Psychiatry.pdf

17-11-2023, morning Psychiatry Matteo Tonna E-mail: [email protected] https://karger.com/psp/article/54/1/18/285273/Exploration-of-Everydayness-in-Schizophrenia-A ? PSYCHOPATHOLOGY OF SCHIZOPHRENIA I’m a psychiatrist and a professor of psychiatry of the University of Parma. We are...

17-11-2023, morning Psychiatry Matteo Tonna E-mail: [email protected] https://karger.com/psp/article/54/1/18/285273/Exploration-of-Everydayness-in-Schizophrenia-A ? PSYCHOPATHOLOGY OF SCHIZOPHRENIA I’m a psychiatrist and a professor of psychiatry of the University of Parma. We are going to talk about clinical psychiatry and psychopathology. What is psychopathology? Student: the study of pathologies that affect the mind. Between ** means that they were slides skipped/not explained. Psychopathology studies the signs and symptoms of mental diseases, psychiatric conditions, regardless of the categorical diagnosis. For example, psychopathology studies what are hallucinations, what is meant with delusions, regardless of the diagnosis behind these hallucinations and delusions. A very important thing in psychiatry is that most of symptoms are non-specific for the psychiatric conditions, for the diagnosis. For example, if a patient has a delusion, I cant’s say that this patient is suffering from schizophrenia or bipolar disorder or paranoia or organic diseases, because delusions are present in all these conditions. We distinguish between two types of psychopathology: Descriptive psychopathology. It refers to the description of signs and symptoms of mental diseases. Therefore, in descriptive psychopathology I can describe and understand what is meant with hallucinations, delusions, and so on. Phenomenological psychopathology. It refers to the things that are behind the symptoms observed such as delusions and hallucinations. Phenomenology is about the word behind the symptoms of psychiatric conditions. Since symptoms in psychiatry are not specific, the feelings behind are specific for the different mental diseases. In order to have a correct diagnosis, in order to understand what is the psychiatric condition of that patient, we have to grasp the feeling behind the symptom. Anyway, in psychiatry, there are no symptoms specific for any psychiatric disease. We start with the psychopathology of schizophrenia. SCHIZOPHRENIA Schizophrenia is a very important mental condition because it affects 1% of the population, it implies a lot of suffering for the patient, lots of costs for the services. However, schizophrenia is not an easy recognizable disease, because it can be very different from what it is described in literature, movies and so on and normally, we think at schizophrenia in an incorrect way. To show you what I mean, how does a schizophrenic patient express its symptoms in your opinion? Students: delusions, hallucinations. Prof: all these symptoms are actually present in schizophrenia, but they are not the main symptoms! They may be present or not. If we try to identify a schizophrenic patient only with these symptoms, it would not be enough. Schizophrenia was not the first name addressed to this pathology, it used to be called dementia praecox, a latin name that means early onset (praecox) of dementia. This term was coined in 1896 by Emil Kraepelin, a German psychiatrist and psychologist, in order to classify and unify different pathological conditions such as: Schizophrenia Catatonia (Kahlbau, 1893) Hebephrenia (Hecker, 1871) Vesania Typica (Kahlbaum) All the diseases above were grouped into the dementia praecox disease, one single classification.  The main features among them were: Early onset. The disease appeared in the late adolescence, between 16 and 25 years old. Sometimes, the onset occurred also in childhood. Course-outcome. The course of the disease was a progressive deterioration, impairment of mental faculties, through a process of personality destruction. Bad prognosis. So, different diseases with the same outcome and onset. DIAGNOSTIC CRITERIA (LONGITUDINAL VIEW): Age of onset (young) Course (+/- rapidly progressive) Outcome (personality destructuring and mental deterioration) In order to make a diagnosis of dementia praecox, you needed to observe the outcome of the disease, the disorganization of personality. In 1896 there were no pharmacological therapies and psychiatrists could only observe the disease, its course and outcomes in their patients. Psychiatrists separated the most severe psychopathological conditions into two groups: Dementia praecox. This group of patients shared the same outcome: disorganization and dysfunction of personality. In order to reach the diagnosis of dementia praecox you had to wait in order to see the course of the disease, the outcome, you couldn’t have a diagnosis in the first phases of the disease. Manic-depressive disorders. These patients mainly had affective symptoms and the outcome was good because these conditions were not linked to a bad outcome. The course of manic depressive episodes was phasic, meaning that at the end of the episode, the patient could go home. DIAGNOSTIC CRITERIA (CROSS-SECTIONAL VIEW): “spaltung”: loss of structural cohesion of personality/fracture and dissociation of psychic functions. Not necessarily unfavourable prognosis Extending nosographic limits (sch.simplex, latent sch.) In 1911 Eugen Bleuler, a Swiss psychiatrist, defined the dementia praecox in a better way, in order to capture the signs and symptoms that are typical of that disease, regardless the course and the outcome with the aim of having a diagnosis at the beginning of the disease. Schizophrenia, the new name of the disease, has a cross-sectional view and this new term derives from “phrenia” (mind) and “schizo” (broken). It refers to the loss of structural cohesion of the mind, of the personality and a dissociation of psychic functions. The main feature of schizophrenia, according to Bleuler, was the German word “spaltung”, which means disaggregation, fracture of the mind. In schizophrenia, every function such as memory and perception is not impaired per se, but they are not linked to each other, they are all disarticulated. *INTRODUCTION Process (Jaspers, 1913): “quid novi”, primary phenomenon that interrupts "the continuity of meaning of life" (Weitbrecht). Permanent outcome. Poussée/ thrust (schaub). Development: long, abnormal development from a premorbid personality. Spectrum (Kety, 1968): related conditions but di erent clinical consistency (Schizoid PD, Schizotypal PD, Schizophreniform D., Schizophrenia) Schizoa ective continuum (Griesinger's unitary psychosis) SCHIZOIDIA Gradual maladaptation to the environment of a peculiar premorbid personality (Meyer): "Disposition to detach oneself from the environment" (Bleuler) ff ff  “Psychæsthetic proportion” (Kretschmer) Schizophrenic autism: “Loss of vital contact with reality” (Minkowski)* PSYCHOPATHOLOGY OF SCHIZOPHRENIA Bleuler: mental dissociation (spaltung): separation, isolation, discrepancy of psychic functions with psychic fragmentation DIAGNOSTIC CRITERION: - Fundamental symptoms (dissociation of thoughts, a ective attening, ambivalence, autism, volition disorders) - Accessory symptoms (perceptual disorders, delusions, memory disorders, personality disorders, catatonic symptoms) PSYCHOLOGICAL DERIVABILITY: - Primary symptoms (associative d., basic mood disorder) - Secondary symptoms (autism, ambivalence, schizophrenic deterioration, delusions, catatonic symptoms) Bleuler described a list of symptoms which, according to him, were fundamental, peculiar in the diagnosis of the disease and they are referred to as the fundamental symptoms and they are different from the accessory symptoms. The latter may be present, but they are not characteristic of the disease and they represent the symptoms that people (erroneously) associate firstly to schizophrenia (the ones mentioned by the students before), such as perceptual disorders, hallucinations, delusions, catatonia. Fundamental symptoms are symptoms not so apparent, it’s not so easy to identify them, and this is different from accessory symptoms. Affective flattening, apathy are examples of fundamental symptoms. Apathy means that the person doesn’t feel anything, which is very different from depression, he/she doesn’t have an affective resonance with others, he/she is not interested in anything, working, having fun have no importance for the patient. Affective flattening means that the person is not interested in social relationships, in having a girlfriend or a boyfriend. The main consequence of these two fundamental symptoms is abulia (another greek word) that is volition disorders, it means that the patient is not engaged in anything, he/she stays at home, he/ she doesn’t go to school, stays at home or more simply, also personal hygiene is impaired and the person is always in bed. This condition is very different from depression, because depressed patients would like to go out, to go to work, to have relationships, but they can’t, while schizophrenic patients can’t understand why a person should do all these activities, they can’t conceive these things. The third fundamental symptom is ambivalence, meaning that opposite feelings can coexist in the same patient. The patient may love and at the same time hate her/his parents, this is not a personality disorder, it’s more profound because it implies a split, a disruption of mental faculties. Ambivalence is a clear example of the “spaltung”, of the personality fracture. In addition, we have autism. This term was coined for the first time by Bleuler referred to schizophrenia, but it is completely different from the childhood autism or from the autism-spectrum disorders. Childhood autism was named autism because the children affected had some clinical features similar to schizophrenic autism, but the latter is another thing, a very important trait of schizophrenia. The fifth fundamental symptom is dissociation of thoughts, meaning that thoughts are not linked together, associative links are lost. Thinking is disrupted both at a semantic and grammar, syntactic level, so thoughts don’t follow the normal logic way, the common sense. In conclusion, looking at the fundamental symptoms, we can say that they are very different from those shown in movies, like patients only with delusions and that say strange things, it’s not necessarily true. Schizophrenic patients first of all are isolated patients and they are very young, we are talking of 16-25 years old. It is very important to recognize the disease as soon as possible distinguishing it from other types of conditions because the prognosis of the disease depends on the duration of untreated psychoses, if we wait to treat the patient, the prognosis is worse. If we refer only to delusions and hallucinations, we can’t recognize this disease. ff fl SCHIZOPHRENIC AUTISM “Detachment from reality, internalization of affectivity and dereistic thinking prevalence” – Bleuler “Loss of vital contact with reality”/ ”Rich or florid autism (autisme riche) and poor autism (autism pauvre)” / “Autistic activity”: Morbid rationalism/pathologic geometrism/morbid daydreaming (reverie) (Minkowski) “Failure in the transcendental co-constitution of the Other and the Self” Bleuler wrote that schizophrenic autism refers to a profound detachment from reality. The affectivity is not more outward, but inward, internalization of affectivity occurs. Dereistic thinking means that it is completely detached from a concrete reality, the term derives from latin “de re” (“away from the thing”). When we talk about detachment from reality, we refer to detachment from everyday skills, everyday capacities, to a severe detachment of a common sense of reality. What is obvious for normal people, it’s not obvious for the patient. For example, it is obvious for us that on Saturday night we can go out, to a party with friends, drink a beer, staying with others, while for a schizophrenic patients all these activities aren’t obvious, he/ she can’t conceive why he/she has to do all these things. Internalization of affectivity means apathy, where the patient is no more interested in directing his/ her affectivity towards other people or things. Affectivity is isolated in a