Paranoid schizophrenia, simple – symptoms, causes, treatment

Proven content

“As soon as he got out of the boat, a man with an unclean spirit ran to meet him from the tombs. He lived constantly in the tombs and no one could tie him even with a chain. Often, because he was tied in fetters and chains; but he broke the chains, and broke the fetters, and no one managed to tame him. And he was always day and night in the tombs and in the mountains, shouting and beating himself with stones … And he asked him, What is your name? He answered him, My name is Legion, for we are many.

Nearly 1% of the general population in civilized societies develops schizophrenia, however, as can be seen from the quoted Bible quotation, the problem of mental illnesses with psychotic symptoms occurred already in antiquity, although psychiatrists working among the peoples of the so-called Primary groups emphasize that the percentage of schizophrenia is much lower among them than in civilized societies. About a quarter to a half of patients in psychiatric hospitals are patients with schizophrenia.

Schizophrenia most often occurs between puberty and full maturity, i.e. between the ages of 15 and 30. It is therefore a serious social problem, the more acute that it mostly affects young people. Schizophrenia can begin suddenly, dramatically, leaving no doubt that you are dealing with a mental illness, or secretly, when the immediate environment is not aware of the developing disease process for months or even years, only a sudden exacerbation or progressive degradation signals psychosis . Schizophrenia is a very severe, chronic disease that interferes with what is at the heart of everyone’s personality – brain function. The schizophrenic thinks and perceives the world differently. Delusions, hearing and seeing things that others believe are not there, apathy, depression, insomnia, trouble concentrating, suicidal thoughts destroy the patient’s life. Schizophrenia causes almost complete psychological isolation of the patient from the environment. Patients lose their friends, the opportunity to learn, work, and communicate. The greatest tragedy in this disease is the destruction of ties with other people and the lack of acceptance of the environment. Rejection by relatives and friends, fear and stigmatization that accompany the sick exclude them from society.

Symptoms of schizophrenia

In 1911, Eugeniusz Bleuler created the concept of schizophrenia from the Greek schizo – I split, split, tear, and fren – diaphragm, heart, mind, will. He did not treat schizophrenia as a single disease entity, but spoke about schizophrenia or a group of schizophrenia, thus emphasizing the possibility of a different etiology and pathogenesis of the disease process. Contrary to popular belief, schizophrenia does not mean having more than one personality (the so-called multiple personality, split personality). . maladjustment of the patient’s behavior and emotions to the situation and the content of his speech. Schizophrenia is sometimes called royal disease. It is not only the eminent minds that suffer from it, but also its enormous variety of symptoms, which makes an accurate description of schizophrenic disorders extremely difficult. Schizophrenia never gives the same picture. Although delusions and hallucinations may be similar in two patients, the history of each patient is slightly different. So it is not a homogeneous disease. Nevertheless, psychiatry assumes that schizophrenic disorders share some common characteristics, including:

– progressive loss of contact with the world and the predominance of interest in inner experiences

– emotional indifference leading to emotional emptiness and loss of emotional ties with the environment

– personality disintegration manifested by the lack of intellectual contact with reality, the lack of compatibility of the content of feelings and thoughts with the simultaneous occurrence of two contradictory judgments, feelings, or aspirations.

There are four forms of schizophrenia – simple, hebephrenic, catatonic and paranoid. These characters often mix and blend into each other. Sometimes it is even difficult to determine which of them is dominant.

Simple schizophrenia it is characterized by gradually increasing indifference, apathy and depressed mood. The sick person ceases to be interested in the fate of his loved ones and his own. As joyful as sad events flow down him without traces. He sometimes accepts even the death of the closest person with surprising indifference. On the other hand, minor unpleasantness can provoke violent outbursts of bad mood, anger or depression. Initially, the patient does not neglect his duties, but performs them in a stereotypical manner, without initiative, like an automaton. The results at school or at work are getting worse. Sometimes stubbornness comes to the fore. The patient clings to certain stereotypes of behavior, becomes angry when attempts are made to violate them, as if everything would turn to rubble with their overthrow. He cannot be persuaded to change the style of dressing, brushing, eating, agenda, etc. Over time, the quirks multiply.

