Schizophrenia
Davison, G.C. and Neale, J.M. Abnormal psychology.
(2001). Chapter 11. (pp.282-316)
Diagnosis
• Is based entirely upon psychiatric
history and MSE
History
Emil Kraepelin
• In 1898 19th century
• described the disorder as dementia praecox
• As a dementia early in life – so distinguished
from dementia in older ages
Eugen Bleuler
• In 1908 created the term schizophrenia for this
disorder
• Means split mind schizein = split and
phren=mind
Bleuler Four As
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Association
Autism
Affect
Ambivalence
Schneider first rank symptoms
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Audible thoughts
Arguing or discussing voices
Somatic hallucination
Thought withdrawal, Broadcasting,
insertion
• Delusional perception
How common is it?
Lifetime prevalence
• Is approximately 1% (0.7-2%)
• Equally affects males and females
• But it starts early in males (teens, early 20s)
• And later in females (20s-30s)
When it starts?
• it starts early in males (teens, early 20s)
• And later in females (20s-30s)
• Sometimes in childhood
• Have several acute episodes and less severe
episodes between the acute episodes
Infection and birth season
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Born in the winter and early spring
Exposure to influenza
Maternal starvation
Rh incompatibility
Age of the father
Biochemical Factors
• Dopamine Hypothesis
• Serotonin…. Positive and negative
symptoms
• Norepinephrine……. Anhedonia
• GABA….. Regulate the dopaminergic
system
• Glutamate…….. Phencyclidine
Excessive pruning
• Pruning of synapses during adolescence
Is it one disorder?
No.…
• heterogeneity
• Has 5 subtypes
• 2 symptom clusters (positive and negative)
Doctor-patient interaction….
D.: Have you been nervous or tensed lately?
P.: No, I got a head of lettuce.
D.: You got a head of lettuce? I do not understand.
P.: Well, lettuce is a transformation of a dead cougar that
suffered a relapse on the lion’s toe. And he swallowed
the lion and something happened. See. Tommy and
Gloria they are two heads and they are not whales. But
they escaped with herds of vomit and things like that….
POSITIVE SYMPTOMS
Characteristics:
• Excesses or distortions
• Have sudden onset /acute episodes/
• And good response to medication
• 2 symptom clusters (positive and negative)
What these symptoms are?
1. Disorganized speech
2. Incoherence
3. Loos associations
4. Delusions
5. Hallucinations
6. Bizarre behaviour
Disorganized speech
• Problems in organizing ideas and telling them so
others could also understand it
• Once these symptoms were central
• many patients’ speech is not disorganized
• And speech can be disorganized in other psychoses
as well (mood disorders, manic state)
• It is a diagnostic symptoms but not the principal
symptom
D: Who are Tommy and Gloria?
P.:there is Joe DiMaggio, Tommy Henrich, Bill Dickey, Phil
Rizzuto, John Esclavera, Del Grandell, Ted Williams…
D.: Who are they?
P.: Dead people… they want to be fucked …. By this
outlaw…
Incoherence
• Many times it is hard to follow their speech
• They might make references to their central
ideas but it is not connected to the other part of
their speech
Loose associations
• Patient has difficulty sticking to one topic
• Trains of associations – very difficult to follow
•
“my thoughts just jumbled up. I start thinking about
something but I never get there. My trouble is that I
have got too many thoughts.”
Delusions
• Beliefs held contrary to the reality
• Very common symptoms in schizophrenia 65%
• Also found in mania, delusional depression
• But delusions are schizophrenia are the most
bizarre from all of these
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Delusions that people are spying them
Bodily sensations by external agency
Own Thoughts had been replaces by others’
Their thoughts are broadcast or transmitter
Thoughts are stolen from them
Feeling or behaviour is controlled by external force
Impulses to do something (again not exclusive to
schizophrenia
• “I am thinking about my mother and suddenly my
thoughts are sucked out of my mind by a
phrenological vacuum extractor and there is
nothing in my mind, it is empty.”