private world of the patient, who stays alone in his/her room avoiding contact also with parents; affectivity is completely broken. As we have already said, the patient does’t feel the necessity to wash him/herself, change clothes or bed sheets even if he/she stayed in bed for a long time. According to Bleuler autism is a fundamental symptom, so a diagnosis of schizophrenia cannot be made without the autism trait. If we see an hallucinating and delusional patient, but he/she has friends, goes out, he/she wants to work or go to school with good social functioning, it is very difficult that this patient is suffering from schizophrenia. After Bleuler, other scholars tried to describe better, deeper the concept of autism. Another very important author was Eugène Minkowski, a psychiatrist that studied phenomenological psychopathology, because he tried to understand the phenomenology, the things, the world behind signs and symptoms. Minkowski changed the definition of autism. He talked about a “loss of vital contact with reality”, and the adjective vital is very important because it refers to the contact with reality that we have in a pre-reflective way, it’s obvious for us. Nobody has to teach us that it is a good thing to make friends or to go out, nobody has to teach us that if there is a sunny day it would be good to go out and have a walk, all these things aren’t obvious in schizophrenic patients. Minkowski described two subtypes of autism: Rich autism. It is characterized by all the characteristics of autism (detachment from reality, flattening of affectivity and so on), but at the same time the patient is delusional and hallucinated. For example the rich autism patient has the delusion to become president/god/messiah, while not even washing his/her clothes. Poor autism. It’s the worst form of autism in which the main features of autism are not accompanied by delusions or hallucinations. The patient stays in his/her home, and the mind is completely empty, for example that person is able to stay in front of a witched off computer. On one hand autism is isolation, but on the other hand the patient tries to interact with other people, however, these interactions, relationships become strange, difficult to understand. These kind of autistic activities are defined by Minkowski as morbid rationalism, morbid daydreaming or reverie, and pathologic geometrism. Morbid rationalism describes the fact that the patient is detached from common sense of meanings and he/she tries to understand the world in a hyper-rationalistic way. For example, let’s consider a schizophrenic patient with a daughter affected by cancer and with a bad prognosis. He had to decide what kind of gift to buy her for Christmas. He bought her a coffin, which is a hyperrationalistic gift. Nobody has to teach us that a coffin is not the proper gift, it is obvious. Pathologic geometrism. Many years ago I encountered a patient of 16 years old with a schizotypal personality disorder, so a mild form of the schizophrenia spectrum and on saturday night he used to go out with his friends. One of his friends had a driving license and a car, so one night they went to pubs to drink beer and so far, everything is normal. However, he couldn’t understand why a person should go out, drink a beer at a pub, talk with other people, he couldn’t conceive it, so he started to think that the reason why every saturday night they had to go out  was to calculate the area of the squares that the friend’s car did during the route. The friend with the car described some geometrical features and he had to describe the area. The world was conceived in geometrical forms for him. Morbid daydreaming (reverie). Reverie is a French word that means a state of dreaming while awake, like when we were children and we could play for hours thinking to be princesses and inventing a story. In children, daydreaming is normal, while in schizophrenic patients reverie is pathological. Many years ago I encountered a 27 years old patient, when I went into her house she was wearing dirty clothes, air stank, but she started to tell me that she was sad because her boyfriend, Lapo Elkann, had a lot of other girlfriends. She said that she was working in New York as a top-model in the previous week and that Lapo escaped. Actually, she did’t believe that the past week she was in New York, or that she was a model, but this patient was pathologically absorbed in her thoughts. This pathological absorption was due to the fact that she was completely detached from her experiences. It is different from delusions, because in delusions the patient truly believes what he/she is thinking. In this example she knew that during the past weekend she was not in NYC. The three examples above are about schizophrenic autism, something completely different from delusions or hallucinations, they are more basic. If you talk with a delusional patient and you try to tell him that what he is saying is not true, the delusional patient becomes angry, he is convinced, he may tells you that he has the proof. On the contrary the schizophrenia autistic patients change version if you try to contradict them. The problem of the Bleuler conceptualization of schizophrenia is that the fundamental symptoms are symptoms not always easy to classify, they are often difficult to recognize in these patients. If we consider a delusion, everybody can understand that a specific patient is having a delusion, such as if a person comes to you and says: I am Jesus Christ, it’s difficult not to recognize that this patient has a problem. If a patient tells you that yesterday he/she went to Mars and had a lunch with the princess of Mars, it’s difficult to ignore that symptom. Delusions, hallucinations are very easy to understand, to grasp. On the other hand, other symptoms such as apathy, abulia, ambivalence, autism are more difficult to recognize because a person may stay at home for days or weeks because he/she is depressed or because of other problems. The real problem with the conceptualization of schizophrenia is that these symptoms are very important but not so easy to capture. For this reason, another scholar, Schneider re-defined the schizophrenia symptoms. SCHNEIDER (1967) First-rank symptoms: - Auditory hallucinations (imperative, commenting, dialogic voices and teleological voices) - Passivity of thinking (thought withdrawal, thought insertion, thought broadcasting) - Somatic passivity - Passivity of volition and feelings - Delusional perception (passivity of perception) Second-rank symptoms: - Delusional intuition, depressive and euphoric moods, emotional blunting, psycho-sensory disorders Schneider was a German psychiatrist that refined the conceptualization of schizophrenia with a main focus on delusions and hallucinations. He was aware that the main symptoms of schizophrenia were the ones that Bleuler described as fundamental symptoms, he didn’t deny the core-features of schizophrenia. However, Schneider tried to describe delusions and hallucinations that were typical for schizophrenic patients. This psychiatrist, with the description of a list of symptoms called first-rank symptoms, influenced the current diagnostic system for schizophrenia. Anyway, first-rank symptoms cannot cancel the Bleuler fundamental symptoms of schizophrenia. As we can see in the first-rank symptoms delusions and hallucinations are present, but we know that many patients can suffer from schizophrenia without having first rank symptoms. Hallucinations and delusions are very different, but they share a common feature that identifies with a feeling of the patient which is passivity. In this case, we are using a phenomenological approach to psychopathology. Passivity means that a patient doesn’t feel as if his/her thoughts, body, emotions are his/her own thoughts or not, as if other people, external forces influence, manipulate his/her thoughts, body emotions, will and so on. The feeling of passivity may be clinically expressed though specific delusions, for example based on the passivity of thinking. The patient may tell you that his/her thoughts flew away, escaped the brain or that someone is trying to insert thoughts inside his/her head (forced to think someone else thoughts). Other specific types of passivity delusions deal with the body, in this case the patient feels that his/her movements are influenced or directed by other people, such as the movement of an arm. Body passivity means loss in sense of agency, which means that I’m not the active subject of my movements. The more severe form is represented by loss of ownership, it means that a part of my body is not mine anymore, it belongs to another person, as if an arm is implanted in my body during the night for example, so I have to cut off my arm because it is not mine. Loss of agency and ownership deal with a severe, pervasive somatic passivity. In the same way, patients may feel that their emotions and feelings are influenced, inserted by others, made by others. All these feelings are clinically expressed as delusions. Patient may tell you that his/her friend is influencing his/her thoughts through specific device and these feelings are physical. The patient feels in a concrete way that thoughts are escaped, that the thoughts of another person are penetrating into his/her head, as if thoughts are objects. The perception is very physical. Then there are hallucinations, specifically auditory hallucinations, such as voices, the patient hears voices and they may be inside his/her head (pseudo-hallucinations) or they may be outside (real hallucinations). Voices can be dialogic, two or more voices that talk with each other about the patient. Hence, the patient hears voices that are talking badly about him/her. Voices can be also teleological, meaning that they give some advices to the patient and in the most severe forms, voices are imperative, they give orders to the patient and sometimes they order to the patient to kill him/herself or other people. The patient struggles to resist to these voices. Also voices are physical, patients can hear voices inside the brain and they are able to say in which specific part of they brain the voices are talking (left, posterior, frontal..). For this reason sometimes the patients tell you that somebody inserted a microchip inside their brain, they try to explain to you symptoms in a very concrete way. Question from a student. This situation in schizophrenia is different from the personality disorder, where the patient can experience phenomena similar to hallucinations and delusions, however, in the schizophrenic patient hallucinations are physical, while in dissociative disorders they’re more like a dream. Only schizophrenia patients can tell that somebody inserted his/her thoughts inside the brain or the localization of this insertion. Another question: sometimes schizophrenia patients say that they are dead, is it linked to the loss of body ownership? Maybe, but normally this syndrome (called Cotard’s syndrome) is typical of affective states, depressive patients and it is due to a severe disruption of affectivity, implying another kind of feeling, the feeling of guilt. Some schizophrenia patients have Cotard’s syndrome, but in this case it may be linked to the loss of sense of agency, but it is not so frequent. The last first-rank symptoms that needs to be mentioned is the delusional perception or passivity of perception. It is a very important symptom of schizophrenia because perhaps it’s the only symptom very peculiar of schizophrenia. If you see a delusional perception, you can say: this is schizophrenia. This symptom is very rare, not so frequent and it is a delusion linked to a perception that comes from passivity of perception. For example, if I enter into this room and I see a bottle of water, I can recognize that this object is a bottle of water although I am schizophrenic, but suddenly I understand that this bottle of water also means that Jesus Christ is coming here, this is delusional perception. In delusional perception there are two stages, the first one is the perception, which is correct because I perceive and I know that I’m watching a bottle of water, it’s not an illusion or hallucination. The second