Neurobiology of Psychosis

Question 1

other then genetics, what are the other risk factors for schizophrenia?

Answer 1

2nd trimester viral illness
obstetric problems - pre-eclampsia, fetal hypoxia, emergency C section
childhood viral CNS infection

Question 2

what substances increase risk of psychosis?

Answer 2

amphetamines
cocaine
cannabis
novel psychoactive substances (eg ivory wave, spice)

Question 3

what brain structure abnormalities in schizophrenia indicate poor prognosis?

Answer 3

reduced frontal lobe volume
reduced frontal lobe grey matter
enlarged lateral ventricle volume

Question 4

what are the main points about grey matter abnormalities in schizophrenia?

Answer 4

associated with widely distributed GM abnormalities
abnormalities present early in illness and likely pre-morbidly
grey matter reductions due to reduced aborisation and not neurone loss
grey matter reductions likely progressive in initial years

Question 5

there are thought to be white matter abnormalities in schizophrenia - true or false?

Answer 5

true - some evidence

Question 6

what is used to treat schizophrenia and why?

Answer 6

dopamine receptor antagonists because it is assume that schizophrenia is related to overactivity of dopamine pathways in brain

Question 7

what part of the dopaminergic pathway is involved in control of prolactin release?

Answer 7

tuberoinfundibular

Question 8

what part of the dopaminergic pathway is involved in motivation and reward systems?

Answer 8

mesolimbic / cortical

Question 9

what part of the dopaminergic pathway is involved in extrapyramidal motor system?

Answer 9

nigrostriatal

Question 10

what dopamine receptors are located in both limbic and striatal areas?

Answer 10

D1 and D2 (D2 more pharmacologically important but D1 most abundant)

*other subtypes smaller number but more discrete distribution

Question 11

in terms of the dopamine hypothesis, what does:
a) subcortical dopamine hyperactivity
b) mesocortical dopamine hypoactivity
lead to?

Answer 11

a) psychosis

b) negative and cognitive symptoms

Question 12

what other neurotransmitter pathways are thought to be involved in schizophrenia?

Answer 12

glutamatergic and seotonergic

Question 13

what are the identified gene alterations which cause the brain pathology?

Answer 13

neuregulin - signalling protein that mediates cell-cell interactions and plays critical roles in growth and development of multiple organ systems

dysbindin - essential for adaptive neural plasticity

DISC-1 - involved in neurite outgrowth and cortical development through its interaction with other proteins

Question 14

chlorpromazine, thioridazine, fluphenazine, haloperidol and zuclopentixol are all examples of typical / atypical antipsychotics?

Answer 14

typical

Question 15

what is the definition of atypical antipsychotics?

Answer 15

those less likely to induce extra-pyramidal side effects
high 5-HT2A to D2 ratio
better efficacy against negative symptoms

Question 16

olanzapine, risperidone, quetiapine, clozapine, aripiprazole, amisulpride and lurasidone are all examples of typical / atypical antipsychotics?

Answer 16

atypical

Question 17

how do antipsychotics cause extra pyramidal side effects?

Answer 17

block dopamine 2 receptors in nigrostriatum, causing parkinsonism

Question 18

give examples of the EPSE that antipsychotics produce?

Answer 18

acute dystonia (hours-days) and muscle spasms 
- tx with prochlorperazine, procyclidine, orphenadrine 

parkinsonism (days-months)

akathisia (internal restlessness)

tardive dyskinesia (repetitive involuntary purposeless movements eg smacking lips - years)

Question 19

what metabolic side effect does dopamine 2 blockage cause?

Answer 19

hyperprolactinaemia - sexual dysfunction, galactorrhoea / gynaecomastia, amenorrhoea, infertility

*this also causes lower oestrogen and testosterone levels, causing osteoporosis

Question 20

what is the mechanism of action of a lot of the atypical antipsychotics?

Answer 20

5HT2 antagonism

Question 21

which drugs can cause hallucinations and thought disturbance?

Answer 21

psychotomimetic drugs with high affinity for 5-HT2 receptors (hallucinogenic indoleamines and phenylethylamines)

Question 22

what metabolic side effect can be caused by 5-HT2 blockage?

Answer 22

metabolic syndrome

• obesity
• high cholesterol
• hypertension
• diabetes

Question 23

what side effects does histamine blockage cause?

Answer 23

sedation and increased appetite

*newer not sedating because do not cross BBB

Question 24

what side effects does alpha adrenergic blockage cause?

Answer 24

hypotension and interrupts baroreflex response - dizziness, light headedness or orthostatic hypotension

Question 25

what side effects are caused by muscarinic blockage?

Answer 25

blurred vision 
dry mouth 
constipation 
urinary retention 
sedation and confusion

Question 26

how should you go about choosing which antipsychotic to give?

Answer 26

no real difference in efficacy (apart from clozapine)
consider previous use
consider pre-existing comorbidities (diabetes, obesity, parkinsons)
consider patients concern of side effects (weight gain, sedation, restlessness)

Question 27

what is a depot and when can it be useful to administer antipsychotics?

Answer 27

long acting depot IM injection eg every 2-4 weeks

useful for

• detained patient who lacks insight and will not take oral regularly
• informal patient who recognises that they can be irregular taking tablets or who prefers infrequent injection

Question 28

when should clozapine be administered?

Answer 28

when there has been inadequate response to at least 2 other antipsychotics, usually both an atypical and typical

*warning - agranulocytosis and myocarditis

Question 29

when should FBC be done in those on clozapine?

Answer 29

initially
weekly for first 6 months
fortnightly for next 6 months 
every four weeks thereafter 
for one month after cessation of clozapine 

*sore throat in pt on clozapine = get FBC

Question 30

what is present on ECG in pt with myocarditis?

Answer 30

non specific ST segment changes

monitor ECG, BP and pulse when starting clozapine