psychosis Flashcards
What are the 3 biochemical theories of schizophrenia?
- Dopamine Hypothesis
- glutamate hypothesis
- serotonin (5-HT) hypothesis
What change to the dopamine system can cause symptoms of schizophrenia?
hyperactivity
what are the two sources of evidence for the dopamine hypothesis?
- drugs that increase dopamine can cause delusions
2. drugs that block dopamine receptors are effective antipsychotics
Where is the largest population of dopamine neurons found in the brain?
midbrain (ventral segmental area and substantial nigra)
what are the three systems of focus for dopamine neurons?
mesocortical/ mesolimbic system
nigrostriatal system
tuberinfundibular system
Where is the mesocortical system located and where does it project to?
ventral segmental area
projects to striatum and prefrontal cortex
what is the purpose of the mesocortical system?
memory, leaning, thoughts
what effect does blocking dopamine transmission in the mesocortical area have?
reducing positive symptoms of schizophrenia
What are the two types of dopamine receptors and how do they function?
D1 = Gs (adenylate cyclase) D2 = Gi (inhibit adenylate cyclase)
Where does the nigrostriatal system project to & where is it located?
projects to striatum
located in substantia nigra
How does blocking the dopamine neurons in the nigrostriatal system effect the body?
tardive dyskinesias
Where is the tuberoinfundibular system located and what does it do?
located in arcuate nucleus
controls hormone release in the pituitary
how does dopamine blockage in the tuberoinfundibular system affect the body?
hyperprolactinemia (amenorrhea, decreased libido, infertility)
What is the glutamate hypothesis?
deficiencies in glutamate signalling in cortex can cause symptoms of schizophrenia
what is the evidence for the glutamate hypothesis?
NMDA antagonists produce hallucinations
Describe the activity of the following in a schizophrenic individual according to the glutamate hypothesis: NMDA receptors GABA Glutamate sugnallting Dopamine
hypofunctional
hypofunctional
hyperfunctional
hyperfunctional
What is the evidence for the serotonin hypothesis?
- 5-HT agonists that are hallucinogenic (LSD)
2. 5-HT antagonists improves positive stymtoms
Describe the downstream effects of activation of 5HT-2A receptors in the prefrontal cortex?
excitation of glutamate neurons leading to activation of mesolimbic dopamine system
what is the difference between typical and atypical antipsychotics?
typical = D1, D2 atypical = D2, 5HT
What is haloperidol? Describe it’s kinetic activation?
1st generation,
fast on, slow off
What is chlorpromazine? Describe is kinetic activity?
1st generation
fast on, fast off
What is clozapine? Describe its kinetic mechanism?
2nd generation
slow on, fast off
What is the unique side effect about clozapine?
affinity for D4 causing agranulocytosis
