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incidence
characteristics
causes?
treatments?
Copyright © Allyn & Bacon 2007
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Schizophrenia is clearly a disease of the
brain.
◦ Enlarged ventricles
◦ Prefrontal cortex
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Hypofunctionality of the prefrontal cortex
◦ Reduced activity in this region
 concentration and focused attention
Copyright © Allyn & Bacon 2007
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positive and negative symptoms
positive symptoms –
◦ things that you can see; hallucinations, delusions,
etc
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negative symptoms – things that are absent
◦ social withdrawal
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Schizophrenia is clearly a brain
disease with a genetic basis
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twin studies
◦ look at monozygotic (1 egg) twins – 99% genes in
common vs dyzgotic twins – 50% genes in common
◦ look at concordance rates – proportion of cases in
which both twins have the disorder
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family studies
◦ allows you to look at increased concordance rates
(particularly in first-degree relatives)
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Adoption studies
◦ allows you to look at role of environment vs genes
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role of stress?
◦ stress does not cause schizophrenia BUT
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viral exposure?
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role of stress?
◦ stress does not cause schizophrenia BUT
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viral exposure?
fetal insult?
◦ hypoxia, etc
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positive symptoms – could be treated
medically
negative symptoms – would not respond to
drugs but rather was brain damage as a
consequence of whatever schizophrenia did
to the brain
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1950’s - first drugs to treat schizophrenia
appeared
called traditional neuroleptics, antipsychotics
◦ treat the positive symptoms
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Now – atypical neuroleptics – 1989 – 1999
◦ treat positive and negative symptoms
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1950’s – chlorpromazine (Thorazine) and
haloperidol (Haldol)
◦ cheapest way to treat positive symptoms, still
widely used
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many other uses for chlorpromazine
◦ nausea and vomiting, chronic hiccups, severe
itching, manage psychotic component in acute
mania, to treat alcohol hallucinosis
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Blocking DA receptors
Resulted in the DA theory for schizophrenia
D2 receptor subtype important
◦ how well the drug binds to D2 receptor is clearly
linked to reduction in positive symptoms
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drugs that block DA;
drugs that increase DA activity
l-dopa
◦ used to treat Parkinsons Disease
◦ potential side effect:
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amphetamine and cocaine
◦ acute psychosis
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ephedrine
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mesolimbic DA pathway – emotion
nigrostriatal DA pathway –movement
mesocortical DA pathway –
◦ higher cognitive function
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tuberofundibular DA pathway –
◦ within the hypothalamus – controls the release of
certain hormones
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a lot of problems related to movement
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parkinson like symptoms
spastic muscle contractions in head and neck
restlessness, constant movement
tardive dyskinesia
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NO! – these drugs have effects on multiple
other neurotransmitters that also have
significant side effects
block ACh as one
◦ memory deficits, dry mouth, urinary retention,
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first atypical neuroleptic was clozapine
◦ effective in proportion of patients that were
unresponsive to previous medication
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first atypical neuroleptic was clozapine
people who had not been able to leave
hospital for 25 years were suddenly better!
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first atypical neuroleptic was clozapine
◦ effective in proportion of patients that were
unresponsive to previous medication
◦ reduced negative symptoms
◦ reduced tardive dyskinesias
◦ risky side effects – agranulocytosis (potentially
lethal drop in white blood cells ~ 1% of people on
drug)
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Initially, clozapine cost 36,000/year.
◦ required contract with nurses that would take
weekly blood tests
◦ subsequent costs ~ 12,000/year
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now off patent
◦ reduced requirements by the FDA
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at least 7 new atypicals on the market – the
most recent in 2003; one still in clinical trials
none are as effective as clozapine for treating
tardive dyskinesias but none associated with
the potentially lethal side effect
all expensive
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clozapine – Clozaril –
risperidone – Risperdal olanzapine – Zyprexa quetiapine – Seroquel ziprasidone – Geodon aripiprazole Abilify-
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good question – some say the drugs bind to
D2 receptors but also to a certain type of 5HT
receptors
some say these drugs do not bind quite as
well to D2 receptors as the more traditional
ones; but binds to other types of DA
receptors
this is a huge step forward for treating
schizophrenia
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From the basic research phase to completion
of clinical trials.