Psychosis

Question 1

Schizophrenia

Answer 1

2+ symptoms for more than 6 months
positive symptoms: hallucinations, delusions
negative symptoms: loss or impairment of psychological function
cognitive symptoms: poor concentration, memory…
causes: gene x environment

Question 2

Biochemical Theories

Answer 2

biochemical brain disease (neurotransmitters)
altered connectivity → impaired processing → dysfunction

Question 3

Dopamine Hypothesis

Answer 3

symptoms are due to hyperactivity of dopamine system
drugs that increase dopamine cause hallucinations and delusions
drugs that block dopamine are anti-psychotics

Question 4

mesocortical limbic system

Answer 4

dopamine neurons in VTA → striatum → prefrontal cortex
memory, learning, thought organization

Question 5

dopamine receptors

Answer 5

D1 - Gs = stimulate AC → cAMP
D2 - Gi = inhibit AC
blocking D2 receptors = clinical antipsychotic potency

Question 6

nigrostriatal system

Answer 6

substantia nigra → striatum = movement initiation
side effects: extrapyramidal symptoms - tardive dyskinesia

Question 7

tuberoinfundibular system

Answer 7

arcuate nucleus = hormone release in pituitary → inhibits prolactin
side effects: hyperprolactemia

Question 8

Glutamate hypothesis

Answer 8

symptoms linked to deficiencies in glutamate signalling in the cortex
NMDA antagonists like PCP and ketamine produce hallucinations and delusions

Question 9

glutamate mechanism

Answer 9

hypofunctional NMDA receptors on GABA interneurons in cerebral cortex = overactivation of downstream glutamate signalling to VTA = increase dopamine release

Question 10

Serotonin Hypothesis

Answer 10

symptoms due to increased serotonin signalling
5-HT agonists like LCD are hallucinogenic

Question 11

serotonin mechanism

Answer 11

activation of 5-HT2a receptors in pre-frontal cortex cause hallucinations → enhance excitation of glutamate neurons → activation of mesolimbic dopamine system
5-HT2a antagonists block glutamate release in cortex = decrease positive symptoms

Question 12

First generation anti psychotics

Answer 12

typical anti psychotics
Haloperidol
Chlorpromazine
targets both D1 and D2 receptors

Question 13

Second generation anti psychoticcs

Answer 13

atypical anti psychotics
Clozapine
Risperidone
antagonists at 5-HT2a and D2 receptors
lower affinity than 1st gen. = less dopamine side effects
cardiovascular, diabetes side effects

Question 14

Anti-Psychotic Drugs

Answer 14

Effect = 60-80% occupation of D2 receptors
Side effects (dopamine) = 80% occupancy
narrow therapeutic window (2nd gen has higher because of lower affinity)

Question 15

Kinetic Hypothesis

Answer 15

Kd = binding between ligand and receptor; determined by K-on and K-off
high affinity = high K-on, low K-off
mesolimbic/nigrostriatal pathway: dopamine is released into synapse - high receptor rebinding
tuberoinfundibular pathway: dopamine secreted into blood stream - low receptor rebinding

Question 16

Haloperidol

Answer 16

fast on, slow off
high receptor binding at D2 in striatum and pituitary
extrapyramidal and hyperprolactinemia side effects

Question 17

Chlorpromazine

Answer 17

fast on, fast off
high receptor binding at striatum but low in pituitary
only extrapyramidal symptoms

Question 18

Clozapine

Answer 18

slow on, fast off
low receptor binding in striatum and pituitary
less side effects but less effective