Neurobiology of Psychosis Flashcards
A man believes that his parents are trying to poison him because the government are controlling them.
Which psychopathology term is this describing?
Paranoid Delusion
A man believes that news articles on the television about world leaders’ phones being tapped are actually talking about him as he holds important government information.
Which psychopathology term is this describing?
Ideas of Reference
When a man 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.
Which psychopathology term is he describing?
Functional hallucination
- hallucinations triggered by a stimulus in the same modality
- e.g. radio is an auditory stimulus and the man is having auditory hallucinations
A man believes he must not think about the military information as everyone else has access to his thoughts.
Which psychopathology term is he describing?
Thought Broadcasting
There is a higher genetic risk of a psychiatric condition in dizygotic twins than between 1st degree relatives. Why is this?
More environmental similarities (before and after birth) between dizygotic twins than first degree relative (even another sibling)
What structural brain abnormalities present in Schizophrenia patients with poor prognosis?
Reduced frontal lobe volume
Reduced frontal lobe grey matter
Enlarged lateral ventricle volume
Abnormalities of the brain’s grey matter usually present early in schizophrenia and are thought to exist pre-morbidly. TRUE/FALSE?
TRUE
Grey matter reduction is likely to progress in the initial years of schizophrenia. TRUE/FALSE?
TRUE
What causes grey matter reduction in schizophrenia?
reduced arborisation (branching of end of nerve fibre)
NOT due to neuron loss
How are white matter abnormalities in the brain investigated in schizophrenia?
‘diffusion tensor imaging’ (DTI)
Measured using:
‘fractional anisotropy’ (FA)
- high number = healthy white matter tracts
‘mean diffusivity’ (MD)
- high number = unhealthy white matter tracts
It is assumed that schizophrenia is related to overactivity of Dopamine pathways in the brain. TRUE/FALSE?
TRUE
This is because:
- Drugs which release Dopamine in the brain
produce a psychotic state in man.
- Dopamine receptor antagonists are used to treat the symptoms of schizophrenia.
Explain the difference between action of D1 and D2 receptor subtypes?
D1 (and D5) receptor:
- stimulates cAMP
- more abundant than D2
D2 receptor family (D2,D3,D4):
- inhibit Adenylyl Cyclase
- inhibit Ca2+ channels
- open K+ channels
- more widespread in CNS
Give an example of a D2 agonist and a D2 antagonist
AGONIST - ropinirole (D2,3,4 but highest affinity for D2)
ANTAGONIST - Haloperidol
What hypothesis has been generated after proof that negative and cognitive symptoms persist despite D2 blockade with antipsychotics?
- The dopamine system is dysfunctional?
- Subcortical Dopamine HYPERactivity leads to psychosis
- Mesocortical Dopamine HYPOactivity leads to negative and cognitive symptoms
What neurotransmitter problems have been hypothesised to explain schizophrenia?
Glutamate:
- altered NMDA receptor subunit expression
Serotonin
- abnormalities in serotonin 2A binding in the frontal cortex significantly smaller in schizophrenia patients
What proteins cause the brain pathology found in schizophrenia?
Neuregulin - For growth and development Dysbindin - For adaptive neural plasticity DISC-1 - For neurite outgrowth and cortical development
What receptor do most antipsychotics inhibit?
Post-synaptic D2 Dopamine Receptor
Why are 2nd generation/ atypical antipsychotics useful?
- Less likely to induce Extra-Pyramidal side-effects
- High Serotonin 2A to D2 ratio
- Work better against negative symptoms
- Effective in patients unresponsive to typical drugs
Give examples of atypical anipsychotics.
Olanzapine Risperidone Quetiapine Clozapine Aripiprazole Amisulpride
Antipsychotics blocking dopamine 2 receptors in the nigrostriatum can cause what symptoms?
Parkinsonism
D2 blockade can cause what other symptoms?
Acute dystonia - muscle spasms
Akathisia - Internal restlessness
Tardive dyskinesia- repetitive involuntary purposeless movements- smacking, pursing lips, blinking
Hyperprolactinaemia (dopamine inhibits prolactin)
A man finds that the olanzapine helps him to sleep much better at night.
Which neurotransmitter is primarily involved in this effect?
Histamine
A man develops a tremor and muscular stiffness due to his anti-psychotic medication.
Which neuroreceptors are primarily involved in this effect?
Dopamine receptors
Which of these antipsychotics is least likely to cause a Parkinsonism?
A- Risperidone B- Olanzapine C- Chlorpromazine D- Quetiapine E- Zuclopentixol
D- Quetiapine
Haloperidol antagonises dopamine receptors in the pituitary gland. Which of these side effects is caused by this? A- Akathisia B- Sexual dysfunction C- Acromegaly D- Apathy E- Sedation
B- Sexual dysfunction
Why is clozapine used now, and why was it previously withdrawn from the market?
Now used for unresponsive/intolerant schzophrenia where patients have used 2 or more antipsychotics
Was previously withdrawn in 1975 due to agranulocytosis
How should blood tests of patients on clozapine be monitored to prevent agranulocytosis?
Weekly for the 1st 6 months
Fortnightly for the next 6 months
Every four weeks thereafter
For one month after cessation of clozapine
What tests are carried out at a clozapine clinic?
FBC
ECG - due to potential myocarditis
clozapine is also usually dispense from this clinic
