Schizophrenia

- Part 1 -

Tomasz Paweczyk MD, PhD Department of Affective and Psychotic Disorders Medical University of Lodz Head: Prof. Jolanta Rabe- Jablonska MD, PhD

Agenda for Todays Meeting

Lecture approx. 60 min Break 15 min. Cases presentation and discussion 30 min. Break 15 min. Inerview with Mr. Philipe 45 min.

Plan of the lecture

Definition of SCZ Clinical features
History and classification Clinical presentation and symptomatology Course and outcome of schizophrenia

Symptom domains Natural History Epidemiology and risk factors Differential diagnosis Cases

What is schizophrenia?
Schizophrenia is to psychiatry what cancer is to medicine: a sentence as well as diagnosis.
- W. Hall, G. Andrews & G. Goldstein (1985)

... perhaps the most devastating disorder of mankind.

- E.R. Kandel (1991)

What is schizophrenia?
the disconnection or splitting of the psychic functions Eugen Bleuler
Ethymology Dictionary 1912, "a splitting of the mind," from German: Schizophrenie, coined in 1910 by Swiss psychiatrist Eugen Bleuler (1857-1939), from Gk. skhizein "to split + phren (gen. phrenos) "diaphragm, heart, mind," of unknown origin. Slang shortening schizo first attested 1920s as an adj., 1945 as a noun.

Schizophrenia - definition
Schizophrenia is the most chronic and disabling of the severe mental disorders, associated with abnormalities of brain structure and function, disorganized speech and behavior, delusions, and hallucinations. It is sometimes called a psychotic disorder or a psychosis
(Gale Encyclopedia of Mental Disorders)

Psychosis - definition
Psychosis - Mental disorder in which the thoughts, affective response, ability to recognize reality, and ability to communicate and relate to others are sufficiently impaired to interfere grossly with the capacity to deal with reality; the classical characteristics of psychosis are impaired reality testing, hallucinations, delusions, and illusions
(Kaplan & Sadocks Comprehensive Textbook of Psychiatry)

Historical treatment methods

A mentally ill patient in a straitjacket and strapped into a chair. Such chairs of restraint were meant to quieten maniacs by depriving them of the capacity to agitate themselves by violent motion; photograph after a woodengraving, 1908.

1952 Chlorpromazine the 1st antipsychotic drug Introduced to the market

Schizophrenia historical milestones

1893 Emil Kraepelin dementia praecox 1908 Eugen Bleuler schizophrenia, the four As 1950s Kurt Schneider first rank psychotic symptoms 1960s Arvid Carlsson dopamine hipothesis 1960s Jean Delay, Pierre Deniker chlorpromazine the first neuroleptic drug 1980 Timothy Crow type I and II of schizophrenia

Psychiatric disorders (1896): 1. Dementia precox (preterm dementia) - catatonia, hebefrenia 2. Manic-depressive psychosis

Emil Kraeplin (1856-1926): dementia praecox develops relatively early in life and its course is likely deteriorating and chronic, deterioration reminded dementia but was not followed by any organic changes of the brain, detectable at that time
Eugen Bleuler (1857-1939): schizophrenia means splitting of mindits functions: thinking, emotions, memory, perception, behavior are being separated and start to act indepently. The 4 primary symptoms of schizophrenia - reflect the splitting (4 As): affect, association, autism, ambivalence. The other symptoms: hallucinations, delusions, illusions are the secondary symptoms not specific for schizophrenia, could be seen in other psychoses of toxic, infection orgin.

E. Bleuler Head of Burghlzli Clinic, Zurich

Bleulerian criteria the 4 As:

Affect flat, inappropriate, blunt (unchanginig facial, vocal, gestural expression) Associations loose, fragmented thinking, disorganized speech (difficulty or lack of logic verbal contact with a patient) Autism being in a world of ones own (little intrest of what is going around him, not recognizing real situations, living after the wall made of glass) Ambivalence the capicity to believe, to speak, to behaviour, to react emotionally in contradictory ways (laugh when told about death of his mother)

Schizophrenia historical background - cont.

The first rank Schneiderian symptoms: I hear voices arguing to each other. Someone is commenting on what I am doing. Someone is putting thoughts into my head. My thoughts are being transmitted to other people so that they know what I am thinking. I am being made to want things I would not want myself. Some mystical force made me do or say things that I do not intend, as though I was a robot or automation

Schizophrenia historical background - cont.