Hebephrenic schizophrenia characterized by childish and disorganized behavior of the patient, his affection is shallow and mismatched to the situation, and his statements and behavior are chaotic and pointless. Hebefrenik is mobile, has various ideas, which he implements without hesitation, often shocking his surroundings. Here he will make a silly face or show his tongue, there he will burst out laughing at a serious moment, sometimes he will spoil or destroy something just for a joke. He accosts everyone, does not recognize distance, asks stupid questions and laughs for no reason. Even when he is alone, he sometimes laughs to himself or makes silly faces. He fulfills the commands in the wrong way. The answers are ridiculous, unrelated to the question. He often speaks a lot, but not always clearly, jumping from topic to topic, associating according to random similarity of words, repeating the same phrases, creating neologisms

For catatonic schizophrenia the most characteristic is the image of motor inhibition, the patient stiffens and takes unnatural positions (e.g. standing on one leg, raising the head above the pillow), which he maintains for hours or even days; during this time, the patient does not take meals, hence it is a life-threatening condition; this state is called stupor. Stupefied, the sick person, wide-eyed, staring into the distance, stands motionless like a statue. There is a stony calm, fear or delight on the face. The pupils are sometimes maximally dilated and sometimes react poorly to light. One has the impression that nothing reaches the patient, that the normal rhythm of interaction with the environment has been broken, the patient seems to freeze at one point in time, it is not known what will happen in a moment. The patient does not respond to questions, comments and orders. When an attempt is made to actively force him to some activity, he resists (active negativism) or passively gives up (passive negativism). In the second case, the patient can maintain the assigned body position – e.g. a raised arm or leg – for a long time, significantly exceeding the limits of a mentally healthy person. The observer’s impression that a patient in catatonic stupor does not perceive stimuli from the environment because he does not react to them at all is illusory. After recovering from acute stupor, such patients sometimes tell in detail what was going on around them at that time, and their experiences from this period may correspond to objective reality or be related only to their subjective hallucinatory-delusional reality. Stupor may be suddenly interrupted by the patient’s sudden arousal, which may be a threat to the patient’s life or health or his surroundings.

In paranoid schizophrenia the dominant symptoms are delusions (most often persecutory, infidelity, grandiose) and hallucinations (usually auditory, threatening or commanding). In the formation of the delusional structure, we can distinguish three phases – expectations, enlightenment and ordering. The waiting phase is characterized by a state of strange tension, anxiety, a feeling that something must happen, break the feeling of uncertainty, lighten the darkness that surrounds the patient. This moment comes in the dazzle phase. Suddenly everything becomes clear. The new way of seeing that arises in delusional revelation is about life; everything is seen differently from one point forward. If in the first phase the mood of uncertainty, fear that something is happening around the patient and in himself that he cannot understand, then in the second phase he experiences a state of revelatory delight; finally, the essence of the matter was reached, uncertainty was replaced with certainty. The picture of the new world is still chaotic, foggy; you already know the truth, but not everything sticks to its logical whole. It is only in the third phase that everything starts to organize itself into a logical whole. The delusional concept becomes coherent, all the facts of life are organized according to its structure. It is confirmed by events both close and distant in time and space. There is nothing that is not somehow related to it. The sick person tells the story of his life with the smallest details, these details prove his delusional right in a way that is too logical. It happens that the patient with their behavior does not raise any objections to those around him, until he begins to talk about his most personal experiences. “The façade of personality is often preserved here, and the sick person gives the impression of being normal in their surroundings and is not immediately excluded from social life. The delusional system is often directed against the environment, which can lead to attacks of defense, revenge or fulfillment of its delusional mission.

Delusions, delusions and hallucinations are the so-called positive or productive psychotic symptoms, withdrawal from life, limitation of initiative, shallowing of emotions are the so-called negative symptoms.

In order to diagnose schizophrenia, its symptoms must be present for a certain period (1 month).

It is extremely important that the presence of a single symptom of any of the listed schizophrenic disorders is not synonymous with the diagnosis of schizophrenia. The diagnosis should be made only by a psychiatrist.

The causes of schizophrenia

For many decades, some specialists have argued that the disease is not caused by disturbances in the functioning of the brain, but by the destructive intra-family relationships during adolescence. One theory suggested that schizophrenia arises as a result of repeated encounters with a double message from the parents, i.e. a situation when a child receives contradictory information, e.g. the mother tells him that she loves it, but is indifferent to it and repels it from herself. George Bateson (English anthropologist, sociologist and linguist) observed a specific pathological way of communication between mothers and their sons diagnosed with schizophrenia. The mother of the future schizophrenic may tell him that she loves him, admires him, etc. – on the level of words, but she may feel hostile towards him through non-verbal communication (no sensitive gestures, no tone of voice, etc.). This type of behavior may occur if the child evokes a feeling of ambivalence in the mother, i.e. love and hate at the same time. This is possible, for example, when a woman wants to make a career but becomes pregnant unexpectedly and unintentionally. Upon the birth of a child, the mother devotes a lot of time and effort to it, unable to continue to fulfill herself professionally. This can sometimes cause her disappointment, which will be expressed on the level of non-verbal communication, while in verbal communication the mother will emphasize her attachment and love. Double messages cause confusion, cause confusion in the child’s mind, destroy his sense of security and do not allow the meaning of the information to be read adequately to the situation. This situation destroys the child from the inside and impairs his psyche. Many other concepts indicated marriage problems, emotional immaturity of parents or permanent conflict between them as the source of the disease.

