Neurobiology of Psychosis Flashcards
patient believes that their parents are trying to poison them because the government are controlling them. Which psychopathology term is most appropriate?
paranoid delusion
patient believes that news articles on the television about world leaders’ phones being tapped are actually talking about themselves as they holds important government information- what term describes this
ideas of reference
what is a functional hallucination
where the hallucination does not occur in the absence of a stimulus but are triggered by a stimulus in the same modality as the hallucination and can co occur with it
e.g. When Brian listens to the radio he can hear voices from elsewhere in the room telling him he must not think about the military information he has been given
what is heritability
proportion of observable differences in a trait between individuals in a population that is due to genetic differences
what is the inheritance of schizophrenia
multifactorial
does a childhood viral CNS infection increased risk of schizophrenia
yes by 50%
what does a brain look like in a patients with schizophrenia who has a poor prognosis
reduced frontal lobe volume
reduced frontal lobe grey matter
enlarged lateral ventricle volume
what brain abnormalities are seen in schizphrenia
reduction in gray matter in the: temporal cortex medial temporal lobe orbitofrontal cortex parietal cortex basal ganglia
white matter- abnormal neural integration (increased fractional anisotrophy= reduced healthy white matter tracts)
what causes gray matter abnormalities in schizophrenia
reduced arborisation (branching) same number of neurones just abnormal connections in both gray and white matter
what is the dopamine hypothesis of schizophrenia
drugs which release dopamine in the brain or D2 receptors agonists produce a psychotic state
in schizophrenia there is overactivity of dopamine pathways in the brain
how do amphetamines affect schizophrenia symptoms
can worsen them
antagonists of what are used to treat the symptoms of schizphrenia
dopamine receptor antagonists
what are the dopaminergic pathways, what do they do and what areas do they involve
nigrostriatal- extrapyramidal motor system (substantia nigra-> dorsal striatum)
mesolimbic/ cortical - motivation and reward systems (ventral tegmental area-> amygdala, hippocampus, frontal cortex, nucleus accumbens)
tuberoinfundibular- control of prolactin release
what are the two subtypes of dopamine receptors
D1 receptor family (D1 and 5)
D2 receptor family (D2,3,4)
what do D1 receptors do
stimulate cAMP
what do D2 receptors do
inhibit adenylyl cyclase
inhibit voltage activated Ca2+ channels
opens K+ channels
what type of dopamine receptor is most abundant
D1
where are D1 receptors found
neostriatum, cerebral cortec, olfactory tibercle, nucleus accumbens
where are D2 receptors found
neostriatum, olfactor tubercle, nucleus accumbens, pituitary gland
where are D3 receptors found
nucleus accumbens, island of calleja
where are D4 receptors found
midbrain, amygdala
where are D5 receptors found
hippocampus, hypothalamus
which dopamine receptors are found within the limbic ans striatal areas
D1 and 2
what neurobiology causes psychosis
subcortical dopamine hyperactivity
what neurobiology caiuses negative and cognitive symptoms
mesocortical dopamine hypoactivity
what other neurotransmitters are suggested to be involved in schizophrenia
glutamate- altered NMDA receptor expression
serotonin- reduced binding potential in frontal cortex
what genes cause brain pathology in schizphrenia
neuregulin- a signalling protein that mediates cell-cell interactions and plays critical roles in the growth and development of multiple organ systems
dysbindin- essential foe adaptive neural plasticity
DISC-1 - involves in neurite outgrowth and cortical development through its interaction with other proteins
what is a typical antipsychotic
works primarily though inhibition of D2 receptors
what symptoms are typical antipsychotics more likely to cause
extrapyramidal symptoms
name 2 typical antipsychotics
chlorpromazine
haloperidol
which side of synapse do antipsychotics work on
post synaptic receptors
what are atypical receptors
block both D2 and 5-HT2A receptors
are less likely to induce extrapyramidal side effects
better efficacy against negative symptoms
effective in patients unresponsive to typical drugs
give examples of atypical antipsychotics
olanzapine risperidone quetiapine clozapine aripiprazole amisulpride
what does risperidone mainly block
5-HT2A
what does olanzapine mostly block
5-HT2A
what does haloperidol mostly block
D2
Why can antipsychotics cause extrapyramidal side effects
as block D2 receptors in the nigrostriatum (connects substantia nigra and dorsal striatum)
what is an acute dystonic reaction to antipsychotics
acute dystonia- muscle spasms- which takes hours to days
how is an acute dystonic reaction treated
acetycholine antagonists: prochlorperazine, procyclidine, orhphenadrine
how long till parkinsonism develops due to antipsychotics
days to months
what is akathisia
internal restlessness- feel the need to constantly move, fidget, wriggle or pace
SE of antipsychotics, comes on after days- weeks
what is tardive dyskinesia
repetitive involuntary purposeless movements - grimacing, sticking tongue out, lip smacking, pursing lips, blinking
possible SE of antipsychotics, takes years to develop, very hard to treat- try and prevent it happening
how do antipsychotics cause hyperprolactinaemia
secretion of prolactin from the pituitary is inder inhibitory control by dopamine from the hypothalamus
what does hyperprolactinaemia cause
sexual dysfunction, galactorrhoea/ gynaecomastia, amenorrhoea, infertility, (low oestrogen and testosterone) osteoporosis
what syndrome can 5-HT2 blockade cause (atypical antipsychotics)
metabolic syndrome
what dose histamine blockage cause
sedation
increased appetite
what are H1 receptors
histamine receptors
why are new antihistamines not sedative
as do not cross BBB
what can blockage of alpha aderergic receptors cause
postural hypotension (interupts baroreflex)
what system targets muscarinic receptors
parasympathetic
what are the anticholineric side effects (muscarinic blockage)
blurred vision dry mouth constipation urinary retention sedation confusion
what SEs do you avoid if taking a typical antipsychotic
weight gain, cardiovascular risk, sedation
what SEs do you avoid if taking an atypical antipsychotic
extrapyramidal
sexual SEs
which blockage will cause parkinsonism
dopamine receptors (D2)
which blockage will cause metabolic syndrome
serotonin
which blockage is most likely to cause falls
alpha adrenergic, histamine
which blockage is most likely to cause sedation
histamine
which antipsychotic is least likely to cause a recurrence of parkinsonism:
Risperidone Olanzapine Chlorpromazine Quetiapine Zuclopentixol
quetiapine (doesnt block D1/2)
haloperidol antagonises dopamine receptors in the pituitary gland, what SEs will this cause
sexual dysfunction ect (think hyperprolactinoma)
what does clozapine mostly block
histamine
5-HT2A
alpha adenergic
muscarininc actylcholine
what drug causes agranulocytosis
clozapine
how often should you do blood tests when prescribing clozapine
weekly for first 6 months
fortnightly for next six months
every four weeks thereafter
for one month after stopping drug
what symptom should make you worried when taking clozapine
sore throat
what cardiac problem do you get when taking clozapine
myocarditis
what can result from a D2 blockade
extra pyramidal SEs: acute dystonic reaction parkinsonism akathisia tardive dyskinesia
hyperprolactinaemia
main SEs of clozapine
weight gain, sedation, hypersalivation, risk of agranulocytosis
which antipsychotic for avoidance of EPSE
atypicals
which antipsychotic are less sedating
haloperidol
risperdone
which antipsychotic are more sedating
olanzipine
chlorpomazine
which antipsychotic avoid weight gain
haloperidol
aripiprazole
which antipsychotic for treatment resistant schizophrenia
clozapine
which antipsychotic can be given as IM depot
risperidone
which antipsychotic can be used for anxiety
olanzipine