T. Crow proposed a classification of types I and II based on the presence and absence of positive (productive) symptoms and negative (deficit) symptoms The positive symptoms: delusions and hallucinations, formal thought disorder The negative symptoms: affective flattening, poverty of speech (alogia) or speech content, lack of motivation (avolition), anhedonia, social withdrawal Type I patients have normal CT scans of brain, good response to treatment (mostly) Type II patients have brain abnormalities on CT scans, poor response to treatment

Schizophrenia historical background cont.

A. Carlsson, J. Deley, P. Deniker Dopamine Hypothesis, neurpleptic activity of chlorpromazine Dopamine is a neurotransmitter that acts in the nigrostriatal, the mesolimbic, mesocortical system. Increase of dopamine neurotransmition via D2 rec. in mesolimbic system is said to be the cause of productive symptoms, the decrease of dopamine neurotransmition in mesocortical system is likely to be the cause of negative symptoms of schizophrenia Chlorpromazine (Fenactil) blocks rec. D2 thus reduces dopaminergic activity and positve symptoms respectively

Diagnosis: DSM-IV TR Criteria

Schizophrenia subtypes DSM -IV

Schizophrenia paranoid type
MOST FREQUENT SUBTYPE of SCZ

40% of patients

Auditory hallucinations, delusions of persecuction or grandeur

Karl Ludwig Kahlbaum Described the clinical picture of Catatonia (1874)

7% of patients

Schizophrenia Disorganized Type

11% of patients

Ewald Hecker, 18431909 Co-worker and a friend of K. L. Kahlbaum Described hebefrenia 1871
(hence the Greek hebe for youth plus phrenia for mind)

14 % of patients

18% of patients

Schizophrenia subtypes
DSM IV vs ICD-10

DSM IV classifies the 5 subtypes based mainly on clinical picture. The subtypes are not closely correlated with different prognoses. ICD 10 classifies 9 subtypes (additionally postschizophrenic depression, simple schizophrenia, other schizophrenia, schizophrenia unspecified)

The Criteria of Diagnosis: ICD-10

For the diagnosis of schizophrenia is necessary presence of one very clear symptom - from point A to D or the presence of the symptoms from at least two groups - from point E to H for one month or more: A) the hearing of own thoughts, the feelings of thought withdrawal, thought insertion, or thought broadcasting B) the delusions of control, outside manipulation and influence, or the feelings of passivity, which are connected with the movements of the body or extremities, specific thoughts, acting or feelings, delusional perception C) hallucinated voices, which are commenting permanently the behavior of the patient or they talk about him between themselves, or the other types of hallucinatory voices, coming from different parts of body D) permanent delusions of different kind, which are inappropriate and unacceptable in given culture

The Criteria of Diagnosis

E) the lasting hallucination of every form F) blocks or intrusion of thoughts into the flow of thinking and resulting incoherence and irrelevance of speach, or neologisms G) catatonic behavior H) the negative symptoms, for instance the expressed apathy, poor speech, blunting and inappropriatness of emotional reactions Expressed and conspicuous qualitative changes in patients behavior, the loss of interests, hobbies, aimlesness, inactivity, the loss of relations to others and social withdrawal Symptoms are not an effect of organic brain disease, intoxication, substance dependency or withdrawal
Diagnosis of acute schizophorm disorder (F23.2) if the conditions for diagnosis of schizophrenia are fulfilled, but lasting less than one month Diagnosis of schizoaffective disorder (F25) - if the schizophrenic and affective symptoms are developing together at the same time

Diagnosis DELUSIONS

Delusions may be classified in terms of their content, for example delusions of... Persecution - An outside person or force is in some way interfering with the sufferers life or wishes them harm, e.g. The people upstairs are watching me by using satellites and have poisoned my food. Reference - The behavior of others, objects, or broadcasts on the television and radio have a special meaning or refer directly to the person, e.g. A parcel came from Sun Alliance and the radio said that the son of man is here, on a Sunday, so I am the son of God. Control - The sensation of being the passive recipient of some controlling or interfering agent that is alien and external. This agent can control thoughts, feeling and actions (passivity experiences), e.g. I feel as if my face is being pulled upwards and something is making me laugh when Im sad. Doubles - A person known to the patient, most frequently their spouse, has been replaced by another (also known as Capgras syndrome or, confusingly, illusion of doubles)

A delusion is a fixed, false personal belief held with absolute conviction despite all evidence to the contrary. The belief is outside the persons normal culture or subculture and dominates their viewpoint and behavior.