stage is represented by delusion, which is the meaning that I confer to the perception, the meaning that I give to the perception, to the bottle of water in this case, is delusional. Delusional perception is very typical of schizophrenia, because it is characterized by a feeling of passivity, meaning that the patient doesn’t give the meaning to the bottle in an active way. I see the bottle and I think, what is the bottle referring to? There’s not an active thinking, the significance of the meaning “Jesus Christ is coming” arises suddenly from the bottle as a revelation. We’ll study delusions in the next lessons. This delusion is more than a belief, it is a complete alteration, disruption of our relationship with the world and if you try to convince your patient that this is not real, you can’t. Only the psychopharmacological therapy can reduce delusions, it’s a biological symptom. It’s a sort of private truth of the patient, he/she is not interested in convincing you that the bottle is Jesus Christ, he/she knows that it’s like that, it’s enough. Delusional perception is an all or nothing phenomenon and for this reason it is very rare, unfrequent. Usually, delusional perception comes at the end of the specific state that precedes the onset of the psychoses, which is called pre-delusional state, wahnstellung in German (wahn=delusion, stellung=feeling). The pre-delusional state lasts one, two days, one week, so it’s very brief and during this period the patient is perplexed because the usual meanings of things start to vanish. For example, during the pre-delusional state, so before the onset of psychoses, the patient can see the bottle and he/she starts to feel that the bottle is the belle, but there is also something else, the bottle means something else. So, the patient starts to be perplexed, he/she starts to see other meanings, hidden meanings in common objects, although, at the same time he/ she is not able yet to grasp these hidden meanings. In the previous example, during this phase, the bottle can have many meanings. While in the delusional perception the patient comes back to a unique meaning, which is delusional; after the delusional perception the worldview of the patient changes abruptly and completely. For example, from now, the patient will wait for Jesus Christ, for years, based on this perception. In a natural course of schizophrenia, the onset of psychoses follows the delusional perception and once the onset of psychoses occurs, it would be difficult to go back. Nowadays, with psychopharmacological treatments you can try to counteract the delusional interpretation, you can try to reduce or stop the delusional symptoms, but it’s difficult to keep the patient in the common structure of reality. The therapy for fundamental symptoms is lithium. Question. Why is there a big difference between schizophrenia and sect/cult? Why can’t the leader of a sect be schizophrenic? Because the leader is not detached from social relationships, the leader is at the center of the social group. The schizophrenia patient can’t be the leader, he is isolated. The leader may be psychopath, he/she may suffer from paranoia, different diseases from schizophrenia. Schizophrenia means isolation. Question. Student: you often mentioned Jesus, is this kind of delusion always present? No, I often mentioned Jesus because it is a very clear and simple example. However, religious contents of delusions were very frequent in Italy and in Europe until the half of the 20th century. Now, they’re not so frequent because culture has changed a lot. As we will see in the next lessons the content is not so important, the structure behind is much more important. For example, in the example of the bottle, the former feature is a delusion perception, this is important. Then, I can feel this structure with Jesus Christ that is coming, aliens, the president Putin and so on. The content of the delusion is influenced by the cultural background. In the 19th century the content of a lot of delusions was religious. In conclusion, don’t forget that first-rank symptoms (very important) are complementary to the Bleuler conceptualization of schizophrenia. When we see a patient and we have the suspect of schizophrenia disease, first of all we have to understand if behind the clinical expression there are the fundamental symptoms. In the first stages of schizophrenia or during its development, but before the onset of psychoses, we have different kinds of symptoms, also from other diseases. The patient may tell you that he/she is depressed, or he/she may report obsessive compulsive symptoms, but if you grasp behind these signs, fundamental symptoms of schizophrenia appear. For example, if the patient comes to you and tells you that he/she suffers from obsessive-compulsive disorders complaining compulsive rituals such as washing hands, and if, in addition to them you can observe that the patient is isolated, doesn’t work/attend school, doesn’t do anything, he/she doesn’t wash him/herself, we have to think about schizophrenia. *Three forms of “failed existence” (Binswanger) Extravagance (Verstiegenheit) Perverseness (Verschrobenheit) Manneristic behaviour (Maniertheit)* CLINICAL DIMENSIONS Positive symptoms (delusions, hallucinations) Negative symptoms (apathy, avolition, anhedonia, alogia and social withdrawal) Disorganization (thinking, affectivity, behaviour) In the current diagnostic systems, we won’t see Kraepelin, Bleuler or Schneider, what we described until now are the earlier conceptualization of schizophrenia that shaped the current diagnosis of schizophrenia. Today, the symptoms of schizophrenia are classified as positive, negative and disorganization symptoms. As you can see above, symptoms are the same, because positive symptoms refers to delusions and hallucinations and these ones can also be named as psychotic symptoms. Positive symptoms are called in this way because delusions and hallucinations are phenomena that the patient has, but he/she should not have. If I see a cat in the class and the cat is not there in reality, it is a positive symptoms because the cat is something that I should not see. Negative symptoms are essentially the Bleuler fundamental symptoms that we explained before such as apathy, avolition or abulia, social withdrawal, anhedonia. They are named now as negative symptoms because affectivity should be present, but it is lacking. Do you know what is meant with anhedonia? Lack of pleasure. Pleasure may derive from ordinary things, such as sexuality, food, stable friends, a sunny day in autumn. The schizophrenic patient has no pleasure, he/she can’t conceive why eating food may give pleasure, but is different from depression. Disorganization symptoms are represented in part by the dissociation of thoughts that we saw in the Bleuler fundamental symptoms, but inside this category we have also disorganization of affectivity and behavior. A very important concept is that in the DSM (Diagnostic and Statistical Manual of Mental Disorders, a document) schizophrenia is mainly described through positive symptoms, because in order to have the diagnosis of schizophrenia the patient has to express delusions or hallucinations, this is the American conceptualization of schizophrenia, which is very different from the European one. The European conceptualization of schizophrenia highlights the importance of negative symptoms and not of positive symptoms and this is crucial because many schizophrenic patients do not show positive symptoms. On the contrary there is no schizophrenic patient who doesn’t have negative symptoms. The logic is historical, because the first editions of the DSM (1960s) were based on Schneiderian schizophrenia, but American psychiatrists received Schneider detached from the historical background, Kraeplin and Bleuler. They saw first-rank symptoms and they stated them as the core symptoms of schizophrenia, but Schneider was aware that first-rank symptoms are important and present, but behind there are negative symptoms. If we see a young patient with delusions or hallucination does not necessarily means that the patient is schizophrenic and this is the real problem, because the patient may be affected by other diseases such as depression, intoxication, paranoia. On the other hand, if we base our diagnosis of schizophrenia on positive symptoms, we are not able to diagnose young people who are schizophrenic that don’ show hallucinations or delusions. Question. Since these patients are very isolated, how can we reach them? It’s very difficult. Normally, the patient has his/her first contact with the psychiatric services only when positive symptoms are present, or when his/her behaviour is very disorganized, because parents and friends understand that there is something wrong. While if the patient presents mainly negative symptoms, it’s very difficult to diagnose it because we are used to think at schizophrenia through psychoses and also because in Italy the prejudice towards schizophrenia and mental illnesses in general is very strong. So, if a young person is showing negative symptoms, before thinking at schizophrenia we think a lot of other things. It’s easier that the patient may contact a priest, a psychologists, a neurologist rather than a psychiatrist, because psychiatrists are considered only for mad people. In America, Canada, Great Britain, the stigma is not so strong, schizophrenia and mental diseases are equal to other diseases. If I hear voices, I go to the specialist, which is the psychiatrist to stop them. But it’s very difficult if the patient is isolated and this is a big problem because the prognosis depends on the duration of untreated psychoses. If a patient starts the therapy after two years from the onset of the disease, it’s not so easy to have the recovery. Question. Is there a difference in the brain activity between negative and positive symptoms? Yes, there’s a big difference that we are going to see in the next lessons, but I can anticipate something. Positive symptoms are due to an excess of dopamine in the limbic system, while negative symptoms are due to a lack of dopamine in the cortical system (prefrontal cortex), so opposite conditions. Question. Is there a relationship between delusions and leaders? Are they present at different levels? (Not clear question) Not necessarily, but they may be. In this case delusions are symptoms of other psychiatric conditions. A very frequent psychiatric condition linked to leaders is paranoia, delusional disorders. With schizophrenia is not possible to become a leader, the schizophrenic patient is completely detached from humankind. A schizophrenic patient can’t be a leader, he/she is alone, with a distort kind of logic. Question. Could be logical to think that religion started from a paranoid individual, like if God talked to persons? No, because as I said at the beginning of this lesson, delusions and hallucinations are very frequent as symptoms, so for example you can find them in bipolar disorder, depression, so basically Moses could be depressed or suffer from a manic episode, such as San Francesco. You don’t have to think about a rigid dualism between some cultural expressions and psychopathology because certain phenomena are normal in some historical and cultural background and not normal in others. Culture may shape our way of thinking and our worldview. In Italy, in Middle Ages, a lot of people could see angels in the sky, there were collective hallucination, not psychoses, so there can be other reasons, not necessarily psychopathological ones. During Renaissance a lot of people could see angels but it was due to a collective intoxication from bread, have you ever heard about “segale cornuta”, “ergot”? If we start to see an angel and you are embedded in a specific context, your friend may start to see angels in the clouds, suggestion is important, it’s not necessarily pathological. In Middle Ages thousands of women were killed because thought to be witches, this is not a collective delusion! How is possible that all those people believed in these things? Every kind of delusion, by definition, is a detachment from a social, cultural background, because the former structure is completely