Contemporary Study For Schizophrenia - Carlsson (2000)

Question 1

Aim

Answer 1

• To provide an up-to-date review of the current status of the dopamine hypothesis
• To raise awareness of the potential role of other neurotransmitters, e.g. glutamate, serotonin and GABA
• To present suggestions for future drug treatments for the wide range of people with schizophrenia, many of whom are “treatment resistant” or who live with the extreme side effects (e.g. extra-pyramidal dysfunction)

Question 2

What does Carlsson say about the function of neurotransmitters in relation to schizophrenia?

Answer 2

• excess dopamine may be a by-product of dysfunction of another neurotransmitter
• excess in one area of the brain may be a way of compensating for a deficiency in another brain area

Question 3

Why does Carlsson think hyperdopaminergia is only part of the answer?

Answer 3

• some people with schizophrenia show dopamine levels within the normal range
  dopaminergic dysfunction may only accounts for symptoms in a sub-group of patients
• some people with ‘catatonic’ symptoms have hypodopaminergic activity

Question 4

What does he say about other neurotransmitters?

Answer 4

• dopamine levels may be controlled by serotonin levels
• if serotonin levels are too high, this could be linked to increased dopamine levels
• low levels of glutamate, may allow both serotonin and dopamine levels to become too high
  glutamatergic failure in …
  the cerebral cortex may lead to negative symptoms
  the basal ganglia could be responsible for the positive symptoms

Question 5

Glutamate as a dopamine “accelerator”

Answer 5

In the meso-cortical pathway:
- glutamate acts as an accelerator leading to increased dopamine activity

if this goes wrong…
and glutamate levels fall too low and dopamine levels drop leading to negative symptoms

Question 6

Glutamate as a dopamine “brake”

Answer 6

in the meso-limbic pathways…
glutamate acts as a brake signalling to GABA neurons to inhibit dopamine production

if the brake does not work…
glutamate levels are too low leading to low levels of GABA thus high levels of dopamine resulting in positive symptoms

Question 7

What does Carlsson say regarding future drug treatments for schizophrenia?

Answer 7

• serotonin antagonists to bring down serotonin levels
• glutamate agonists - to increase glutamate levels
• differing symptoms may be the result of differing neurochemical aetiologies requiring differing treatments
  (Different people have different reasons for schizophrenia)

Question 8

Evaluation of theory - studies of PCP - Angel dust

Answer 8

• PCP / angel dust = a street drug that can induce schizophrenic like symptoms (hallucinating) similar to ecstasy
• PCP is an antagonist on the NMDA (glutamate receptor).
• PCP has effect of reducing glutamate levels which increases dopamine
• suggest schizophrenia is linked to hypoglutamatergic (low levels of glutamate) activity

HOWEVER
- sometimes PCP actually enhances rather than reduces the release of glutamate and
this ambiguity casts doubt on hypoglutamatergia as a cause of schizophrenia.

Question 9

Evaluation of theory - post mortem studies

Answer 9

• hyperserotonergic (high levels of serotonin) function in people with paranoid schizophrenia
• therefore this has application to treatments like clozapine as it is both anti-dopaminergic and anti-serotonergic.

HOWEVER
- post mortem is correlation not causational so not reliable

Question 10

Evaluating theory - Carlsson experiments with mice

Answer 10

• gave mice drugs to reduce motor activity
• found they could induce motor activity again by blocking glumate receptors