Week 2 - Schizophrenia Flashcards
What are the positive symptoms of shizophrenia?
Delusions, hallucinations, thought disorders (episodic)
What are the negative symptoms of schizophrenia?
Chronic disturbances in motivation, experiences of pleasure, social interactions, spontaneous speech, mood expression, intellectual, memory, executive function, attention
What does sensorimotor gating mean?
Unable to respond appropriately to environmental stimuli
What does theory of mind mean?
Inability to gauge the mental state of others - inappropriate social interaction, no empathy, enourages belief
What part of the brain has too much dopamine in schizophrenia?
Basal Ganglia (BA)
Nucleus Accumbens (NA)
What are the main neurotransmitters in schizophrenia?
Dopamine
Serotonin
Glutamate
Gaba
What is the dopamine hypothesis for schizophrenia?
Increased Dopamine in NA and decreased Dopamine in pre-frontal cortex
What is the PFC/Dopamine Hypothesis
Hypofrontality
Decreased dopamine leads to negative and cognitive symptoms
Mesocorticolimbic dopamine system
What is the NA/Dopamine Hypothesis?
Increased dopamine leads to positive symptoms (psychoses and euphoria)
What dopamine system is in the PFC?
Mesocortical dopamine - decreased
negative cognitive symptoms
What dopamine system in the NA?
Mesolimbic dopamine - increased
positive symptoms
What receptors are in the Mesolimbic dopamine system/NA?
Increased d2 receptors
Generally considered that enhances dopamine neurotransmission at D2 receptors produces positive symptoms of schizophrenia
How did the first generation of anti-psychotics/neuroleptics work?
Antagonise D2 and D1 receptors - block/stop effect of dopamine in NA
High affinity due to the ability for drugs to bind to D2 receptors - reduce positive symptoms
What are the limitations of the first generation of anti-psychotics/neuroleptics?
Antagonise both D2 and D1 receptors
D1 receptos are for movement
No effect on negative cognitive symptoms
30% ineffective - 20% re-lapse rate
What are D1 receptors important for?
Normal movement
What is the nigrostriatal dopamine system?
Important for movement
Decreased dopamine in nigro area produces parkinsons symptoms
What is pyramidal movement?
Primary motor cortex
Spinal cord and Muscle
VOLUNTARY MOVEMENT
What is extrapyramidal movement?
SUBCONSCIOUS movement - walking, breathing etc
Nigrostriatal dopamine
What serotonin receptor is involved in Schizophrenia?
5hT2A
Too many receptors in PFC can decrease dopamine - negative and cognitive effects
What does serotonin do in schizophrenia?
Modulates the mesocorticlimbic dopamine system which encourages dopamine defecit in prefrontal cortex
What does hyperactivity of 5HT2A receptors do?
Too much release on glutamate neuroins in the PFC stimulates activity which will drive them to Ventral Striatum (NA - positive symptoms)
How do 2nd generation anti-psychotics work?
D2 Receptor antagonists (NA - positive symptoms)
5HT2A receptor antagonists (PFC - negative/cognitive symptoms)
What does 5hT2A antagonism help with?
Negative/cognitive symtpoms of schizophrenia
What is glutamate
An excitatory amino acid
What are the main glutamate receptors
NMDA - unique - need to bind with glycine and glutamate - in the brain glycine facilitates activation of NMDA receptors
AMPA
Kainate
What do NMDA glutamate receptors do?
Create EPSP
Allows positive charge to go through channels
What is PCP
An antagonist at NMDA receptors - can induce psychosis in humans with one dose
Stops positive ions from entering the cell
What does glutamate do in schizophrenia?
NMDA receptos are hyperactive in PFC which leads to less GABA activation of outgoing glutamate neurons, driving dopamine to be release in NA / VA
What do novel antipsychotics do?
NMDA receptor modulators
Glycine - acts on glycine site to enhance NMDA receptor function - improves negative symptoms
D-Serine - full agonist on glycine site - improves negative symptoms, psychosis and cognition
What is the GABA - A theory?
Activation of gaba a receptors reduces dopamine cell firing - gaba cell function is reduced in PFC
What do antipsychotic treatments aim to do?
Reduce dopamine effect at D2 receptors
Reduce serotonin effect at 5Ht2 receptors
Increase glutamate neurotransmission (NMDA and AMPA receptors)
Stabilise dopamine neurons (Gabga a agonists)
