schizophrenia pathophysiology

Question 1

what is the pathophysiology of schizophrenia

Answer 1

increased ventricle size
loss of grey and white matter (less oligodendrites that make myelin sheaths)
reduced synaptic connections - dendritic pruning
altered activity at
- pre frontal cortex (decision making/emotion)
- amygdala (emotion)
- hippocampus (memory)

Question 2

what are the 2 hypothesis for schizophrenia

Answer 2

dopamine and glutamate hypothesis

Question 3

what is the dopamine hypothesis for schizophrenia

Answer 3

• Over-activity of dopaminergic neurons in mesolimbic pathway
• There is decreased activity in the Mesocortical pathway, which contributes to the negative symptoms of schizophrenia

Question 4

what are the examples supporting the dopamine hypothesis for schizophrenia

Answer 4

cocaine = dopamine release = psychosis
reserpine = depletes dopamine = reduces psychosis
levodopa = s/e hallucinations - +tive symptoms

Question 5

what is the glutamate hypothesis for schizophrenia

Answer 5

• Decreased activity at glutamatergic synapses in the pre-frontal cortex
• Reduced NMDAR signalling in post-synaptic neurons
• Explains all of the symptoms of schizophrenia
• Less signalling here = dopamine overactivity

Question 6

what is the evidence supporting the glutamate hypothesis for schizophrenia

Answer 6

ketamine NMDAR antagonist enhances downstream effect of dopamine

Question 7

how do antipsychotics work

Answer 7

mainly block D2 R in mesolimbic pathway

Question 8

what effects do antipsychotics have on the Tuberhypophyseal pathway

Answer 8

hyperprolactinaemia
breast development
amenorrhea
sexual dysfunction

Question 9

what effects do antipsychotics have on the nigrostriatal pathway

Answer 9

EPSEs
pseudoparkinsonisms
akathisia
dystonia
tardive dyskineasias

Question 10

what effects do antipsychotics have on the mesocortial pathway

Answer 10

blocking an already deficient pathway

Question 11

what effects do antipsychotics have on the mesolimbic pathway

Answer 11

reduces reward pathway

Question 12

how do second generation antipsychotics work

Answer 12

• D2 antagonists and 5HTA antagonists
  o Increase dopamine in striatum
  o Increase glutamate release in cortical pyramidal cells
• Rapidly dissociates from D2 – no EPSEs
• Muscarinic action
  o Nigrostriatal pathway has a balance between Ach and DA (when one is disrupted, the other can increase)

Question 13

what are the S/E of 2nd gen antipsychotics

Answer 13

A1 antagonism - postural hypotension
H1 antagonism - sedation
neuroleptic malignant syndrome
metabolic syndrome
- weight gain
- insulin resistant
- hyperlipidaemia
QT prolongation
neutropenia