It is now known that schizophrenia is a biological brain dysfunction. Its reasons are unknown, but there are many theories about it. Imaging results indicate neuroanatomical abnormalities; widening of the ventricles of the brain, changing the volume of some basal ganglia and the hippocampus in patients with schizophrenia. Functional abnormalities of the structures of the frontal and temporal lobes were also shown, manifested under conditions of burdening with cognitive tasks.

How these changes are related to the symptoms of schizophrenia is still unclear. The viral hypothesis of the development of schizophrenia says that infecting the brain with a virus, e.g. influenza in the uterus, may have consequences in the form of the disease. It has been shown that there is a temporal relationship between certain influenza epidemics and the periodic spike in schizophrenia. This is also confirmed by statistical studies showing that children born in winter are more prone to schizophrenia, perhaps due to the increased risk of the mother being attacked by influenza viruses. According to this hypothesis, the cause of brain damage may not only be viruses that directly damage the fetal brain tissue, but also those that have the ability to trigger an autoimmune reaction against the cells of the central nervous system of the unborn child. The virus can cause a response against the body’s own cells through a direct cytotoxic effect, releasing intracellular autoantigens which have not yet come into contact with the immune system and therefore have not developed tolerance to them. Another mechanism considered is the expression of viral proteins on the surface of the host cell which does not lead to direct damage to it, but stimulates an autoimmune response. In support of these assumptions, studies are cited that find in the brains of people with schizophrenia antibodies directed against their own cells belonging to such important structures of the brain as the septum, frontal cortex, hippocampus, amygdala and cingulate gyrus. Rubella virus and toxoplasmosis are also considered potential infectious agents that may affect pregnancy and may play a role in the etiology of schizophrenia.

The causes of schizophrenia are also believed to be microdamages to the nervous system that may occur during fetal development. A possible pathogenetic factor may be fetal hypoxia leading to damage to the hippocampus – a structure of the brain that is assigned an important role in the pathophysiology of many mental diseases

There are ideas that schizophrenic disorders have psychogenic causes. The future development of schizophrenia is favored by dysfunction of the stress response system, the so-called stress axis: cerebral cortex – hypothalamus – pituitary gland – adrenal glands. Simply put, a person who develops schizophrenia is genetically highly susceptible to stress. Such a person perceives stressful situations several times more strongly than the average person and when the limit of mental endurance is exceeded, symptoms of the disease appear. This hypothesis is also suggested by the most common age of schizophrenia, 15-30 years of age, i.e. the period of entering adulthood associated with the emergence of situations requiring independent, highly stressful decisions.

Research also supports the importance of the hereditary factor in schizophrenia. The genetic basis of schizophrenia is clearly documented and is manifested by an approximately 15-fold increase in the risk of developing schizophrenia in the presence of this disease in the family. However, it is not hereditary. It is not the disease that is inherited, but the predisposition to it. The search for genes predisposing to schizophrenia led to finding and describing many genes located on several chromosomes. Unlike, for example, Huntington’s chorea or sickle cell anemia – where a single mutation in a given gene determines whether someone falls ill – in schizophrenia there can be hundreds of genes whose mutations increase the risk of schizophrenia. Schizophrenic genes are located mainly on chromosomes 1, 3, 8,13, 22 and XNUMX. Most of them are genes influencing the development of brain tissue and metabolism in key brain neurotransmitter systems such as dopaminergic, serotonergic and glutamatergic systems.

Abnormal coding sequences in the genes encoding catecholamines methyltransferase (COMT), an enzyme that plays a role in dopamine metabolism in the prefrontal cortex, are associated with susceptibility to schizophrenia. Disruptions in how this enzyme works can affect our working memory; interfere with remembering and make it difficult to distinguish between images and actual events – which is quite a common symptom in paranoid schizophrenia.

Research on the polymorphism of genes encoding dopamine receptors (i.e. the sites with which dopamine binds its effect on cells) is one of the most widespread research topics in the molecular genetics of mental disorders. The greatest amount of data indicating a relationship with a predisposition to schizophrenia concerns the gene for the dopaminergic D3 receptor, which in humans in the central nervous system is highly concentrated in the limbic system and the cerebral cortex.

