Schizophrenia

Question 1

Define and describe schizophrenia

Answer 1

Positive symptoms- Delusions, hallucinations, thought disorder

• Negative symptoms- social withdrawal, decreased emotional response, low motivation
• Dementia- cognitive dysfunction

Question 2

Which neurones and receptors are affected in schizophrenia?

Answer 2

• Over activity of subcortical and limbic D2 dopamine receptors
• Post synaptic D2 and D4 receptors
  Hypofunctional dopamine D1 receptors
• Dysfunctional development of frontal cortex- negative and cognitive symptoms
• 5HT and cortical glutamate hypofunction
  DA hyperactivity

Question 3

Is it developmental or degenerative?

Answer 3

Developmental-
brain structure abnormalities present at onset of psychosis and not progressive
- Enlarged ventricles and reduced temporal lobe vol (6-10%)- hippocampus

Question 4

Describe:
Early lesion hypothesis
Late lesion hypothesis

Answer 4

Early lesion- Foetal or perinatal event- virus, hypoxia, premature, low birth weight birth interacting with normal development
- Late lesion- deviation in maturation during adolescence- cannabis?

Question 5

How are dopamine pathways affected?

Answer 5

Mesocortical - reduced

Mesolimbic- ventral tegmental area enhanced

Question 6

Describe amphetamine psychosis

Answer 6

Release of DA in brain
Amphetamine effects antagonised by antipsychotics/neuroleptic drugs
Anti psychotics are D2 receptor antagonists

Question 7

Which is more effective- alpha or beta flupenthixol

Answer 7

a isomer

Question 8

List the extra pyramidal side effects of Chlorpromazine

Answer 8

H1 antagonist- sedation
D2 antagonism in chemoreceptor zone- antiemesis
Tuberoinfundibular pathway- hyperprolactinaemia
Nigrostriatal pathway- extra pyramidal effects

Acute dystonia
Parkinsonism- lack of dopamine in striatum
Akathisia
Tardive dyskinesia- dopamine excess in striatum

Question 9

How do dopamine antagonists affect prolactin?

Answer 9

increase prolactin release

Question 10

Describe 4 types of dopamine receptors

Answer 10

D1- post synaptic (&D5 excitatory, increase cAMP)
D2- pre and post
D3- post synaptic, in nucleus accumbens (decrease cAMP) not in striatum
D4- low expression cortex and limbic system

Question 11

When is Clozapine used?

Answer 11

Pt resistant to benefit from 2 other antipsychotics

5HT serotonin receptor antagonism in frontal cortex
D2 antagonism in mesolimbic pathway
Works for +ve symptoms, less for -ve
combined with CBT

Side effects: lower affinity for D2 receptors- less EP side effects
No hyperprolactinaemia
Muscarinic receptor antagonism
Alpha1 antagonism- miosis, cutaneous flushes, postural hypotension
5HT2 antagonism- increased appetite, weight gain

Question 12

Describe attention deficit hyperactivity disorder (ADHD)

Answer 12

Inattentive, impulsive and hyperactive behaviour- early onset

• Polygenic- small contribution from each gene
• Several genes related to dopamine function
• Structural abnorms in cortical region and basal ganglia
• DA and NA dysfunction- increased striatal DAT (DA transporter)

Question 13

Describe how ADHD is treated

Answer 13

Non pharmological behavioural therapy
- Stimulant drugs- release DA and NA
- Methylphenidate- DA reuptake blocker
- Dexamphetamine- reuptake blocker and causes release
- New drugs non stimulants
Reuptake inhibitor- atomexetine
a2 agonist- guanfacine
- Increase cortical function- improve attention