Schizophrenia Flashcards
What is schizophrenia?
Chronic mental disorder characterised by a triad of core symptoms
What are the 3 core symptoms of schizophrenia?
- positive symptoms
- negative symptoms
- cognitive symptoms
What types of symptoms are ‘positive’?
Hallucinations delusions agitation Disorganised thinking (psychotic symptoms)
What types of symptoms are negative?
(remove of normal processes/decreased emotions)
- introversion
- apathy
- low self-esteem
- personal neglect
What types of symptoms are cognitive?
Poor memory
Attention deficit
Executive dysfunction
How is schizophrenia diagnosed?
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
What is catatonic behaviour?
Variety of abnormal motor postures
How is schizophrenia classified?
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)
What other ways can you test/classify schizophrenia?
Frontal Cortical Dysfunction Testing
- via Wisconsin Card Sorting Test
Which genes are associated with schizophrenia?
- dysbindin
- COMT
- DISC 1
- BDNF
What are the main structural changes in schizophrenia?
- increased rate of gray matter loss (larger ventricles and smaller temporal lobes)
- hypofrontality (decreased frontal activation)
- overall brain volume loss
How does schizophrenia start?
- decreased synaptic spines/dendritic complexity in cortex
- abnormalities in formation/maturation of circuits
How are corticolimbic circuits and dopaminergic systems affected?
- hypofrontaltiy - excessive striatal dopamine release
- explains psychotic symptoms
- hyperactivity in the mesolimbic pathway
- hypoactivity in the mesocortical pathway
What is brain connectivity altered?
- mainly of default brain network = increased synchrony when subjects rest/allow mind to wander
- explains psychotic symptoms
Which receptors are D1 type?
D1 and D5
Which receptors are D2 type?
D2, D3, D4
Which receptors are main targets for schizophrenia?
D2
Antagonise it
Which drugs are typical atnipsychotics? (remember 2 or 3 from each category)
Chlorpromazine - 1st discovered Thioridazine Fluphenazine Haloperidol Flupenthixol
What are the adverse effects of anti-pyshcotics?
- extrapyramidal effects (acute dystonias, parkinsonism, tardive dyskinesia)
- weight gain
- QT interval prolonged
- sudden death
- hyperprolactinaemia
Which drugs are atypical antipsychotics?
- risperidone
- olanzapine
- clozapine
- quetiapine
- paliperidone
- aripiprazole
What do atypical antipsychotics do apart from antagonise D2 receptors?
Antagonise activity at 5-HT2 receptors
What does clozapine do?
Blocks D4 receptor with high affinity
What does aripiprazole do?
- Combining antagonist/partial agonist effect on different D2 receptors
What are the adverse effects of atypical antipyschotics?
- weight gain
- dyslipidaemia
- T2D
- cardiovascular disease
How may atypical anti-psychotics be better than psychotics?
- less tardive dyskinesia
- less cardiac toxicity as less QT prolongation
- less hyperprolactinaemia
In drug resistance which is the drug of choice?
Clozapine
But risk of agranulocytosis so blood monitoring is essential
What are the general side effects of antipsychotics?
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
What are the extrapyramidal effects?
- acute dystonias
- parkinsonism
- tardive dyskinesia
What are some rare complications of antipsychotics?
- neuroleptic malignant syndrome
- irreversible complications (tardive dyskinesia)
What is neuroleptic malignant syndrome?
- rare but potentially lethal
- medical emergency
- hyperpyrexia, tremor, confusion, autonomic instability
What is tardive dyskinesia?
- involuntary movements of lips/jaw/face/constant chewing
- if taken typical antipsychotics for longer than years/few months
What are some non-pharmacological approaches?
Cognitive behavioural therapy
Family therapy
- do not replace pharmacological treatment
What are some new approaches to schizophrenia treatment?
- associated with decreased glutamatergic transmission so possible potentiate NMDA receptor activity