The gene encoding neuregulin, discovered in 2002, is of great importance in the etiology of schizophrenia1. Neuregulin is a protein that covers axons. A decrease or increase in the amount of this protein causes the formation of more or less layers of myelin, or sheaths of nerve fibers. The speed at which nerve impulses are conducted through the axons depends on whether the axon is myelinated (the coated axon conducts impulses faster) and the ratio of the naked axon’s diameter to the total fiber diameter (i.e., along with the myelin). Many people with schizophrenia have a defect in the gene that regulates the production of neuregulin. Thus, disturbances in myelin synthesis may underlie the brain abnormalities found in schizophrenia. This is confirmed by the fact that the formation of myelin in the prefrontal cerebral cortex occurs in the final period of puberty and in adolescence, which is consistent with the moment when symptoms of schizophrenia are revealed. Interestingly, scientists suspect that a mutation in the gene encoding neuregulin can cause symptoms of schizophrenia in some people and trigger creativity in others. The link between schizophrenia and genius suggests its occurrence in extremely gifted and talented people, including with Salvador Dali, Vincent van Gogh, or the Nobel laureate in economics, John Nash, whose story was presented in the film A Beautiful Mind. Another gene whose mutation may be responsible for the development of schizophrenia is the gene encoding calcineurin. Calcineurin is an enzyme with a role in regulating synaptic plasticity. The results of the statistical studies carried out have shown that in people suffering from schizophrenia, there is a mutation that reduces the activity of this enzyme.

Recently, a correlation has been found between a mutation in the DISC 1 gene (disrupted in schizophrenia) and the occurrence of schizophrenia. This mutation was first identified in a Scottish family where schizophrenia and related disorders were common. The abnormally altered DISC 1 causes disturbances in the development of nerve cells. Studies in mice have shown that the damaged gene inhibited cell division, and symptoms appeared in experimental models of schizophrenia in rodents.

Clinicians have long pointed out the amazing resistance of schizophrenics to pain, injuries, wounds, and possibly infectious diseases, with the exception of tuberculosis, which is easier to develop than the general population. Taking into account that patients with schizophrenia leave about 30% less offspring than the general population, one should expect the disease to gradually fade away. However, if the carriers of schizophrenic genes, i.e. those who did not manifest symptoms of schizophrenia, had these genes, left more than those offspring, then the losses suffered by the reduced fertility of patients with schizophrenia would compensate. The question of what a better biological adaptability of schizophrenic gene carriers would be remains unresolved. However, it cannot be ruled out that it may be the increased resistance to injuries and infectious diseases that characterize people with schizophrenia.

It should be remembered that genetic studies have only shown that polymorphism of certain genes is more common in patients with schizophrenia. However, it has also been found in other mental illnesses as well as in healthy people. So far, despite intensive research and research using molecular genetics methods, it has not been possible to identify genetic associations that could constitute an unambiguous genotypic indicator of susceptibility to schizophrenia.

As you can see, there are many theories trying to explain why schizophrenia occurs, but none of them gives a complete answer. Recent research suggests that a combination of genetic and environmental factors influencing brain function is conducive to the onset of the disease, rather than a single etiological factor. Based on this assumption, the neurodevelopmental theory of schizophrenia was formulated in the early 90s. This theory assumes that interactions between genetic and environmental factors occurring early in development can negatively affect the growth of neurons, their stratification and spatial arrangement, resulting in serious disturbances in the cytoarchitecture of the brain.

According to her, the process leading to the disease has several stages. First, during fetal life and shortly after birth, the central nervous system is damaged, the condition of which is the action of the damaging factor and genetic predisposition. As a consequence, brain development proceeds abnormally (changes in synaptic formation and neuronal migration disorders are likely to occur), and one of the significant effects is reduced resistance to psychosocial and biological stress factors. During adolescence and early adulthood, this ultimately triggers brain dysfunction as manifested by symptoms of an episode of schizophrenia. According to the neurodevelopmental theory, the process leading to the disease is many years earlier than the onset of the manifest clinical symptoms and its beginnings reach the fetal period. The neurodevelopmental theory integrates, in a coherent way, elements of earlier concepts.

Not only the cause, but also the nature of the disorders responsible for the onset of schizophrenia symptoms remain unclear. The accepted theory is that the brain of people with schizophrenia is experiencing an imbalance between the chemicals (neurotransmitters) that transmit signals to the brain. The idea that disorders of dopaminergic transmission are at the root of schizophrenia was formulated in 1963 by Carlsson and Lindqvist. In its original version, it assumed that in this disease we are dealing with an overactive dopaminergic system. 20 years later, the introduction of the division of schizophrenia symptoms into positive symptoms (productive, i.e. hallucinations and delusions) and negative symptoms (loss, manifestations of a deficit or loss of some mental functions) led to the development of a modified dopaminergic theory of schizophrenia, according to which the excessive function of dopaminergic neurons mainly in the mesolimbic area of ​​the brain is responsible for the positive symptoms of schizophrenia. On the other hand, the presence of negative symptoms would probably result from a dysfunction of dopaminergic neurotransmission in the prefrontal cortex. The mechanism of the disorders would therefore be a misregulation of neurotransmission rather than dopaminergic hyperactivity.

