Introducing Schizophrenia

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Introducing Schizophrenia

• Dr Eddy Mellor

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Historical background

• First descriptions of symptoms appear in ancient
  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

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• On the one hand we observe a weakening of 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

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Epidemiology

• Schizophrenia is a world wide public health
  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

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• 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.

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Aetiology

• Several models which can be grouped
• into.
• Biological
• Social
• Psychological

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Biological theories

• Again the precise aetiology remains unknown 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

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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

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• 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.

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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

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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

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• 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

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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

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• 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.

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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.

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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

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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

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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

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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

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• 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

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ICD-10 criteria-1

• Based on First Rank symptoms described by Kurt
  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

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Schneiders 1st Rank Symptoms

• Schneiders 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.

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Major symptoms/signs

• 1-Thought echo, thought insertion, withdrawal 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

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Minor Symptoms

• Persistent hallucinations in any modality,
  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.

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Symptom development and Dopamine

• Understanding the normal function of Dopamine 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.

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• 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.

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• 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

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• Using this model it is easy to see how anyone
  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?

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Prognosis/ course

• 1/3 recover 1/3 relapse and remit 1/3 become
  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

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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

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• 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

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Differential diagnosis

• 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

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Differential Diagnosis 2

• Schizotypal Disorder
• Personality Disorders
• Paranoid
• Schizoid
• Emotionally unstable, borderline type
• Dissociative Disorders
• Malingering

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Sub types

• Classically divided into four sub types
• Paranoid
• Hebephrenic
• Simple or undifferentiated
• Catatonic

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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.

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Hebephrenic Schizophrenia

• Prominent affective changes
• delusions and hallucinations fleeting/rudimentar
  y
• 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

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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

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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.

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Treatment

• 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

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Medication-1

• ?Older anti-psychotics (conventional) vs
• newer anti-psychotics
• ?Older ones had more side effects (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

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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.

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Medication-ECG

• 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

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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

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• 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 patients will
  require fluids and may need dialysis, urgent
  transfer to medical unit is indicated

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Tarditive dyskinesia

• Distressing condition in which involuntary
  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.