Lecture 17 - Schizophrenia

Question 1

What do we know about schizophrenia?

Answer 1

-neurodevelopmental disorder
-present in 1% worldwide (doesn’t vary across cultures)
-symptoms appear around 16-21 years old, when PFC is developed
-no cause found; probably environmental factors [stress]
-due to birth complications 0.01%
-no cure but there are treatments (antipsychotics)

Question 2

What are the 3 different types of symptoms?

Answer 2

-positive symptoms
-negative symptoms
-cognitive symptoms

Question 3

What are positive symptoms?

Answer 3

behaviours present in people with schizophrenia that are not present in healthy individuals:
-delusions
-hallucinations [auditory]
-disorganized speech
-disorganized behaviours

Question 4

What are negative symptoms?

Answer 4

behaviours that are absent in people with schizophrenia but present in healthy individuals:
-flattened affect [numb]
-alogia - absence of speech
-avolition - absence of goal-directed behaviour [movement]

Question 5

What are cognitive symptoms?

Answer 5

-slow thinking
-poor concentration
-poor memory
-difficulty understanding concepts

Question 6

Which types of symptoms are the hardest to treat?

Answer 6

-cognitive symptoms
-current antipsychotics cannot treat these

Question 7

What are some of the past/early treatments of schizophrenia?

Answer 7

-sanatoriums: sedation and maintenance but no real treatment
-lobotomies: severed the frontal lobe from the rest of the brain, rendering patients compliant but removing their agency

Question 8

What is the origin of the first antipsychotics?

Answer 8

-in WWII, Henri Laborite noticed a drug that was good at treating “shell shock” [PTSD]
-Hans Lehman tested chlopromazine (thorazine) on nurses at Douglas; he basically brought on the new era of antipsychotics

Question 9

What are the characteristics of the first generation of typical antipsychotics?

Answer 9

-chlorpromazine (Thorazine) and haloperidol (Haldol)
-they are dopamine D2 receptor antagonists
-they were initially called neuroleptics because they induced a state of immobility in lab animals

Question 10

What is the mechanism of action of typical antipsychotics (first gen)?

Answer 10

-block D2 receptors, reducing dopamine transmission
-to be effective, typically require a 70-80% D2 receptor occupancy rate

Question 11

What are the side effects of typical antipsychotics?

Answer 11

-extrapyramidal side effects (a.k.a Parkinsonian side effects)
-include difficulty initiating movement, tremors, and difficulty completing complex movements.
-other side effects can include worsening of negative and cognitive symptoms

Question 12

What is the Dopamine hypothesis of Schizophrenia?

Answer 12

-suggests that schizophrenia is caused by a dysregulation of DA in the brain
-excess dopamine in the VS is thought to cause positive symptoms
-insufficient DA in the PFC may contribute to negative and cognitive symptoms

Question 13

What is Amphetamine sensitization?

Answer 13

-the brain becomes increasingly responsive to the drug with repeated exposure, particularly with intermittent use (e.g., every other day or weekend)
-get more sensitive to the drug instead of building a tolerance

Question 14

Which area of the brain is affected by amphetamine sensitization?

Answer 14

-amphetamine sensitization disrupts the VS, a brain area associated with reward and motivation.
-exaggerated DA release in the VS in response to even a small amount of amphetamine or a stressful stimulus
-effects of amphetamine sensitization on the DA system can be long-lasting, if not permanent

Question 15

What is amphetamine psychosis?

Answer 15

-arises from amphetamine sensitization
-symptoms are identical to the positive symptoms of schizophrenia
-both are treated with antipsychotics

Question 16

What is cross-sensitization?

Answer 16

-history of amphetamine sensitization can make individuals vulnerable to experiencing psychosis triggered by stress, even if they have stopped using amphetamines
-a stressful life event can trigger a psychotic episode in individuals who have previously experienced amphetamine psychosis or have a predisposition to schizophrenia

Question 17

What are the atypical antipsychotics (gen 2)?

Answer 17

-D2 receptor antagonists (lower occupancy rate than typical antipsychotics; 35-45%).
-5-HT2 antagonists: 5-HT2 receptors are 5-HT receptors that inhibit DA release, particularly in the DS

Question 18

What is the mechanism of action for atypical antipsychotics?

Answer 18

-block D2 receptors in the VS, reducing DA transmission and alleviating positive symptoms.
-block 5-HT2 receptors, disinhibiting DA release in the DS and mitigating Parkinsonian side effects

Question 19

What are the side effects of atypical antipsychotics?

Answer 19

-fewer Parkinsonian side effects than typical antipsychotics and may even improve negative symptoms
-but they do not appear to have a significant impact on cognitive symptoms

Question 20

What is the Glutamate Hypothesis of Schizophrenia?

Answer 20

-schizophrenia is caused by a dysfunction in the Glu system, particularly involving NMDA receptors in the PFC
-blocking NMDA receptors with drugs like ketamine or PCP can induce psychosis in people with schizophrenia, supporting this hypothesis

Question 21

Which hypothesis is correct, dopamine or glutamate?

Answer 21

-don’t know
-the dopamine and glutamate hypotheses are not necessarily mutually exclusive and may both contribute to the development of schizophrenia