Transcript The dopamine hypothesis

A biological explanation for
schizophrenia
L.O. To be able to describe and
evaluate the dopamine
hypothesis of schizophrenia
Schizophrenia:
brain chemicals
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We know what the neurotransmitter
acetylcholine does in the nervous
system……. But how might neurotransmitters
be implicated in mental illness?
Source: science photo library
Neurones
Neuronal cell
bodies
Axons
Synapses occur
at the junctions
Synapses
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Neurones transmit signals electrically along
their axons
The synapses (junctions between neurones)
transmit signals chemically
Synapse
Source: neuroscience.wustl.edu
Vesicles filled with
neurotransmitter
Synaptic cleft
Location of
receptors (postsynaptic density)
Dopamine animation
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http://www.youtube.com/watch?v=VdfZnxlQfr
4
Vesicles release neurotransmitter
into synaptic cleft
Neurotransmitter binds to
receptors & activates them
Enzymes are released to break
down the neurotransmitter
Excess neurotransmitter is taken
up by the pre-synaptic neurone
Vesicles are replenished with new
& reused neurotransmitter
The dopamine hypothesis
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Schizophrenia is caused by excessive activity
at synapses that use dopamine as their
primary neurotransmitter
This causes abnormal functioning of DAdependent brain systems, resulting in
schizophrenic symptoms
Schizophrenia & dopamine
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The dopamine hypothesis:
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Schizophrenia is caused by excessive DA activity.
This causes abnormal functioning of DAdependent brain systems, resulting in
schizophrenic symptoms
DA can increase or decrease brain activity
depending on the system you’re looking at
Positive and negative
INCREASE IN DOPAMINE IN THE
MESOLIMBIC SYSTEM
INCREASE IN DOPAMINE IN THE
MESOCORTICAL SYSTEM
POSITIVE SYMPTOMS OF
SCHIZOPHRENIA
NEGATIVE SYMPTOMS OF
SCHIZOPHRENIA
Examination question – describe
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Describe one explanation for schizophrenia. (4 marks)
Dopamine:
Excess dopamine in the brain possibly causes schizophrenia/eq;
There is an increase of activity at dopamine synapses/eq;
This is associated with increased feelings of paranoia/eq;
It also explains why hallucinations may occur as the brain is too
active/eq;
Over stimulation of the mesolimbic pathway is thought to be linked
to positive symptoms of schizophrenia/eq;
Problems with dopamine functioning in the pathway connecting the
midbrain to the frontal lobes is associated with negative symptoms
Evaluation of the dopamine
hypothesis
Who would you rather be for the
day…….?
OR
…….why?
Interview
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http://www.youtube.com/watch?v=i4b_bNsajY
Lindstroem et al. (1999)
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Evidence for the dopamine hypothesis is mixed. There is certainly
evidence to suggest that dopamine levels are higher in the brains of
people with schizophrenia. In one study Lindstroem et al. (1999)
radioactively labelled a chemical called L-DOPA, which is used by
the brain to produce dopamine. They administered the L-DOPA to
ten untreated patients with schizophrenia and a control group of ten
people with no diagnosis. Using a brain scanning technique called
PET scanning; they were able to trace what happened to the LDOPA. The L-DOPA was taken up more quickly in the patients with
schizophrenia, suggesting that they were producing more dopamine
than the control group.
Lewine (1990)
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Folens p141 – classic research – use this to
fill out p39 (MRI) of your workbooks.
The dopamine hypothesis
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Wise & Stein (1973) report abnormally low
levels of DBH in post-mortem studies of S
patients
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Would suggest abnormally high DA activity as
DBH needed to break DA down
Can’t rule out cause of death or post-mortem
changes as a source or error
The dopamine hypothesis
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Overdose of amphetamine (DA agonist) can
produce S-like symptoms. S patients have
abnormally large responses to low
amphetamine doses
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Suggests a role for DA in S symptoms
Suggests that the issue is over-sensitivity to DA
rather than excessive DA levels
Synoptic - Making Connections
Make a connection between:
Eye Witness Testimony
Rosenhan
The dopamine hypothesis
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S symptoms can be treated with DA
antagonists (e.g. chlorpromazine). These are
effective in 60% of cases with more impact
on positive symptoms.
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Supports role of DA again, but what about 40%
who don’t respond?
Lack of impact on negative symptoms hints at two
separate syndromes
Biology and Schizophrenia
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Consistent evidence for abnormal brain
functioning in S patients but no single factor
identified.
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Two syndromes? One caused by DA activity &
associated with +ve symptoms; other caused by
brain degeneration & associated with –ve
symptoms.
Cause & effect issues everywhere
Confounding effects of drug treatment
On the board……
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Draw the strength and weaknesses of the
dopamine hypothesis on the board. NO
WORDS!
