Week 2 - Schizophrenia

Question 1

What are the positive symptoms of shizophrenia?

Answer 1

Delusions, hallucinations, thought disorders (episodic)

Question 2

What are the negative symptoms of schizophrenia?

Answer 2

Chronic disturbances in motivation, experiences of pleasure, social interactions, spontaneous speech, mood expression, intellectual, memory, executive function, attention

Question 3

What does sensorimotor gating mean?

Answer 3

Unable to respond appropriately to environmental stimuli

Question 4

What does theory of mind mean?

Answer 4

Inability to gauge the mental state of others - inappropriate social interaction, no empathy, enourages belief

Question 5

What part of the brain has too much dopamine in schizophrenia?

Answer 5

Basal Ganglia (BA)
Nucleus Accumbens (NA)

Question 6

What are the main neurotransmitters in schizophrenia?

Answer 6

Dopamine
Serotonin
Glutamate
Gaba

Question 7

What is the dopamine hypothesis for schizophrenia?

Answer 7

Increased Dopamine in NA and decreased Dopamine in pre-frontal cortex

Question 8

What is the PFC/Dopamine Hypothesis

Answer 8

Hypofrontality
Decreased dopamine leads to negative and cognitive symptoms
Mesocorticolimbic dopamine system

Question 9

What is the NA/Dopamine Hypothesis?

Answer 9

Increased dopamine leads to positive symptoms (psychoses and euphoria)

Question 10

What dopamine system is in the PFC?

Answer 10

Mesocortical dopamine - decreased
negative cognitive symptoms

Question 11

What dopamine system in the NA?

Answer 11

Mesolimbic dopamine - increased
positive symptoms

Question 12

What receptors are in the Mesolimbic dopamine system/NA?

Answer 12

Increased d2 receptors

Generally considered that enhances dopamine neurotransmission at D2 receptors produces positive symptoms of schizophrenia

Question 13

How did the first generation of anti-psychotics/neuroleptics work?

Answer 13

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

Question 14

What are the limitations of the first generation of anti-psychotics/neuroleptics?

Answer 14

Antagonise both D2 and D1 receptors
D1 receptos are for movement
No effect on negative cognitive symptoms
30% ineffective - 20% re-lapse rate

Question 15

What are D1 receptors important for?

Answer 15

Normal movement

Question 16

What is the nigrostriatal dopamine system?

Answer 16

Important for movement
Decreased dopamine in nigro area produces parkinsons symptoms

Question 17

What is pyramidal movement?

Answer 17

Primary motor cortex
Spinal cord and Muscle
VOLUNTARY MOVEMENT

Question 18

What is extrapyramidal movement?

Answer 18

SUBCONSCIOUS movement - walking, breathing etc
Nigrostriatal dopamine

Question 19

What serotonin receptor is involved in Schizophrenia?

Answer 19

5hT2A

Too many receptors in PFC can decrease dopamine - negative and cognitive effects

Question 20

What does serotonin do in schizophrenia?

Answer 20

Modulates the mesocorticlimbic dopamine system which encourages dopamine defecit in prefrontal cortex

Question 21

What does hyperactivity of 5HT2A receptors do?

Answer 21

Too much release on glutamate neuroins in the PFC stimulates activity which will drive them to Ventral Striatum (NA - positive symptoms)

Question 22

How do 2nd generation anti-psychotics work?

Answer 22

D2 Receptor antagonists (NA - positive symptoms)
5HT2A receptor antagonists (PFC - negative/cognitive symptoms)

Question 23

What does 5hT2A antagonism help with?

Answer 23

Negative/cognitive symtpoms of schizophrenia

Question 24

What is glutamate

Answer 24

An excitatory amino acid

Question 25

What are the main glutamate receptors

Answer 25

NMDA - unique - need to bind with glycine and glutamate - in the brain glycine facilitates activation of NMDA receptors AMPA Kainate

Question 26

What do NMDA glutamate receptors do?

Answer 26

Create EPSP Allows positive charge to go through channels

Question 27

What is PCP

Answer 27

An antagonist at NMDA receptors - can induce psychosis in humans with one dose Stops positive ions from entering the cell

Question 28

What does glutamate do in schizophrenia?

Answer 28

NMDA receptos are hyperactive in PFC which leads to less GABA activation of outgoing glutamate neurons, driving dopamine to be release in NA / VA

Question 29

What do novel antipsychotics do?

Answer 29

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

Question 30

What is the GABA - A theory?

Answer 30

Activation of gaba a receptors reduces dopamine cell firing - gaba cell function is reduced in PFC

Question 30

What do antipsychotic treatments aim to do?

Answer 30

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)