Currently, the dopaminergic concept of schizophrenia is undergoing a significant revision. Generally, it is not believed that one neurotransmitter system plays a decisive role in the pathogenesis of the disease. Multiple relay and interaction concepts are emerging. Recently there have been theories assuming a malfunction of the glutamatergic system in psychotic disorders. Glutamic acid is the most important excitatory messenger in the central nervous system. It is believed to play an important role in plasticity, growth and development of synapses, learning and memory processes, and modulation of motor activities, i.e. processes that are disturbed in patients with schizophrenia. It was found that substances blocking NMDA receptors (receptors for glutamic acid) cause symptoms of psychosis in healthy people and exacerbation of schizophrenia in patients. It was also found that agents activating glutamatergic transmission in the brain, administered alone or in combination with some neuroleptics, reduce the severity of negative symptoms and the deficit of attention processes in people with schizophrenia. The conclusion of the facts presented above would be the concept of the underactive glutaminergic system in the pathomechanism of schizophrenia. Unfortunately, there are many studies indicating an overactive glutamatergic system in patients with schizophrenia. For example, an increase in the concentration of glycine in the brain of deceased schizophrenics has been shown, and it has also been found that some patients have elevated levels of this amino acid in the blood. Glycine stimulation of the NMDA receptor plays an important role in the maturation of neurons, its excessive concentration may cause neurotoxicity and psychopathological changes. Thus, it seems that the full formulation of the glutamatergic theory of schizophrenia requires further research to explain its paradox of contradictory results.

Treatment; past, present and future

Madness is as old as humanity. The problem of mental disorders was known to the Sumerians around 2600 BC and the ancient Egyptians. Probably they saw mental illnesses as being possessed by an evil spirit, some researchers claim that the trepanation of the skull performed in ancient times was intended to cure mental illnesses by creating an exit for the demons inhabiting the patient’s head. Throughout its history, mankind has repeatedly reverted to the idea of ​​mental illness as a result of being possessed by evil powers.

In ancient Greece, an attempt was made to scientifically explain the causes of mental disorders. 2400 years ago Hippocrates developed the theory of the 4 fluids in the human body; phlegm, yellow bile, blood and black bile. According to Hippocrates, the disruption of the balance between the fluids was the cause of mental illnesses. The famous Arab scholar, Abu Ali al Hussein ibn Sinie, called Avicenna (980–1037), also professed the theory of the four fluids and considered mental disorders as a result of disturbances in their balance in the patient’s body, especially in the brain. Avicenna in the Canon of Medicine describes a schizophrenia-like condition he called Junun Mufrit (Serious Insanity), distinguishing it from other forms of madness (Junun) such as mania, rabies and bipolar disorder psychosis. The theory of the four fluids (humoral theory) and the methods of treating mental disorders proposed in it (i.e. enema, bleeding and moistening with warm baths), having the status of officially recognized and promoted by the academic community, survived until the XNUMXth century.

We also find views on the existence of material causes of mental illness in the Middle Ages. Various types of herbal infusions were used as treatment methods, as well as trepanation of the skull and surgical removal of “madness stones”.

The first closed institutions for the mentally ill appear in the 1792th century. The mentally ill are locked up with patients suffering from venereal diseases and forced to undergo therapies involving whipping, bloodletting, and ice-cold showers. It was common to use a whip or chaining patients in chains. In XNUMX, the French scientist Philippe Pinel, considered the father of modern psychiatry, introduced humane methods of treating mental disorders. He found that exercise causes patients to be properly active and improves their functioning. He was the first to remove the shackles of mentally ill patients and began using occupational therapy in their treatment.