• “I look out the window and I think the garden
looks nice and the grass looks cool, but the
thoughts of Eemonn Andrews come into my mind
There are no other thoughts there, only his. He
treats my mind like a screen and flashes his
thoughts on it like you flash a picture”
Disorders of perception and Hallucinations
• The world is unreal
• Depersonalised feeling from the body
• Hallucinations: sensory experiences in the
absence of any stimulation from the
environment
• Hallucinations are mainly auditory (74% and
can be frightening
•
A patient reports hearing a man;s voice speaking
with intense whisper to her. The voice repeats most
of the patient’s goal-directed thinking.
•
A housewife experienced a voice was commenting
her behaviour from a house across the road with
critical comments.
NEGATIVE SYMPTOMS
Characteristics:
• Behavioural deficits
• Chronic course
• poor good response to medication
• Many negative symptoms are predictors of poor
prognosis
• (side effect of medications!)
What these symptoms are?
1. Avolition - apathy
2. Alogia
3. Anhedonia
4. Flat affect
5. Asociality
Avolition – apathy
• Lack of energy
• Absence of interest
• Patients do not care with themselves just sitting
around doing nothing
Alogia
• Poverty of speech
• Or they speak enough, but without content
Anhedonia
• Inability to experience pleasure
• Do not enjoy recreation, or others’ company
• Usual pleasure activities are not enjoyable for
these persons
Flat affect
• No stimulus can elicit emotions
• 66% of patients have this symptom
• EMG while watching emotions: patients with
schizophrenia had less intense facial activity,
while the same self-report of feelings
Asociality
• Some patients have severe impairment in their
social relationships
• Fewer friends
• Poor social skills
• Sometimes these symptoms are present before
the other symptoms even in childhood
OTHER SYMPTOMS
Catatonia
• Motor abnormality
• Repeated gestures with peculiar movements
• Sometimes unusual activity and lots of energy in
movements (similarly as in mania)
• At the other end : catatonic immobility –
patients stay in unusual postures for long time
• Waxy flexibility :you can place the patients’
limbs in any position, then they will maintain it
for long time
OTHER SYMPTOMS
Inappropriate affect
• Rapid shift from one emotional state to other
• Inappropriate affect – laughing at sad stories or
anger at a simple question
• Not frequent, but if present an important
diagnostic symptom
Consequences
• Of these symptoms are devastating
• Loss of friends
• Job
• Money, home
• Substance abuse
• suicide
Suicide & Homicide
• 20-50% of patients
• 80% have a MMD episode
• Best prognosis related to highest risk of
suicide
• 2/3 have seen the clinician 72 hours
before death
• The patients are no more commit
homicide than general population
HOW TO DIAGNOSE?
DSM-IV diagnosis
At least two of these symptoms must present for at
least one month:
• Delusion
• Hallucinations
• Disorganized speech
• Disorganized behaviour or catatonic
• Negative symptoms
One symptoms is enough if
• That symptoms is hallucination of voices
• Or bizarre delusions
HOW TO DIAGNOSE?
DSM-IV diagnosis
Diagnosis require 6 month of disturbance
(including the one month with the specific
symptoms) in the rest of the time symptoms are:
• Social withdrawal
• Lack of initiative
• Vague or circumstantial speech
• Impairment in hygiene
• Odd beliefs
• Magical thinking
• Unusual perceptual experiences
HOW TO DIAGNOSE?
DSM-IV diagnosis
What is NOT schizophrenia?
• Mood disorders
• Schizoaffective disorder
• And not drug induced symptoms
• Delusional disorder related but not
schizophrenia
SUBTYPES
1. Disorganized
Incoherent speech and thoughts
2. Catatonic
Negative symptoms are dominant
3. Paranoid
Presence of prominent delusions
4. Undifferentiated
Meet the diagnostic criteria of
schizophrenia but do not fit to
subtypes
5. Residual
No longer schizophrenic but shows
symptoms of the illness
Disorganized schizophrenia
Main symptoms:
• Disorganized speech difficult to follow
• Incoherence
• Inventing new words
• Labile affect – flat affect or shifts in moods
• Behaviour is disorganized and not goal directed
• Neglects his/her appearance, hygiene
Characteristics
• Rare
• Poor prognosis
• More typical to schizophrenia with early onset
Catatonic schizophrenia
Main symptoms:
• Motor symptoms ranging from
• excitement to (talks continuously, shouts,
nervous, etc.)
