1. DOPAMINE HYPOTHESIS

2. Lets remind ourselves how neurotransmitters work

3. Lets remind ourselves how neurotransmitters work

4. DOPAMINE HYPOTHESIS
The Dopamine hypothesis states that the brain of schizophrenic patients produces more dopamine than normal brains.
Evidence comes from
studies with drugs
post mortems
pet scans

5. Lowering DA activity helps remove the symptoms of schizophrenia
Elevated Level of Dopamine In The Brain of a Schizophrenic Patient
(specifically the D2 receptor)
Normal Level of Dopamine In The Human Brain
Neurons that use the transmitter ‘dopamine’ fire too often and transmit too many messages or too often.
Certain D2 receptors are known to play a key role in guiding attention.
Lowering DA activity helps remove the symptoms of schizophrenia

6. ROLE OF DRUGS Amphetamines (agonists) lead to increase in DA levels
Large quantities lead to delusions and hallucinations
If drugs are given to schizophrenic patients their symptoms get worse

7. Parkinson’s disease
Parkinson’s sufferers have low levels of dopamine
L-dopa raises DA activity
People with Parkinson's develop schizophrenic symptoms if they take too much L-dopa
Chlorphromazine (given to schizophrenics) reduces the symptoms by blocking D2 receptors

8. POST MORTEM Falkai et al 1988
Autopsies have found that people with schizophrenia have a larger than usual number of dopamine receptors.
Increase of DA in brain structures and receptor density (left amygdala and caudate nucleus putamen)
Concluded that DA production is abnormal for schizophrenia

9. Schizophrenia or Faulty Chemicals?
Chickens hatch from eggs, but a mother chicken must keep an egg warm in order for it to hatch
Which Came First?
The Chicken or the Egg?
Schizophrenia or Faulty Chemicals?
Faulty chemicals cause schizophrenia but schizophrenia may cause faulty chemicals
Movie clip: house (ao2 points …… ethics & side effects of biological model approach)
Drugs may influence other systems that impact on schizophrenia so cant be 100% sure about their effects

10. Limbic System A variety of structures under the cortex (subcortical)
Many functions, including
Emotion, memory formation and arousal

11. Limbic System
Nerve pathways connect the limbic system to other subcortical structures and the cerebral cortex.
Two main pathways:
The Mesolimbic Pathway
The Mesocortical Pathway

12. The Mesolimbic Pathway
Connects Ventral Tegmental Area (VTA) to the nucleus accumbens.
The VTA makes dopamine and sends it to the Nucleus Accumbens as a “reward”
Too much dopamine or too much firing by these neurons causes Positive symptoms of schizophrenia
This area is targeted by antipsychotic drugs

13. The Mesocortical Pathway
Connects Ventral Tegmental Area (VTA) to the frontal lobe
The VTA makes dopamine and sends it to the frontal lobe passing on information about emotional responses
Davis et al (91) too little dopamine hits D1 receptors in frontal lobe leading to negative symptoms

14. Evaluation 1 Genes Genes and Family studies
Concordance rates suggest genes are involved – Gottesman (1991)
There may be 108 genetic loci (areas) involved – Psychiatric Genomics Consortium 2014
Ie – it’s very complicated! Surprised?

15. Evaluation 2 Measuring Metabolites
Issue of estimating neurotransmitter levels from cerebrospinal fluid.
What’s the issue?
What’s the conclusion?

16. Evaluation 3 Role of Serotonin
Conventional antipsychotics only target dopamine and work for some people
Atypical antipsychotics also target serotonin receptors and work for others
Suggests both are involved
What does this suggest about the dopamine hypothesis?

17. Evaluation 4 Cause or effect
Are dopamine levels caused by schizophrenia or do they cause schizophrenia?

18. ACTIVITY Wrote Cornell Notes on the Revised Dopamine Hypothesis
Explain the role of dopamine in:
The Mesolimbic Pathway
The Mesocortical Pathway
What is the role of each pathway in schizophrenic symptoms?

19. ACTIVITY
Use the evaluation points to write effective AO2 commentary for the studies on the handout
• You must comment on how the evidence you use supports or challenges the DA hypothesis.
• You should comment on evidence both for and against the hypothesis.
• You could use your own skills and knowledge to make additional critical and evaluative points.

20. EVALUATION POINTS
There is a lack of correspondence between taking the drugs and signs of clinical effectiveness. It takes 4 weeks to see any sign that the drugs are working when they begin to block dopamine immediately. We can not seem to explain this time difference.
It could be that the development of receptors in one part of the brain may inhibit the development in another.
Type 1 cases respond well to conventional anti-psychotic drugs. Drugs such as CHLOPROMAZINE: Only effective at relieving the Positive Symptoms of the Illness.
Not good at explaining negative symptoms. Therefore suggested that Type 2 is related to a different kind of abnormality such as brain structure.
PET scans have suggested that drugs did not reduce symptoms of patients diagnosed with disorder for 10 yrs or more
There may be other neurotransmitters involved.
Possible that social and environmental factors trigger the condition.