Contemporary Study - Carlsson et al. (2000)

Question 1

What are some of Carlsson’s most credible achievements?

Answer 1

Pioneered the discovery of Dopamine in 1957. He also pioneered the Dopamine Hypothesis in the 60s. Invented the first SSRI antidepressant in late 70s.

Question 2

Why is this study significant?

Answer 2

Shows scientific research procedures of biological approach as the studies cited use PET scans to investigate neurological networks.

Question 3

What is falsibility?

Answer 3

Being open to criticism.

Question 4

Does Carlsson have falsibility?

Answer 4

Yes. He discovered Dopamine, but continues to look for better explanations.

Question 5

What is the Dopamine Hypothesis?

Answer 5

Dopamine is an NT that regulates mood and attention and has been linked to SZ. Carlsson suggests too much Dopamine can cause SZ.

Question 6

What is hyperdopaminergia?

Answer 6

Too much dopamine.

Question 7

What is hypodopaminergia?

Answer 7

Too little dopamine.

Question 8

What is Glutamate?

Answer 8

Chemical that works as NT when it is outside of brain cells. 99.9% is stored inside brain cells, but high quantities of it outside brain cells is toxic and could be the cause of SZ.

Question 9

What does Glutamate control and how?

Answer 9

Human memory and learning by binding to Glutamate receptors like NDMA.

Question 10

What type of study was Carlsson et al. (2009)?

Answer 10

A review study.

Question 11

What were the aims?

Answer 11

To present current view of relationship between SZ and dopaminergic dysfunction. Also to explore rival theory of hypoglutamatergia.

Question 12

What were the IV and DV?

Answer 12

The study did not have IV or DV but did refer to those mentioned in other studies.

Question 13

Did the study have a sample?

Answer 13

No, but other studies are cited that use SZ patient samples.

Question 14

Does the study have a procedure?

Answer 14

No, but refers to studies that use PET scans.

Question 15

How does PET scanning work?

Answer 15

• Radioactive tracer injected into patient.
• Tracer is carried by blood to the brain where it dissolves.
• In the brain, tracer concentrates around active areas of the brain.
• Detects radioactivity, converts it to digital image.

Question 16

What colour are active areas of the brain in PET scans?

Answer 16

Red and yellow.

Question 17

What colour are underactive areas of the brain in PET scans?

Answer 17

Green and blue.

Question 18

How were results set out?

Answer 18

Set out in 7 sections.

Question 19

What is Section 1 of results called?

Answer 19

Introduction to Dopamine Hypothesis.

Question 20

What is Section 2 of results called?

Answer 20

Beyond Dopamine.

Question 21

What is Section 3 of results called?

Answer 21

Glutamatergic Control of Dopamine Release.

Question 22

What is Section 4 of results called?

Answer 22

Glutamate-Dopamine Interaction at Postsynaptic Level.

Question 23

What is Section 5 of results called?

Answer 23

Thalamic Filter.

Question 24

What is Section 6 of results called?

Answer 24

Comparing 2 Experimental SZ Models - Therapeutic Implications.

Question 25

What is Section 7 of results called?

Answer 25

Is Therapeutic Option of Dopaminergic Agents Exhausted?

Question 26

What were the conclusions of Carlsson’s study?

Answer 26

• Suspects a subpopulation of SZ patients. They may be suffering from glutamatergic deficiency.
• Lack of Glutamate might cause exaggerated response to Dopamine at post synapse.
• Researchers could start looking into roles of other NT’s like Neuropeptides.

Question 27

Generalisability of the study?

Answer 27

• Study cites 33 total studies (Carlsson was part of 14), making it representative of the field at the time.
• The study may be time locked if research has moved on. Research has moved on but Carlsson’s ideas continue to be improved.

Question 28

Reliability of the study?

Answer 28

• Cited studies are all lab experiments, using scientific techniques such as PET scans.
• Techniques used in the studies are standardised and replicable, making research reliable.
• Studies like Laruelle et al. are cited, which were unpublished at the time - undermines reliability.

