contemporary study: network interactions in schizophrenia - therapeutic implications (Carlsson et al., 2000) Flashcards
1
Q
what does dopaminergic mean?
A
- related to dopamine
2
Q
what is hyper?
A
- overactive
3
Q
what is hypo?
A
- underactive
4
Q
what is the difference between hyperdopaminergia and hypodopaminergia?
A
- hyper: condition of having too much dopamine activity
- hypo: having too little
5
Q
who was the study carried out by?
A
- carlsson
6
Q
what was the study a review and analysis of?
A
- the Dopamine Hypothesis of schizophrenia
- an analysis of the possible role of a different neurotransmitter, glutamate, as a biological explanation for schizo
7
Q
what is Carlsson credited for?
A
- with ’discovery’ of dopamine in 1957
- 1960s: pioneered the Dopamine Hypothesis as explanation of schizophrenia
- therefore significant he should propose different neurotransmitter as possible explanation
- the same year, Carlsson received nobel prize in medicine
- also invented Zimelidine, first SSRI antidepressant, in late 1970s, way before Prozac
8
Q
how is the study significant?
A
- shows how scientific research proceeds, because although Carlsson developed Dopamine Hypothesis, he still investigates better explanations of schizophrenia. this is falsifiability - theory being open to criticism
- focuses on biological explanations for schizophrenia
- illustrates features of biological approach, since it uses PET scans to investigate neurological networks
9
Q
what is the aim of the study?
A
- isn’t an investigative study - it’s a review summing up research so far and suggesting where it should go next
- aim is to present the current (1999 (no change since) view of relationship between schizophrenia and dopaminergic dysfunction (problems relating to dopamine)
- another aim: explore rival theory, glutamatergic decency or hypoglutamatergia (too little of glutamate)
10
Q
what is the iv?
A
- isn’t an exp so no iv
11
Q
what is the dv?
A
- isn’t a piece of empirical research so no dv
- however, Carlsson et al. describe findings of several earlier studies
12
Q
what did the sample consist of?
A
- aren’t carrying out empirical research so don’t have a sample of their own
- however, they refer to several earlier studies that have samples of patients with schizophrenia
13
Q
what is the procedure of the study?
A
- aren’t carrying out empirical research so no procedure
- however, they refer to few studies that use PET scans
14
Q
results - the dopamine hypothesis revisited
A
- there’s continuing evidence for this hypothesis, eg PET studies show that drug amphetamine (dopamine agonist, increasing levels of neurotransmitter) enhances schizophrenia-like symptoms in people with schizophrenia more than controls
- however, this explanation is insufficient as it doesn’t apply to all people with schizophrenia
15
Q
results - beyond dopamine
A
- it’s unlikely that dopamine is the only neurotransmitter in brain associated with schizophrenia
- interest has focused on glutamate because it was found that PCP (‘angel dust’) induces schizophrenia-like symptoms and is a powerful antagonist of NDMA receptors - type of glutamate receptor
- effect is that glutamate is decreased, and this increases dopamine activity, acting like an ’accelerator’
16
Q
results - glutamatergic control of dopamine release
A
- glutamate molecules also affect release of a third neurotransmitter, GABA, producing opposite effect
- acts like a ’brake’, reducing dopamine activity
- normally there’s a balance between ’accelerator’ and ’brake’ but disruption of either can produce symptoms linked to schizophrenia
17
Q
results - glutamate-dopamine interaction
A
- hypoglutamatergia in cerebral cortex may lead to negative symptoms of schizophrenia
- in contrast, hypoglutamatergia in subcortical basal ganglia (including stratum) could be responsible for positive symptoms but may be linked to negative
- therefore, proposal is that dopamine and glutamate pathways interact and affect stratum
18
Q
results - the thalamic filter
A
- further area of the brain is involved in suggested ’psychotogenic pathway’ ie brain system which governs a psychotic responses
- the thalamus may be switched on or off, depending on which pathway is activated
- normally inhibitory glutamate pathway dominates
19
Q
results - comparing 2 experimental schizophrenia models
A
- research reviewed leads to two different models of schizophrenia
1. hyperdopaminergic model: traditional view of role of dopamine in schizophrenia that increased dopamine produces psychotic symptoms. this is not challenged by second model but extended
2. hypoglutamatergic model: suggests that glutamate can produce an increase or decrease in dopamine activity, depending on whether accelerator or brake is applied
20
Q
results - is the therapeutic potential of dopaminergic agents exhausted?
A
- further understand of machinists that moderate dopamine activity may point to new ways to stabilise dopamine system and avoid some negative effects of current antipsychotic drugs
- eg number of partial dopamine agonists are currently being trialled
21
Q
what are the conclusions of the study?
A
- Carlsson suspects there are probably different groups of schizophrenia patients (subpopulations) whose symptoms have different biological explanations - not always the Dopamine Hypothesis
- researchers should start looking into the role of other neurotransmitters, like GABA, acetylcholine and neuropeptides
22
Q
strengths: generalisability
A
- Carlsson is one of the world’s foremost researchers researchers into dopamine and schizophrenia, so the studies he cites in his review - 33 studies in all, 14 that he took part in - will be a very representative selection of what was going on at the time in his field
23
Q
strengths: reliability
A
- studies that were cited are all lab exps, which use modern PET brain imaging techniques. these techniques are standardised and replicable, making the research reliable. they are scientific and credible pieces of research
24
Q
strengths: application
A
- main application is in development of new antipsychotic drugs - improved dopaminergic drugs that have fewer side-effects based on better understanding of dopamine pathways and new atypical drugs that affect other neurotransmitters like serotonin and glutamate
- glutamatergic antipsychotics are still ”in development” (Papanastasiou et al 2013). these drugs promise to bring relief to people who don’t respond and don’t have the same side-effects (eg weight gain)
25
strengths: validity
- Carlsson argues that **both hypothesis** may be **true**, and research should **continue** in both. over the **last 20 years**, most other research scientists have agreed
26
strengths: ethics
- 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 produce **psychotic symptoms**
27
weaknesses: generalisability
- however, that time was **2000**, nearly **two decades ago**. study may be **”time-locked”** if research has moved on since then and it’s no longer representative of the state of scientific ideas today. research almost certainly has moved on. it makes you wonder why research from 1999 is a “contemporary study”. however, Carlsson’s ideas has been **improved** on rather than refuted
28
weaknesses: reliability
- Carlsson cites one study **(Laruelle et al.)** that was **unpublished** at the time and therefore hadn’t been **peer-reviewed**
29
weaknesses: validity
- Carlsson is questioning validity of **Dopamine Hypothesis** that he himself pioneered back in 1960s. he lists some of the evidence that has called into question, eg **new atypical antipsychotics** eg **clozapine**, which **reduce psychotic symptoms** without influencing dopamine. he considers an alternative, the **Glutamate Hypothesis**
30
weaknesses: ethics
- other studies involve humans **with or without schizophrenia** being given **amphetamines or PCP or other drugs which increase psychotic symptoms**. these ppts are **”drug naive”**, meaning they don’t know whether they’re being given real drug or placebo. there are ethical issues here involving **deception and risk**
