Neurobiology of Psychosis Flashcards
other then genetics, what are the other risk factors for schizophrenia?
2nd trimester viral illness
obstetric problems - pre-eclampsia, fetal hypoxia, emergency C section
childhood viral CNS infection
what substances increase risk of psychosis?
amphetamines
cocaine
cannabis
novel psychoactive substances (eg ivory wave, spice)
what brain structure abnormalities in schizophrenia indicate poor prognosis?
reduced frontal lobe volume
reduced frontal lobe grey matter
enlarged lateral ventricle volume
what are the main points about grey matter abnormalities in schizophrenia?
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
there are thought to be white matter abnormalities in schizophrenia - true or false?
true - some evidence
what is used to treat schizophrenia and why?
dopamine receptor antagonists because it is assume that schizophrenia is related to overactivity of dopamine pathways in brain
what part of the dopaminergic pathway is involved in control of prolactin release?
tuberoinfundibular
what part of the dopaminergic pathway is involved in motivation and reward systems?
mesolimbic / cortical
what part of the dopaminergic pathway is involved in extrapyramidal motor system?
nigrostriatal
what dopamine receptors are located in both limbic and striatal areas?
D1 and D2 (D2 more pharmacologically important but D1 most abundant)
*other subtypes smaller number but more discrete distribution
in terms of the dopamine hypothesis, what does:
a) subcortical dopamine hyperactivity
b) mesocortical dopamine hypoactivity
lead to?
a) psychosis
b) negative and cognitive symptoms
what other neurotransmitter pathways are thought to be involved in schizophrenia?
glutamatergic and seotonergic
what are the identified gene alterations which cause the brain pathology?
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
chlorpromazine, thioridazine, fluphenazine, haloperidol and zuclopentixol are all examples of typical / atypical antipsychotics?
typical
what is the definition of atypical antipsychotics?
those less likely to induce extra-pyramidal side effects
high 5-HT2A to D2 ratio
better efficacy against negative symptoms
olanzapine, risperidone, quetiapine, clozapine, aripiprazole, amisulpride and lurasidone are all examples of typical / atypical antipsychotics?
atypical
how do antipsychotics cause extra pyramidal side effects?
block dopamine 2 receptors in nigrostriatum, causing parkinsonism
give examples of the EPSE that antipsychotics produce?
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)
what metabolic side effect does dopamine 2 blockage cause?
hyperprolactinaemia - sexual dysfunction, galactorrhoea / gynaecomastia, amenorrhoea, infertility
*this also causes lower oestrogen and testosterone levels, causing osteoporosis
what is the mechanism of action of a lot of the atypical antipsychotics?
5HT2 antagonism
which drugs can cause hallucinations and thought disturbance?
psychotomimetic drugs with high affinity for 5-HT2 receptors (hallucinogenic indoleamines and phenylethylamines)
what metabolic side effect can be caused by 5-HT2 blockage?
metabolic syndrome
- obesity
- high cholesterol
- hypertension
- diabetes
what side effects does histamine blockage cause?
sedation and increased appetite
*newer not sedating because do not cross BBB
what side effects does alpha adrenergic blockage cause?
hypotension and interrupts baroreflex response - dizziness, light headedness or orthostatic hypotension
what side effects are caused by muscarinic blockage?
blurred vision dry mouth constipation urinary retention sedation and confusion
how should you go about choosing which antipsychotic to give?
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)
what is a depot and when can it be useful to administer antipsychotics?
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
when should clozapine be administered?
when there has been inadequate response to at least 2 other antipsychotics, usually both an atypical and typical
*warning - agranulocytosis and myocarditis
when should FBC be done in those on clozapine?
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
what is present on ECG in pt with myocarditis?
non specific ST segment changes
monitor ECG, BP and pulse when starting clozapine
