Introducing Schizophrenia
Dr Eddy Mellor
Historical background
• First descriptions of symptoms appear in ancient
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Greek texts
Changing attitudes in the 18th century led to an
increase interest in studying mental illness;
previously there behaviour was regarded as
reprehensible
The discovery of the pathology and treatment of
general paresis of the insane led Emil Kraepelin
to identify another unique syndrome which he
named Dementia Praecox
• “On the one hand we observe a weakening of
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those emotional activities which permanently
form the mainsprings of volition. In connection
with this , mental activity and instinct for
occupation become mute. The result of this part
of the process is emotional dullness, failure of
mental activities, loss of mastery of volition, of
endeavour and of ability for independent action.
The essence of personality is thereby destroyed,
the best and most precious part of being; torn
from her….”
Kraepelin Dementia Praecox 1919
Epidemiology
• Schizophrenia is a world wide public health
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concern being present in all countries and
cultures
Interestingly its incidence is almost uniform
across geographical, cultural and religious
borders
Just less than 1% of people suffer from
schizophrenia, if the schizophrenia spectrum
disorders are included this rises to 5%
• Almost equal sex distribution with a slight
excess of male patients.
• Females tend to develop the disease on
average 4 years later than males
• Female distribution of the disease also
shows a second “spike” at menopause
• Also a third spike occurs for both sexes at
around 60-65 years, these patients are
termed late onset schizophrenia. Many
clinicians view this as a distinct clinical
entity to schizophrenia.
Aetiology
• Several models which can be grouped
into….
• Biological
• Social
• Psychological
Biological theories
• Again the precise aetiology remains unknown
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but there is good evidence to support a
biological cause for Schizophrenia and several
promising lines of enquiry
Many people would regard schizophrenia as a
syndrome. A collection of disease entities
producing similar clinical picture but with distinct
aetiologies. Much like Learning disability being
classified a s a single disease entity before a
plethora of causes were identified
Genetics
• Family twin and adoptive studies have
shown beyond doubt that a large degree
of risk of Schizophrenia is genetically
determined
• Risk as high as 55% for identical twins.
Around 15 5 if one parent is affected
rising to almost 40% if both parents
affected
• Eight linkage sites have thus far been
identified on the 1st 6th 8th 10th thirteenth
and 15th chromosomes.
• Several specific genes have also been
identified each of which confers a degree
of vulnerability to the disease
• Although genetic studies do support a
biological causation they also demonstrate
that other factors must be involved as
many genetically risky individuals never
develop schizophrenia.
Pathology contribution
• Post mortem studies of schizophrenic
brains first identified morphological
features of the condition
• Brains show enlarged lateral ventricles at
PM and reduced volume of hypocampus
• There brains are lighter than controls
• Newer imaging techniques have shown a
more rapid reduction of cortical volume
during first illness episode
Identified risks
• A number of interesting possibilities
supported by studies…
• An excess of birth and gestational
complications leading some to postulate
anoxic brain injury as a risk factor
• An excess of winter births of individuals
with the disease has led to speculation of
a viral or post-viral autoimmune process
• Studies of incidence rates have also shown
an increased incidence of children who
were in utero during influenza epidemics
• The same has also been demonstrated for
children born during times of famine.
• Another risk factor which has shown
statistical significant association is that
children with rhesus incompatibility also
show an increased risk
The Dopamine hypothesis
• “normal” individuals exposed to dopamine
releasing drugs such as amphetamines
over a period of days will develop a
psychosis clinically indistinguishable from
schizophrenia which generally disappears
with abstinence from the drugs
• All effective antipsychotic drugs have
dopamine blocking properties
• Overactivity in dopaminergic meso-frontal
and mesocortical neurones and their
associated dopamine-D2 receptors has
been suggested as the basis of “positive”
features of schizophrenia such as acute
hallucinations and delusions.
• When psychotic scizophrenic patients are
given amphetamine they release
substantially more dopamine than healthy
controls.
Beyond the dopamine hypothesis
• The improvement in “negative” features
(such as lack of volition or planning
ability) achieved by the newer atypical
antipsychotic drugs suggests that neuronal
pathways other than just dopaminergic
ones are important in some of the
symptoms schizophrenia.
Neuro-cognitive testing
• Schizophrenic patients perform worse as a
group on all neuropsychological tests
compared to IQ matched controls.