different from our way of thinking, so if one patient has a delusion, necessarily he/she will loose the social background. In schizophrenia there is a primary detachment from the social background, while in other kinds of conditions, such as delusional disorders, if the delusion is very small, it can be difficult to recognize it, but over time it becomes very evident. Psychopathology always refers to formal structures of perception, of thinking, that are completely different from the normal way. We’ll see these things in the next lesson. Killing a witch doesn’t necessarily means psychopathology, it’s cultural construct. In Middle Ages, in case of earthquake, the fault was attributed to a poor witch woman, for example. Psychiatry 20/11/2023 morning lecture Prof. Matteo Tonna SCHIZOPHRENIA (2) In the previous lesson we have talked about the historical background of schizophrenia. The first conceptualization of schizophrenia was made by Emil Kraepelin, who gave the original name to the pathology: dementia praecox. His definition was based on a longitudinal perspective, in which the diagnosis is made by the prognosis. Later on, Eugen Bleuler proposed another concept of schizophrenia: a cross-sectional perspective based on fundamental symptoms; these symptoms are now called “negative symptoms” of schizophrenia. Lastly, Kurt Schneider defined the so-called first rank symptoms, which are mainly delusions and hallucinations based on a feeling of passivity. In this lesson we will continue talking about the classification of symptoms of schizophrenia (negative symptoms, positive symptoms and disorganization symptoms). Onset of schizophrenia The typical onset of schizophrenia is in late adolescence, between 16-25 years old. However, there can be cases of early onset schizophrenia, between 13-18 years old, and even cases of very early onset which occur during childhood, before 13 years old. Schizophrenia has two possible types of onset, each with specific characteristics: onset as a process and onset by development. The concepts of process and development are based on Karl Jaspers’ “General Psychopathology” (1913); Jasper was a general psychiatrist but also a philosopher. These definitions are typical of European psychopathology and are not usually found in American literature; however, this classification is very important because the type of onset tells a lot about the type of schizophrenia and its prognosis. - Onset as a process: primary phenomenon, in this case the continuity of life of the subject is abruptly interrupted (with the term “abruptly” we refer to a timespan of 2-3 weeks to 1 month). Before the onset, the patient’s functioning is good; for example, they might go to school, have friends and play sports. Then, the patient abruptly starts having delusions and hallucinations, which are positive symptoms. Therefore there is a fracture in the patient’s life, there is a “before the onset” and an “after the onset”. This type of schizophrenia is mainly characterized by positive symptoms and disorganization symptoms. - Onset by development: in this case there is a longer and slow development, starting from premorbid personality traits. Therefore there is a continuity between personality traits and the disease, and the social functioning of the subject is impaired before the onset of the symptoms. For example, the patient might already be shy and introverted, with very few social relationships, no hobbies and difficulty at social contact. In this case, schizophrenia is mainly characterized by negative symptoms. Among these two types of schizophrenia, the one with onset by development has the worst prognosis because it is characterized by negative symptoms. Moreover, since the onset by development is very slow, this kind of schizophrenia is also harder to diagnose: the patient, already introverted, progressively starts isolating from the outside world, but this is not easily detectable by people close to them. It is much easier to detect the onset as a process, because the symptoms (delusions and hallucinations) emerge from a good function. Definitions: Process (Jaspers, 1913): "quid novi", primary phenomenon that interrupts "the continuity of meaning of life" (Weitbrecht). Permanent outcome. Poussée/ thrust (schaub). Development: long, abnormal development from a premorbid personality.  Spectrum (Kety, 1968): related conditions but different clinical consistency (Schizoid PD, Schizotypal PD, Schizophreniform D., Schizophrenia). Schizoaffective continuum (Griesinger's unitary psychosis). Symptoms of schizophrenia: clinical dimensions - Positive symptoms: delusions, hallucinations (onset by process). - Negative symptoms: apathy, avolition, anhedonia, alogia (= inability to speak) and social withdrawal (onset by development). - Disorganization: thinking, affectivity, behavior (onset by process). Negative symptoms Negative symptoms can be primary or secondary. - Primary: intrinsic to the disorder, long-lasting, treatment-resistant; these symptoms do not change over the years. - Secondary: resulting from side effects of pharmacological therapy, from social deprivation, or may represent a coping mechanism. For example, social withdrawal might be secondary to positive symptoms such as delusions or hallucinations (e.g. if the patient is afraid of being killed, they will not leave the house); these symptoms can be treated. The more severe the primary negative symptoms, the more serious the course and prognosis of the disease will be and the higher the probability that the onset is by development. If there are two or more primary negative symptoms “enduring” (Carpenter, 1988), we refer to deficit schizophrenia; this type of schizophrenia is mainly characterized by primary negative symptoms. It represents the most severe and, at the same time, the less apparent form of schizophrenia. When primary negative symptoms are present there is a very disrupted global function; for example, the patient might not be able to wash themselves. However, schizophrenia characterized by these symptoms is not easy to detect, while delusions and hallucinations are more apparent, and that might also be because they are more linked to stigma (for example, if someone states that they are Jesus Christ, the people around them understand that there is a problem; if the person simply stays at home, the issue is less apparent). Positive symptoms Delusions and hallucinations are positive symptoms. Disorders of perception The term “hallucination” is a very broad term, therefore it is important to make a distinction between hallucination in sensu strictu, pseudo-hallucination, hallucinosis and illusion. - Hallucinations s.s. [strictu sensu] (auditory, visual, olfactory, coenesthetic, haptic, tactile, thermal): the “real” hallucination is a false perception, like the visual perception of an object that is not there, or the auditory perception of voices that are not present. In this case the perception is out of the patient’s head, the objects and sounds are located in the external world. Coenesthetic hallucinations are hallucinations about our own body; for example, the patient might see their arm waving when it isn’t, perceive their heart moving inside the body, feel their stomach in the leg, or feel as if their body does not fit well and is too large. Haptic hallucinations are very frequent and there is a feeling of electricity inside the body. Tactile hallucinations occur when the patient feels as if someone is touching them, or as if they are being raped (there is a feeling of violation). - Pseudo-hallucinations: in this case the false perception is located inside the patient’s head, with the voices and images not present in the external world. Both hallucinations s.s. and pseudo-hallucinations are present in schizophrenia. - Hallucinosis: this phenomenon is very similar to hallucinations, there is the perception of something located in the external world. The difference between hallucination and hallucinosis is that, in this case, the patient is aware of the fact that what they are seeing  does not exist. Hallucinosis is not frequent in schizophrenia and, more in general, in psychiatric conditions; it is more recurring in neurological conditions, such as Lewy body Dementia or temporal seizures. - Illusions: in this case the object is present and real, but it is perceived in a distorted way. For example, a water bottle on the desk could be seen with blurred boundaries and water spilling out; a patient could be scared of their doctor because of visual illusions showing the doctor distorted as a monster, with bloody eyes and dreadful skin. In general, in schizophrenia the most frequent phenomenon is hallucination, while illusions are less frequent. However, hallucinations are not exclusive to schizophrenia: they are also present in other psychiatric conditions, for example auditory hallucinations are frequent in bipolar disorder and in psychotic depression. So, even though hallucinations and delusions are not specific to schizophrenia, if there is a specific kind of hallucination (first-rank symptoms) the specificity for schizophrenia is higher. Content thought disorders (primary delusion) In schizophrenia delusions are, by definition, primary delusions; this means that, in other psychiatric conditions, delusions are not primary, but secondary. For example, in depression delusion may be present, but it derives from the mood disorder (not primary). There are three types of delusion in schizophrenia: - Delusional perception: abnormal significance attached to a real perception without any cause that is understandable in rational or emotional terms. This is a first-rank symptom: once recognized, the doctor can assert that the patient suffers from schizophrenia. - Delusional intuition: (delusional) idea that appears abruptly, out of the blue, in the patient’s mind; the delusional belief is not linked to a perception. This is also present in other psychiatric disorders. For example, the patient might be walking and abruptly “understand” that they are the Messiah, without a link with perception. - Delusional memory: memory image that is given abnormal significance. In this case a real memory becomes linked to a delusion; for example, the patient remembers that their parents used to beat them as a kid and now they “understand” that they are not actually related to the parents, but they are the son of the King of England. This is also present in other psychiatric disorders. Disorganization Disorganization can regard thoughts, affectivity or behavior. With disorganized thinking, the speech of the patient may also be disrupted, with weak associations and links between words. The patient’s common sense and logical connections of thought are impaired. A disorganized behavior is impossible to understand rationally; for example, while the patient is talking with the doctor they might suddenly stand up and crush against the wall. Formal thought disorder - Thought dissociation - Thought structure disorders (von Domarus principle, pathological symmetry, dereistic thinking) - Concrete thinking Volition disorders - Catatonic stupor - Catatonic excitement - Stereotypes - (Active and passive) negativism A symptom of disorganization is catatonia: a catatonic patient is completely blocked, with severe motor retardation; the main feature of catatonia is a very severe rigidity of muscles. There are some signs that can be detected to diagnose catatonia, such as flexibilitas cerea: because of the rigidity, when the patient’s arm is raised upwards it remains up and does not fall down. Catatonia is a severe psychiatric condition and it is also present in other psychiatric disorders, such as severe forms of depression. Catatonia is a neurological symptom because it can be caused by severe dopamine depletion in the brain. This condition must be recognized as soon as possible because it can become lethal for the patient; it is not a positive or negative symptom, but rather a disorganization symptom. Schizophrenic syndromes The different kinds of symptoms characterize different kinds of schizophrenia (according to DSM- IV). The categorisation of schizophrenia in subtypes is not recommended anymore, because symptoms may