Question 29

Applications of the study?

Answer 29

• Development of new antipsychotics. Could have less side effects based on better understanding of Dopaminergic pathways, as well as other NT’s like Serotonin and Glutamate.
• Papanastasiou et al. (2013): Glutamatergic AP’s developing. Promise relief to those irresponsive to Typical AP’s.
• Jones and Pilowsky (2002): Research into dopaminergic antidepressants continues. Focus on looking for drugs that select particular dopamine receptor sites and pathways.

Question 30

Validity of the study?

Answer 30

• Carlsson questions validity of Dopamine Hypothesis. There is evidence questioning it, such as Atypical AP’s like Clozapine, which work by blocking Serotonin.
• Glutamate is the alternative hypothesis.

Question 31

Ethics of the study?

Answer 31

• Some cited studies are animal studies. Might be ethical issue as mice are injected with drugs to simulate psychotic symptoms.
• Other cited studies use humans. Given drugs to increase psychotic symptoms, but they don’t know if drug is real or placebo. This is an issue for deception and risk of harm.

Question 32

What does Section 1 of the results show?

Answer 32

• There is PET scan evidence for dopamine hypothesis but there are issues:
• SZ patients have more dopamine activity in basal ganglia.
• Laruelle et al. (1999) show that remissive SZ’s had normal Dopamine levels.
• Carlsson says that remissive SZ’s that are on AP’s and show side effects have had their dopamine levels corrected, and it is actually drugs that cause hyperdopaminergia.

Question 33

What does Section 2 of the results show?

Answer 33

• NT’s interact and affect each other.
• There is a focus on glutamate because drugs like PCP and Ketamine create psychotic symptoms without activating dopamine. Instead they stimulate the glutamate receptor NDMA.
• Lodge et al. (1989) confirm that glutamate at NDMA receptors cause psychotic symptoms.

Question 34

What does Section 3 of the results show?

Answer 34

• Glutamate can act as an accelerator or a brake for dopamine levels.
• Miller and Abercrombie (1996): dopamine levels rise when glutamate levels fall when NDMA receptors become blocked.
• There is also evidence suggesting that psychotic symptoms of drugs like PCP can be reduced by other chemicals that work by increasing glutamate, instead of dopamine.

Question 35

What does Section 4 of the results show?

Answer 35

• Low levels of glutamate have been linked to both + and - symptoms.
• Carlsson locates glutamate activity in areas of the brain such as the striatum in the basal ganglia and the cerebral cortex.
• The striatum is the brain’s reward centre so low levels of glutamate there have been linked to - symptoms of SZ.
• Low glutamate activity in the cerebral cortex has been linked to + symptoms of SZ.

Question 36

What does Section 5 of the results show?

Answer 36

• Hypodopaminergia or hypoglutamatergia in direct pathways of the brain will reduce protective influence of the thalamus and excite the cerebral cortex. This produces + symptoms.
  Hypodopaminergia or hypoglutamatergia in indirect pathways of the brain will excite the thalamus and starve the cerebral cortex. This produces - symptoms.

Question 37

What does Section 6 of the results show?

Answer 37

• There are 2 models for SZ: hypodopaminergia or hypoglutamatergia.
• Some SZ’s may be more glutamatergic and others might be more dopaminergic.
• Those that are irresponsive to dopaminergic drugs may be glutamatergic and vice versa.
• Clozapine is an atypical AP that works by blocking serotonin, instead of dopamine, which suggests other NT’s might be at play.

Question 38

What does Section 7 of the results show?

Answer 38

• Carlsson predicts a future in dopaminergic research and continues his search for drugs that will regulate dopamine without producing harmful side effects.
• These drugs would work at the presynapse, where dopamine is produced, instead of at the post synapse. This would mean that SZ could be treated without upsetting the brain’s natural balance and way of processing dopamine.