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A NEW METHOD FOR THE TREATMENT OF SCHIZOPHRENIA WITH A COMPOSITION OF CYTOKINES. AS A RESULT OF A CLINICAL EXPERIMENT, A LONG-TERM 100% REMISSION HAS BEEN REPEATEDLY OBTAINED


Voronov Alexandr Ivanovich

Candidate of Medical Sciences, Psychiatrist

Clinic of Pathology of Higher Nervous Activity

Novosibirsk, Russia

Mulka Bernd Germany, Munich.

Automation engineer, stepfather of one of the patients who took part in the clinical experiment, retired

Abstract. In our experiment, non-invasive cytokine monotherapy in more than half of the cases led to a long-term 100% remission in patients with an established diagnosis of "schizophrenia" (F20). The signs of the existing defect were reduced, including autism (in the understanding described by E. Bleyer). Independent physiological sleep was completely restored (according to the results of polysomnography). The ability to learn and work returned, social ties were restored. All patients taken in the experiment, prior to treatment with cytokines, were repeatedly treated with neuroleptics in psychiatric hospitals in Russia and the European Union without results.

Based on the results of the experiment, we have proposed a fundamentally new model of the pathogenesis of schizophrenia, which is based on:

1. Recognition of a defect in the astroglial network as the initiating and leading cause of the pathogenesis of all types of schizophrenia, including autism!

2. Damage to astroglia changes the sensitivity of tripartite synapses to dopamine, serotonin, and a number of other mediators. We abandoned the idea of neurocentricity in favor of the equality of astroglial and neural networks in the pathogenesis of psychosis.

3. A schizophrenic defect develops as self-poisoning of the brain due to a drop in the volume of the draining flow of cerebrospinal fluid in the glymphatic system. Delta sleep deficiency is the main cause of autointoxication. Normalization of slow sleep, in some, not neglected 107  cases, makes it possible to reduce the defect.

4. The CSF flow separating the dense layer of astrocyte pedicles from the cell layer of the vascular wall is an integral part of the blood-brain barrier! A multiple amplification of this flow occurs exclusively in the phase of slow sleep. The breakdown of this drainage mechanism is the main cause of the development of schizophrenia.

5. Exacerbation of F20 psychosis is always associated with a violation of the normal balance of cytokines. The goal of our therapy is to restore this balance. Psychotropic drugs bind dopamine in the synaptic cleft, artificially and temporarily stopping not the root cause, but only the consequences of this pathological process. By regulating the balance of cytokines, we gradually restore the draining mechanism of slow sleep, reduce autointoxication, so astroglia is revived. The remaining oligodendrocytes proliferate, as a result, axon myelination is restored. Astrocytes again become able to energetically support neurons. The clinical manifestations of schizophrenia gradually disappear. The genetic burden remains. This leads us to call the result obtained not a cure, but a remission, although clinically we see the regression of psychosis, often with a complete reduction of the defect.

Keywords: Monotherapy with cytokines gives a long-term 100% remission of F20.

The amount of non-REM sleep is an objective instrumental predictor of schizophrenia. The use of cytokines, in some cases, leads to the reduction of the schizophrenic defect.

For the first time in the history of psychiatry, we have cured schizophrenia! Of course, it would be more correct to say - to achieve a long-term 100% remission. This remission is complete, stable and lasts for many years. Our first F20 patients have already given birth to children, received education, including higher education, work successfully and live quite independently, forgetting about psychiatrists and not receiving any maintenance therapy… And it all started by chance... Not for nothing they say; "Chance is a great organizer!"

We were led to the discovery of this method of treating schizophrenia by a case of suicide that occurred in the spring of 1997 in the village of Novosibirsk Oblast. A local hunter, born in 1964, attempted suicide and was shot twice in the heart with a 12-gauge hunting rifle. The video is on our website; https://schizophrenia8.ru/video. On the same site you can read most of the articles to which we will refer. The patient's interview is on YouTube. https://www.youtube.com/watch?v=BkAtq6L1jKU&t=13s 

Both bullets went right through. The heart was not hurt. After the operation, a cryopreserved mixture of cytokines (CPRC) was instilled into the vein of the patient - a course (200 ml №7 each). The drug was developed at the Institute of Immunology and at that time was experimentally used in severe, often "hopeless" cases of extensive traumatic injuries, as well as after operations for resection of the lung lobes in case of tuberculosis, etc.