fluctuate. Nevertheless, it is important to know which types of schizophrenia are mainly characterized by positive symptoms and which by negative or disorganization symptoms. Listed here are the main subtypes of schizophrenia: - Schizophrenia Simplex: there are only negative symptoms and no positive symptoms; the onset is by development. This is the most severe form of schizophrenia, but also the less apparent. - Disorganized schizophrenia (Hebephrenia): the main symptom is disorganization. - Paranoid schizophrenia: mainly characterized by positive symptoms; note that negative symptoms are present in all kinds of schizophrenia, but here they are less severe than positive symptoms. These patients are delusional and hallucinated; the onset is by process. - Catatonic schizophrenia: characterized by catatonia. - Residual schizophrenia: mainly characterized by disgregation after many years of untreated illness. Before the advent of psychopharmacological treatments, schizophrenia was much more severe, with very dramatic outcomes. - Undifferentiated schizophrenia: here the different dimensions of schizophrenia are equally present. - Pseudoneurotic schizophrenia (Hoch and Polatin, 1949): very similar to the simplex form; with negative symptoms as the main ones. However, here the negative symptoms are hidden by other symptoms, which are typical of other diseases (e.g. obsessive compulsive symptoms, anxiety, phobic symptoms). This form of schizophrenia is very difficult to detect because on the surface it is not possible to see the negative symptoms. For example, a patient might complain about symmetry compulsions, order compulsions and ritual compulsions, but behind these there are negative symptoms (the patient has been isolated in their room for years, does not change their clothes, etc.). Genetics Schizophrenia is a complex disease in which genetic and environmental factors are intertwined. The prevalence rate of schizophrenia is about 1% regardless of country, culture and era. The genetic component explains 57% of schizophrenia, therefore there is a biological substrate; this was discovered thanks to the Danish studies conducted in the 80s on monozygotic twins. It is possible to understand that the biological component is not complete: for 20-30%, schizophrenia is not based on genetic factors. - Susceptibility genetic loci on chromosomes 5, 6, 8, 22. - Several genes involved, incomplete penetrance. - Increased susceptibility to environmental factors and/or carriers of specific neurobiological alterations (endophenotypes). Environmental factors Environmental factors account for 30-50% of schizophrenia (genes modify the threshold of susceptibility to environmental factors). These factors can occur from birth until the time of the onset. They are: - Increased perinatal complications (e.g. prematurity, preeclampsia, toxaemia, hypoxia) (NB: high hippocampal sensitivity to hypoxia). Obstetrics complications could also be secondary to neurodevelopmental abnormalities (NB: absence of gliosis). - Seasonality: the mother could be subjected to some viral infections during pregnancy; this explains the increased incidence of schizophrenia in autumn and spring (viral hypothesis: slow viruses, retroviruses, autoimmune reactions). - Malnutrition of the mother (1st trimester): twice-increased risk of schizophrenia. Consider that schizophrenia is a neurodevelopmental disorder, therefore a biological vulnerability is present at birth. However, this vulnerability must interact with the environmental factors in order to have the onset of the disease in late adolescence, so it is always an interaction between different factors. Other environmental complications are psychosocial factors during infancy and substance abuse during childhood and adolescence. The most important drug that specifically interacts with schizophrenia vulnerability is cannabis; cannabis abuse without a schizophrenia vulnerability will not increase the risk of developing the disease, but if a biological vulnerability is present, it could be triggered by the drug. This is what happens, for example, in hypertension: a person with vulnerability for hypertension who has a bad lifestyle can more easily trigger a clinical condition. Environmental factors motor abnormalities: Reviewing home videotapes made it possible to identify pre-schizophrenic children based on motor abnormalities in the first 2 years of life (choreic movements, altered upper limb posture, reduced motor skills) (Walker et al., 1994). Such motor abnormalities are associated with increased ventricular diameter in adulthood. Neurodevelopmental alterations would already be present at an early age. Conclusions Since schizophrenia is a neurodevelopmental disorder, by detecting the high risk population the disease could be prevented. However, this is not easy; in the last fifteen years, researchers have tried to describe reliable biomarkers of schizophrenia vulnerability. At the time of Kraepelin and Bleuler, the onset was when symptoms first appeared; nowadays, the onset is actually considered the end of a neurodevelopmental pathway. The primary pathogenetic event can be ascribed as a neurodevelopmental disorder (fetal neuronal migration). So, the first problems arise in the earliest three months of pregnancy and are linked to the migration of neurons. This vulnerability then has to interact with the normal development, so with the factors related to the maturation of the brain (environmental factors). The potential action of one or more causal agents would be relatively short. The clinical manifestations remain latent for a long time after the action of the pathogenic event. -> Biopsychosocial model (Paris; 1996,2003) An endophenotype is a sign that represents a bridge between the genotype (biological and genetic vulnerability) and the phenotype (clinical onset). It could be a cognitive, motor, language or behavioral sign. Endophenotypes precede the clinical onset and are present in childhood: by detecting these specific biomarkers for schizophrenia vulnerability it is possible to distinguish the people that are at risk for the disease, in order to prevent its onset and avoid the appearance of symptoms. If schizophrenia is a neurodevelopmental disorder with complex processes starting from the prenatal period, why is the onset in late adolescence and not in childhood? There are two main reasons for this: 1. Biological process in late adolescence, called ”pruning”, which causes the destruction of neural connections that have not been frequently used; at the same time, neural connections that are more used are preserved. Pruning is a potential biological cause of schizophrenia onset, since this process of destruction can decompensate the equilibrium and a vulnerability may arise. 2. Psychosocial factor: schizophrenia is, in its essence, a problem of social relationships (schizophrenic autism). As a child, the patient is able to cope with social problems because relationships are not too complex, but in adolescence and early adulthood social relationships become much more difficult to manage. This may cause the precipitation of a preclinical condition into a clinical onset. The reason why some children might develop schizophrenia earlier than in adolescence is the neurodevelopmental load: the heavier the load, the more severe the neurodevelopmental substrate, the earlier the onset. Neurodevelopmental hypothesis (Weinberg) Meehl (1912): schizotaxia (“neurointegrative defect underlying schizotype pathophysiology”). Weinberger (1987): as a neurodevelopmental disorder: early brain injury (altered program of synapse formation and neuronal migration in the prenatal period) interacts with specific maturational physiological events that occur at a much later stage. Feinberg (1982): role of late developmental events (cortical synaptic "pruning" in adolescence). Neurophysiology EEG: Iperarousal (due to hyperactivity of the Ascending Reticular Activating System). Increased delta and theta rhythms in bilateral frontal (mainly left) (due to functional deactivation). SPECT, PET: Decreased perfusion and metabolic activity in frontal lobes (hypofrontality). Alterations in slow eye tracking movement, syst. impairment). Neuropathology In schizophrenia there is a widespread disruption of neural connectivity and every area is impaired: FRONTAL LOBES: - Prefrontal cortex: loss of neuronal connections and cytoarchitectural abnormalities. - Orbitofrontal cortex: morpho-functional abnormalities. CINGULATE GYRUS: abnormalities of the anterior cingulate cortex. TEMPORAL LOBES: - Mesial structures: altered laminar distribution of rostral entorhinal cortex neurons (abnormal neuronal migration?). - Hippocampus: decreased number, size and orientation of pyramidal cells. - Amygdala: reduced volume. BASAL GANGLIA: Caudate and putamen: increased volume (altered elimination process and synaptic rearrangement; compensation to afferent fiber reduction; antipsychotic effect?). Lateral and third ventricle dilatation (associated with cognitive-intellectual impairment and "schizophrenia deficit"). Expansion of brain grooves (mainly frontal lobes). Absence of gliosis (findings not related to active inflammatory process or typical degenerative process but secondary to early onset neurodevelopmental abnormalities). Dopamine All neurotransmitters are involved in schizophrenia, but the most important one is dopamine and this is due to the fact that antipsychotic drugs block D2 receptors in the limbic system. With positive symptoms there is an excess of dopamine in the limbic system, while negative symptoms are mainly due to a loss of dopamine in the prefrontal cortex. Therefore, the problem of antipsychotics is that they are very effective in reducing positive symptoms by blocking dopamine receptors in the limbic system, but they are not so effective in treating negative symptoms. For this reason, in the last twenty years there has been the development of second-generation antipsychotics. While first-generation antipsychotics simply block dopamine, with no effect on negative symptoms, second-generation antipsychotics try to balance dopamine in the different systems of the brain, acting on the complex balance between serotonin and dopamine. In fact, second-generation antipsychotics block a specific kind of serotonin receptor and allow the entrance of dopamine in the cortical area. L-DOPA, Amphetamine and DA agonists induce psychotic symptoms. Increased plasma levels of HVA in untreated patients (correlated with severity of clinical picture and response to treatment). Early sensorimotor disturbances The endophenotypes of schizophrenia precede the clinical onset of the disease; there is a vulnerability already from the first 2 years of life. The most important endophenotypes are motor deficits, language impairment and subjective experiences of the self. The first motor signs are gait and balance deficits. At risk individuals present, as children, delayed gross motor milestones and dyscoordination, with postural instability. Usually, postural stability depends on the visual inputs: with closed eyes, instability increases. In schizophrenic patients, however, postural instability occurs independently from open or closed eyes. This means that there is early impairment in motor development and maturation of sensorimotor integration systems (frontoparietal, basal ganglia, cerebellum). Multisensory integration Animals' perceptual view of the world is an integrated and holistic one in which sensory cues are blended seamlessly into a singular perceptual Gestalt. Multisensory integration is the process through which information from different senses is combined by the brain to influence our behaviors and shape our perceptions. In schizophrenia, the basic processes of multi sensory integration are impaired in space and in time. Space principle: stimuli detected within a specific spatial distance (cm) are integrated. Within the peripersonal space, which surrounds the body, multisensory integration is enhanced; in schizophrenic patients, this space is very narrow and there is no possibility to integrate the stimuli and to consequently respond through a motor behavior. Time principle: stimuli detected within a specific