• Immobility (can be waxy rigidity, mute)
Characteristics
• Sudden onset
• Good prognosis to medications
• Similarities to encephalitis lethargica
Paranoid schizophrenia
Main symptom:
• Present of delusions
• Grandiose delusions – exaggerated sense of
their own importance
• Delusional jealousity (about their partners’
faith)
• Persecution, being spied on, etc.
• Ideas of reference: unimportant events get
unrealistic importance in their thought
• Agitated, emotional, sometimes violent
• Language is not disorganized
Characteristics
• Good prognosis to medication
Cognitive-Behavioral Classification
• Sensitivity disorder
Genetically weighted, begin in adolescence, low stress, negative symptoms
• Anxiety disorder
delusions arise after intense anxiety, middle life, systematized delusion, positive
symptoms
• Traumatic psychosis
trauma, often sexual assault, borderline traits(2/3 of female chronic
hallucinators have suffered from childhood sexual abuse)
• Drug-induced psychosis
High EE in family, poor comliance
• Catatonia
oxford texbook of psychotherapy
ETIOLOGY OF SCHIZOPHRENIA
1.
2.
3.
4.
5.
6.
Genetics
Biochemical/biological
Abnormal brain function and structure
Stress and schizophrenia
Some other factors and predictors
And we basically do not know exactly…
GENETIC FACTORS
Schizophrenia has a genetic component
• Increased risk as the genetic relationship is
closer
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first cousins, nieces, uncles, aunts – 2-3%
Parents : 9%
Siblings : 7%
Dizygotic twins 12%
Monozygotic twins 44% - but not 100% so
genetic factors are not solely responsible for
schizophrenia
GENETIC FACTORS
Schizophrenia has a genetic component
Adoptions studies
• 50 children of schizophrenic women
separated and adopted at birth compared with
50 children of non-schizophrenic women
adopted at birth
• Later assessed: none control but 16.6% of the
schizophrenic group did have schizophrenia
In general
•Not a single gene but more genes are responsible
•Genetically based factors (such as eye-tracking) are impaired
in schizophrenia and in their relatives too
BIOCHEMICAL FACTORS
Dopamine theory
• Antipsychotic drugs are effective treatment for
Sch. They block postsynaptic dopamine (D2)
receptors
• Amphetamines – cause release of
catecholamines including dopamine and prevent
their inactivation – can induce psychosis
How the dopamine theory works?
• People with Sch do not have more dopamine in
their brain but
• More D2 receptors and oversensitive receptors
Neurotransmitters
Presynaptic neuron
Terminal
Buttons
(end of the
presynaptic
cell)
Synapsic
cleft
Receptors
Postsynaptic
membrane
Postsynaptic neuron
BIOCHEMICAL FACTORS
Brain injury in the prefrontal cortex
DA neurons underactive in the PFC
Negative symptoms
Mesolimbic dopamine system is
Out of inhibitory control
Positive symptoms
BIOCHEMICAL FACTORS
Dopamine theory
• Controversial
• Long time (more weeks) until the antipsychotics
start to be effective, however, blockade of
dopamine starts immediately
• Receptor activity must be brought below normal
for therapeutic effect – why normal activity is
not enough? catecholamines including dopamine
and prevent their inactivation – can induce
psychosis
BIOCHEMICAL FACTORS
Serotonergic theory
Role of the glutamates
• Low level of glutamate
• Low level of enzymes to produce glutamate
• Decrease of glutamate from the prefrontal cortex
could produce increased dopaminerg activity in
the limbic system and in the striatum
THE BRAIN IN SCHIZOPHRENIA
Abnormalities on series of tests testing
attention
memory
emotions
social behaviour
perceptual/motor integration
Other abnormalities
• Abnormal eye-tracking (low level neural
systems)
• Abnormal habituation (sensory gating)
• Abnormal facial muscle activity (affect)
THE BRAIN IN SCHIZOPHRENIA
Where is the problem in the brain structure?