Among the doctors was a psychiatrist... He was delighted with the disappearance of imperative "voices from outer space" - pushing the patient to commit suicide. Antipsychotics and psychotropic drugs were not used in the described case. But! The most surprising was the complete disappearance of not only pseudo-hallucinations, but also of all productive symptoms against the background of sound independent sleep, immediately after the first droppers. Prior to the use of cytokines, this patient was observed in a psychodispensary, was repeatedly hospitalized and was discharged from the army due to paranoid schizophrenia.

For five years, no signs of psychosis occurred in the patient. Only then did the understanding of the special value of the use of cytokines in F20 arise. Subsequently, CPRC has been used to treat schizophrenia in a number of other patients. The result was excellent, but the experiments were not carried out regularly, and the film material was lost. Finally, in 2008, a real experiment was launched. As F20 monotherapy, CPRC was used in the form of a solution for a nebulizer, slowly inhaled, through the nose, or a sterile CPRC preparation was instilled into the eyes and nasal passages. Parenteral, intravenous administration of CPRC was carried out until 2017, but was discontinued after several cases of idiosyncrasy. All cases ended successfully, however, I did not want to risk the very idea, with the threat of complications. This could put an end to the entire experiment. The paradox was that patients recovered after cytokine therapy, but we did not understand the mechanism of action of cytokines. We tried to explain our results by stimulating stem cells in the olfactory zone, followed by homing of neurons to the hippocampus, etc. Now, it’s ridiculous for us to remember these clumsy attempts ourselves…[2,3,5]

Finally, we noticed that shortly before the reduction of psychoproductive symptoms, our patients had a strong long sleep, continuously up to 12-15 hours. Then, in addition to MRI and prepulse inhibition, we began to conduct polysomnography for our patients without fail. As a result, we were able to link the quality and quantity of delta sleep with the dynamics of the disappearance of psychoproductive symptoms and the reduction of the defect. In 2018, we published a figure [1,3,4,5] theoretically explaining the mechanism of CSF movement through the glymphatic system. We 109  realized that astroglial autointoxication is directly related to the lack of non-REM sleep and is completely dependent on the balance of cytokines.

Finally, in June 2021, we sent a paper to a conference in Birmingham about the "three vicious circles of the pathogenesis of schizophrenia". In the figure for this article, we schematically outlined three pathogenetic mechanisms [1] leading to the emergence of psychoproductive symptoms and the formation of a defect. At the same time, we drew attention to the limited therapeutic effect of neuroleptics and the impossibility of curing psychosis with their help... At the same time, we by no means call for the abandonment of neuroleptics, although we ourselves cancel them, but - "THE BEST IS THE ENEMY OF THE GOOD!"

