contemporary (Carlsson)

Question 1

aims

Answer 1

-Review evidence for and against the dopamine hypothesis. consider other neurotransmitters (e.g glutamate, serotonin). Explore new antipsychotics (help with treatment resistance).

Question 2

dopamine hypothesis revisited

Answer 2

evidence still supports this hypothesis, e.g studies using PET scans show amphetamine (dopamine agonist) enhances psychotic symptoms. But this doesn’t apply to all people with schizophrenia.

Question 3

Beyond dopamine

Answer 3

Glutamate- PCP induces schizophrenia-like symptoms, antagonist of NDMA (glutamate) receptors.
Leads to increased dopamine activity (acts as accelerator).

Question 4

Glutamatergic control of dopamine release.

Answer 4

Glutamate also affects release of GABA, with opposite effect (a ‘brake’, reducing dopamine activity).
Therefore, low glutamate (hypoglutamatergia) may cause an increase or decrease in dopamine.
Normally there is a balance between ‘accelerator’ and ‘brake’ but disruption of either can produce schizophrenia symptoms.

Question 5

Glutamate- dopamine interaction.

Answer 5

Hypoglutamatergia in cerebral cortex - negative symptoms.
in basal ganglia - positive symptoms.
Dopamine + glutamate pathways interact and affect striatum

Question 6

Thalamic filter

Answer 6

in suggested psychotogenic pathway the thalamus may be ‘turned’ on or off depending on which pathway is activated.
Normally the inhibitory glutamate pathway dominates.

Question 7

comparing two experimental schizophrenia models

what two models are compared?
What does haloperidol tackle?
what differs for people with different symptoms ?

Answer 7

1. hyperdopaminergic model- traditional view of dopamine (increase produces psychotic symptoms) is not challenged by the second model, merely extended.
2. Hypoglutamatergic model- Glutamate can produce an increase or decrease in dopamine activity, depending on whether the accelerator or the brake is applied.
   Haloperidol tackles hyperdopaminergia (affecting GABA via serotonin).
   people with different symptoms could be treated with different drugs. Or use combined drugs to tackle both problems.

Question 8

what’s the hyperdopaminergic model?

Answer 8

traditional view of dopamine (increase produces psychotic symptoms) is not challenged by the second model, merely extended.

Question 9

what’s the hypoglutamatergic model?

Answer 9

Glutamate can produce an increase or decrease in dopamine activity, depending on whether the accelerator or the brake is applied.

Question 10

is the therapeutic potential exhausted?

Answer 10

understanding mechanisms that moderate dopamine activity may show new ways to stabilise dopamine system.
May avoid some negative effects of current antipsychotics.

Question 11

Concluding remarks

what could more attention be focused on?
what does this suggest?
What would this have serious implications for?
What might cause patients to have an exaggerated response?

Answer 11

The study concludes that more attention could be focused on other neurotransmitters (e.g acetylcholine) and other pathways on the brain.
suggests that schizophrenia may have different types that could be caused by abnormal levels of different neurotransmitters and not just dopamine. This would have serious implications for the future treatment developments for schizophrenia. lack of glutamate might cause patients to have an exaggerated response to dopamine at the post-synapse. in other words, even though only normal levels of dopamine are being produced, the dopamine receptors have an extreme reaction.

Question 12

method

what does the study review research from?
What’s well-documented?

Answer 12

literature review of research and current theory, therefore Carlsson uses secondary data. The study reviews research from a variety of sources investigating neurochemical levels in patients diagnosed with schizophrenia, as well as studies into drugs known to induce symptoms of psychosis. it is well documented that high levels of dopamine are related to psychosis and the researchers consider evidence from brain scans for this.

Question 13

strengths

what did Carlsson and Carlson 1989 give mice?
what’s MK-801?
what did MK-801 do?
what does this suggest that schizophrenia may be caused by?

Answer 13

support from research on glutamate antagonists.
Carlsson and Carlsson (1989) gave mice a drug to reduce motor activity followed by MK-801 (reduces glutamate and increases serotonin and dopamine in the nucleus accumbends).
MK-801 restarted motor activity but continued use resulted in highly abnormal, psychotic-like behaviour.
This suggests that schizophrenia may be caused by glutamate irregularity and also implies that glutamate agonists may be effective treatments.