temporal window (msec) are integrated. This temporal window is heavily impaired in schizophrenic patients: if it is too large, stimuli that are separated from each other might mistakenly integrate. Effectiveness principle: stimuli that are obtained singularly have weaker effectiveness; the effectiveness is enhanced when the stimuli are combined. Sensorimotor integration In schizophrenia there are important basic deficits in the matching between expected and actual results in motor enactment. Sensory inputs are linked to motor outputs and there are feedback loops which give information to the sensory areas. These simple basic loops are disrupted in schizophrenia and there is no sensory motor integration. This is also reflected in deficits of “corollary discharges” (CD), which link impairment of the sense of agency with motor dyscoordination in childhood. Another endophenotype has to do with language impairment: there is a strong association between childhood dyspraxia, speech and language organization and adult schizophrenia outcome. Language is impaired at different levels, from syntax to semantics to prosody, and this is due to the fact that language is linked to the motor system. Language processing in our brain evolved from our sensory motor system, so a disruption in sensory motor integration also means a disruption in language processing. Specifically, disruptions in prosody are very important because prosody regulates the affective meaning of a conversation through intonation and synchronization with the other person. Endophenotypes are present in most patients with schizophrenia (but not all) and they are signs of schizophrenia vulnerability: people who present one or more endophenotypes will not necessarily become schizophrenic, but when these signs are associated, for example, with family history, there is a stratified risk of schizophrenia; this is also useful in detecting high-risk individuals. High-risk individuals could also show subclinical symptoms, for example they might experience delusion-like symptoms that only last for brief periods of time and disappear spontaneously. These spontaneous and intermittent symtpoms show that the schizophrenia process is arising; the difference with actual symptoms of the disease is the consistency. The most important sign is functioning: if a young person shows an important function decline, coupled with endophenotypes and family history, it is time to intervene. Early interventions can use a pharmacological therapy coupled with psychomotor therapy to ameliorate and act on the motor deficits; the social functioning must also be improved to prevent these individuals from becoming isolated. In general, the more severe the neurodevelopmental load is, the more severe the symptoms will be. If there is an abrupt onset, without previous endophenotypes and prior good functioning, the psychosis will mainly be characterized by positive symptoms, so delusions and hallucinations, with a better prognosis (and it might not even be schizophrenia). “Real” schizophrenia is characterized mainly by negative symptoms and before the onset all the endophenotypes will be present, along with behavioral isolation. 26/11/2023 - Morning lecture Psychiatry Matteo Tonna DELUSIONAL DISORDERS Until now we have studied the psychopathology of schizophrenia, we have defined its important phenomena, such as symptoms, in particular hallucinations, but we didn’t give a proper definition of delusion. We have talked about delusions, but I would like to provide a definition of it, because delusion is complex phenomena. DEFINITION How can a delusion be defined? Where do you hear about delusional patients? What are the fundamental features? The definition of delusion is very complex because, at the beginning the contextualization of delusion was mainly based on the content of it, what the patient says. The first definition of delusion is the “morbid error of judgement” (Kraepelin; Bumke), there is a mistake in the judgement. If I tell you that last month I was on Mars, for example, you know this is a delusion because it is impossible. If somebody tells you I am Jesus, you know the person is delusional. This is the definition of delusion based on the content, on what the patient is telling you. Unfortunately, the phenomenon of delusion is far more complex because sometimes the content may be not so strange: for example, a patient may tell you he is persecuted by his boss, which is not so strange, or that his wife has another man, which is not strange as well. It may be the truth, but at the same time the patient is delusional. So in the delusion is not important its content, but the structure, the features that are behind that judgement, or in another way it’s much more important the way the patient comes through that judgement, not the judgement itself. Some examples: if a patient tells you that he travelled to Mars, it’s easy to say that this is a delusion, but if he says that he is persecuted it’s not so easy; so we have to pay attention to the formal structure behind that judgement. It’s not easy because we are used to focus on the content. The second definition, and more correct one, is the following: delusion is a “pathological falsified judgement” (Jaspers), no matter what the patient says but the way he/she comes to the judgement. The definition is by Jaspers, who wrote an important book of general psychopathology in 1913, it was the beginning of psychopathology. Jaspers defined 3 main features of delusion: the first was the subjective certainty, a patient is sure that what he’s saying is true, he is convinced of it. The second feature is linked to the first one, it is not possible to convince the patient that it is not true, so the delusional judgement is sustained by other experiences and it is not possible by words to convince the patient that it is not true. The third feature is the impossible content. I’ll give you some examples: let’s imagine that a patient comes to you and he tells you that he is persecuted by his boss, this judgement is not so strange, so you must ask him why and how you are persecuted by your boss. This patient may tell you that he knows that his boss persecuted him because last night he saw a crow upon a tree, and as soon as he saw it he understood that his boss was persecuting him. So the content may be even true, but the structure behind is delusional. This formal structure is the delusional perception. If you are able to capture the formal structure behind it, you can confirm the diagnosis of the patient, and this patient could be schizophrenic, because this delusional perception is first rank symptom of schizophrenia. Second example: another patient comes to you, and also he tells you that his boss is persecuting him, so you ask him why this is happening, and how he recognized this. He can answer in this way: I know I am persecuted because one week ago my boss started to look at me in a strange way, then I saw three colleagues of mine talking to each other. It seemed to me as they were talking about me. They referred to me. And in the last few weeks, all these things increased. Everyone looked at me and referred to me, so I know I am persecuted. This is a different kind of structure behind, in this case delusion is built upon a process of interpretation. Every aspect of reality is distorted and interpretated, in order to build the delusion. In this case the patient is probably not suffering of schizophrenia but it is a delusional disorder of paranoia. The judgment, the content of the delusion, is the same; but the formal characteristics behind are very different and these are two different psychopathological conditions. The third and last example: another patient comes to you and also this patient tells you that he’s persecuted by his boss. But this patient starts to say, for example: I am persecuted because I'm not able to do anything, I’m a bad person, It's better that I stay at home because everything I do is wrong. He's persecuting me because he wants that I stay at home to protect me because I can't have a job, I can't have a work. I'm not good as a worker, I'm not good as a man. I'm not good as as a father, husband and so on. So this is another kind of delusion. The theme accounted is the same (persecution) but in this case the structure behind is linked to depression, so the patient is depressed and and his delusion is linked to a depressive depression. The persecution is covering another feeling, the feeling of guilt. So for example, you have to treat this patient with antidepressant because if you treat this patient only with antipsychotics, the delusion still remains. The contents are on the surface, you have to grasp to understand the formal characteristics that are behind. When you see the delusion, you know that from a neuro-biological point of view, the neurochemical characteristics are the same, too much dopamine in the limbic system. But in depression, for example, this condition is secondary to other neurobiological conditions. So if you try to manage delusional depression only with antipsychotics, you can’t reduce delusion because it is sustained by depression, so you have to treat depression with antidepressants. Delusion is like a fever: you could have a fever, but the causes may be very different. CLASSIFICATION There are different kinds of classifications of delusions. In psychopathology, in psychiatric syndromes, the delusional patient is in a condition of lucidity state of consciousness. In other conditions, for example in neurological diseases, in brain injuries, in delirium (profound altered state of consciousness) delusions arise from the disruption of the state of consciousness. In psychiatry, state of consciousness is intact and preserved. So if a patient with schizophrenia has a delusion, this delusion is not linked to an impaired state of consciousness. Second important classification: The delusional structure. Delusions may be well organized in their structure, well elaborated, this is the typical example of delusional disorders. And in this case the structure of delusion is paranoia-like. In this case the elaboration of the illusional themes is very complex, very rich. In the second example I did, the patient told you that his boss was persecuting him because his colleagues talked about him and he started to understand that they looked at him in a bad way. But every object of reality, everything he sees seized is a source of interpretation, and all these interpretations are linked together to build the delusion. So in this case the delusion is well organized and very rich. The construction of delusion is elaborated and rich as well. The patient may tell you that his boss is persecuting him because he is very good at work. He is afraid of him, so he started to create a network of people against me, that follow me at home. This is because I should be the boss. This is an example of very well organized delusion. In schizophrenia, instead, the structure of delusion is not well organized, it's very poor, because the patient doesn't have the possibility to organize the contents, because of his disorganization, and his negative symptoms. So delusional themes are somehow isolated, separated from each other, they are not so linked with each other and systematized. So a schizophrenia patient could tell you: my boss is persecuting me, because I saw crow, I don't know why, but I know that my boss is persecuting me, so it’s enough. This kind of structure is paranoid. The first was paranoia-like, the second is paranoid. It’s very important this kind of distinction, because in American textbooks you can't find this distinction because they are typically based on European psychopathology. The third kind of structure is Paraphrenic. Paraphrenic means that delusion is due or caused by hallucinations, so the patient is hallucinated. He/she hears voices, for example, and from these hallucinations he/she builds the delusional themes. So in this case, delusion is secondary to hallucination. In the first two examples there are no hallucinations; in the third example, hallucinations create the delusion. So we have paranoia-like, paranoid and paraphrenic. Paranoia-like is typical of paranoia, of