The first proven method of treating schizophrenia was to use an intentional insulin coma in the early 30s. The method was introduced into medicine by Manfred Sakel in 1933. Manfred Sakel, a doctor of Polish origin working in Vienna, accidentally overdosed on insulin in one of his patients – a compulsive morphinist. She fell into a coma, and when she woke up, she stated that she no longer felt the need to take morphine. Sakel began experimenting with other patients and found that insulin therapy works not only in drug addiction, but also in a large percentage of cases of diseases such as e.g. schizophrenia. For several decades, insulin shock has been a popular method of treating schizophrenia. This method was eventually abandoned because it had a high mortality rate. In the 20s of the twentieth century. Ladislas J. Meduna, a Hungarian doctor, based on the observation of the number of glial cells in the brain of patients who died of epilepsy and schizophrenia, noticed that in epilepsy patients the amount of glial in the brain is greater than in schizophrenics. Based on this observation, he put forward the theory that inducing epilepsy attacks in schizophrenics should increase the amount of glial in the brain and, consequently, have a therapeutic effect. This theory was supported by data showing a very low incidence of epilepsy in patients with symptoms of schizophrenia. He induced epilepsy using substances such as strychnine, brucine or camphor. Ultimately, the drug used in this type of therapy was metrazol (a substance that inhibits the activity of the inhibitory GABA neurotransmitter and increases the excitability of neurons). Unfortunately, due to the intensity of muscle contractions, about 40% of patients had spine injuries. Further studies showed that chemical convulsions are much more applicable in the treatment of bipolar disorder (up to 80% effective). Due to the development of electroconvulsive therapy and neuroleptics, the Meduna method was finally abandoned at the turn of the 50s. Since the chemical method was very dangerous for patients due to the inability to control seizures, Italian physician Ugo Cerletti, as a neurologist specializing in epilepsy, conducted numerous experiments on animals, trying to induce seizures with electric current. Based on his experience, he designed a device capable of delivering short, controlled electrical pulses that induce convulsions in animals. The first trials on humans – patients with severe schizophrenia, were carried out in 1937. The improvement of the patients’ condition was observed after 10-20 procedures spread over several days. Additionally, it was observed that all electroconvulsive patients experienced amnesia, including the procedure itself, so showed no negative associations with this type of therapy. Another advantage of electroconvulsions over chemically induced convulsions was the ability to control the strength and duration of the induced convulsions more easily. The electroconvulsive therapy method has become the most popular of the developed shock therapies. Over the years, improvements have been made such as the use of pharmaceuticals for muscle relaxation, anesthetics, pre-oxygenation of the patients’ brain, shock control with EEG, as well as more modern equipment and the form of electrical pulses used. Currently, electroconvulsive therapy is effectively used in cases such as: catatonia, acute schizophrenia, drug-resistant depression or with contraindications to pharmacotherapy. The standard is anesthesia of the patient, as well as the administration of muscle relaxants, due to which most of the unpleasant complications are eliminated.

Attempts at treating mental illnesses at the beginning of the XNUMXth century also brought spectacular failures. Psychosurgery should be mentioned here, especially lobotomy procedures. It is a neurosurgical procedure that involves cutting the nerve fibers connecting the frontal cerebral lobes with the structures of the diencephalon (most often the hypothalamus or the thalamus). Lobotomie was invented by the Portuguese neurologist António Caetano de Abreu Freire Egas Moniz. In 1935, Carlyle Jacobsen of Yale University described changes in the behavior of aggressive chimpanzees after disrupting the nerve pathways connecting the cortex of the frontal lobes of the brain with the rest of its parts. Chimpanzees became lethargic, quiet and, unlike before the operation, they easily obeyed orders. Moreover, these changes occurred without any noticeable loss of memory capacity and intelligence. Another researcher at this university, Dr. Jon Fulton, observed that two chimpanzees could not induce experimental neurosis after the complete removal of both frontal lobes of the brain. The results of both presentations inspired Moniz to use this procedure in patients with particularly severe forms of psychosis. Moniz guessed that selected cases of psychosis, such as paranoia or OCD, were associated with recurring thought patterns that dominated other thought processes. On this basis, he proposed surgical disruption of the connections of the frontal cortex with the thalamus, which was to interrupt the return of impulses to the cortex. In 1936, he performed the first procedure of drilling a hole in the skull and cutting the frontal cortex lobes from the diencephalon by injecting alcohol into the tissue connecting these two sites. The Moniza method has evolved towards surgical intervention in the frontal, orbital and orbital areas. Its promoter in the USA was Walter Freeman, who in almost 30 years of his medical career, independently performed 3400 such procedures. His best known method was transorbital lobotomy. Since the human skull is made of extremely hard bone tissue, Freeman punctured the thin, side wall of the eye socket to reach the brain. Just under the eyelid, so as not to damage the eyeball, he inserted a long thin skewer, which he then beat with a hammer to pierce the bone. For the first years, Freeman used an ice pick for this operation, because at that time a suitable surgical tool did not exist yet. As a result of the lobotomy, the patient – if he survived the operation – no longer experienced hallucinations or hallucinations, and did not show fits of rage. The price was amnesia, loss of self-continuity, and loss of the ability to feel emotions. Many people died on the operating table or were left with irreversible damage: mindless, losing their sense of identity, apathetic and passive, and unable to hold their urine or stool. Lobotomy made a career in the 40s, which was due to the economic factor. The costs of the procedure were incomparably lower than keeping the patient in a psychiatric hospital. By the 50s, about 50 jobs had been made in the United States. lobotomy procedures. In Europe and the USA, even homosexuals were operated in this way to restore their morals, while in Japan, children were subjected to lobotomies, which were difficult to educate. At the end of the 50s, the voices of criticism about lobotomy began to become more frequent around the world. The conducted research and clinical observations negated its effectiveness. According to these data, only about 30% of patients experienced an improvement in their mental state. In another 30% of patients, the procedure did not bring any results, and in 30% it deteriorated significantly. If we combine this with the assumed occurrence of spontaneous improvement in unoperated patients, which is 25–30%, it turns out that the positive results of the lobotomy did not have to result from the performed surgery.