It is easy to find a detailed description of the patients cured by us in the articles on the website https://schizophrenia8.ru/ so we decided not to clutter up the limited volume of publication with clinical examples, especially since in this article for the first time we called for co-authors not a doctor - a psychiatrist, but the stepfather of a participant in the experiment born in 1992, who conflicted with psychiatrists in Munich (Germany) for years about the treatment of his adopted daughter. Over the years, trying to help his daughter, he was forced to read a large amount of specialized literature on psychiatry and psychopharmacology, studied the law and gained invaluable experience in communication between psychiatrists, psychiatric institutions, police and relatives of patients with F20. The daughter has been ill since the age of 13. At the Munich University of Psychiatry and Psychotherapy, the adopted daughter of our co-author, after long ordeals, was diagnosed with hebephrenic schizophrenia (ICD-10 F20.1) in 2017. The daughter was hospitalized eight times in psychiatric institutions in Munich, and four times she was taken to psychiatrists by the police. We have 110  tried to preserve the style and way of presenting the thoughts of our coauthor. Here is his monologue: The diagnosis of "schizophrenia" is a blow of fate for close relatives and good friends. The person feels at the mercy of the disease without any hope. Find out what I went through. As parents, you do not want to accept the truth that a son or daughter has schizophrenia. Very important: this is a special type of disease that is difficult to diagnose at the initial stage using the methods adopted by psychologists and psychiatrists. The disease may occur in outbreaks. It comes back with other symptoms and may not respond to previously effective medications. BUT: the disease progresses and cannot be stopped by antipsychotics and similar psychotropic drugs, let alone cured! Treat only the symptoms, not the causes. You cannot rely on the testimony of psychologists and psychiatrists, even if their information seems to be very reliable. It is possible to help the patient alleviate his suffering with psychotropic drugs, but only for a limited time. Unfortunately, psychiatrists, especially in psychiatric clinics, all too often give too high doses of psychotropic drugs, without taking into account the significant side effects that the patient must suffer. In addition, the abolition of these drugs is a complex process that requires unconditional attention. It is also important that close relatives are concerned about the patient's capacity. When making a diagnosis of schizophrenia, I strongly recommend that you obtain a notarized power of attorney from the patient so that he has the rights of a guardian. When a patient is seen by his actions in public, he can be placed in a closed department, and then a foreign guardian can be established by the court. And all this without information to relatives. Without a certified power of attorney, parents and friends do not receive any information from doctors and even from authorities, especially if the patient is already an adult. I first met my adopted daughter at the end of 2002-beginning of 2003. She was a quiet, reserved and kind child. But even then I noticed her shyness. I really got to know her later, after she moved to Germany, in September 2005. She really wanted to study, especially in terms of learning German. Unfortunately, as parents, we received instructions from the German class teacher that the daughter stood out from other students and avoided contact with them. In the beginning, we were looking for a child psychologist. Then, we were instructed by a doctor to see a child psychiatrist in Landshut. There, the daughter was at receptions from February 2007 to July 2010. Initially diagnosed with "childhood social anxiety disorder" (F93.2) Later: "Social phobia" (F40.1 G). Paroxetine 20 mg was prescribed. As parents, we were not well aware of the side effects of paroxetine. We later learned that "Paroxetine should not be used to treat children and adolescents under the age 111 of 18, it produces suicidal behavior". At the beginning of 2011, my daughter passed the 12th grade of a technical school with a degree in economics. This was the level at which in the summer of 2011 the school ended with Abitur. It was a big stress for my daughter. In the spring of 2011, the daughter expressed thoughts of suicide, after which she was first placed in a psychiatric clinic in the city of Taufkirchen (from March 08 to April 29, 2011). A diagnosis of paranoid psychosis (F20.0) was made. Quetiapine 600 mg/day was promptly given. Doctors have not tried to succeed with lower doses. For us, as parents, being diagnosed with "schizophrenia" was like a punch in the face. Especially when it was predicted that the daughter would not bathe, take a shower, wash her hair. The daughter was prescribed paroxetine 20 mg once a day in the morning and 600 mg quetiapine in the evening. Further treatment took place through the psychiatric day clinic and the Freising institute ambulatory. Until the end of 12th grade, the medicine was not changed. The daughter successfully graduated from a technical school with a degree in economics in 2012 and began teaching by profession in September 2012. From 07.11.2016 to 21.12.2016 she was treated at the Westendstrasse Psychiatric Day Clinic in Munich. The following diagnoses were made there: "Social phobia" (F40.1), "Depressive episode of moderate severity" (F32.1) "Combined personality disorder with anankastic and schizoid proportions" (F60). In a conversation with the head physician, autism was suspected and contact with an autism specialist from the Max Planck Institute of Psychiatry was recommended. In the autumn of 2017, she also suffered from delirium and was admitted to the closed ward of the Nord Psychiatric Clinic for Psychiatry and Psychotherapy (Station P3) in Munich, after she ran away from home. She was diagnosed with "hebephrenic schizophrenia". During the stay, they tried to treat her with medicines, but this failed, as she secretly spit them out. On October 31, 2017, the daughter was discharged from the hospital. In February 2018, the daughter was still being examined by a psychiatrist from the Max Planck Institute for Psychiatry. 