How are symptoms classified in schizophrenia?
Five symptom domains:
- positive symptoms
- negative symptoms
- anx/dep
- aggressive symptoms
- cognitive symptoms
Describe the presentation of symptoms in schizophrenia.
Periods of acute presentation of positive symptoms interspersed with periods during which the neg symptoms predominate.
As disease progresses, neg symptoms become more dominant.
What are some positive symptoms of schizophrenia?
- Delusions (often paranoid)
- Hallucinations
- Thought disorder
- Abnormal behaviours (e.g. aggressive behaviours)
What are some negative symptoms of schizophrenia and how do they arise?
- Withdrawal from social contacts
- Flattening of emotional responses
Could be due to:
- Primary deficit of the illness
- Secondary to environmental deprivation
- Secondary to positive symptoms
- Secondary to depression
- Secondary to extrapyramidal symptoms
Why is recognition of cognitive dysfunction important in schizo pts?
Cognitive dysfunction includes impairment of selective attention and working memory. These symptoms predict level of social and vocational functioning, and hence treatment outcomes, better than pos symptoms.
What is the usual age of onset of schizophrenia?
Late adolescence to early adulthood
Aetiology of schizophrenia
- Genetic
- incomplete hereditary tendency
- some genes for susceptibility to schizo have been identified, but not all pts have same mutations of susceptibility genes - Environmental
- various theories relating to possible neurodevelopmental abnormalities ➝ e.g. maternal viral infx during pregnancy, obstetric complications
- abnormalities involving myelination of cortico-cortical pathways
- evidence of enlarged ventricles, abnormal laminar organisation of cortical cells
What are the neurochemical theories for schizo?
- Dopamine theory (dopaminergic overactivation)
- 5-HT theory (too much serotonin)
- Glutamate theory (deficiency in glutamate activity)
What is the diff between typical and atypical antipsychotics?
Atypical produces less extrapyramidal side effects than typical.
What are extrapyramidal side effects?
EPS are motor side effects such as acute dystonias and tardive dyskinesia & akathisia.
Extrapyramidal pathway involves the basal ganglia, including striatum and substantia nigra. EPS arise due to D2 blockade of nigrostriatal pathway by antipsychotics.
Differentiate the presentation of acute dystonia vs tardive dyskinesia and akathisia.
Acute dystonia: Parkinsonism-like syndrome (cogwheel rigidity, tremors at rest)
VS
Dyskinesia: Repetitive and stereotyped involuntary movements of face, tongue and limbs
VS
Akathisia: Involuntary movements and compulsion to act associated with restlessness, agitation and anxiety
Onset of acute dystonia vs tardive dyskinesia and akathisia
Acute dystonia - within first few weeks of treatment, reversible when drug is stopped.
Tardive and akathisia - develops over months or years, often irreversible. Akathisia correlates directly with duration on meds.
Cause of acute dystonia vs tardive dyskinesia and akathisia
Acute dystonia - D2 antagonism in nigrostriatal pathway
Tardive and akathisia - upregulation of supersensitivity of dopamine receptors in nigrostriatal pathway
Which receptors do chlorpromazine target and what are the associated /therapeutic side effects?
- D2 antagonist - reduce dopamine activity, treat pos symptoms
- mAChR antagonist - dry mouth, constipation, blurred vision
- Histamine H1 antagonist - sedation, weight gain
- alpha1-adrenergic antagonist - postural hypotension, dizziness
Why does haloperidol have fewer side effects than chlorpromazine?
Haloperidol targets fewer receptors - only D2 and alpha1
List a few key typical antipsychotics.
chlorpromazine, fluphenazine, haloperidol, trifluoperazine
Clinical use of clozapine is limited by which serious adverse effect?
Agranulocytosis - rare but fatal. Regular blood counts needed to monitor pts.
What are common adverse effects of atypical antipsychotics?
- Anticholinergic effects due to mAChR antagonism (esp clozapine and olanzapine)
- Postural hypotension and reflex tachycardia due to alpha1-adrenergic antagonism (esp for risperidone)
- Sedation due to histamine H1 receptor antagonism (esp clozapine and olanzapine)
Amisulpride is selective for which receptors?
D2 and D3
How are the side effects of amisulpride diff from other atypical antipsychotics?
Amisulpride doesn’t block alpha-adrergic, histamine H1 or mACh receptors.
Causes adverse effects on mammary glands and tissues:
- due to increased prolactin secretion due to block of dopamine receptors in anterior pituitary gland (part of tuberoinfundibular system).
- breast swelling, pain and lactation
- gynaecomastia in males
What are some additional side effects of atypical antipsychotics?
- New onset or exacerbation of diabetes
- effect is strong for clozapine, olanzapine and risperidone
- for risperidone higher chance of diabetes not reversing when drug is stopped - Weight gain
- esp clozapine, olanzapine and risperidone
Why do atypicals produce less EPS?
- Potent 5-HT2A receptor antagonism vs weak D2 antagonism ➝ lower EPS and higher efficacy against neg symptoms (clozapine and olanzapine)
- High D4 to D2 antagonism ratio favours actions in prefrontal cortex over striatum (clozapine)
- High D3 to D2 antagonism ratio favours action on the nucleus accumbens over striatum (amisulpride)
- High D2 to D1 antagonism ratio reduces impact of antagonism in the striatum (amisulpride, risperidone)
What are some additional benefits of atypical antipsychotics?
Some more effective against neg symptoms and may be better at mood stabilisation than typicals
- clozapine, olanzapine, risperidone
- but effect on neg symptoms still weak, only relevant for pts who start out with severe neg symptoms
Some may ameliorate cognitive dysfunction better than typicals
- clozapine, risperidone