• First degree relatives also perform worse
on average than controls
Social
• Studies have shown an excess of schizophrenic
patients in lower socioeconomic groups and in
urbanised areas. This used to be attributed to
“social drift”
• Newer studies following children from various
backgrounds suggest this is not the case and
living in a highly urbanised area is indeed a risk
factor for schizophrenia
Psychosocial
• abnormalities in processing sensory
information, in separating “signal from
background noise”, or in manipulating
abstract information
• Consistently demonstrate “Jump to
conclusion” reasoning or JTC
• Excess life traumas against controls at first
presentation
Clinical features
• The prodrome- Increasingly recognised is
a prodromal state of 1-2 years duration
preceding the onset of psychosis
• Typical features of the prodrome are:
anxiety, depression, reduced
concentration, difficulty communicating
,reduced motivation and suspiciousness
• Brief and transitory psychotic ideas lasting
minutes or hours may also feature
• These problems often lead to a reduced
level of functioning and may lead to
unemployment or below expected
educational achievement
• When taking a history from a patient with
new onset psychosis establishing a
prodromal phase raises suspicion of a
diagnosis of Scizophrenia
• Collateral history is often of value in
screening for prodromal symptom's
ICD-10 criteria-1
• Based on First Rank symptoms described by Kurt
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Schneider, German Psychiatrist
There are two groups of symptoms:
Major: at least one of these must be present to
make a diagnosis of schizophrenia
Minor: at least two of these must be present to
make a diagnosis.
These symptoms must be present most of the
time for at least one month
Schneider’s 1st Rank Symptoms
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Schneider’s 1st Rank Symptoms
Auditory Hallucinations: running
commentary, discussing him among
themselves, thought echo
Thought insertion, withdrawal, broadcast
Passivity phenomena: actions, feelings
Delusional perception: a normal perception
happens, and a delusional interpretation is
attached to it.
Major symptoms/signs
• 1-Thought echo, thought insertion, withdrawal
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or broadcasting
2-Delusional perception OR delusions of control
(passivity phenomena)
3-Hallucinatory voices: Running commentary,
discussing him among themselves or coming
from some part of the body.
4-Delusions that are culturally inappropriate &
completely impossible, e.g.: controlling weather
Minor Symptoms
• Persistent hallucinations in any modality,
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everyday for at least 1 month, when
accompanied by delusions without affective
content
Neologisms, incoherent/irrelevant speech
Catatonic behaviour (excitement, mutism….)
Negative symptoms (apathy, paucity of
speech, etc) which are not due to
depression or medication side effect.
Symptom development and
Dopamine
• Understanding the normal function of Dopamine
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in the brain is key to understanding the
psychopathology of schizophrenia
Dopamine is released in the healthy subject in
response to innately rewarding or adverse
events.
An example would be playing a difficult level on
a computer game and unexpectedly succeeding.
Another would be in response to seeing on
hearing footsteps behind you in a dark alley.
• In the schizophrenic patients brain, during
a psychotic episode, dopamine can be
released at any time and can lead to the
individual falsely attributing significance or
fear to objects, sensory information or
thoughts.
• They may for instance get a feeling of
intense significance, such as one might
get when the killer is unmasked in a
murder mystery, whilst looking at a car
number plate.
• Alternatively they might get a surge of
dopamine whilst concentrating on their
own thoughts and interpret their thoughts
as alien, (thought insertion)
• They could get a surge of dopamine whilst
watching television and suddenly feel they
are somehow related to or responsible for
the death of Michael Jackson or the Credit
Crunch
• Using this model it is easy to see how anyone
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could quickly build up a complex delusionary
system. We all want to make sense of what is
happening around us and we all trust our own
senses.
Patients delusions are often built up from a
single or several unusual experiences which they
then try and rationalise.
If you heard voices that no one else could hear
would it not be preferable to think it was a
microchip implanted in your skull rather than
face up to the fact you might be mentally ill?