08.23.2019. Again she was taken by the police to the psychiatric clinic in Taufkirchen. Then she was diagnosed with "paranoid schizophrenia" (F20). Severe control limitations and auditory hallucinations were found. On 10.11.2019, the daughter was again hospitalized by the police at the Taufkirchen clinic. She was now diagnosed with "hebephrenia" (F20.1). Hallucinations and various obsessions were revealed. The 600 mg dose of quetiapine was immediately increased to 700 mg. However, it didn't get any better. The daughter showed herself very tired in the morning. Switching to haloperidol started on 10/30/2019 to 6 mg/day. However, akathisia and delusional symptoms soon appeared, 112  with the presence of the grandmother and vision or talking with ghosts. Then, starting on 11.19.2019, she was switched to clozapine up to 250 mg/ day. Then on 09.12.2019 haloperidol was cancelled. The daughter grew strong anxiety episodes, especially when she was alone in the room, the ghosts frightened her, and the deceased grandmother talked to her louder and badly assessed her. On 12.17.2019, risperidone was prescribed along with clozapine. 12.27.2019. Tiredness appeared, as well as hypersiallorrhea. As part of this antipsychotic combination, the daughter continued to report auditory hallucinations. The condition was horrendous for us as parents at the end of 2019. In addition to severe obsessions and hallucinations, we felt that the daughter was suffering from the side effects of haloperidol and clozapine. I had to listen to the phrase from the head physician: "Yes, you are resistant to therapy." The daughter was discharged on 12.31.2019. From 02.11.2020 to 05.25.2020, the daughter was hospitalized at the Clinic for Psychiatry and Psychotherapy at the University of Munich. They continued to drop psychotropic drugs from Taufkirchen. Was started with taking abilify (aripiprazole) up to 20 mg until 03.12.2020. Starting from March 24, 60 mg/day of duloxetine was additionally administered. In an MRI study, it was found that expanded internal and external CSF spaces that exceeded the age norm appeared without specific signs of atrophy or signs of acute accumulation of CSF, which is in good agreement with the picture in paranoid schizophrenia.From 07.01.2020 to 08.28.2020, the daughter was in the day outpatient clinic for psychiatry and psychotherapy at the University of Munich. However, all this time her condition did not change. After a long journey of suffering through German psychiatric clinics and after unsuccessful treatment with statements like "You are resistant to therapy!" my wife managed to find a Russian doctor who treats schizophrenia with cytokines. His approach was not the same as usual in Western Europe. We found hope and began planning our daughter's trip and stay with her mother. As of 10.09.2020, daughter started treatment in Novosibirsk, Russia. Antipsychotics prescribed so far have been cancelled. An analysis was made of only 9% delta sleep at a rate of 26%. An MRI of the head at 3 Tesla was performed. These objective methods quickly made it clear that the daughter was, in fact, suffering from schizophrenia. Thus began the treatment with cytokines, which are inhaled through the nose and dripped into the eyes. During my first telephone conversations with my daughter, I felt that she was again suffering from hallucinations, attention disturbances and thought circles. I attributed this to the discontinuation of antipsychotics. Then at the end of 2020, the hallucinations disappeared. The daughter was also more outspoken on the 113  phone. She answered not only "yes" and "no", but already with whole sentences. She began to be interested in many things. In the 1st quarter of 2021, the situation improved even more. She began to show emotions. Her features were no longer petrified. She understood jokes and tales and began to laugh contagiously at the same time. She became more and more natural. However, what is left is her circle of thoughts and her trouble concentrating. In the 2nd quarter of 2021, it developed for the better. She was interested in many things in life, cooking in the kitchen and much more. You could talk to her the right way. She began to pay attention to her hair. For some time, delta sleep rose to 17%, which showed that the treatment with cytokines was successful. The cycle of thoughts, unfortunately, was still very disturbing. In the 3rd quarter, the daughter proved to be very helpful and very interested during her stay in Germany. She was much more open and easy to talk to. In later phone conversations, I got the impression that she was happy, and each time it became an interesting conversation. Only the circle of thoughts has not yet gone and greatly hinders. I know that one should never give up hope, even if it can sometimes be a deceptive hope. My daughter is recovering. This is objectively evidenced by the increase in % delta sleep over time. 2020 09 11 9 % Norm: 26 % 2021 02 12 17 % Norm: 26 % 2021 05 27 17 % Norm: 26 % 2021 08 05 20 % Norm: 26 % Delta-sleep Delta-sleep Delta-sleep Delta-sleep 114


References

1. Voronov A.I. Vicious circles in the pathogenesis of schizophrenia. International conference. Process managemtnt and scientific developments juli 21. 2021 Birmingham.

2.Voronov A.I. A new look at the pathogenesis and treatment of schizophrenia // Academic Journal of Western Siberia. - 2018. - №3. - volume 14.

3. Voronov A.I. Reduction of defective symptoms as a result of longterm use of cytokines // Academic Journal of Western Siberia. - 2018. - №6. - volume 14.

4.Voronov A.I. et al. The leading role of astroglia in the pathogenesis of schizophrenia // Scientific Forum Siberia. - №2. - volume 6. - 2020.

5. Voronov A.I. Mechanisms of formation of schizophrenic defect // Scientific forum Siberia. - №1. - volume 7. - 2021