Examination question – evaluate
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Evaluate the explanation for schizophrenia you have given in (b)(i). (4 marks)
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As excess dopamine is only measured after onset it could be effect not cause/eq;
However paranoia in drug users where dopamine levels are kept too high does
support the role of dopamine/eq;
Also effectiveness of drugs that reduce availability of dopamine supports its role as
implicated in the disorder/eq;
Though antipsychotic drugs reduce dopamine availability in a very short time the
effect on symptoms takes several weeks to appear, suggesting other factors are
involved/eq;
PET scans in those who have had the disorder for many years show blocking of
dopamine receptors by antipsychotic drugs does not match a reduction in
symptoms/eq;
The positive correlation between schizophrenia and dopamine is consistent and
according to Seeman (2006) without exception/eq;
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What could be done to make dopamine
synapses less active?
TREATMENT FOR
SCHIZOPHRENIA
Before the 1950s schizophrenia was
considered untreatable and patients
were interned in mental institutions
Over time there have
been a variety of
different methods to
treat schizophrenia
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Rosenhan & Seligman vividly explain
the back wards of mental hospitals as
‘snake pits’, filled with inmates who
were unreachable or mutely catatonic,
or were wild with delusions and
straitjacketed.
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Attempts to treat schizophrenia such as
insulin shock, ECT and drugs had failed.
Introduction
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Psychological problems are both distressing
and disruptive for the individual sufferer.
So, there is an immediate need to alleviate
these conditions through appropriate forms of
therapy and/or treatment.
Treatment v Therapy
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Definition of Treatment: the medical or surgical management and
care of a patient.
Examples: Chemotherapy, prescription of medicines to cure/treat
symptoms of a disease or disorder.
Definition of Therapy: In the broadest sense, Therapy is a term that
can be applied to any form of treatment for any illness or disorder.
For example, antacid is a form of therapy for heartburn,
rehabilitation is a form of therapy for addiction, and exercise is a
form of therapy for obesity.
As it relates to mental health and mental disorders, therapy is
usually a general term used to reference the sessions held between
a therapist and a patient. E.g. Cognitive Behavioural Therapy (CBT),
Family Therapy, etc.
Chemotherapy
Since 50s use of drugs to treat
mental disorders is
widespread
Types of drugs fall into
following categories
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Anti-anxiety
Anti-depressant
Anti-psychotic
Anti-manic
Stimulants
They work to either increase or reduce the levels
of neurotransmitters
ANTIPSYCHOTIC DRUGS
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Anti-psychotic drugs have provided a
breakthrough in treating schizophrenia
and remain the main form of treatment
Provide a calming effect
BUT
 Have little effect on Type 2
 Have side effects
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1.
Phenothiazines: decreases
dopamine activity.
a.
Reduces positive symptoms
(hallucinations, delusions, etc.).
b.
Fails to reduce negative
symptoms (flat affect, low
motivation, etc.).
c.
Unpleasant side effects:
dizziness, nausea, sexual
impotence, tardive dyskinesia
(involuntary facial
movements), etc.
d.
May cause permanent
biochemical changes reducing
possible eventual full
recovery.
2. Clozapine: blocks less
dopamine and blocks more
serotonin.
a. Reduces both positive
and negative symptoms.
b. Fewer side effects; .
c. Problem: produces a
potentially lethal blood
disorder.
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The knowledge that
Chlorpromazine improves
symptoms of schizophrenia while
blocking D2 receptors for
Dopamine has led to the
development of drugs that have
similar pharmacological
properties to chlorpromazine.
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The symptoms that are most
responsive to these types of drugs
came to be called ‘positive’
symptoms because they showed a
positive response to drug therapy.
Dopamine / serotonin pathways in the
brain
DISCOVERY
In mid 1950s discovered that large daily
doses of Amphetamines could produce a
psychosis identical to schizophrenia
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Amphetamine increases D2 transmission
Chlorpromazine improves symptoms of
schizophrenia
2.
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Prevents Dopamine from activating
Antipsychotic medication
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Neuroleptics (e.g. chlorpromazine) bind to DA
receptors without activating them
Dopamine antogonist
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http://www.youtube.com/watch?v=DRHWJ8L
CSjQ
Effectiveness
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Older (typical) drugs (e.g. chlorpromazine)
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Short term beneficial effect in 75% of patients
(Davis et al, 1989)
Long term beneficial effect in 55-60% (Davis et al,
1993)
Most effective against positive symptoms
High risk of side effects
Side effects
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Extrapyramidal side effects (EPS)
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Parkinson’s-type symptoms
Postural & motor abnormalities
Other side effects
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Sedation
Weight gain
Seizures
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What implications arise from the side effects
of antipsychotic drugs?
Effectiveness
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Newer (atypical) drugs (e.g. clozapine)
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As effective as typical drugs on positive
symptoms; better for negative symptoms (Bilder
et al, 2002)
More effective with treatment-resistant patients
(DeNayer et al, 2003)
Less risk of EPS, but other side effects may occur
(e.g. blood disorders)
Meltzer et al. (2004)
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P253 thick book.
Typical vs. atypical
PEE table (L for A*)
Point
Schizophrenia
is believed to
be biological
(dopamine
Hyp)
Explain
Evidence
Evaluate
Link
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https://www.youtube.com/watch?v=UXSedtig
Neo