Aetiology & tx of psychosis (symposium)

Question 1

EPIDEMIOLOGY

i) do relatives of affected subjects have higher risk of psychosis?
ii) what % risk does a child of two affected partents have?
iii) what is the heritability %? what does this mean?

Answer 1

i) yes
ii) 46% increased risk
iii) 80% heritability - 80% of differences in genes explain the likelihood of developing schizophrenia

Question 2

GENETICS

i) which molecular entity do GWAS studies implicate the association of schizophrenia with? (which chromosome)
ii) what functions is this locus related to? (3)
iii) is inheritence mendelian or non mendelian?

Answer 2

i) GWAS studies implicate an association of schizophrenia to MHC locus on chromosome 6
ii) this locus is related to neuronal function, synaptic organisation and neurotransmission
iii) inheritance is non mendelian

Question 3

ENVIRONMENTAL AND BIOLOGICAL STRESSORS

i) name three obstetric complications that are associated with increased risk of psychosis
ii) name thing that may lead to immune activation that is associated with schizophrenia
iii) name three environmental factors that can influence developement of psychosis

Answer 3

i) premature birth, low birth weight, perinatal hypoxia
ii) intrauterine infection in 1st/2nd trimester can lead to immune activation
iii) adverse life events, migration, social isolation

Question 4

DOPAMINE AND PSYCHOSIS

i) what is seen when radiolabelled LDOPA is administered to the brain of a person who has schizophrenia?
ii) what does this indicate?

Answer 4

i) there is increased uptake in schizo brains
ii) indicates greater synthesis and accumulation of dopamine in patients with schizophrenia

Question 5

GLUTAMATE

i) do abnormalities in Glu occur before or after abnormalities in DA?
ii) which type of symptoms does it play a role in?
iii) what effect does reduced activity of Glu in the frontal cortex have on dopamine?
iv) which drug inhibits Glu?

Answer 5

i) before
ii) Glu plays a role in negative and cognitive symptoms
iii) low Glu in the PFC causes increased DA release from the NAcc (due to less GABA inhibition in the VTA)
iv) ketamine inhibits Glu

Question 6

PHYSICAL TREATMENT

i) which class of antipsychotics has parkinsonian side effects?
ii) for typical and atypical APs - is drug efficacy seen to be the same initially or for chronic illness?
iii) how long does it usually take to see treatment benefit?
iv) what can side effects be predicted by? what receptor is this measured against?
v) which antipsychotic is a partial agonist?
vi) what treatment may be useful for psychosis associated with depression or catatonia?

Answer 6

i) typical
ii) drug efficacy is seen to be the same for first episode but different for chronic use
iii) usually takes 2 weeks to see clinical benefit

iv) can predict side effects by receptor affinity for the drug
- measured against affinity for D2

v) partial agonist = ariprazole
vi) electroconvulsive treatment

Question 7

ADVERSE EFFECTS OF BLOCKING RECEPTORS

give side effects of blocking each receptor

a) D2
b) 5HT2
c) A1 adrenergic
d) H1
e) M1 (cholinergic)

Answer 7

a) parkinsonism, tardive dyskinesia and raised prolactin
b) positive effects to offset parkinsonism
c) postural hypotension
d) sedation and weight gain
e) constipation, blurry vision, confusion

Question 8

ANTIPSYCHOTICS

i) which receptor do typical principally block?
ii) give two examples of typical APs?
iii) which receptors do atypical block? what does this cause?
iv) give two examples of atypical APs
v) name another method of admin for long acting duration
vi) which AP is good for patients that dont respond to other drugs?

Answer 8

i) typical block D2Rs
ii) typical APs = haloperidol and chlorpromazine, risperidone
iii) atypical block D2/D4 receptos and 5HT2 therefore less likely to give EPSPs
iv) atypical = ariprazole and clozapine
v) long acting injections
vi) clozapine

Question 9

CLOZAPINE

i) is it typical or atypical?
ii) what can it cause? is this fast or slow onset?
iii) which patient population may it be especially useful in?
iv) are parkinsonian symptoms seen?
v) name three side effects

Answer 9

i) atypical
ii) can cause neutropenia (slow onset)
iii) may be useful in patients that are resistant to other treatments
iv) not really
v) sedation, weight gain, dribbling

Question 10

METABOLIC SYNDROME

i) which type of APs is this associated with?
ii) give three examples
iii) what is it associated with higher rates of?
iv) how is this monitored?

Answer 10

i) atypical
ii) obesity, hypertension, dyslipidaemia
iii) associated with higher rates of coronary heart disease
iv) monitored by routine screening and advice about diet and exercise