course; paraphrenic is typical of paraphrenia, another delusional disorder; paranoid is typical of schizophrenia, but also depressive delusions. Other type of classification of delusions: delusions may be primary or secondary. The term Primary is synonym of schizophrenia. So when we talk about primary delusion, we talk about schizophrenia. Whole other types of delusions, outside schizophrenia, are secondary delusions. so For example: if I am depressed and I have a delusion. In this case, delusion is secondary to the crash. If I am in manic state and I have a concussion, in this case, delusion is secondary to depression. In delusional disorders, for example in paranoia, delusion is secondary to specific personality traits. So only in schizophrenia, delusion is primary, because it arises directly from schizophrenic backgrounds. If a delusion is secondary, for example, to personality traits such as in paranoia, the onset of delusion is often quite development (difference between process and development). If I have specific personality traits, for example if I'm very suspicious, I don't rely on other people. Over time, these personality traits may develop into a real delusion. Primary delusions in schizophrenia are not restricted to delusional perception. We have three kinds of primary delusions in schizophrenia: delusional perception, delusional intuition and delusional representation. Delusion perception is linked to a perception: an example is that a bottle is a bottle, but at the same time it means that Jesus Christ is coming down to the earth. This is a delusional perception. Delusional perception is a primary delusion because it's typical of schizophrenia, and it is the first rank symptoms, that it’s very characteristic of schizophrenia. The second one, delusional intuition, is primary delusion, but it is not a first rank symptom because delusion intuition may be found also in other psychopathological conditions, for example in mood disorders. If delusional intuition is in schizophrenia, it is primary, but delusional intuition may be also another psychopathological condition, for example in manic states, and in this case delusional intuition is secondary. The third one, delusional representation: in this case representation is a memory. Representation means memory in psychopathology. I have a memory of myself when I was a child and my mother shouted at me. Now I remember this episode and understand that my mother was not my mother. But my mother was the Queen Elizabeth. This is a delusion based on a true memory, and it is named delusional representation. There are not first rank symptoms at all, not so typical schizophrenia. Also in this case, in schizophrenia delusional representation is primary, in other conditions is secondary. It's important to note that in depression, the content of delusions is always the same. The contents of delusion in depression are very rigid, very restricted to specific contents. These contents are guilt, ruin and hypochondria. These contents are present regardless of culture, social status, historical backgrounds. Delusion of guilt means that the patient is convinced to have done something terrible: for example, a patient of mine was convinced that she was responsible for destruction of the Twin Towers. This is a typical delusion based on depression. The feeling of guilt may be expressed in different ways. For example, the patient may tell you that he is not a good father, is not a good husband, he is a bad person, he has to go to jail. As you can notice, the delusional theme is feeling of guilt based on depression. The second theme is ruin: ruin means “I don't have anything, I don't have money to survive, I don't have clothes, I don't have anything, my wife and my children disappeared”. Ruin is linked to guilt. If I don't have anything, it is because it's my fault. The third team is hypochondria. A patient is convinced to have a disease, he is convinced he's dying, for cancer or for degenerative disease for example. These themes, hypochondria, guilt and ruin, are linked together. You have to recognize depressive delusion because it's not so easy to recognize these kinds of delusion. For example, if a patient comes to you and he says he is very sad, he is depressed because he doesn't have anything, he doesn't have money to survive and to sustain his family. You may believe me, you may think that it's a bad situation. Then he may tell you that actually he's very rich. So it's it's not so easy to understand that behind specific statements there is psychopathology. You have to recognize the delusions, but you have to conceptualize the delusion themes within frameworks of other depressive symptoms. A specific type of depressive delusion is the Cotard’s syndrome: in this syndrome delusions of guilt, ruin, hypochondria are mixed together to create this kind of structure. A patient is convinced to be dead and somehow he is forced to live his death everyday. There is also a variation of this theme: the patient is alive but other people are dead, in paradise for example. Cotard's syndrome is typical of depression and is typical of depression in the elderly. Depressive delusions are secondary delusions, and they are linked to the mood congruent delusions, or mood congruent delusion-like ideas. In depression, delusions may be congruent, but also not congruent to the mood. So a patient may be depressed and have a delusion of persecution that is not linked to the mood, for example. In the last hour we will start to talk about the specific delusion disorders. Until now, we have talked about the schizophrenia. Kraepelin separated Schizophrenia that he named Dementia Precox, from Manic Depressive Disorders. Patients with dementia precox had a progression of the disease, instead patients with manic depressive disorders had a good prognosis. Splitting psychosis into these two main categories created a lot of problems because there were certain psychopathological conditions that couldn't be classified as dementia precox or manic progressive disorders. So these conditions fell apart. These conditions are delusional disorders and brief psychotic disorders. Both delusional disorders and brief psychotic disorders are psypathological conditions characterized by psychosis, so by psychotic symptoms, through which I mean delusions and hallucinations. But they don't fall into one of the main categories of schizophrenia or depressive illness. Delusional disorders is a broad category mainly characterized by one symptom: delusion. The name delusion disorders means that the main psychopathological feature is the onset of delusion. Now we will describe two different kinds of delusional disorders: paranoia and paraphrenia. It's better to distinguish between paranoia and paraphrenia, because they actually represent two distinct phenomena of psypathological conditions. PARANOIA Usually the term paranoia is used in no proper way, because in psychopathology paranoia means a specific kind of delusional disorder, so separated from schizophrenia and from mood disorders as well. The first scholar who described systematized term and the conceptualization of paranoia was Kraepelin, the same author of the dementia precox. He described Paranoia as an autonomous and specific disorder, characterized by an insidious development of a permanent and unshakable delusional system. So the main and unique symptom in paranoia is delusion. Patients don’t have hallucinations, don’t have other kinds of symptoms, only delusion. This delusion has a well organized structure. The main characteristics of this delusional are high level of organization of the delusional structure and high level of elaboration. Delusion arises from a mechanism of interpretation as we have seen in the example before: the patient starts to interpret every object of reality, interpretation of every episode of reality to create a delusional system, which becomes bigger and bigger. At the beginning, the delusional system may be limited to, for example, the work or the family, but during the course of the disease, the delusion of contents starts to occupy every aspect of reality. For example, the patient may start to be convinced to be persecuted by his boss. At the beginning persecution is only within the office and the content of the delusion may be very close to reality. It is difficult to recognize that actually there is the raise of a pathological condition behind these beliefs. So the patient for example goes home and tells his wife that his boss is persecuting him, and the wife may understand him. But during the course of the disease, the delusional system increases. So other people outside of the office are in some way linked to the persecution, the patient may go out for a walk and see other people which are in some way linked to the persecution, and seems like everyone wants to know and speak about the persecution. At the end, the entire world knows about this persecution and the patient is completely absorbed in defending himself from his enemies, who are all around, of course. So the entire life and the entire existence is destroyed by this kind of delusion. So in paranoia, delusion starts very slowly. Delusion comes to substitute completely the life of the patient. The contents are always very close to reality, jealousy, persecution and they are about everyday life themes. So these contents are not so strange and bizarre as in schizophrenia, but they deal with everyday life. A specific kind of paranoia is the Automatic delusion. In automatic delusion the patient is convinced that another person fell in love with the him/her what we need. Characteristics are that the person who fell in love with the patient is a special guy, rich, beautiful. And the patient builds the delusion upon this affective relationship. An example: many years ago, a woman 40 year entered into our hospital because she had an automatic delusion, convinced that a personal trainer fell in love with her. She didn’t know this person, she saw him once and didn’t even know his name. But she started to have psycopathological interpretations. The first interpretation was a kind of gesture, when she saw this person she recognized a specific gesture, which meant that he was waiting for her because she was married, so she had to divorce from her husband. After this interpretation, she started to havepathological interpretations of everything and every episode of her life. When she came into our hospital, all her life was completely absorbed by this delusion and the entire world could be divided into friends, who wanted this union, and enemies, who was contrary and created obstacles. So every person she met and she could meet in the street was a friend or an enemy. This is automatic delusion. Delusional disorders are very difficult to recognize the beginning, but it's very important to try to capture the development of the delusion in the first phases, because these patients can respond well to the therapy only in the first stages. If the patient comes to you after two years, five years of delusions, it's very difficult to destroy the delusional system. These patients don’t have other orders symptoms, they don't have hallucinations, negative symptoms but only the delusion. And this delusion is a secondary delusion because it is a development from specific personality traits. Typical premorbid personality traits of these patients are rigidity, they are very suspicious, these traits may be labeled as paranoid personality traits or narcissistic personality traits. But these personality traits interacted with specific life events. So there is a transition from personality traits to the disease, to delusions due to specific life events, which are not so dramatic or so catastrophic. For example a patient with narcissistic traits may wait for higher positions in his work, but this position doesn’t come and so the patient starts to think that his boss is persecuting him. These life events are not so dramatic, but they interact with the personality traits. The main treatment of paranoia is based on antipsychotics, first or second generation of antipsychotics. But in this case it's very important and mandatory to recognize and to treat