Schizophrenia (Theme D)

Question 1

What are the +ve symptoms of Schizophrenia?

(Gain of function symptoms)

Answer 1

Delusions
Hallucinations
Disorganised thinking / speech
Disorganised behaviour
Lack of insight (individuals unaware that delusions aren’t real)

Question 2

What are the -ve symptoms of schizophrenia?

(Loss of function symptoms)

Answer 2

Blunted (flat) affects
Alogia
Avolition
Anhedonia

Question 3

What are the symptoms of psychosis?

Answer 3

Very similar / identical to the +ve symptoms of schizophrenia

Characterised by abnormal thoughts, perceptions, language & behaviour

Question 4

What are the causes of psychosis?

Answer 4

Schizophrenia (more likely to have persecutory delusions)
BPD (more likely to have grandiose delusions during mania episodes)
Severe stress / anxiety / depression
Postnatal psychosis (1:1000)
Lack of sleep
Encephalitis
Substance misuse (particularly cannabis)
Can occur in several medical conditions (e.g., AD, PD, malaria, hypoglycaemia, MS, brain tumour)

Question 5

Diagnosis of schizophrenia is based on what 3 things?

Answer 5

1. Observed behaviour
2. Reported behaviour / experiences
3. Operational criteria (i.e., the DSM-5)

Question 6

What are the changes in brain structure in SCZ

Answer 6

Ventricular enlargement (lateral + 3rd)
Reduced brain size & weight (-3%)
Decreased grey matter & cortical volume (-4/6%) - not from neurodegeneration

Question 7

What is the evidence for reduced glutamatergic synapses in SCZ?

Answer 7

Recent study:
Synaptic density marker SV2A reduced in SCZ patients and unaffected by antipsychotics in rats

Question 8

What area of the brain is reduced in volume in SCZ?

Answer 8

Medial temporal lobe
(Hippocampal formation, subiculum, parrahippocampal gyrus)

Question 9

Treatment for SCZ: Antipsychotics

Answer 9

Mechanism of actions: Block D2 DA receptors in striatum

Dose-dependent relationship: more = better
But side effects can lead to movement disorder similar to PD due to impact on nigrostriatal DA system - tremor, rigidity, dystonia, tardive dyskinesia

Question 10

Evidence for the “Dopamine Hypothesis” in SCA

Answer 10

1st gen antipsychotics block D2 DA receptors in striatum, potency of drug correlates with affinity for D2 receptors

Amphetamine (binds & bocks DA re-uptake transporter, increasing extracellular DA) - can mimic SCZ symptoms + antipsychotic drugs alleviate some symptoms of amphetamine psychosis

Excess DA release in SCZ patients
Increased DA receptor binding, esp. D2 receptors in brain scans of SCZ patients

Question 11

Evidence for the “Glutamate Hypothesis” in SCZ

Answer 11

NMDA receptor antagonists (PCP, Ketamine) can cause SCZ-like psychotic & cognitive abnormalities

NMDA receptor agonists (e.g., D-serine, glycine, sarcosine) improve symptoms and have therapeutic benefits

Reduced NMDA receptor expression in mouse model displays SCZ-like symptoms

Question 12

Is disrupted inhibition in SCZ linked to NMDA receptor hypofunction?

Answer 12

Reduced NMDA receptor expression in mouse model displays SCZ-like symptoms

Question 13

Environmental risk factors for SCZ

Answer 13

Urban populations > rural populations
Migrant populations more at risk
Obstetric complications - premature birth, low birth weight, pre-eclampsia, resuscitation at birth, prenatal nutritional deficiency
Seasonal influence
Drug use - persistant use of THC, amphetamine, cocaine