Schizophrenia: neurobiology and treatment

Question 1

Aetiology of schizophrenia

Answer 1

Genetic risk

Partial penetrance (interaction of genes and environment)

Likely to be polygenic

Question 2

Genes

Answer 2

Do not encode hallucinations, delusions or thought disorganisation

Variation in a gene could lead to changes in interactions that cell has with other cells

Question 3

Neuropathology

Answer 3

Ventricular enlargement

Reduced brain volume

Cytoarchitectural differences in cortex and hippocampus

Parcingulate sulcus morphology associated with hallucinations

Question 4

Neurophysiology

Answer 4

Hypofrontality during periods of high cognitive lead

Increases in activity in diPFC seen in healthy volunteers absent in schizophrenics

Auditory cortex activation during hallucinations

High frequency oscillations and synchrony emerge during the transition from adolescence to adulthood

Question 5

Oscillations

Answer 5

Important organisers of brain activity, plasticity and connectivity

Question 6

Neuronal synchrony

Answer 6

Well timed coordination and communication between neural populations

Question 7

Neurophysiology summary

Answer 7

Hypofrontality

Hyper-excitable sensory cortex

Abnormal neural oscillations

Question 8

Psychopharmacology

Answer 8

Dopamine neurones

• cell bodies in the midbrain
• project into the forebrain

Nigrostriatal system

• mesolimbic system
• mesocortical system

Question 9

Dopamine hypothesis- evidence

Answer 9

1. Typical antipsychotic D2 receptor antagonists prevent positive symptoms
2. DA agonists cause positive symptoms of schizophrenia

Question 10

Atypical antipsychotics

Answer 10

Can work in patients resistant to typicals

Do not have same pyramidal side effects

(lower activity at D2 receptors)

Question 11

Clozapine

Answer 11

Activity mainly at D4 receptors and 5HT receptors

Improves positive and negative symptoms

Side effects: weight gain, sedation, hypersalivation, tachycardia, hypotension, neutropenia

Question 12

Atypical antipsychotics

Answer 12

Clozapine

Risperidone

Olanzapine

Increase DA activity in PFC and decrease DA in NAcc

Question 13

Glutamate hypothesis - evidence

Answer 13

1. PCP
   - causes many positive, negative and cognitive symptoms of schizophrenia
   - NMDA receptor antagonist
2. Genetically engineered mice with fewer NMDA receptors

Question 14

Neurocognitive deficits

Answer 14

Enduring symptom of the disease

• typical antipsychotics- no effect on these symptoms
• atypicals- some improvement e.g. increase verbal fluency

Lower IQ

Attentional deficits

Working memory

Planning and information processing deficits