studies with various neuroimaging methods
(MRI, fMRI, PET, EEG, MEG)
Enlarged ventricles
• Probably from increased subcortical cell loss
Frontal cortex
• Reduced grey matter
Temporal lobe
• Amygdala (reduced volume)
• Hippocampus (reduced volume)
Reduced volume of basal ganglia
Prefrontal theory
1. impairments in series of neuropsychological test
(Wisconsin test for example)
2. Frontal cortex plays role in speech, decision
making – disrupted in schizophrenia
3. Reduced grey matter in the frontal cortex with
structural imaging
4. Neuroimaging (PET and fMRI) studies show less
activation in the frontal cortex
5. Frontal activation is related to negative
symptoms of schizophrenia
Major difference between controls and patients with schizophrenia
In this word-encoding task is the activation of the frontal cortex
In control, but the lack of the activation in schizophrenic subjects
Temporal lobe dysfunction
1. Volume reduction in the temporal lobes
2. Volume reduction in the left posterior temporal
gyrus (language processing)
3. Volume reduction in the superior temporal
gyrus (auditory cortex – hallucinations)
4. Reduced volume of hippocampus (related to
memory problems)
5. Abnormal activity of the amygdala – in positive
symptoms (problems with emotion)
PSYCHOLOGICAL STRESS
How stress can be related to schizophrenia?
Stress
HPA axis (hypothalamic-pituitary-adrenerg)
Cortisol
DOMAPINE
INCREASED SYMPTOMS OF SCHIZOPHRENIA
Middle and superior temporal gyrus activation is reduced with
The increasing severity of schizophrenia. Contributes to incoherent
Speech (Kircher et al.; Arch. Gen. Psyxhiatry, 2001, 58:769-774)
STRESS AND SCHIZOPHRENIA
1. Life-stress increases the likelihood of relapses
2. People with the lowest social class have the
highest prevalence for schizophrenia
1. Sociogenic hypothesis – stress comes from
the social status
2. Social selection-theory (people with
schizophrenia will drift to the poverty
sooner or later
3. Studies with immigrants supports more
the social-selection hypothesis
FAMILY AND SCHIZOPHRENIA
1. Theory of schizophrenogenic mother – and
double-bind theory is not supported by research
cold, rejecting, overprotective, rigid,
moralistic, fearful about intimacy
Double-bind: apparent gap between verbal
and nonverbal communication and
expectations
2. Level of expressed emotions in the family
introduce a vicious circle
family members criticise bizarre thoughts of
patients
this in turn elicit to express more bizarre
thoughts from patients!
DEVELOPMENTAL MODELS
1. Influenza infection in pregnancy
seasonal changes in birth of schizophrenic
people: there is a winter-spring excess of
births
higher rate of schizophrenia in children
neurodevelopmental model. Virus disrupts
the developing brain
2. Complications at birth
hypooxygenia, acidaemia
Prognosis
• 20-30% somewhat normal life
• 70% achieved remission
• First episode: 1-2 years treatment may
not adequate
• Multiepisode: 5 years or for lifetime
THERAPY
1. Biological therapy
1. Surgery, shock
2. Drug therapies
2. Psychological therapy
1. Psychodynamic therapy
2. Social-skill training
3. Family therapy
4. Cognitive-behavioural therapy
Surgery and shock therapy
Electroconvulsive (ECT) therapy rarely
used
Insulin coma (not used)
Prefrontal lobotomy – not used
1. Neuroleptic drugs
1. Block the postsynaptic dopaminerg
receptors
2. Reduce positive symptoms (but not the
negatives)
3. For example phenotiazine and
chlorpromazine
4. 70% of patients respond well
5. Maintainance doses are needed
continusouly
6. Extrapyramidal side effects (similar to
Parkinson disorder) tremor, gait,
akasthesia, tardive dyskinesia, neuroleptic
malignant syndrome
Atypical neuroleptic drugs
1. Clozapine (Clozaril)
1. Fewer motor side effects
2. But destroys the immune system
2. Olanzapine (Zyprexa) and risperidone
(Risperdal)
1. Fewer side effects
2. Affect memory, cognition, attention
3. Affects the serotonergic system too