Schizophrenia + antipsychotic drugs

Question 1

What is schizophrenia?

Answer 1

Chronic mental disorder characterised by a triad of symptoms:
positive
negative
cognitive

Question 2

What are positive, negative + cognitive symptoms?

Answer 2

Positive: hallucinations, delusion, agitation, disorganised thinking

Negative: introversion, apathy, low self-esteem, personal neglect

Cognitive: poor memory (working/short term memory particularly affected), attention deficit, executive function

Question 3

How is schizophrenia diagnosed?

Answer 3

At least 2 of the following symptoms:
- delusions
- hallucinations
- disorganised speech 
(at least one of these is required)
- disorganised or catatonic behaviour 
- negative symptoms 
Signs of disturbance must be continuous for at least 6 months -> pt must experience at leat 1 month of active symptoms, with social/occupational deterioration prblems

Question 4

Which genes have been associated with schizophrenia?

Answer 4

BDNF
COMT
DAOA
Neuregulin 1 - involved in synaptic plasticity and myelination** important
Dysbindin: may affect dopamine D2 receptor level sand glutamate + GABA transmission
DISC 1

Question 5

What structural differences in the brain are seen in someone with schizophrenia?

Answer 5

Larger ventricles + smaller medial temporal lobe
Grey matter loss is widespread
- significant progressive loss of parietal, motor, supplementary motor, and superior frontal cortices
- severe loss in the temporal cortex + superior temporal gyrus

Question 6

What functional differences in the brain are seen in someone with schizophrenia?

Answer 6

Hypofrontality: fMRI shows reduced frontal lobe activation in schizophrenia during a cognitive task

Question 7

What is the association between schizophrenia and inflammation?

Answer 7

Prenatal infection increased levels of cytokines during pregnancy increases the risk of schizophrenia in offspring
proinflammatory cytokines are increased in the PFC of SCH pts –> display greater signs of immune cell migration into the brain

Question 8

Why is oligodendrocyte density reduced in SCH?

Answer 8

may be due to inflammation and immune activation leading to oligodendrocyte damage

Question 9

How are the mesolimbic and mesocortical pathways affected in SCH?

Answer 9

Hyperactivity in the mesolimbic pathway
Hypoactivity in the mesocortical pathway

Part of the dual dopaminergic imbalance

Question 10

Give examples of typical antipsychotics.

Answer 10

Chlorpromazine
Thioridazine
Fluphenazine
Haloperidol
Flupenthixol

Question 11

Give examples of atypical antipsychotics.

Answer 11

Risperidone
Olanzapine
Clozapine
Quetiapine
Paliperidone
Aripiprazole

Question 12

Which receptors do atypical antipsychotics affect?

Answer 12

They antagonise 5-HT2 receptors

Question 13

Which receptors does clozapine block?

Answer 13

D4 receptors

Question 14

Which receptors does aripiprazole act on?

Answer 14

Partial agonist of presynaptic D2 receptors

Antagonist of postsynaptic D2 receptors

Question 15

What are the adverse effects of antipsychotics?

Answer 15

1. Extrapyramidal effects = acute dystonia, parkinsonism, tardive dyskinesia
2. Rise in prolactin = weight gain, dyslipidaemia, T2D
3. General = allergies + toxic reactions
4. Anticholinergic effects (clozapine + haloperidol)
5. Postural hypotension

Question 16

Compare atypical and typical antipsychotics.

Answer 16

Atypical:

• Less EPS
• Less cardiac toxicity (QT segment prolongatin)
• Less hyperprolactinaemia
• Weight gain
• hyperglycaemia, diabetes
• insulin resistance
• dyslipidaemia
• cardiovascular disease

Typical:

• EPS
• Tardive dyskinesias
• weight gain
• Qt segment prolongation
• sudden death
• hyperprolactinaemia

Question 17

What is neuroleptic malignant syndrome? How is it treated?

Answer 17

Potentially lethal reaction to antipsychotic drugs 
S+S:
- hyperpyrexia
- muscle rigidity 
- tremor 
- confusion 
- autonomic instability 

Can be treated with:

• Amantadine
• Bromocriptine
• Dantrolene

Question 18

What is tardive dyskinesia?

Answer 18

IRREVERSIBLE complication of taking antipsychotics
Involuntary movements of the lips, jaw, face, also cause grimacing and constant chewing
*mostly associated with typical antipsychotics which have been taken for >few months/years

Question 19

How many patients are resistant to drug treatment? Which drug is used in antipsychotic drug resistance? What is the risk with taking this drug?

Answer 19

30% of patients
Clozapine
Can cause agranulocytosis = weaken the immune system

Question 20

What non-pharmacological methods of treatment are there for SCH?

Answer 20

CBT
Family therapy
**non-pharmacological does not replace pharmacological

Question 21

What are the risk factors for schizophrenia?

Answer 21

• complication during pregnancy/at birth
• older father
• immune system activation
• excessive use of cannabinoids