Carlsson

Question 1

What did Carlsson hypothesise about dopamine?

Answer 1

Developed dopamine hypothesis of Schizophrenia which stated that excess dopamine could contribute towards the symptoms of Schizophrenia,

Question 2

What did Carlsson hypothesise about D2 receptors?

Answer 2

That there are too many D2 receptors in the brains of schizophrenics and they are far too sensitive that causes overfiring of dopamine.

Question 3

What are the three other neurotransmitters he believes are in differing levels for those with Schizophrenia?

Answer 3

Serotonin, glutamate and GABA which have been shown to have an effect on Schizophrenia symptoms in more recent research

Question 4

What was the problem with drug treatments?

Answer 4

Anti-psychotics didn’t seem to be working for all patients (15%) and the rest were drug resistant and so wanted to see why this was and if drug treatments could be adapted to make this change.

Question 5

Which neurotransmitter did he deem most important?

Answer 5

Glutamate

Question 6

What were the four aims of Carlssons research?

Answer 6

• Is the dopamine hypothesis still accurate?
• Is there any truth in glutamate deficiency?
• To review if anti-psychotics are really working
• To look at the relationship between NT levels and symptoms of schizophrenia

Question 7

What type of study did he conduct?

Answer 7

A literature review consisting of 33 studies (32 published, 1 unpublished) in which he read and summarised journal articles. The articles all looked at neurotransmission.

Question 8

What are some examples of journal articles that he used?

Answer 8

• Lindstroem et al who used PET scans to measure the effects of L-DOPA
• Carlsson and Carlsson that was an animal study into MK-801
• Laruelle et al - acute Schizophrenia and amphetamine

Question 9

What did some of the studies look at?

Answer 9

• Recreational drugs such as angel dust
• Animal research in NT functioning
• Studies with acute Sz and Sz in remission as well as treatment resistant patients
• SPECT and PET scans of patients to determine NT functioning etc

Question 10

How many of the studies were Carlssons own research?

Answer 10

14

Question 11

What did Carlsson find in terms of the Thalmic Filter and the direct pathway?

Answer 11

• The direct pathway is excitatory, therefore abnormal levels of glutamate and dopamine reduce excitation and of the thalamus and causes negative symptoms.

Question 12

What did Carlsson find in terms of the Thalmic filter and the indirect pathway?

Answer 12

The indirect pathway - too much dopamine or too little glutamate which reduces the “protective influence” of the thalamus

Question 13

What did Carlsson find in terms of the Thalmic filter?

Answer 13

Both relate to pathways that relate to filtering sensory information to protect from sensory overload

Question 14

What did he find in terms of dopamine?

Answer 14

• Dopamine is easier to study in the live brain than other NT’s.
• The review lists serotonin, glutamate and GABA and others to NT’s.
• Excess dopamine is likely to be too simplistic.

Question 15

What did he find out about glutamate in terms of PCP?

Answer 15

• PCP leads to psychosis and blocks glutamate receptors (specifically NMDA)
• Glutamate deficiency has a role in psychosis
• Glutamate deficiency leads to cognitive disturbances, loss of flexibility (impacts negative symptoms
  -PCP resulted in psychosis quicker than studies that used amphetamines

Question 16

What else did he find out about glutamate?

Answer 16

• Glutamate failure:
  1. Cerebral cortex: negative symptoms
  2. Basal ganglia: positive symptoms
• Reduced glutamate is associated with increased dopamine release.
• Dopamine neurons are in part controlled by glutamate neurons

Question 17

What did he find about Clozapine?

Answer 17

• Clozapine increases serotonin activity which in turn increases glutamate levels = reduction in symptoms
• Research is shown that Clozapine is highly effective and it has both antidopaminergic and serotonergic impulses.

Question 18

What else did he find out about drug treatment?

Answer 18

• Highly effective for treatment resistant patients because of the relationship between serotonin and glutamate.
• Suggests that those links are treatment resistant may have as that is affected by increased glutamate.
• Reciprocal interaction between serotonin and glutamate occurs in frontal areas of the brain.

Question 19

What did he conclude?

Answer 19

• Schizophrenia may have different types that could be caused by abnormal levels of different NT’s.
• Further research is needed in developing drugs to treat Sz that avoid negative side effects, possibly by considering the role of the other NT’s in development of the disorder.