Schizophrenia natural history

Prodrome Active Phase Residual Phase

Prodrome

Active Phase

Residual Phase

Prodrome

Active Phase

Residual Phase

Total duration at least 6 months The active phase at least 1 month

Schizophrenia natural history

Schizophrenia natural history

Epidemiological findings
morbid risk - 1% of population lifetime morbidity 0,6-8,3/1000 (avr. 15/1000) prevalance 0,09-0,7/1000/year (avr. 0,2/1000) begins mainly in young age (1625), earlier in men (avr.21) than in women (avr.27) standard mortality ratio avr. 2.0 suicide risk 10%

Schizophrenia - age of onset

schizophrenia youth schizophrenia between 15 - 45 years - 80% late-onset schizophrenia below 15 years - 4% above 45 years - 15% below 10 years - 0,1-1%

Epidemiological findings - role of criteria

Epidemiological findings cont. Place of Birth

Epidemiological findings cont. Gender

Epidemiological findings cont. Month of Birth Effect

Schizophrenia-Differential Diagnosis Summary

drug or substance abuse induced psychotic symptoms (phencyclidine, cocaine, amphetamine, alkohol, corticosteroids, levodopa, anticholinergic agents) laboratory tests, psychoses usually develop within 2 weeks after the last use and disappear within 1 month psychoses due to general medical condition (infections, tumors of CNS, endocrine disorders, temporal lobe epilepsy, dementia) diagnosis of the basic disease, CT, MRI psychotic decompensation in the course of Borderline Personality Disorder psychotic depression, psychotic mania schizoaffective disorder delirium

Lets Have a Break!

15 min.

Cases - presentation

Cases discussion
Medical/Psychatric History? Presenting signs and symptoms? Diagnosis? What subtype of illness? Differential diagnosis? Management?

Case study #1
History Eddy is 24 years old. He worked as a mechanic until recently, giving up his job out of the blue, saying it was a waste of time. He did reasonably well at school, was sociable and positive in his outlook, last year proposing marriage to his girlfriend. He smoked cannabis occasionally at weekends, but used no other drugs and didn't drink alcohol. His parents are divorced and he lives with his mother. Her boyfriend, with whom she has a long-term and stable relationship, has recently moved in. Over the last 6 months Eddy's mother has noticed that he has become increasingly introverted. He stopped going out and no longer returns his friends' calls. He has lost his appetite over the past month and has obviously lost weight. His fiance has left him, saying she was fed up with him being depressed and moody all the time. Eddy has told his mother that he is concerned for her safety, but he would not explain further. When questioned about his concerns he became upset and angry. At other times he has shut himself in his room. She has heard him talking angrily, sometimes shouting; he denies this. His uncommunicativeness, anger and suspiciousness have gradually increased, and things came to a head one evening when he became agitated and smashed the mirror in the sitting room, cutting his hand. He was so agitated and distressed that his mother's partner felt it necessary to restrain him physically; Eddy got a black eye in the process. His paternal uncle has a history of schizophrenia, and his father has been described as isolated and "a loner". The following day, Eddy's mother attended her primary care centre and expressed her concerns. She has been unable to persuade him to come and see the doctor, who agreed to visit. When he did, he could not gain access to Eddy, who locked himself in his room, and would only answer "I'm alright, go away" to all questions. The physician arranged an emergency multidisciplinary assessment with the local psychiatrist. At this visit Eddy reluctantly emerged from his room, and seemed frightened and agitated. He was initially unwilling to discuss the events of the previous evening, but eventually admitted that he felt he had to smash the mirror because it was the door to another frightening world from which he felt electric currents entering his spine and thereby controlling his stomach and bowels. He is convinced that he and his mother are in terrible danger, and is unsure whether his mother's boyfriend is part of a conspiracy against them emanating from this place. He has heard voices describing his bodily functions, though did not wish to elaborate. At times these voices have spoken directly to him, threatening him with damnation, and he admits it is this that has frightened him and caused him to shout when isolated in his room.

