Symptoms of schizophrenia
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Transcript Symptoms of schizophrenia
incidence
characteristics
causes?
treatments?
Copyright © Allyn & Bacon 2007
Schizophrenia is clearly a disease of the
brain.
◦ Enlarged ventricles
◦ Prefrontal cortex
Hypofunctionality of the prefrontal cortex
◦ Reduced activity in this region
concentration and focused attention
Copyright © Allyn & Bacon 2007
positive and negative symptoms
positive symptoms –
◦ things that you can see; hallucinations, delusions,
etc
negative symptoms – things that are absent
◦ social withdrawal
Schizophrenia is clearly a brain
disease with a genetic basis
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
family studies
◦ allows you to look at increased concordance rates
(particularly in first-degree relatives)
Adoption studies
◦ allows you to look at role of environment vs genes
role of stress?
◦ stress does not cause schizophrenia BUT
viral exposure?
role of stress?
◦ stress does not cause schizophrenia BUT
viral exposure?
fetal insult?
◦ hypoxia, etc
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
1950’s - first drugs to treat schizophrenia
appeared
called traditional neuroleptics, antipsychotics
◦ treat the positive symptoms
Now – atypical neuroleptics – 1989 – 1999
◦ treat positive and negative symptoms
1950’s – chlorpromazine (Thorazine) and
haloperidol (Haldol)
◦ cheapest way to treat positive symptoms, still
widely used
many other uses for chlorpromazine
◦ nausea and vomiting, chronic hiccups, severe
itching, manage psychotic component in acute
mania, to treat alcohol hallucinosis
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
drugs that block DA;
drugs that increase DA activity
l-dopa
◦ used to treat Parkinsons Disease
◦ potential side effect:
amphetamine and cocaine
◦ acute psychosis
ephedrine
mesolimbic DA pathway – emotion
nigrostriatal DA pathway –movement
mesocortical DA pathway –
◦ higher cognitive function
tuberofundibular DA pathway –
◦ within the hypothalamus – controls the release of
certain hormones
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
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,
first atypical neuroleptic was clozapine
◦ effective in proportion of patients that were
unresponsive to previous medication
first atypical neuroleptic was clozapine
people who had not been able to leave
hospital for 25 years were suddenly better!
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)
Initially, clozapine cost 36,000/year.
◦ required contract with nurses that would take
weekly blood tests
◦ subsequent costs ~ 12,000/year
now off patent
◦ reduced requirements by the FDA
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
clozapine – Clozaril –
risperidone – Risperdal olanzapine – Zyprexa quetiapine – Seroquel ziprasidone – Geodon aripiprazole Abilify-
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
From the basic research phase to completion
of clinical trials.