Schizophrenia

陳鴻儀
May 29 2007

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Introduction and
Pathophysiology

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 The Human Brain Parietal cortex:
Memory, visual recognition,
Speech, hearing

Prefrontal cortex
(PFC):
Affective, attention,
cognitive and Cerebellum:
emotional functions
Motor coordination,
balance, posture

Limbic System: Brain stem:

Also known as ‘the centre of Emotional reactions, role in sleep-
emotions’ awake cycle
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www.brainchannels.com/evolution/ physicalbrain.html
 The Limbic
Thalamus:
Connected to emotional regulatory
System
centres, PFC and hypothalamus

Amygdala: Putamen:
Mood expression Part of striatum –
control, particularly motor functions
fear, anxiety, rage &
aggression – survival

Hypothalamus: Hippocampus:
Associated with motivational Memory, (mainly long-term) &
behaviours & expression of emotions learning
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www.brainchannels.com/evolution/ physicalbrain.html
 What is Schizophrenia?
• Severe brain disorder

• Debilitating, severe social and

emotional consequences
– Approx. 10% of sufferers will commit
suicide

Lifetime duration

Affects approx. 1% of population

– Males and females equally (?)
– Onset generally earlier in males at 17-22
yrs
– Disorder can be more severe in males
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 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

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 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
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Examples Of What Patients With
Schizophrenia See.
• Louis Wain was a 20th century artist.
He was greatly interested in cats and
would paint many pictures, over a time
period of which he got Schizophrenia.
These pictures show the stages in the
disorder and accent what
Schizophrenia does to people who are
unfortunately, affected by it.
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Examples Of What Patients With
Schizophrenia See (cont’d)

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 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. Loose associations
4. Delusions
5. Hallucinations
6. Bizarre behaviour
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 Positive symptoms
• An increased activity, or exaggeration, of
normal brain functions

– Auditory and visual hallucinations

– Delusions
– Disorganisation of thoughts, language and
behaviour
– Agitation
– Paranoia
• Psychotic episodes are
usually acute
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 Positive Symptoms
• loose associations
• hallucinations
– linked to increased activity in cortical (Broca’s)
area
• bizarre behavior

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 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?
• Avolition - apathy
• Alogia
• Anhedonia
• Flat affect
• Asociality
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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

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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
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 Cognitive Deficits
Cognition: The conscious process of
knowing or being aware of thoughts or
perceptions, including understanding
and reasoning. Conceptual
change
Impairments in working memory
Critical Self-
thinking regulation
Cognition
Attention deficits
Creativity Problem
Linked to solving
MOTIVATION
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 OTHER SYMPTOMS
Catatonia
Inappropriate affect (aggressive symptoms?)
Consequences

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 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

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 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

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 Diagnosis Of Schizophrenia
• Schizophrenia is very hard to diagnose. There is
no test to identify if someone has Schizophrenia or
not. The reason it is so hard to diagnose is
because, people with brain tumors, drug abuse,
and/or epilepsy have similar symptoms. This
makes problems, because the illness is not caught
until it has progressed a great deal. Doctors take
blood and urine samples to see if the patient is
abusing alcohol or drugs. For a normal diagnosis
to be made, the symptoms have to last for at least
six months.
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 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
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 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
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 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

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 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
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ETIOLOGY OF SCHIZOPHRENIA

• Genetics
• Biochemical/biological
• Abnormal brain function and structure
• Stress and schizophrenia
• Some other factors and predictors
• And we basically do not know exactly…

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 GENETIC FACTORS
Schizophrenia has a genetic component

• Increased risk as the genetic relationship is

closer
• Parents : 9%
• Siblings : 7%
• Dizygotic twins 12%
• Monozygotic twins 44% - but not 100% so
genetic factors are not solely responsible for
schizophrenia

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 GENETIC FACTORS
Schizophrenia has a genetic component

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

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 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

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 Presynaptic neuron
Neurotransmitters

Terminal
Buttons
(end of the
presynaptic
Synapsic cell)
cleft
Receptors

Postsynaptic
membrane 31
Postsynaptic
 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 not necessarily have more
dopamine in their brain but more D2 receptors
and oversensitive receptors

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 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
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 BIOCHEMICAL FACTORS
Serotonergic theory: Neuromodulation

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

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 Prefrontal theory
• Frontal cortex plays role in speech,
decision making – disrupted in
schizophrenia

• 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 35
 Temporal lobe dysfunction
• Volume reduction in the temporal lobes

• Volume reduction in the left posterior temporal

gyrus (language processing)

• Volume reduction in the superior temporal

gyrus (auditory cortex – hallucinations)

• Reduced volume of hippocampus (related to

memory problems)

• Abnormal activity of the amygdala – in positive

symptoms (problems with emotion)
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 STRESS AND SCHIZOPHRENIA
• Life-stress increases the likelihood of relapses

• People with the lowest social class have the

highest prevalence for schizophrenia
• Sociogenic hypothesis – stress comes from
the social status
• Social selection-theory (people with
schizophrenia will drift to the poverty
sooner or later
• Studies with immigrants supports more
the social-selection hypothesis

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 More than one disorder?
• Symptom overlap with other mental disorders

• Perhaps there is a cycle of symptoms?

– E.g. bipolar disorder (manic depression)

? Mania

?
Depression

– Cycle between positive and negative states?

