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Schizophrenia: brain chemicals

How might neurotransmitters be implicated in mental illness?

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Today’s session

You will learn about Context

Commenting on evidenceSynaptic transmissionDrug treatments for psychological disorders

SchizophreniaThe dopamine hypothesis of schizophrenia

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Neurones

Sou

rce:

sci

ence

pho

to li

brar

y

Neuronal cell bodies

Synapses occur at the junctions

Axons

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Synapses

Neurones transmit signals electrically along their axons

The synapses (junctions between neurones) transmit signals chemically

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Synapse

Vesicles filled with neurotransmitter

Location of receptors (post-synaptic density)

Synaptic cleft

Sou

rce:

neu

rosc

ienc

e.w

ustl.

edu

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Vesicles release neurotransmitter into synaptic cleft

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Neurotransmitter binds to receptors & activates them

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Enzymes are released to break down the neurotransmitter

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Excess neurotransmitter is taken up by the pre-synaptic neurone

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Vesicles are replenished with new & reused neurotransmitter

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The dopamine hypothesis

Schizophrenia is caused by excessive activity at synapses that use dopamine as their primary neurotransmitter

This causes abnormal functioning of DA-dependent brain systems, resulting in schizophrenic symptoms

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Biology and Schizophrenia

Consistent evidence for abnormal brain functioning in S patients but no single factor identified. Two syndromes? Cause & effect issues everywhere Confounding effects of drug treatment

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What could be done to make dopamine synapses less active?

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Antipsychotic medication

Neuroleptics (e.g. chlorpromazine) bind to DA receptors without activating them

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Effectiveness

Older (typical) drugs (e.g. chlorpromazine) 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

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Side effects

Extrapyramidal side effects (EPS) Parkinson’s-type symptoms Postural & motor abnormalities

Other side effects Sedation Weight gain Seizures

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What implications arise from the side effects of antipsychotic drugs?

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Effectiveness

Newer (atypical) drugs (e.g. clozapine) 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)

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Typical vs. atypical

DA receptor

tightly bound; slow release

from receptor

loosely bound; fast release

from receptor

Drug