Prognosis/ course
• 1/3 recover; 1/3 relapse and remit; 1/3 become
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chronic 6-10% suicide
Increased rates violence about 5x to carers and
staff, least often strangers
Similar number to suicide dies prematurely from
physical illness
Increased rates dependent living,
homelessness, unemployment
As become older negative symptoms increase
whilst positive symptoms diminish
Investigation
• As always in psychiatry your first objective
should be to exclude an organic problem
• In the case of patient presenting with
symptoms suggestive of schizophrenia
there are two important organic
differential diagnosis
• A Drug induced psychosis can closely
resemble a schizophrenia presentation
• Undiagnosed temporal lobe epilepsy can
present in a similar way to an acutely
psychotic patient
• Always complete a urine drug screen on
admission, Amphetamines can be clear
from the urine in 48 hours
• Patients should routinely have an ECG at
first presentation
• ALWAYS complete a thorough neurological
exam rarely malignancy can masquerade
as psychosis
Differential diagnosis
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Acute & Transient Psychotic Disorders
Persistent Delusional Disorder
Bipolar Disorder (manic or mixed episode with
psychosis)
Severe Depressive Episode (with psychosis)
Schizo-affective Disorder
Drug Induced Psychosis
Organic Delusional Disorder: epilepsy; brain
tumours, etc
Delirium
Dementia
Differential Diagnosis 2
• Schizotypal Disorder
• Personality Disorders
• Paranoid
• Schizoid
• Emotionally unstable, borderline type
• Dissociative Disorders
• Malingering
Sub types
• Classically divided into four sub types
• Paranoid
• Hebephrenic
• Simple or undifferentiated
• Catatonic
Paranoid type
• Relatively stable, often persecutory
delusions
• Usually hallucinations, particularly of the
auditory variety, and other perceptual
disturbances
• Affect, volition and speech disturbances,
and catatonic symptoms are either absent
or inconspicuous.
Hebephrenic Schizophrenia
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Prominent affective changes
delusions and hallucinations: fleeting/rudimentary
Irresponsible and unpredictable behaviour
Mannerisms
Shallow and inappropriate mood
Disorganised thought
Incoherent speech
Social isolation
Usually poor prognosis (because of the rapid
development of "negative" symptoms, particularly
flattening of affect and loss of volition
Catatonic Schizophrenia
Prominent psychomotor disturbances that
may alternate between extremes such as
violent excitement & stupor, or automatic
obedience & negativism. Constrained
attitudes and postures may be maintained
for long periods.
Uncommon in industrialised countries
Undifferentiated Schizophrenia
• Psychotic conditions meeting the general
• diagnostic criteria for schizophrenia but
not
• conforming to any of the other subtypes,
or
• exhibiting the features of more than one
of
• them, without a clear predominance of a
• particular set of diagnostic characteristics.
Treatment
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Treatment & Management
This should be again 3-fold: Bio-psychosocial
Medication
Risk reduction (to himself & others)
Observation
Psychology (CBT for delusions)
Occupational therapy
Family therapy
Social integration
Medication-1
• ►Older anti-psychotics (conventional) vs
• newer anti-psychotics
• ►Older ones had more side effects
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(Extrapyramidal
Side Effects [EPSEs])
►Anti-muscarinic meds are used to counter
EPSEs (eg: procyclidine, orphenadrine, etc)
►Newer ones are much more expensive
►Depot vs Oral
Clozapine
• Targets Serotonin 2 receptors and D4
• receptors; the ordinary old and new
• antipsychotics target D2 receptors.
►NICE advises to use Clozapine, once 2
• different anti-psychotics (of 2 different
• groups) have been tried for appropriate
• periods (each 6-12 weeks) and the
• psychosis continues termed treatment resistant
scizophrenia.
Medication-ECG
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Possibly serious ECG abnormalities
At least once yearly ECGs requiresd
QTc prolongation: the normal range is from 370
ms to 450 in men & 470 in women.
If pre-existing abnormalities, more prone for
Sudden Cardiac Death.
Consider referral or senior review if not sure
Neuroleptic Malignant syndrome
• Potentially fatal complication of
antipsychotic use
• More common in neuroleptically naïve
patients
• Presents with- Severe muscle rigidity, High
fever, mutism, delirium.
• Caused by muscle break down leading to
Rhabdomyalysis
• Patient will often appear confused and
may be agitated
• The clinical picture may be mistaken for
catatonia or acute psychosis
• Bloods will show a marked elevation in Ck
in the 1000s
• It is a medical emergency and patient’s
will require fluids and may need dialysis,
urgent transfer to medical unit is indicated
Tarditive dyskinesia
• Distressing condition in which involuntary
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movements (chewing, sucking grimacing) occur
persistently
This occurs more commonly with typical
antipsychotic drugs and is usually first noticed
when stopping or changing medication
Believed to be caused by dopamine
hypersensitisation no universally effective
treatment exists.