healthy controls in Iran (2014)

    This Iranian study focused on a total of 114 psychiatric patients admitted to psychiatric departments: 64 bipolar disorder patients, 12 major depressive disorder patients, 18 schizophrenia patients, 15 schizoaffective patients and 5 obsessive compulsive disorder patients.

    They found that in total, 40% of these psychiatric patients had BDV CICs, compared to 30% of healthy controls. In particular, in the bipolar, major depression and OCD patients, the BDV infection rates were high: 45%, 50% and 40% respectively.



    Borna Disease Virus and ME/CFS

    What all this means for ME/CFS is not clear. Although the1999 study by Lipkin et al found no evidence of Borna disease virus infection in ME/CFS, the study did not detect BDV infection by means of BDV CICs. So might BDV CICs exist in ME/CFS patients, indicating a BDV infection? I am not aware of any studies that have looked at this.



    Borna Disease Virus Testing Laboratory

    The following German laboratory tests for Borna disease virus infection by means of BDV CICs:

    MVZ Diamedis Diagnostische Medizin Sennestadt
    Dunlopstraße 50
    33689 Bielefeld

    www.diamedis.eu/Bornavirus.html (English translation here).

    Info sheet in English here.

    Note though that BDV CICs are found in around 30% of the general population, so it probably does not make much sense for individual ME/CFS patients to get tested. It would be more interesting to see if ME/CFS patients as a whole have a higher prevalence of BDV CICs, but that would require a study.



    Borna Disease Virus Antiviral Treatments

    The following drugs have efficacy against Borna disease virus:

    Amantadine 200 mg daily. 1 (Though others claim amantadine does not work for BDV).
    Ribavirin. 1
    Ribavirin + interferon alpha synergistic for avian bornavirus in parrots. 1
    Interferon gamma. 1
    2'-fluoro-2'-deoxycytidine. 1
    Favipiravir (Avigan) may have a strong antiviral activity against a broad range of bornaviruses. 1 Favipiravir has been approved in Japan for the treatment of influenza virus infections.



    Bornavirus Taxonomy

    Note that there are seven species of bornavirus identified, which each infect different animals, including humans. It is the mammalian 1 bornavirus species (which comprises two viruses: Borna disease virus 1 and Borna disease virus 2), that infects humans and other mammals and can cause Borna disease.

    And it is specifically Borna disease virus 1 (BoDV-1) that has been associated with psychiatric disorders in humans.
     
    Last edited: Mar 29, 2018
  2. IreneF

    IreneF Senior Member

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    Major psychiatric diseases are physical diseases, otherwise psychiatric drugs would have no ameliorating effects. They tend to run in families, too.
     
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  3. NotThisGuy

    NotThisGuy Senior Member

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    the german lab doesn't offer test for borna virus anymore.
    the new lab that plans to offer the test is:

    https://dedimed.com/

    But its unkown when exactly they plan to do it.
     
  4. ebethc

    ebethc Senior Member

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    @Hip

    slightly off-topic question:
    If you wanted to take a general test for CIC's, what is that test called?

    one of the top 3 supplements I've taken is Wobenzym which is pancreatic enzymes, plus rutin and bromelain. the literature says it breaks down CIC's, so i'm looking for the pathway reverse engineer the problem..

    thanks.
     
    merylg likes this.
  5. Hip

    Hip Senior Member

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    I am not sure about such tests, but Quest, LabCorp and ARUP all offer CIC tests. I don't know if these would have any relevance for testing for borna disease virus CICs.
     
    Last edited: Mar 29, 2018
  6. Hip

    Hip Senior Member

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    Here is an information sheet from www.diamedis.eu about Borna disease virus (BDV) infection in humans:
     
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  7. pattismith

    pattismith Senior Member

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    CIC test is also available in France in the main reference laboratory.

    Here what they say about it:

    "High levels of CIC are present in systemic lupus erythematosus, various autoimmune diseases and in some chronic infections including bacterial endocarditis.The specificity of a positive result is poor."
    and:
    "High concentrations of CIC are found in various pathological, autoimmune, infectious or neoplastic situations"


    "Circulating immune complexes (CICs) are antigen-antibody aggregates of variable size, non-covalently bound to the corresponding antigens. Their formation results from a classical reaction of protection of the immune system against the introduction of a foreign antigens. These CICs normally need to be rapidly cleared by the macrophage system. In certain pathological conditions, it is poorly eliminated and deposited at the level of the vascular endothelium causing damage by activation, including a complement system. High concentrations of CIC were found in various pathological, autoimmune, infectious and neoplastic conditions. The nature, size, and concentration of the antigen and antibody in the immune complex influence its ability to eliminate, and thus its pathogenicity. The antigens involved may be exogenous (whole microorganisms, toxins, viruses, allergens) or endogenous (rheumatoid factor, enzymes or circulating proteins). The complement system and the erythrocyte CR1 receptors are involved in the elimination of CICs: the activation of the proteins of the classical pathway allows the solubilization of the complexes and the erythrocyte CR1 receptors allow their transport to the phagocytic cells. The persistence of CIC may be due to a deficiency of C2 or C4 complement protein, often observed in systemic lupus erythematosus, or a decrease in the density of erythrocyte CR1 that can be observed in different situations (systemic lupus erythematosus, rheumatoid arthritis, hematology, etc.). CIC tissue repository can activate complement and trigger a series of destructive events."
     
