Neurotransmitters explaining Sz Flashcards
What are the mesolimbic and mesocortical pathways?
Mesolimbic - involves neuronal connections from the VTA (Ventral Tegmental Area) to the NA (Nucleus Accumbens) and limbic system
Mesocortical - involves neuronal connections from the VTA (Ventral Tegmental Area) to the prefrontal cortex
What are the terms you need to know for the neurotransmitter explanation of Sz? (3 points)
Hypo/hyper - decreased/excess
Dopaminergic - dopamine release at synapse
Glutamatergic - glutamate release at synapse
What are the 2 molecules to the neurotransmitter explanation of Sz?
MK-801 - a molecule which is a glutamate NMDA antagonist (non-competitive inhibitor)
M100907 - a molecule which is a selective serotonin receptor 5-HT2A antagonist
What is the dopamine hypothesis for schizophrenia? (3 points)
Proposes an increase in D2 receptors in a Sz patient’s brain
Hyperdopaminergic activity in the neurone synapse of the mesolimbic pathway causes positive symptoms like psychoactive auditory and visual hallucinations
Hypodopaminergic in the neurone synapse of the mesocortical pathway causes avolition and speech poverty
What is the glutamate hypothesis? (3 points)
Proposes that dopamine is not the only neurotransmitter associated with Sz
Excitatory neurotransmitter Glutamate binds to NMDA receptors - normally regulates dopamine release in the brain by lowering levels of it
- Hypoglutamatergic activity in a Sz patient’s brain
- Hyperdopaminergic release at the synapse
- Positive and negative symptoms of Sz
What is the serotonin hypothesis? (5 points)
Hyperserotinergic activity can also lead to the positive and negative symptoms of Sz
- Increased serotonin binding to 5HT2A receptors on Glutamate neurones
- Decreased Glutamate release in the VTA
- Mesolimbic pathway activated - excess of dopamine release in the Ventral Striatum
- Psychotic positive symptoms
What are the supporting and refuting arguments for the neurotransmitter explanation for Sz?
Supported by:
S - Carlsson
C - PET/SPECT + drugs
A - Clozapine
Refuted by:
O - Depatie & Lal (2001) + genetics
D - Reductionist (Luhrmann)
What is the strength of the neurotransmitter explanation of Sz? (3 points)
Supported by empirical studies such as Carlsson et al (2000) meta-analysis which reviewed 32 research studies involving neurotransmitters
Laurelle et al (1996):
Findings highlight that an increase in dopamine release is correlated with positive symptoms of Sz
Hietala et al (1994):
Sz patients’ brains have increased dopamine in their basal ganglia compared to non-Sz controls - found using PET scans
How credible is the neurotransmitter explanation of Sz? (3 points)
Can be considered credible due to the nature of empirical research studies
Many of the studies reviewed by Carlsson’s meta-analysis used PET/SPECT scanning techniques
They provide objective measures of neurotransmission where brain activity can be directly observed
How do drugs support the credibility of the neurotransmitter explanation of Sz? (4 points)
The explanation has also been falsified by the use of synthetic drugs in studies to demonstrate their mode of action
Amphetamines
+ Increase dopamine levels, causing ‘amphetamine psychosis’
+ Similar to Sz positive symptoms
PCP (angel dust) and ketamine
+ Used for hallucinatory effects
+ Glutamate NMDA receptor antagonists, resulting in Sz
Phenothiazine anti-psychotic drugs(PTZ) block dopamine receptors - effective at alleviating positive Sz symptoms ONLY
Are there any other explanations for Sz other than the neurotransmitter explanation? (4 points)
Limited by the ever-changing nature of the explanation, which is constantly being updated
The Dopamine Hypothesis has been revisited numerous times by researchers like Carlsson (2000) - they have suggested new drug targets should be designed using serotonin antagonists
Depatie & Lal (2001)
+ Administered apomorphine to people to increase their production of dopamine
+ Did not create the symptoms of Sz, as would be expected if excess dopamine caused Sz
Credibility undermined by a lack of new drug targets being invented - conflicting empirical evidence
How is genetics an alternate explanation to the neurotransmitter explanation of Sz? (5 points)
Neurotransmission explanation of Sz fails to account for genetic factors
E.g. the C4 gene
+ Associated with excess synaptic pruning during adolescence
+ Leads to lower brain volume and a thinner cerebral cortex observed in Sz
Gottesman & Shields (1966):
Found higher rates of concordance for Sz in monozygotic MZ twins (75%) compared to dizygotic DZ twins (22%)
Heston (1966):
+ Investigated Sz using 58 participants born in 1915-1945
Sz diagnosis for adopted participants
Experimental group: 10.6%
Control group: 0%
A significant genetic predisposition to Sz could be the actual underlying biological cause - alters brain anatomy which in turns
alters brain chemistry
How can the neurotransmitter explanation of Sz being considered reductionist? (4 points)
Biologically reductionist - fails to consider sociocultural factors; perceptions and acceptance of Sz as a clinical disorder vary across the world
Luhrmann et al (2015):
+ Compared 20 people from different cultural backgrounds with serious psychotic disorder including Sz
Perception of hearing voices:
California: ‘intrusive unreal thoughts’
South India: ‘useful guidance’
West Africa: ‘morally good and causally powerful’
Hearing voices was seen as a negative experience in Western society like America but a positive one in more Eastern societies
Ignoring a holistic range of factors and reducing Sz patients down to single brain regions and neurotransmitters leads to patients’ personal beliefs and feelings not being considered
How does Clozapine support the neurotransmitter explanation of Sz? (3 points)
The most abundantly used treatment for Sz is antipsychotic medication - directly impacts neurotransmitters
Clozapine:
+ One of the most effective drugs for treating Sz in humans
+ Has a high affinity for binding to the 5HT2A serotonin receptor
The neurotransmitter explanation is shown to have widely impactful applications for drug development to help Sz patients manage their symptoms