– Frequency?
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 What Triggers Schizophrenia?
• There are many factors which all contribute
to triggering schizophrenia. Those factors
are:
• Genetic Factors
• Environmental Factors
• Psychological Factors

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 Genetic Factors (cont’d)
• “Loss of brain volume
associated with
schizophrenia is clearly
shown by magnetic
resonance imaging (MRI)
scans comparing the size of
ventricles (butterfly
shaped, fluid-filled spaces
in the midbrain) of identical
twins, one of whom has
schizophrenia (right). The
ventricles of the twin with
schizophrenia are larger.
This suggests structural
brain changes associated
with the illness."- Source:  
Daniel Weinberg, MD, NIMH 
Clinical Brain Disorders Branch--
used with permission

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 Hollywood Involvement
• Movies such as A Beautiful Mind, which
was a true story, increase people’s
knowledge on the disorder. The main
character in the movie, was John F. Nash.
• As more involvement is made with
Hollywood and famous individuals, we are
paying more attention to Schizophrenia.

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 Hollywood Involvement (cont’d)

• John F. Nash (1928-)

• Premio Nobel 1994
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 Mental Status
Findings/Appearance
• Broad range of possible findings
• Malodorous/poor grooming
• Lack of or overabundance of spontaneous
speech
• Echopraxia/echolalia possible
• Can have “normal” appearance

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 Mental Status/Mood & Affect
• Can look depressed--? pseudoparkinsonism
• Ambivalence or apathy possible
• Possibly fearful (paranoid)
• Bizarre and incongruent affect (giggling for
no obvious reason) OR flat affect
• MANY different findings

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 Mental Status/Thought Content
• Most common hallucinations are auditory
• Voices can be threatening, obscene,
accusatory or insulting
• Two or more voices conversing
• Voices commenting on or commanding
behavior
• Non-auditory hallucinations may indicate
presence of medical/neurologic d/o
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 Mental Status/Thought Content,
continued
• Ideas/ Delusions of reference
• Thought blocking
• Thought insertion/ withdrawal /
broadcasting
• Delusions of control/ passivity

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 Mental Status/Thought Process
• Can be logical (paranoid type)
• Tangential, flight of ideas, loose
associations, word salad, echolalia,
neologisms are all possible findings

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 Mental Status-- Cognitive
• Oriented to date and place
• Memory often intact
• If severe impairment or altering level of
consciousness, consider delirium

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 Seasonality
• (Northern hemisphere) Jan- April births
• Seasonal virus?

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 Medical Illnesses
• Higher mortality from accidents/ natural
causes
• 80% with significant concurrent medical
illness

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 Cigarettes
• 75% of schizophrenics smoke
• Alters drug levels-- cigarette smoke
activates liver enzymes
• Decreased Parkinsonism with smokers

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 Substance Abuse
• Co-morbidity very common
• 30- 50% schizophrenic patients are alcohol
abusers
• 15-25% use cannabis
• 5-10% use cocaine

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 Suicide
• 50% schizophrenic patients-- at least 1
suicide attempt
• 10% die by suicide

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 Suicide Risk Factors
• command aud. hallucinations, insight into
illness, college education, young age,
improvement after relapse, high ambition,
living alone, dependence on hospital,
change in course of disease, prior suicide
attempts

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 Relationship to Violence
• A schizophrenic patient is no more likely to
commit homicide than a member of the
general population
• When violence occurs, it can be due to
bizarre delusions or command
hallucinations
• Risk Factors for Homicide: prior history of
violence, dangerous behavior while
hospitalized, delusions & hallucinations
involving violence 55
 Cultural and Socioeconomic
Factors
• Social drift hypothesis vs social causation
hypothesis
• Effect of immigration/ abrupt cultural
change
• 33-50% of homeless are schizophrenic

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 Developmental Theories
• No well controlled studies indicate any
specific family pattern plays a role but :
• Double Binds worsen the situation &
• High Expressed Emotions can lead to
increased rate of relapse---characterized by
criticism, hostility and overinvolvement

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 Etiologies: Neuropathologic vs
Neurodevelopmental Theories
• Brain Imaging: lateral and 3rd ventricle
enlargement
• Decreased cortical volume
• In discordant MZ twins: affected twin has
larger ventricles
– and is more likely to be the “B” twin
• Cytoarchitectural abnormalities in the brain

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 Etiologies: Genetics
• Increased rate in MZ twins
– MZ 46%, DZ 14%
• Other familial associations increase risk
– Non twin Sib 10%
– 0ne parent-- 6% for offspring
– Both parents-- 46% for offspring

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 Course of Schizophrenia
• Premorbid symptoms often only recognized
retrospectively
• Gradual recovery after psychotic episodes
but relapses usually occur
• Probability of rehospitalization is 40-60%
after 1st hospitalization
• High “Expressed Emotions” families
associated w/ relapse
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 Course of Schizophrenia (cont)
• Schizophrenics fail to return to baseline (as
opposed to those w/ mood disorders)
– residual subtype
• Pts are at increased vulnerability to stress
• Positive symptoms can improve with age
but negative symptoms sometime worsen
• “Post-Psychotic Depression of Schizophrenia”
• 75% relapse if on placebo vs 15-25% who are on
medication
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 Prognosis
• After 5-10 years following first
hospitalization only 10-20% described as
having a good outcome
• >50% described as having poor outcome
• With new medications, this can change

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