Case study #2
History Matt Briggs is 37 years old and has just registered with the health centre. The previous notes are not available, but a recent hospital letter was faxed in advance. Matt was diagnosed at the age of 26 as suffering from paranoid schizophrenia. He had a history of substance abuse, including cannabis, LSD, ecstasy, cocaine and amphetamines. His illness had a gradual onset over a period of 2 years, including growing suspiciousness, withdrawal from his family and social networks, and loss of his job, culminating in an acute psychotic breakdown. At the time of his breakdown he suffered from an elaborate delusional system, including the belief that he was a "Messiah". He was admitted to a mental hospital in London under section 2 of the Mental Health Act. This was changed to a section 3, and he spent a total of 8 months in hospital, the last two as a voluntary patient. According to the letter, his symptoms have always been difficult to control, and he has already had treatment with trifluoperazine, chlorpromazine, thioridazine, pimozide and a year on depot flupenthixol, during which he relapsed. All have been at therapeutic doses. He presents with a request for your advice on his medication. He has, until recently, had some contact with the community mental health team in his area, and has had a reasonable relationship with a community psychiatric nurse. However, he has never been enthusiastic about his antipsychotic medication and has stopped taking it on at least three occasions in the past 10 years. Each time he has ended up in psychiatric hospital. He is now on oral haloperidol (10 mg, three times a day) and an anticholinergic drug. He wants to stop taking his medication again and wonders what you think about this. He has the mask-like face and slow movements of drug-induced Parkinsonism. He is restless and shows evidence of akathisia. There is some evidence of facial involuntary movement. When you question him more closely about his reasons for wanting to stop taking medication he begins to become excited. He points out, quite reasonably, that the physical side-effects of the medication are difficult for him to tolerate. He argues that the medication is acting as a barrier between him and his mission to the people. He believes that he has been sent on this mission by a higher power. When you ask him what the mission consists of, he replies that he must spread the truth, and speak to people about their lives and what they really need. He feels he cannot do this as long as he is taking antipsychotics, as they are blocking his thoughts and preventing the message getting through to him. He is not experiencing auditory hallucinations, and seems to want to engage in a discussion with you.

Case study #3
History Mrs Philodopolous is 68 years old and lives with her husband, who is 10 years her senior. She has had a number of psychotic breakdowns in her life. These began when she was in her mid-30s, after she had been married for 10 years. She has been admitted to mental hospital on a number of occasions, sometimes as a voluntary patient, sometimes under compulsion. She has been treated with a number of antipsychotics in her life, including chlorpromazine, haloperidol, thioridazine and finally settling on depot medication, flupenthixol decanoate (80 mg, administered every 2 weeks), at her primary care centre. None of these treatments have ever entirely abolished her psychotic symptoms, although they have been effective to different degrees in reducing her agitation and distress. Mrs Philodopolous initially presented with thought insertion and broadcast, intensely distressed that sexual thoughts put into her mind by a neighbour were available to anyone in her house, who would look down on her and think she was dirty because of their content. She felt she was responsible for the thoughts and tried to resist them. She kept her house spotlessly clean so as to suggest to her neighbours and friends her pure heart and good housekeeping, and was very anxious at the thought of dirt that would confirm these people's negative views of her. By her second admission and consistently since, she had a delusional system which includes the belief that she has been visited by an unknown man during the night who sexually assaults her while she and her husband sleep; she thinks she may be pregnant. Mr and Mrs Philodopolous have never had children. Until 5 years ago she had been attending a psychiatric outpatient clinic regularly, every 6 months. She had been under the care of the same consultant psychiatrist for over 20 years. After his retirement she had stopped attending outpatients. She had become increasingly withdrawn and suspicious, and had refused to leave her house over the last 4 months. During this period she had stopped attending her GP's surgery for her depot medication, so this had been administered by a community psychiatric nurse who visited the home. Her husband, who suffers from chronic obstructive pulmonary disease, has become increasingly unwell during this period and is less able to care for her. He seems less tolerant of her, and appears exhausted. In response to this she has withdrawn from the sitting room to her bedroom, and her delusion of pregnancy has become stronger, and increasingly preoccupies her thoughts. She has shouted in the night that she is in labour on more than one occasion. An increase in the dose of the depixol has not produced any improvement in her mental state. Unfortunately, she has developed Parkinsonian-type adverse effects on the higher dose.

Case #1
A young, unmarried woman, age 20, was admitted to a psychiatric hospital because she had become violent toward her parents, had been observed gazing into space with a rapt expression, and had been talking to invisible persons. She had been seen to strike odd postures. Her speech had become incoherent. She had been a good student in high school, then went to business school and, a year before admission to the hospital started to work in an office as a stenographer. She had always been shy, and although she was quite attractive, she had not been dating much. Another girl, who worked in the same office, told the patient about boys and petting and began to exert a great deal of influence over her. The second girl would communicate with her from across the room. Even when they went home at night, the patient would get voice messages telling her to do certain things. Then pictures began to appear on the wall, most of them ugly and sneering. Those pictures had namesone was named shyness, another distress, another envy. Her office friend sent her messages to knock on the wall, to hit the pictures. The patient was agitated, noisy, and uncooperative in the hospital for several weeks after she arrived, and required sedation. She was given a course of insulin coma therapy, with no significant or sustained improvement. Later she received several courses of electroconvulsive treatment, which also failed to influence the schizophrenic process to any significant degree. Ten years later, when antipsychotic drugs became available, she received pharmacotherapy. Despite all those therapeutic efforts, her condition throughout her many years of stay in a mental hospital has remained one of chronic catatonic stupor. She is mute and practically devoid of any spontaneity, but she responds to simple requests. She stays in the same position for hours or sits curled-up in a chair. Her facial expression is fixed and stony.

