schizo Flashcards
what are symptoms of psychosis
a range of mental symptoms indicating the patient is out of touch w reality
hallucinations, delusions and thought disorder
can be seen in a number of different disorders not just schizo
all psychoses are treated with and respond to antipsychotics
describe hallucinations in schizo
auditory hallucinations; voices talking to eachother about the patient, commanding the patient to do things, can be heard outside the head in space or coming from some part of the body
visuals
what is the neurodevelopmental hypothesis of schizo
genes: polygenic inheritance; monozygotic co twin 50:50 chance
disrupted corticogenesis and reduced IQ
foetal malnutrition, perinatal ischemia, early cannabis abuse and being brought up in a city are all risk factors
synaptic pruning later in life leads to further cortical changes and impaired cognition, reduces the neuropil which is a prelude to psychosis
what is the dopamine hypothesis of schizo
symptoms are a result from increased dopamine transmission
based on:
chronic amphetamine abuse can cause hallucinations and delusions, amphetamine causes increased dopamine release
antipsychotics block D receptors
what is evidence for and against dopamine hypothesis
post mortem studies show no increase in dopamine or metabolites in brain tissue
increased dopamine in left amygdala in untreated patients
in CSF increased dopamine metabolites but may be an artefact of treatment and no evidence of increased dopamine metabolites in drug free patients
antipsychotics block D receptors within hours however psychosis can take weeks to resolve
traditional antipsychotic drugs do not treat negative symptoms, 30% of patients positive symptoms fail to respond fully to antipsychotics
against: does not acount for negative and cognitive symptoms, treatment resistance
what evidence does brain imaging provide dopamine hypothesis
PET and SPECT scans;
measure D2 receptor occupancy in vivo found antipsychotics block D2 receptor at doses that are clinically effective, however need greater than 50% occupancy for clinical effect, greater than 75 increase risk of extrapyramidal side effects
65% occupancy threshold defines who will and will not respond to treatment, responders have over 65% occupancy and vice versa for those who dont
however dopamine dysregulation is never treated for first episode psychosis patients, during prodrome dopamine synthesis capacity increases in those who go on to become psychotic and increases further following psychosis onset
how does reward process effect schizo
normally dopamine signals when important or salient events occur in environment, dopamine dysregulation in ventral striatum causes irrelevant environmental stimuli to become salient; basis of formation of psychotic symptoms
what is the glutamate hypothesis of schizo
PCP and ket can cause psychosis like symptoms, both antagonists at NMDA receptor
causes:
positive symptoms: hallucinations and delusions
negative symptoms: withdrawal, poverty of speech and thought
glutamate neurones project to dopamine cell body areas
evidence that decreased NMDA mediated glut transmission in midbrain results in increased striatal dopamine release
what is the glutamate pathway in schizo
reduced NMDA receptor availability which function on GABAergic interneurones leads to
disinhibition of glutamatergic projections onto midbrain dopamine neurones leads to
increased glutamate release leads to
increased activation of dopaminergic neurones
how does synpatic pruning effect glut hypoth
synaptic pruning leads to removal of glut receptor in cortex; mediates cognitive impairment and negative symptoms and disinhibition of subcortical dopamine which explains positive symptoms
may drugs modifying glut function alleviate psychosis
no, main treatment is D2 receptor block
describe antipsychotic drugs
all drugs are equally effective in reducing symptoms except clozapine
they differ with respect to adverse effects
wanted effects are D2 block in certain areas of brain
unwanted effects;
due to dopamine block in certain areas of brain
due to actions of various drugs on non dopaminergic systems such as Ach, NA, histamine or 5HT
what are the dopamine pathways
the mesolimbic/cortical:
VTA to the ventral striatum/ frontal cortex
^reward and cognitive systems, site of antipsychotic action
nigrostriatal:
substantia nigra to dorsal striatum, part of the motor system, is the site of action of unwanted effects, movement disorders or extrapyramidal symptoms
what is wanted action of D2 blockade of drugs
early (hours) actions: tranquilisation
medium late (days to weeks): suppression of hallucinations, delusions and disorderd thinking, prevention of relapse
what are wanted indirect actions of antipsychotics
early: sedation due to antihistamine and alpha-adreno blocking action
