A WONDERFUL HYPOTHESIS TO CURE "SCHIZOPHRENIA"
EBV-infected B cells can be "immortalized" and then when they become Plasma Cells they can live longer than non infected mature B cells. It can give in my opinion an immune benefit (better response to re-infections by the same infective agents long-life).
But, EBV, Herpes Simplex and Varicella-Zoster Viruses belong to Herpesviridae Family, and all these Herpes are Neurotropic (= go to live in neurons and can cause neuritis). If a virus goes to live in a neuron, he steals (he takes away) nutrients to the hosting neuron. It means a competition for nutrients begins. This competition involves that the neuron has less nutrients, and then it works worse and can be irritated (where from the hallucinations). For example, Ribonucleotide Reductase of the Herpes is more affine for Iron than human Ribonucleotide Reductase and so the iron can be preferentially stolen so making neuron working worse.
In particular, Herpes Simplex I and EBV can be selective for the temporal lobe: the site in the Brain where acoustic neurons work.
It seems to me obvious that all diseases affecting Cerebral Temporal Lobe can cause auditive Hallucinations. It is important because a patient who hear the Voices can be treated as primitive schizophrenic patient!
Horton Arteritis, Chronic Active EBV (CAEBV), and Herpes Simplex silent Encephalitis are suspected in my hypothesis to cause a "false schizophrenia". It means a patient hear the Voices but not for idiopathic schizophrenia: differential diagnosis is important for the health and the wellfare of entire Society (and even NOT because to Schizophrenic patients is payed a Disability Pension, but especially because a young schizophrenic patient is a "LOSER").
It could be scientifically interesting to try a challenge with Acyclovir for 2-4 days, at right anti-encephalitis dosage, in suddenly onset unexplained "schizophrenia" of new diagnosis in young students who were in good health untill few days before the psychosis.
But, if in a detalied anamnesis Horton Arterits can be elicited, it could be interessant to try a challenge with a "sweet" immunosuppressive that is L-Tryptophan (plus vitamin D) for a week at about 700 mg / die dosage.
Normally, in lymph nodes of EBV carriers only one B cell among 100000 are EBV infected: this EBV infected B cell remains silent: it means it does not expose on the membrane the EBV antigens.
When a EBV infected B cell places EBV antigens in its cytoplasmic membrane, but T cytotoxic lymphocytes do not kill them (for example, for a defect in FAS pathway), the patient has a Chronic Active EBV.
EBV in our modern society by its re-activation can cause immunedysregulation with HLA alterations and can infect temporal lobe neurons and for that psychosys and schizophrenic traits, especially when combined with other predisposing conditions.
Predisposing conditions can be genetic or other preexisting diseases: maybe, for example, can be reported psychosis induced by "Juvenile Horton Arteritis" (a secondary form of cephalalgia) in patients suffering from EBV re-activation.
Professor Riccardo Dalla Favera explained how EBV helps the endemic form of Burkitt lymphoma onset: 1) First a chronic infection giving an antigen stimulation: it can be Malaria, Leishmania, Toxoplasma 2) Second, the immortalization of B cells by EBV (endemic in Africa and Est Guinea) 3) Overproliferation gives an error probability increased ant then the deregulation of c-Myc by a traslocation of Heavy or LIght chain promoter on c-Myc promoter in the chromosome 8 4) Finally, a p53 inactivation and a Ras hyperactivation.
IN MY OPINION EBV syndrome can cause auditive hallucinations by three ways:
- by activating endothelium in temporal lobes
- by infecting acoustic neurons ibidem
- by causing Horton Arteritis, an autoimmune disease I think EBV is able to induce
If a young patient has the onset of a light incipient Horton Artheritis can have auditive hallucinations especially in presence of EBV reactivation.
I propose as therapy for "Juvenile Horton Arteritis" vitamin D (1000 UI per day morning) and L-Triptophan at dosage of 175 to 525 mg per day once or twice or trice per day: for example 175 mg before breakfast; and if it is not enough also 175 mg before lunch, and 175 mg fasting in the evening (to increase KYNURENINE synthesis in the nigth). Corticosteroids can not be easily used in psychotic people because they worsen psychosis.