these patients as soon as possible. The age of onset is a bit later with respect to schizophrenia, because the onset paranoia is between 30 and 40 years old (the adult age). Schizophrenia is earlier instead, because it is in late adolescence. Sometimes it may happen that two people, each with delusional disorders may share their delusional beliefs. This condition is named induced “Induced psychotic disorder”, or in French “Folie a deux”. In this case two people who are very bound together linked by affective relationship, for example mother and daughter, or husband and wife, may develop the same delusional beliefs. Generally there is one of the two who starts to have delusion, and the other receive the delusion. But both of them contribute to the development and the construction of the delusional themes. For example, a couple of delusional patients, which delusion was shared by a woman, who was a lawyer, and her mother. Delusion started from the mother, and the delusional belief was transmitted and shared with the daughter. Both of them contributed to built the delusional themes. The strange thing is that the daughter was a lawyer, and so she wrote her letters to an Italian ministry; she wrote that they were persecuted by evil people, that were linked to different criminal organizations, which at the beginning was not so absurd to believe. PARAPHRENIA The other kind of delusional disorder is named Paraphrenia. Paranoia and Paraphrenia are both labeled as delusional disorders, but they are distinctly different. Paranoia is mainly characterized by delusion, which is well organized and with high organized structure. In Paraphrenia, delusions are based on every kind of hallucinations. Delusions come after the hallucinations. In this case delusional themes are not so close to reality as the case of Paranoia, but they resemble more the themes of schizophrenia, so they are more bizarre and strange, much more detached from everyday life. Typically, delusions in paraphrenia are about struggle between the angels and demons, between the good and evil, and so it is a cosmic struggle, where the patient is at the centre of it. Many of the hallucinations are about the body of the patient. The onset of this kind of delusion is similar to the paranoia’s one, the adult age 30-40, until 60 years old. What is the difference between suffering of Paranoia or Paraphrenia? The structure of delusion is not paranoia-like delusion, so it's not so organized as in paranoia, but it's more similar to the structure of delusions in schizophrenia. These patients may have hallucinations. Schizophrenia patients have hallucinations as well. So the main difference are the negative symptoms, that are the main responsible for the disgregation of the personality. In paraphrenia there are no negative symptoms, and therefore there is a preservation of the personality. In other words, in paraphrenia “functionings” are not affected. This specific condition creates a very typical feature of paraphrenia, that is named as “double book-keeping". It is the condition where the patient may live at the same time in his work of delusions and hallucinations, for example they believe they are at the balance between thegood and the evil, at the center of the cosmic struggle between angels and demons; but at the same time, the same patient goes to work, has friends. This phenomenon is called double book-keeping. If this patient has the preservation of his function, while at the same time having delusions and hallucinations, is it necessary to treat him/her? Of course yes, for three main reasons: his delusions and hallucinations create a lot of suffering, even though they have a big role in their cosmic struggle they suffer. Second reason: every psychotic symptom has to be treated because psychotic symptoms are toxic for our brain, so we have to treat psychosis, even though functioning is preserved. Third reason: a the end, after many years, the delusional world is so big that at the real world is impaired, so these balancing between the everyday life and the delusional world crashes. But for many years, these patients can continue to have delusions and hallucinations and nobody recognizes that. An example: many years ago a woman with paraphrenia, who was a doctor, was admitted to our hospital. Until the admission she worked at the hospital, she had also a husband and children, but at the same time she was in the middle of a cosmic struggle between angels and demons. At night, these angels came to her bed and they made love with her, she felt and had a body perception of this. But at the same time she worked, she had children, and so on. Her husband recognized, understood that she had a problem only when he discovered a lot of papers where she wrote every delusional experience. But for years, she continued to have delusions and hallucinations, and she continued to work. This is a phenomenon of Paraphrenia. Question made by a student: how does the patient feel after the therapy if they feel better or not? Usually if we treat the patient early, he/she stops to produce delusions and hallucinations, but they still remain convinced about the contents, but they are no more interested. As if all this stuff has fallen apart. If we treat these patients after many years, it's difficult to stop the production of the delusions and hallucinations, because their entire life, has been somehow reshaped in favor of the delusion. So to sum up: in paraphrenia, delusions have a typical structure, in which delusions are based on different hallucinations. In paranoia there are no hallucinations, just delusion, which is built upon interpretation and is of course paranoia-like delusion, very organized. Finally, in schizophrenia, the structure of delusion is paranoid, that is not so organized and elaborated. 29-11-2023, morning Psychiatry Professor Matteo Tonna BRIEF PSYCHOTIC DISORDERS In this lesson we’ll talk about brief psychotic disorders. If you remember, in the last lesson we talked about delusional disorders which are psychopathological conditions characterized by chronic course and onset by development. Brief psychotic disorders are the opposite, in this case psychotic symptoms emerge abruptly, not by development but by process and the course is characterized by the complete remission of symptoms after few days or weeks, without therapy. So, there is a spontaneous complete remission. If you remember Kraepelin divided psychotic conditions into two broad categories: dementia preacox and manic-depressive illnesses. After this, some psychopathological conditions didn’t fall within one or the other of these categories, so delusional disorders and brief psychotic disorders were independent from dementia praecox and manic-depressive diseases. Brief psychotic disorders are in some ways the opposite of delusional disorders because the onset is very abrupt, by process and the remission is complete. Usually, these psychotic disorders arise and after few days they disappear completely and the patient returns to his premorbid function. These conditions are very important for many reasons: they are very frequent, they represent about the 3% of admissions in psychiatry services and they represent a sort of training for your psychopathological skills. Brief psychotic disorders are characterized by acute brief delusional and/or hallucinatory episodes (typical psychotic symptoms, delusions and/or hallucinations), often triggered by stressful events (there is often a connection with life events), in the absence of premorbid schizoid/schizotypal personality characteristics (absence of schizophrenia vulnerability), with a favorable prognosis: symptoms disappear in a brief time (couple of days) without any medications. These conditions are very evident in their symptoms, since they are mainly characterized by delusions and hallucinations that appear in people who before the onset don’t have any psychiatric problem. The premorbid functioning is perfect, they don’t have any symptoms before the episode, they don’t have any traits linked to schizophrenia vulnerability. So, everyone can experience a psychotic episode like this. Episodes are sudden, not expectable. For this reason, it’s frequent that during the episodes the patient contacts the doctor or emergency services since delusions and hallucinations are evident and often very severe. Even dough the clinical presentation is so severe, the prognosis is very good, since after one/two days all the symptoms disappear. If you have to visit a patient with acute onset of hallucinations and delusions without any premorbid condition, you have to understand if these symptoms can be explained by a brief psychotic condition or if they instead represent the onset of a more severe clinical picture such as schizophrenia. SIGNS AND SYMPTOMS There can be a prodromal phase, but it is not necessary, 2/3 days before the onset of symptoms. The patient may feel anxious, he can experience mood swings and more often the patient can complain about vegetative alterations: he can’t sleep for example or on the contrary he sleeps too much (insomnia or hypersomnia). These prodromal symptoms are non-specific and very often there’s not even a prodromal phase, the onset of the disease is very acute: the patient wakes up in the morning and suddenly presents hallucinations, delusions, disorganized behavior. It’s a typical onset by process. These delusions are very typical: they change, delusional believes are not stable, they fluctuate a lot. The patient for example may start with delusions of persecution and then turn them into delusion of jealousy. The structure of delusions is poorly organized, delusions are not organized, they have a paranoid structure. In a similar way hallucinations involve different senses: auditory, visual hallucinations and so on. They are very rich and fluctuate a lot too. Behavior may be disorganized, and the patient may present an impairment in the state of consciousness. Consciousness may be impaired in a sort of oneiric state or in a very narrow field (twilight condition) which means that the patient is focused only on one aspect of reality, without noticing the rest. After few days, all symptoms disappear and the patient often doesn’t have memory of what happens, if the state of consciousness is disrupted. This is the main clinical picture. Other important symptoms are affective symptoms: mood may have sudden swings, fluctuating rapidly from depression to excitement. So, the mood is very unstable. If we consider these symptoms, what are the main criteria that allow you to differentiate between brief psychotic disorder and typical schizophrenic syndrome? The age of onset is similar to schizophrenia, from 16 to 25 years old, so it is a frequent scenario that of having to distinguish between the two. 1. The mood changes rapidly, while in schizophrenia the mood is stable. 2. Absence of negative symptoms that instead characterize schizophrenia. If the patient has negative symptoms, also before the onset of psychotic symptoms he may be isolated for example. The absence of negative symptoms means that affectivity is not flattened, there is no apatia, abulia, no social withdrawal and this means that the premorbid functioning is good. 3. Hallucinations and delusions change a lot, while in schizophrenia hallucinations are mainly auditory (voices in the head) and they are stable; delusions in schizophrenia are now well elaborated but fixed, they don’t change. 4. Remission of symptoms after 2/3 days, it doesn’t happen in schizophrenia. 5. Impaired state of consciousness which in schizophrenia is generally preserved. It is quite paradoxical because if you visit a young patient with a lot of delusions and hallucination and his state of consciousness is highly impaired, this looks like a more severe clinical picture. But on the contrary, it is a good prognosis element. Why a disrupted state of consciousness means good prognosis? Because the state of consciousness is impaired in affective states, so if you see an impairment in the state of consciousness, it is more probable that the clinical picture is sustained by mood, so no schizophrenia. There is a general very important law in psychiatry which is that if you