Schizophrenia

Question 1

Schizophrenia

Answer 1

A disorder of the mind, affecting thoughts, feelings & behaviours

May also result in cognitive defects such as premature dementia and depression which are resistant to treatment

Question 2

Positive symptoms of schizophrenia

Answer 2

Positive symptoms = delusions, hallucinations, disorganised behaviours, catatonia

Associated with an increased level of dopamine

Question 3

Negative symptoms to schizophrenia

Answer 3

Negative symptoms = withdrawal, emotional flattening, anhedonia

Associated with a decreased level of dopamine

Question 4

Dopamine

Answer 4

Schizophrenia is associated with dopamine

Mesolimbic area = induces positive symptoms (via D1 receptors)

Pre-frontal cortex = induces negative symptoms (via D2 receptors

Amphetamines increase dopamine release and can induce schizophrenic episodes in mice

Question 5

Glutamate

Answer 5

Glutamate is also seen in schizophrenia

A reduced expression of the VGluT transporter is seen

Question 6

Glutamate - negative symptoms

Answer 6

VGluT transporter = aids glutamate packaging into vesicles

A reduction in the VGluT transporter reduces glutamate release, causing negative symptoms

This is because adjacent dopaminergic neurons receive less glutamate stimulation, causing a reduction in dopamine release

Question 7

Glutamate - positive symptoms

Answer 7

In schizophrenia, glutamate release is reduced due to a reduction in VGluT expression

If the pathway involving glutamate involves a GABA interneuron, this can increased dopamine release

This is because the GABA neuron receives less stimulus and so does not release as much GABA, meaning that dopamine release is not inhibited

Question 8

Sensory filtering

Answer 8

Individuals suffering from schizophrenia can have difficulty identifying and concentrating on important stimuli

The interaction between GABA and glutamate is thought to be responsible for this

Question 9

Normal sensory filtering pathway

Answer 9

1. Sensory input is received at the thalamus and glutamate is released and the action potential is communicated to the pre-frontal cortex
2. Glutamate is release in the pre-frontal cortex, stimulating a second glutaminergic neuron, lining linking to the nucleus accumbens
3. The NcA links to the VTA and modulates stimuli from this area
4. Glutamate is released at the NcA and stimulates a GABAergic neuron which links back to the thalamus
5. GABA is released into the thalamus, hence inhibiting the reception of sensory information in a negative feedback

Question 10

Pathological sensory filtering

Answer 10

In schizophrenia, dopamine release is increased

Dopamine is released from the VTA into the NcA and binds to D2 receptors

Binding to D2 receptors inhibits the GABAergic neuron and hence the negative feedback system breaks down, leading to sensory overload

Question 11

Neurodegeneration

Answer 11

Schizophrenia may eventually lead to dementia

This is thought to be due to the cytotoxic effects of glutamate