Maybe vitamin D can induce immunoregolatory cytokines. I do not know if Vitamin D good levels in serum are protective only for non genetically-predisposing autoimmunities or even for genetically predisposing autoimmunities. For example, Lupus Erythematodes Systemic is predisposed maybe by mutations in CR-1 (Complement Receptor 1). Alterations in H component of Complement predisposes to HUS (Haemolitic Uremic Syndrome), and HUS can be triggered by Streptococcus, Shigella, E. coli. For example, type I Diabetes is favoured in Vitamin D deficiency only in some HLA carriers, or for all individuals?
Vitamin D receptors are importantly on T-regulatory lymphocytes. T-reg lymphocytes are strong immunosoppressive in autoimmune reactions.
Horton Arteritis, also called Giant Cell Arteritis, can even cause meningitis.
As it is known, Horton Arteritis involves many organs (for example: the liver with granulomas and gammaGT rises) and evolves in blindness for retinic artery involvement.
IN MY OPINION: a young patient who has Horton artheritis, but he does not know, can refer to the physician only auditive hallucinations, AND NOT a slight pain (not the algic symptoms), because a patient can have the "avoidance" behaviour (underreporting), or even not to refers to physician (underreferral).
Anti-sense DNAs, anti-sense RNA, or RNA-interference agents, or miRNA strategies maybe will can eradicate EBV and Herpes Simplex.
IRON deficit can favour Herpes replication: why pregnant women in labour can HAVE genital herpes? Because they can be deficient in IRON!
In pregnancy oral bicarbonate and other alkalinizatings lower IRON absorption: it can be necessary for pregnant to take iron supplements.
Sodium bicarbonate can be usefull for nausea and for cephalalgia in pregnancy, but it can be necessary to supplement iron.
It is IMPORTANT to detect secondary forms of psychosis to avoid further costs for the entire society (schizophrenic people is "interdicted or inabilitated").
Are reported by doctors strange cases of brillant students suddenly become ill by Auditive Hallucinations.
In all, EBV infection (Common Mononucleosis), by immortalizing cells and summoning over-excessive immune response, DOES trigger MANY autoimmune syndromes (in function of individual HLA aplotype):
- Lupus Erithematodes Systemic, and Hughes also called ANti Phospholipid SYndrome (positivity for LUpus anticoagulant, anti-Cardiolipin, anti- Beta 2 Glicoprotein: these antibodies can cause cephalalgia)
- Multiple Sclerosis
- Primary Biliary Cirrosis
- Crohn Disease
- Horton Arteritis
- Rheumatoid Arthritis
- DIlatative CardioMioPathy
P.S.: It is interesting how EBV infection favours slatentization of HSV (herpes labialis and genitalis), I do not know why.
In Italian:
Propongo una ipotesi di vantaggio nella selezione Naturale offerto dalla infezione da EBV in passato.
Propongo una ipotesi di beneficio immunitario complessivo, dal momento che, a differenza delle altre infezioni congenite come quelle appartenenti al complesso TORCH, l'infezione da EBV non è quasi mai dannosa per il prodotto del concepimento.
Mentre la infezione ad esempio da CMV causa ritardo mentale e ipoacusia in numero cospicuo di neonati, mentre l'EBV al massimo puiò causare una sindrome linfoproliferativa rarissima e forse la sindrome rarissima di Duncan o di Purtilo nel neonato.
La mia ipotesi è che la infezione da EBV "immortalizzi" le plasmacellule memoria di lunga durata e così dia e soprattutto abbia dato una protezione nei confronti di infezioni alle persone infette.
Un tempo, fino a qualche centianaio di anni fa, le persone stavano molto più esposte al Sole, producevano più vitamina D, erano molto meno esposte a vagonate petroliere di antigeni che invece sono presenti oggi nell'ambiente: antigeni sintetici, farmacologici, infettivi a causa della globalizzazione e crescita della popolazione.
Quello che io penso è che, anticamente, l'EBV abbia in realtà aiutato a difendersi dalle altre malattie infettive senza creare un danno di tipo autoimmunitairo come invece avviene oggi....
Sappiamo infatti che l'EBV immortalizza i linfociti bloccando l'apoptosi mitorcondriale...
Se una persona si infetta a 14 anni di "influenza" (intesa largamente come qualunque infezione) e poi a 30 anni reincontra un ceppo simile ad esempio di virus, se è portatore di infezione da EBV secondo me se la cava meglio nei confronti della risposta anticorpale generata dalle long lasting Memory Plasma Cells alla nuova infezione.
Guido Emanuele Galasso MD