1952 marks the beginning of the era of psychotropic drugs. Undoubtedly, the first antipsychotic drug was reserpine. It is an alkaloid obtained from the root of the Rauwolfia serpentine plant. Hundreds of years ago, Rauwolfia Serpentina was used in India as a sedative, in modern medicine, reserpine was only isolated in 1952 and was used as the first neuroleptic drug. The mechanism of action of reserpine is to flush out neurotransmitters (incl. dopamine) from neurons and preventing their build-up at synaptic endings. Currently, it is rarely used in medicine as a medicine to reduce high blood pressure. In 1950, Charpentier, in his search for an antihistamine and an aid to general anesthesia, synthesized chlorpromazine. An accidental discovery in 1952 its effectiveness in the treatment of schizophrenia has revolutionized the treatment of this ailment. Chlorpromazine was the first drug from a new group of drugs used successfully in patients with schizophrenic psychosis, named in 1955 by Jean Delay and Pierre Denier as neuroleptics. Soon after, the antipsychotic activity of haloperidol was discovered, followed by many other compounds with very different chemical structures. The main mechanism of action of this group of drugs, now called typical neuroleptics, is the blocking of dopamine D2 receptors. The therapeutic effect of typical neuroleptics mainly concerns the positive symptoms of schizophrenia, i.e. hallucinations, hallucinations, delusions. Unfortunately, they do not eliminate the negative symptoms of schizophrenia, i.e. cognitive disorders, inertia and emotional flatness. What’s worse, they cause a number of troublesome side effects. One of the more troublesome symptoms is similar to those in idiopathic Parkinson’s disease: immobility, slowness, muscle stiffness, and tremors. In addition, severe muscle spasms of the tongue and face, neck and back may appear, leading to abnormal body posture. These symptoms usually appear within the first few days, no later than 2 months after starting treatment. Continuation of treatment for more than six months usually leads to the appearance of the so-called tardive dyskinesia. It is characterized by the occurrence of grotesque facial grimaces that are uncontrolled by the patient. The discovery that Parkinson’s disease is caused by damage to dopaminergic neurons and that the side effects of neuroleptics coincide with the symptoms of this disease, was the first suggestion regarding the anti-dopamine effect of this group of drugs. Since in the 70s it was supposed that schizophrenia was caused mainly by an overactive dopaminergic system, it seemed that the therapeutic mechanism of anti-psychotic drugs (D2 receptor blockade) was inherently associated with the side effects described above. The emergence of the modified dopaminergic schizophrenia theory and the multi-messenger and interaction concepts played an inspiring role in initiating the search for new antipsychotic drugs acting on the negative symptoms of schizophrenia and not showing such bothersome side effects. Further studies have shown that the therapeutic effect of neuroleptics is associated with the blocking of dopamine D2 receptors in the mesolimbic system, while the antidopaminergic effect in the brain structure known as the striatum causes the symptoms of Parkinson’s disease. The search for new antipsychotic substances went in two directions. We searched for compounds that bind selectively to dopamine receptors located in limbic structures and compounds that act on the dopamine system through other neurotransmitter systems, i.e. substances that bind to various types of non-dopamine receptors, mainly serotonin, noradrenergic and glutamate receptors. These studies have resulted in the emergence of a new class of antipsychotic drugs now known as atypical neuroleptics. These include clozapine, risperidone, olanzapine, quetiapine or ziprasidone, which are currently used in medicine. In the course of the conducted experiments, it was shown that moderate blockade of the D2 receptor is sufficient to counteract the positive symptoms of schizophrenia and, importantly, does not lead to the occurrence of bothersome side effects associated with the use of typical neuroleptics. Moreover, it was found that the new drugs bind more strongly, especially in limbic structures, to serotonin 5-HT2A receptors than to dopamine D2 receptors. This feature, i.e. strong binding to 5-HT2A receptors and moderate binding to D2 receptors, seems to be the most important distinguishing feature of new generation neuroleptics. An important advantageous feature of this group of drugs (unfortunately not all, but a large part of it) is the elimination of cognitive dysfunctions, i.e. influencing the negative symptoms of schizophrenia. This effect is attributed to the effect of atypical neuroleptics on serotonin transmission through antagonism to the 5-HT2A serotonin receptors.

