psychlotron.org.uk Schizophrenia: brain chemicals How might neurotransmitters be implicated in mental illness?

psychlotron.org.uk Today’s session You will learn aboutContext Commenting on evidence Synaptic transmission Drug treatments for psychological disorders Schizophrenia The dopamine hypothesis of schizophrenia

psychlotron.org.uk Neurones Source: science photo library Neuronal cell bodies Synapses occur at the junctions Axons

psychlotron.org.uk Synapses Neurones transmit signals electrically along their axons The synapses (junctions between neurones) transmit signals chemically

psychlotron.org.uk Synapse Vesicles filled with neurotransmitter Location of receptors (post- synaptic density) Synaptic cleft Source: neuroscience.wustl.edu

psychlotron.org.uk Vesicles release neurotransmitter into synaptic cleft

psychlotron.org.uk Neurotransmitter binds to receptors & activates them

psychlotron.org.uk Enzymes are released to break down the neurotransmitter

psychlotron.org.uk Excess neurotransmitter is taken up by the pre-synaptic neurone

psychlotron.org.uk Vesicles are replenished with new & reused neurotransmitter

psychlotron.org.uk 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

psychlotron.org.uk 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

psychlotron.org.uk What could be done to make dopamine synapses less active?

psychlotron.org.uk Antipsychotic medication Neuroleptics (e.g. chlorpromazine) bind to DA receptors without activating them

psychlotron.org.uk

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

psychlotron.org.uk Side effects Extrapyramidal side effects (EPS) Parkinson’s-type symptoms Postural & motor abnormalities Other side effects Sedation Weight gain Seizures

psychlotron.org.uk What implications arise from the side effects of antipsychotic drugs?

psychlotron.org.uk 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)

psychlotron.org.uk Typical vs. atypical DA receptor tightly bound; slow release from receptor loosely bound; fast release from receptor Drug