Question 14

who gave mice a drug to reduce motor activity followed by MK-801 (reduces glutamate and increases serotonin and dopamine in the nucleus accumbends).

Answer 14

Carlsson and Carlsson 1989

Question 15

counter argument

what did Crippa et al 2015 do?
what was also suggested that neurotransmitter imbalances may arise from and who suggested this?

Answer 15

However, this is not the full story. since the study, two further neurotransmitters (anandamide and nitric oxide) have been identified as important in psychosis and may lead to new treatments (crippa et al 2015). It has also been suggested that neurotransmitter imbalances may arise from autoimmune problems (severance et al 2018) - this means even glutamate is not the end of the story.

Question 16

who suggested that two further neurotransmitters (anandamide and nitric oxide) have been identified as important in psychosis and may lead to new treatments.

Answer 16

Crippa et al 2015

Question 17

weaknesses
what did the research ignore?
what did Luhmann 2015 show?
what’s a problem with animal studies?
What does the evidence overlook?
who might respond differently?

Answer 17

research ignored the role of culture.
Luhmann 2015 showed that US participants were more likely to hear violent and frightening voices whereas Ghanaian and Indian people had more positive experiences.
it may be that the viewer ignored cultural factors because the conclusions of the research studies in the review are based on animal models.
Thus animal models may fail to capture the holistic lived experience of schizophrenia, which includes other peoples reactions to the symptoms (truer reflection).

The evidence overlooks the wider experience.
Some evidence for the dopamine hypothesis was based on people with schizophrenia during acute episodes.
But people with chronic schizophrenia may respond differently to drugs when they’re are in between episodes. (e.g more side effects).
Therefore, research should consider all the phases of the disorder so better conclusions can be made about efficacy and adherence.

Question 18

who showed that US participants were more likely to hear violent and frightening voices whereas Ghanaian and Indian people had more positive experiences.

Answer 18

Luhmann 2015

Question 19

Application
what two things are effective in reducing both positive and negative symptoms?
what advances have led to helping people who are treatment resistant or who have experienced side effects?

Answer 19

Research has led to development of new drug treatments.
Serotonin antagonists and glutamate agonists are effective in reducing both positive and negative symptoms.
By tackling more precisely the disturbances of neurotransmitter systems, their action is less likely to have detrimental effects.
These advances have helped people who are treatment-resistant or who experienced side effects.

Question 20

generalisability

Answer 20

-Study uses research from 20 years ago where data would be ‘time-locked’ to that era’s societal behaviour of schizophrenia
Therefore it would not represent people with schizophrenia and their symptoms today

Question 21

reliability

lab experiments
data from many studies
what study did Carlsson cite that was unpublished at the time?

Answer 21

High
The studies Carlsson et al. cite are all lab experiments, many of them on animals, which use modern PET or SPECT brain imaging techniques. These techniques are standardised and replicable, making the research reliable.

High
Secondary data of many different studies allows for high quantity of findings. Therefore there is more to compare for consistency

low
Carlsson cites one study (Laruelle et al.) that was unpublished at the time and therefore hadn’t been peer-reviewed.

Question 22

validity

looked at wide spectrum of different types of schizophrenia.

what’s a problem with the secondary data that involved animal studies?

Answer 22

High
Looked at the wide spectrum of different types of schizophrenia and whether or not it was in remission
Therefore findings have more credibility due to the volume, more accurate conclusions.

Low
Secondary data of studies that involve animal research
Wouldn’t know about subjectivity or researcher bias in whether the animals were actually displaying symptoms of schizophrenia which decreases credibility

Question 23

ethics

ethical issues with many of the studies that Carlsson et al. cites including animals?

what’s a problem with some studies involving humans with or without schizophrenia being given drugs to increase symptoms?

Answer 23

This is a review study so there are no ethical issues directly connected to it.

Many of the studies Carlsson et al. cite are animal studies involving lab mice. These might involve ethical issues, since the mice are being injected with drugs to bring on psychotic symptoms.

Other studies involve humans with or without schizophrenia being given amphetamines or PCP or other drugs that increase psychotic symptoms. These participants are “drug naive”, meaning they don’t know whether they are being given a real drug or a placebo. There are ethical issues here involving deception and risk.