114/115b - Schizophrenias and Psychotic Disorders

Question 1

What is the general mechanism of action of every antipsychotic medication?

Answer 1

Inhibit dopamine signaling

(Dopamine signaling is implicated in both positive and negative symptoms of schizphrenia)

Question 2

What is a delusion?

Answer 2

Firmly held, fixed, false belief

Can be bizzare or non-bizzare

(Bizzare violates the laws of physics; non-bizzare is physically possible)

Question 3

Dopamine dysregulation in the mesocortical dopamine tract results in [positive/negative] symptoms

Dopamine dysregulation in the mesolimbic dopamine tract results in [positive/negative] symptoms

Answer 3

Dopamine dysregulation in the mesocortical dopamine tract results in negative symptoms

Dopamine dysregulation in the mesolimbic dopamine tract results in positive symptoms

Question 4

What is the most common psychotic disorder?

Answer 4

Schizophrenia

Question 5

What changes can be seen in the brain of a person with schizophrenia?

Answer 5

• Enlarged ventricles

No neurodegeneration!!

Schizophrenia is caused by abnormal neuronal migration during development, not neurodegeneration

Affects both white and grey matter

Question 6

What are the diagnostic criteria for schizophrenia?

Answer 6

2+ of the following for >6 months, resulting in marked impairment in role function

• Delusions
• Hallucinations
• Disorganized speech
• Grossly disorganized or catatonic behavior
• Negative symptoms (deficits in traits that should be there — > anhedonia, flat affect)

Question 7

What is the difference between a positive symptoms and a negative symptom of schizophrenia?

List some examples of each

Answer 7

• Positive sypmtom = new things overlaid on normal psyche that shouldn’t be there
  
  • Delusions
  • Hallucinations
  • Disorganized speech
  • Disorganized or catatonic behavior
• Negative symptom = absence of normal behaviors
  
  • Apathy
  • Affective flattening
  • Alogia
  • Avolition
  • Anhedonia

Question 8

Which neurotransmitter is implicated in patients with schizophrenia and psychosis?

Answer 8

Dopamine

• Dysregulation in the mesolimbic dopamine tract -> positive symptoms
• Dysregulation in the mesocortical dopamine tract -> negative and cognitive symptoms

Serotonin, NMDA are likely also involved

Question 9

Describe the pathophysiology of schizophrenia

Answer 9

Impaired neuronal migration during development

• This results in the symptoms of schizophrenia, around age 18-25

NOT neurodegenerative

Question 10

What are the risk factors for schizophrenia?

Answer 10

• Genetic factors contribute the most risk
• Environmental factors: Mother experiences during early neurogenesis or in the prenatal period
  
  • Fetal hypoxia, birth trauma
  • Maternal infection
  • Winter birth months
  • Low SES
  • Extreme stress

Question 11

Definition of psychosis:

Answer 11

• disturbance in the perception and understanding of reality; not a diagnosis in itself, but is a sign (just like fever, pain, etc)

Question 12

How does cannibis affect schizophrenia?

Answer 12

• there is an association btwn cannabis as a risk factor for developing schizophrenia, but the politics are complicated

Question 13

What is chlorpromazine?

Answer 13

• Chlorpromazine was first medication shown to have anti-psychotic properties and has a low potency
• MOA: it blocks receptors in the brain and causes reversed epinephrine (catecholamines; alpha 1), anti-emetic effects, causes catalepsy, and indifference (blockage of dopamine), atropine-like effects (acetylcholine), and prevents bronchospasm (histamine)
• first generation antipsychotic

Question 14

Differentiate btwn efficacy and potency:

Answer 14

• Efficacy = ability to achieve a desired clinical effect
  
  • efficacy correlates strongly w/ degree of blockade of mesolimbic D2 dopamine receptors; efficacy is achieved at 65-70% of D2 receptor occupancy
  • with treating positive symptoms, all antipsychotics have a similar efficacy EXCEPT for clozapine, which has a greater efficacy.
• Potency = measure of how much medication is needed to achieve the desired efficacy
  
  • for antipsychotics, potency correlates w/ affinity for mesolimbic D2 receptors.
    
    • high relative affinity high potency less molecules of medication needed

Question 15

Describe haloperidol

Answer 15

• Haloperidol is a high potency anti-psychotic that causes anti-emetic effects, indifference, reversal of amphetamines, and cataplexy in rats, all due to the selective blockage of dopamine
  
  • since it has high potency, it has a greater risk of dopamine-related side effects (dystonias, Parkinsonism, and akathisia, which is an uncomfortable sense of inner restlessness)
• is a first generation antipsychotic

Question 16

Describe clozapine

Answer 16

• Clozapine was called atypical b/c it doesn’t cause movement related side effects, and because it blocks serotonin + dopamine (and blocks serotonin way more than dopamine)
  
  • has the greatest efficacy of any other antipsychotics and it reduces suicidal behavior

Question 17

Describe resperidone

Answer 17

• Risperidone blocks serotonin and dopamine, and is a 2^nd generation anti-psychotic, just like clozapine.
  
  • clozapine and risperidone are atypical/2^nd generation anti-psychotic and don’t have movement related side effects, and block serotonin + dopamine (but higher affinity for 5HT)

Question 18

What is the main side effects of first generation antipsychotics?

What makes second generation antipsychotics “atypical”?

Answer 18

First generation antipsychotics have neuroleptic side effects (ataxia, etc)

second generation antipsychotics do not cause these side effects