Due to the development of new concepts in the pathophysiology of schizophrenia (the glutamatergic hypothesis), there are attempts to use substances that affect glutamatergic transmission in the treatment of schizophrenia. So far, only preliminary clinical trials have been carried out with the use of compounds previously used in the treatment of epilepsy that reduce glutamatergic transmission. Unfortunately, these attempts did not bring satisfactory results. On the other hand, clinical trials of compounds increasing glutamate transmission look more promising. It was found that high doses of glycine (a substance activating the NMDA receptor) reduce the severity of negative symptoms in patients with schizophrenia. However, it should be noted that also these trials were relatively sparse and the effectiveness of the compounds enhancing glutamatergic transmission in the treatment of schizophrenia remains debatable.

It should be noted that the described interactions of neuroleptics with receptors and neurotransmission processes appear quickly within a few to several hours. Days, if not weeks, are required for the full clinical effect of the antipsychotics. The described effects are therefore the starting point for the development of adaptive changes, intensively researched at the moment, but still an unexplained issue.

It should not be forgotten that the use of drugs should not be the only therapeutic effect. There is no doubt that psychotherapy plays an important role in the treatment of mental disorders. Psychotherapy is clearly distinguishable from pharmacological and other biological treatments. He uses what is generally referred to as “psychological”. These include, first of all, discourse (conversation) and therapeutic reflection with an analysis of the life situation with an emphasis on reaching and experiencing repressed emotions and reacting them. Its task is to show the patient the mistakes in recognizing reality and help him return to it.

Taking into account the still valid Bleuler theory that schizophrenia is not one, but a group of diseases with different pathomechanisms and the unprecedented diversity of patients’ personalities, psychotherapy is an indispensable element of any pharmacological treatment. A psychiatrist cannot just be a prescription writer. Establishing close mental contact with the patient allows not only to identify the source and nature of the mental problems that plague him, but also to assess the effectiveness of pharmacological treatment, thus enabling the correct selection of the drug.

Literature

Kempiński A: Schizophrenia Wydawnictwo Literackie, November 2009 ISBN: 978-83-08-04408-7

Kostowski In: Perspectives of research on anti-psychotic drugs. Neuropsychopharmacology. Today and tomorrow. Ed. M. Bijaki W. Lasoń. Krakow 2000. Ed. Platanus.

Kostowski In: Neuroleptic drugs from the perspective of psychopharmacology. Schizophrenia: Pathogenesis and Therapy. XIX Winter School of the Institute of Pharmacology, Polish Academy of Sciences, Mogilany 2002. Red B. Przewłocka

Michalik R: Psychosurgery. Surgical treatment of mental disorders

Ossowska K: Neural basis of extrapyramidal disorders after neuroleptics. Schizophrenia: Pathogenesis and Therapy. XIX Winter School of the Institute of Pharmacology, Polish Academy of Sciences, Mogilany 2002. Red B. Przewłocka

Pietraszak M: The glutamatergic theory of schizophrenia. Schizophrenia: Pathogenesis and Therapy. XIX Winter School of the Institute of Pharmacology, Polish Academy of Sciences, Mogilany 2002. Red B. Przewłocka

Clinical psychology edited by H. Sęk WN PWN Warsaw 2005

Robakowski J: The influence of psychotropic drugs on neuronal plasticity. Pharmacology in Psychiatry and Neurology., 2005, 2, 143.153

Rzewuska M: Pharmacotherapy of schizophrenia. Neuropsychopharmacology. Today and tomorrow. Ed. M. Bijak and W. Lasoń. Krakow 2000. Ed. Platanus.

Sanak M: Gene polymorphism in schizophrenia. Schizophrenia: Pathogenesis and Therapy.

XIX Winter School of the Institute of Pharmacology, Polish Academy of Sciences, Mogilany 2002. Red B. Przewłocka

Stefansson H, Sigurdsson E, Steinthorsdottir V, Bjornsdottir S, Sigmundsson T, Ghosh S, Brynjolfsson J, et al: Neuregulin1 and susceptibility to schizophrenia. Am J Hum Genet 71:877–89, 2002

Wolfarth S, Ossowska K: Pharmacology of antipsychotic drugs. Neuropsychopharmacology. Today and tomorrow. Ed. M. Bijaki W. Lasoń. Krakow 2000. Ed. Platanus.

Youssef, Hanafy A.; Youssef, Fatma A.; Dening, T. R.: Evidence for the existence of schizophrenia in medieval Islamic society. History of Psychiatry 7: 55–62 [57]. 1996

Vetulani J: Is psychiatry a biological science? Schizophrenia: Pathogenesis and Therapy.

XIX Winter School of the Institute of Pharmacology, Polish Academy of Sciences, Mogilany 2002. Red B. Przewłocka