Schizophrenia

Question 1

What is schizophrenia?

Answer 1

Chronic mental disorder characterised by a triad of core symptoms

Question 2

What are the 3 core symptoms of schizophrenia?

Answer 2

• positive symptoms
• negative symptoms
• cognitive symptoms

Question 3

What types of symptoms are ‘positive’?

Answer 3

Hallucinations
delusions
agitation
Disorganised thinking
(psychotic symptoms)

Question 4

What types of symptoms are negative?

Answer 4

(remove of normal processes/decreased emotions)

• introversion
• apathy
• low self-esteem
• personal neglect

Question 5

What types of symptoms are cognitive?

Answer 5

Poor memory
Attention deficit
Executive dysfunction

Question 6

How is schizophrenia diagnosed?

Answer 6

At least 2 DSM-5 symptoms

• delusions
• hallucinations
• disorganised speech
• disorganised/catatonic behaviour
• negative symptoms

(at least 1 symptoms must be delusions/hallucinations or disorganised speech)

• continuous signs of disturbance must persist for 6 months with 1 month of active symptoms with deterioration problems

Question 7

What is catatonic behaviour?

Answer 7

Variety of abnormal motor postures

Question 8

How is schizophrenia classified?

Answer 8

DMS-IV

• paranoid (prominent hallucinations/delusions)
• disorganised (behaviour without purpose)
• catatonic (unusual movements between active and still)
• undifferentiated
• residual (history of psychosis but only negative symptoms)

Question 9

What other ways can you test/classify schizophrenia?

Answer 9

Frontal Cortical Dysfunction Testing

- via Wisconsin Card Sorting Test

Question 10

Which genes are associated with schizophrenia?

Answer 10

• dysbindin
• COMT
• DISC 1
• BDNF

Question 11

What are the main structural changes in schizophrenia?

Answer 11

• increased rate of gray matter loss (larger ventricles and smaller temporal lobes)
• hypofrontality (decreased frontal activation)
• overall brain volume loss

Question 12

How does schizophrenia start?

Answer 12

• decreased synaptic spines/dendritic complexity in cortex

- abnormalities in formation/maturation of circuits

Question 13

How are corticolimbic circuits and dopaminergic systems affected?

Answer 13

• hypofrontaltiy - excessive striatal dopamine release
• explains psychotic symptoms
• hyperactivity in the mesolimbic pathway
• hypoactivity in the mesocortical pathway

Question 14

What is brain connectivity altered?

Answer 14

• mainly of default brain network = increased synchrony when subjects rest/allow mind to wander
• explains psychotic symptoms

Question 15

Which receptors are D1 type?

Answer 15

D1 and D5

Question 16

Which receptors are D2 type?

Answer 16

D2, D3, D4

Question 17

Which receptors are main targets for schizophrenia?

Answer 17

D2

Antagonise it

Question 18

Which drugs are typical atnipsychotics? (remember 2 or 3 from each category)

Answer 18

Chlorpromazine - 1st discovered
Thioridazine
Fluphenazine
Haloperidol
Flupenthixol

Question 19

What are the adverse effects of anti-pyshcotics?

Answer 19

• extrapyramidal effects (acute dystonias, parkinsonism, tardive dyskinesia)
• weight gain
• QT interval prolonged
• sudden death
• hyperprolactinaemia

Question 20

Which drugs are atypical antipsychotics?

Answer 20

• risperidone
• olanzapine
• clozapine
• quetiapine
• paliperidone
• aripiprazole

Question 21

What do atypical antipsychotics do apart from antagonise D2 receptors?

Answer 21

Antagonise activity at 5-HT2 receptors

Question 22

What does clozapine do?

Answer 22

Blocks D4 receptor with high affinity

Question 23

What does aripiprazole do?

Answer 23

• Combining antagonist/partial agonist effect on different D2 receptors

Question 24

What are the adverse effects of atypical antipyschotics?

Answer 24

• weight gain
• dyslipidaemia
• T2D
• cardiovascular disease

Question 25

How may atypical anti-psychotics be better than psychotics?

Answer 25

- less tardive dyskinesia - less cardiac toxicity as less QT prolongation - less hyperprolactinaemia

Question 26

In drug resistance which is the drug of choice?

Answer 26

Clozapine | But risk of agranulocytosis so blood monitoring is essential

Question 27

What are the general side effects of antipsychotics?

Answer 27

Have affinity for alpha-1 noradrenergic, serotonin, 5-HT2, dopamine D1, histamine H1 receptors so: ``` extrapyramidal effects hyperprolactinaemia weight gain allergic/toxic reactions anticholinergic effects postural hypotension ```

Question 28

What are the extrapyramidal effects?

Answer 28

- acute dystonias - parkinsonism - tardive dyskinesia

Question 29

What are some rare complications of antipsychotics?

Answer 29

- neuroleptic malignant syndrome | - irreversible complications (tardive dyskinesia)

Question 30

What is neuroleptic malignant syndrome?

Answer 30

- rare but potentially lethal - medical emergency - hyperpyrexia, tremor, confusion, autonomic instability

Question 31

What is tardive dyskinesia?

Answer 31

- involuntary movements of lips/jaw/face/constant chewing | - if taken typical antipsychotics for longer than years/few months

Question 32

What are some non-pharmacological approaches?

Answer 32

Cognitive behavioural therapy Family therapy - do not replace pharmacological treatment

Question 33

What are some new approaches to schizophrenia treatment?

Answer 33

- associated with decreased glutamatergic transmission so possible potentiate NMDA receptor activity