Case #2
An unmarried man, aged 27, had been working as a teacher and was admitted to a psychiatric hospital because he had become increasingly agitated and irrational after several nights of wakefulness. He was extremely talkative and ran about aimlessly. His behavior became very strange; for instance, he tried to clean everything in the house, moved his wristwatch up to his shoulder, stripped his clothes off, chewed large wads of paper in the belief that it was good for him, talked about killing himself, and then said that he might already be dead. He heard voices ordering him about incessantly, and he frequently laughed without any apparent cause. After chewing the paper he would spit in it and then drink his saliva. He rolled into odd postures on the bed, with his tongue sticking out. He started to jump and dance when taken to the bathroom by a nursing assistant for a shower and destroyed the bathroom furnishings. His gait was manneristic. His speech was utterly incomprehensible. He refused to take any medication and had to be sedated by parenteral medication. He remained noisy, excited, destructive, and irrational in his behavior for a month; then he improved in response to high dosages of antipsychotic medication and a few electroconvulsive treatments. Three months after admission he was discharged from the hospital, symptom free, with good insight into the nature of his illness. For more than 10 years he has been employed as a teacher.

Case #3
A 56-year old woman, X-ray technician who had emigrated as an adult from Europe, and married late in life, presented to the emergency room. Her complaints were that her husband's business partner of many years intended to get her husband to resign from the business and to destroy their home. Over a number of months she had become gradually aware that a variety of apparently inconsequential incidents (such as unusual cars parked on her isolated residential street, seeing individuals she knew at restaurants, and feeling as if she were being followed each time she drove her car) pointed to a conspiracy to disrupt and ultimately destroy their lives. Her delusion of persecution was remarkably systematized and detailed; her mood in describing this was tense and irritable. There was no evidence of hallucinations, confusion, thought disorder, or mood disorder. Cognition was intact. The patient was quite intelligent and saw the clinical consultation as a means of assisting her husband to deal with the distress of being targeted in such a manner. (The husband had accompanied his wife on these consultations. He also had experienced some delusional thinking in accord with hers.) The patient showed no evidence that suggested suicidality or potential for violence toward others. She initially refused all medication but gradually over several months of therapy and parallel frequent legal consultations agreed reluctantly to take risperidone (Risperda) and later, for postpsychotic depression, paroxetine (Paxil). She responded within weeks to 0.5 to 1 mg of risperidone administered daily or on alternate days; she refused to take the medication continuously. Within a year, she began to focus on other issues and the emotional intensity of the delusional concerns diminished although they could be aroused with modest stimulation in conversation or from happenings in her home or neighborhood.

Case #4
A 15-year-old girl attended a summer camp where she had difficulties in getting along with the other children and developed animosity toward one of the counselors. On her return home, she refused to listen to her parents, and she heard the voice of a man talking to her, although she could not see him. She rapidly began to show bizarre behavior, characterized by grimacing, violent outbursts, and inability to take care of herself. Her school record had always been good, and she was fluent in three languages. Her parents described her as having been a quiet, rather shut-in child, with no abnormal traits in childhood. Family relations were reported as having been satisfactory. When the patient was admitted to a psychiatric hospital, her speech was incoherent. She showed marked disturbances of formal thinking and blocking of thoughts. She was impulsive and seemed to be hallucinating. She stated that she heard voices in her right ear and that a popular singer was running after her with a knife. She also thought that her father was intent on killing her and that she was pregnant because she had hugged one of the residents. Two months of neuroleptic treatment brought no apparent improvement. She was then given a course of intensive electroconvulsive therapy and continuous sleep treatment. Over a period of a year, she received close to 200 electroconvulsive treatments and 50 subcoma insulin treatments, with little improvement. She was then transferred to another mental hospital, where her behavior has remained very disturbed for almost 20 years. She is often incontinent and most of the time neglects her physical appearance. Occasionally she spends hours dressing herself, looking in the mirror, and putting on excessive makeup. At times, she has been discovered eating her feces. Occasionally, she adopts the role of a singer or a dancer. She makes statements like "Will I live forever? Nurse, I didn't throw my love away. It is in my stomach, and it hurts." In the dining room she attempts to grasp the genitals of male patients. High doses of neuroleptics are continuously required to control her behavior. The ultimate prognosis is very poor.

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