Psychosis: basic sciences Flashcards
What structural brain features are seen in a patient with poor prognosis?
reduced frontal lobe volume
reduced frontal lobe grey matter
enlarged lateral ventricles
What happens to grey matter volume in schizophrenic patients?
Reduced
In schizophrenia, grey matter loss occurs in focal points - T/F?
False - widely distributed
Neuronal loss causes the grey matter reduction in schizophrenia - T/F?
False - reduced arborisation causes grey matter loss.
What imaging modality is used to investigate white matter in the brain?
Diffusion tensor imaging
is it possible to diagnose schizophrenia by radiology?
No - normal variation in healthy brain structure precludes this.
Is ventricular enlargement progressive when found at diagnosis?
No - non-progressive
Is gliosis a common feature of schizophrenia?
No
Which neurotransmitter is commonly thought to be responsible for the pathology in schizophrenia?
dopamine - drugs which release dopamine in the brain induce a psychotic state in man.
AMPHETAMINE
Why can dopamine receptor antagonists be used to treat schizophrenia?
it is assumed that schizophrenia is related to overactivity in dopamine pathways of the brain.
What are the 3 main dopaminergic pathways in the brain?
nigrostriatal
mesolithic/cortical
tuberinfundibular
What is the function of the D1 receptor family?
stimulate cAMP
What is the function of D2 receptor family? (D2,3,4)
inhibit adenylyl cyclase
inhibit voltage-activated Ca2+ channels
open K+ channels
Which drugs inhibit D2 receptors?
haloperidol
raclopride
Which receptors does raclopride block?
D2 + D3
Where are D1 and D2 receptors found?
limbic and striatal areas
Where are D5 receptors found?
hippocampus
hypothalamus
Where are D4 receptors found?
midbrain
amygdala
Which medication acts as an antagonist to D4 receptors?
Clozapine
What happens in subcortical dopamine hyperactivity?
psychosis
Which gene alterations are identified in psychotic brain pathology?
neuregulin
dysbindin
DISC-1
What is neuregulins role?
a signalling protein that mediates cell-cell interactions and plays critical roles in growth and development
What is the role of dysbindin?
essential for adaptive neural plasticity
What is the function of DISC-1?
involved in neurite outgrowth and cortical development through its interaction with other proteins
What are some examples of typical antipsychotics?
chlorpromazine thioridazine fluphenazine haloperidol primozide
in antipsychotics, the blockade of D2 is immediate, and clinical effect if instant - T/F?
False - blockade is immediate and clinical effect is delayed.
What is beneficial about atypical antipsychotics?
less likely to cause extrapyramidal side-effects
better efficacy against negative symptoms
effective in refractory patients
Name some atypical antipsychotic drugs
clozapine aripiprazole risperidone quetiapine olanzapine
What are some common side effects of D2 blockade?
EPSE
Hyperprolactinaemia
What side-effects are caused by Serotonin blockade
metabolic syndrome - modulate immune response and inflammation.
weight gain may partially involve antagonist activity at 5-HT2C
What side-effects are seen in histamine blockade?
sedation
increased appetite
What are the side-effects of alpha adrenergic blockade?
increased BP and HR
postural hypotension
What effects are seen in muscarinic receptor blockade?
dry mouth
constipation
urinary retention
dizziness
What are common side effects of clozapine?
weight gain
tiredness
Which serious side-effect of clozapine renders continuous monitoring appropriate?
agranulocytosis
How often is a full blood count done in clozapine patients?
weekly for first 6m
fortnightly for next 6m
every four weeks thereafter
for one month after stopping clozapine
Can clozapine induce myocarditis?
Yes
