Dopamine hypothesis

Question 1

The initial dopamine hypothesis was quite a basic concept. What was this?

Answer 1

Individuals with schizophrenia had too much dopamine.
Therefore they demonstrated symptoms related to these high levels of dopamine.

Question 2

The initial hypothesis was supported by research including research by Griffith et al. What did they do? What did they find?

Answer 2

Induced psychosis in non-schizophrenic volunteers with the administration of dextro-amphetamine.
Found that volunteers demonstrated a generally abrupt onset of paranoid delusions and demonstrated a cold and detached emotional response.

Question 3

What does dexto-amphetamine do?

Answer 3

Increases the amount of dopamine in the brain.

Question 4

What was wrong with the initial dopamine hypothesis? How was this confirmed?

Answer 4

It was too simple.
This was confirmed by the fact administering drugs that reduce the levels of dopamine had little or no effect on those individuals who suffered mainly with the negative symptoms of schizophrenia.

Question 5

Several subtypes of dopamine receptor sites were discovered. What are they? Where are they distributed?

Answer 5

D1-D5.
Widely distributed in the cerebral cortex and also subcortically in the limbic system.
Subcortically = underneath the cortex.

Question 6

Which dopamine receptor site was of particular interest with researchers?

Answer 6

D2 receptors.

Question 7

The limbic system became the main focus on the dopamine hypothesis. Why was this?

Answer 7

D2 receptors are found primarily in subcortical regions.

Question 8

What does the limbic system consist of?

Answer 8

A variety of subcortical structures that are engaged in many functions, but most notably emotions, memory formation and arousal.

Question 9

Nerve pathways leave from the limbic system. Where do they go?

Answer 9

Other subcortical structures.
The cerebral cortex.

Question 10

What are the two main pathways associated with schizophrenia?

Answer 10

Mesolimbic pathway.
Mesocortical pathway.

Question 11

Dopamine is a major neurotransmitter in the mesolimbic pathway. Where does this pathway carry signals from and to?

Answer 11

From the ventral tegmental area (VTA).
To the nucleus accumbens.

Question 12

What could too much dopamine in the mesolimbic pathway cause?

Answer 12

Too much dopamine, either from neurons that fire too often too quickly, cause overstimulation.
This ultimately causes positive symptoms of schizophrenia.

Question 13

How do antipsychotic drugs link to the mesolimbic pathway?

Answer 13

Antipsychotics reduce dopaminergic neurotransmission and as such reduce dopamine activity in this pathway and ultimately reduce the positive symptoms.

Question 14

Dopamine is a major neurotransmitter in the mesocortical pathway. Where does this pathway carry signals from and to?

Answer 14

From the ventral tegmental area (VTA).
To the frontal lobe.

Question 15

What is the mesocortical pathway vital for?

Answer 15

Emotional responses.
Motivation.
Cognition.

Question 16

What did Davis et al note in relation to D1 receptors and the frontal lobe?

Answer 16

Too little dopamine is evident in D1 receptors of the frontal lobe of many individuals with the cognitive impairments and negative symptoms of schizophrenia.

Question 17

If dopamine imbalances are responsible for schizophrenia, what causes the dopamine imbalances?

Answer 17

Many researchers believe that it may be a genetic predisposition.

Question 18

What types of studies indicate there is a genetic basis for schizophrenia?

Answer 18

Twin studies.
Family studies.

Question 19

What did Gottesman study? What did they find?

Answer 19

Incidence of schizophrenia in cousins, grandchildren, half-siblings, parents, siblings, non-identical and identical twins.
As genetic similarity increased so did the probability of both individuals having schizophrenia.

Question 20

Who were the Schizophrenia Working Group of the Psychiatric Genomics Consortium? What did they report?

Answer 20

A group of over 300 scientists from 35 countries.
Reported that there were 108 genetic loci associated with schizophrenia.

Question 21

What did the findings from the Schizophrenia Working Group of the Psychiatric Genomics Consortium show?

Answer 21

Although there may indeed be a genetic basis for schizophrenia, it’s a complex manner - more than just a few abnormal dopamine genes.

Question 22

What is most of the research that supports the dopamine hypothesis based on?

Answer 22

Metabolite research.

Question 23

What do we have measure in order to assess neurotransmitter levels?

Answer 23

Metabolite levels (what neurotransmitters get broken down into) in cerebrospinal fluid.

Question 24

Dopamine becomes metabolised into HVA. What is this measured in? Where can this be obtained from?

Answer 24

Cerebrospinal fluid.
Can only be obtained from a lumbar puncture.

Question 25

What may affect metabolite levels?

Answer 25

Diet. Drug use.

Question 26

Even when research into metabolite levels is conducted under controlled conditions, what may an issue be?

Answer 26

The results can be difficult to interpret with HVA levels varying widely between participants.

Question 27

Considering the issues with researching metabolite levels. What could we suggest?

Answer 27

Until we have refined procedures for measuring neurotransmitters, we should be cautious in the conclusions we draw from metabolite-based research.

Question 28

Dopamine is not the only neurotransmitter implicated in schizophrenia. What is another neurotransmitter that has also been identified as a potential influence?

Answer 28

Serotonin.

Question 29

How do conventional antipsychotics work? What is an issue with them?

Answer 29

Primarily blockading the D2 receptor sites. Not all of those with schizophrenia benefits from these drugs.

Question 30

How do atypical antipsychotics work?

Answer 30

Blocks the D2 receptor. Blocks the serotonin receptor 5-HT2A.

Question 31

What do atypical antipsychotics suggest?

Answer 31

Suggests the dopamine hypothesis cannot explain schizophrenia on its own. Therefore, it could be considered as a partial explanation.

Question 32

The dopamine hypothesis proposes that dopamine imbalances cause schizophrenia. What else could be proposed?

Answer 32

Schizophrenia causes the dopamine imbalances.

Question 33

What has research using PET scans not yet detected? What does this indicate?

Answer 33

Differences in the dopamine activity of the brains of individuals with schizophrenia and those without. Indicates that it may be some time before we know if dopamine imbalances cause schizophrenia or if schizophrenia causes dopamine imbalances.