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  8. Hip

    Hip Senior Member

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    Circulating immune complexes (CICs) are the issue in type III hypersensitivity autoimmune diseases like rheumatoid arthritis and systemic lupus erythematosus.

    Under the Coombs and Gell classification, the various types of hypersensitivity reactions found in autoimmunity and allergy are given in here.

    Circulating immune complexes consist of an antibody which has attached to its antigen.


    But in the case of Borna disease virus, I believe they test for a special type of CIC, caused by Borna disease virus antibodies attaching to their antigens.
     
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  9. pattismith

    pattismith Senior Member

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    Do you have any evidence that any laboratory offers a Borna virus specific CIC test?
     
  10. CFS_for_19_years

    CFS_for_19_years Hoarder of biscuits

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    In the FAQs on Human Borna Disease Virus Infection that Hip posted, the complete PDF is here:
    http://www.diamedis.eu/uploads/_download/FAQs, BDV, Human BDV, engl. 2010.pdf

    On Page 2 it says:
     
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  11. pattismith

    pattismith Senior Member

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    Thank you, it seems that this is the only lab that offers a specific and sensitive CIC test, but I went on the web site, and couldn't find any english page to order a test, no price, no payment terms, etc..;
     
  12. Hip

    Hip Senior Member

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    If you see @NotThisGuy's comment above, he says www.diamedis.eu are no longer providing this CICs Borna disease virus test, and that a new lab that plans to offer the test is https://dedimed.com.

    From this (Google-translated) page of the dedimed.com website, it seem that they are now offering this CICs Borna disease virus test by ELISA.

    But as I mentioned above, they say that 30% of the population have these BDV CICs anyway, so I am not sure that testing for BDV CICs would provide an individual patient with much information. But I don't understand the ins and outs of testing fully.

    Dedimed.com also have a FAQ document about BDV very similar to the original one from www.diamedis.eu I posted above.
     
  13. Lisa108

    Lisa108

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    Differentiated evidence of infection

    Our ELISA-format screening test measures Borna virus-specific immune complexes (CICs), which are made up of viral proteins and patient antibodies and can only be detected if the viruses have multiplied. In order to detect an acute illness, the virus proteins (antigens) are additionally determined, which indicate an acute activation thrust together with the CIC. However, antibodies (AK) say nothing about virus activity. Therefore, an additional antibody test is omitted.
    [https://dedimed.com/borna-virus/]
    (Translation by Google, bold by me)

    Costs: Borna AG (antigens?): 16,76 €; Borna CIC: 73,73€ (plus 5,20 € for blood sample tubes and shipping)
     
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  14. Hip

    Hip Senior Member

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    That is for acute illness, which I presume means the initial infection when you first catch Borna disease virus. But what about chronic BDV infection, which is linked to various neurological diseases?
     
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  15. Lisa108

    Lisa108

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    Hi @Hip! As I understand this, Bo-DV1 infection is a bit like herpes virus infection in that it stays with you once your are infected (= chronic persistent infection).

    So anyone infected should show CICs in the test by Diamedis.

    You can be infected with Borna virus and be asymptomatic, meaning your immunesystem sufficiently suppresses the virus. The test should show CICs.
    You can be infected with Borna virus and have symptoms, meaning your immunesystem can't suppress the virus suffiently. The test should show high CICs and AGs.

    You don't have to have an acute outbreak of symptoms in initial infection. The reaction to initial infection seems to depend on the strain of Borna virus you caught and the strength of your immunesystem at time of infection.

    Well, at least that is my opinion of today. I'm reading more into this, so sorry if I change my point of view tomorrow... ;)
     
    Hip likes this.
  16. Hip

    Hip Senior Member

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    Thank you for that explanation, @Lisa108. The cost of the Borna disease virus (BDV) tests at dedimed.com is not very much, so it may be an interesting test for ME/CFS patients to take, especially patients who also have depression, bipolar or OCD, which are apparently linked to BDV infection.

    I'd like to better understand how this lab tests for BDV; it might be an idea to email dedimed.com at some point, and ask for a more detailed explanation.

    I wonder also if there is any controversy about the reliability of the BDV test provided by dedimed.com (the sort of controversy that you find with some Lyme testing labs like ArminLabs or IGeneX). When tests are not validated by a central medical authority (like the CDC in the US), then there can be concerns about whether the test results are really meaningful.


    When it comes to regular ME/CFS viruses (like enteroviruses and herpesviruses), it is usually high IgG antibody titers that suggest a chronic active infection, and ME/CFS specialist doctors will typically treat patients with antivirals or immunomodulators when they have such high titers.
     
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