19. Schizophrenia Flashcards
What are the different types of symptoms of schizophrenia and give specific examples
Positive symptoms - hallucinations, delusions, agitation, disorganised thinking
Negative symptoms - introversion, apathy, low self-esteem leading to personal neglect
Cognitive symptoms - poor memory, attention deficit, executive dysfunction
How is schizophrenia diagnosed?
No physical tests to diagnosed schizophrenia - clinical diagnosis
Two or more of the following for a significant portion of time during a one month period:
Delusions
Hallucinations
Disorganised speech
Grossly disorganised or catatonic behaviour
Negative symptoms
What is the role of genetics in the development of schizophrenia?
The more you are related to somebody who has schizophrenia, the higher your risk is of developing it
There is a very strong genetic component but it is not a monogenic disease so there is not a straight influence
Name some genes which are associated with the development of schizophrenia
BDNF - neurotrphic factor
COMT
DAOA
Neuregulin 1
What type of people tend to develop schizophrenia and at what age does it tend to develop?
Often emerges in patients with an intelligence well above average
Tend to develop signs of the disease averagely around 20
Which symptom type are the drugs to treat schizophrenia generally effective against?
Generally used to treat the positive symptoms - do not currently have sufficient treatment to treat the negative and cognitive symptoms
Name the different types of schizophrenia
Paranoid Disorganised Catatonic Undifferentiated Residual
Are there structural changes of the brain that occur in schizophrenia and if so, what are they?
Generally there is no structural change of the brain in Schiz - so it is hard to understand why there is a profound abnormality in these patients
NB. in some patients there may be a small level of shrinking of grey matter and a increasing size of the ventricles - these tend to happen in patients who have a poor outcome and who do not respond to medication
Why does schizophrenia tend to happen at the start of the 20s?
This is because this is the time when the brain reaches final maturation - especially the prefrontal cortex
What in the brain is most likely to be altered in schizophrenia (if not brain structure)?
Schizophrenia is most likely to effect connectivity in the brain - a disease of altered brain connectivity
Particularly in the mesolimbic pathway (hyperactivity) and the mesocortical pathway (hypoactivity)
Mesolimbic pathway - positive symptoms
Mesocortical pathway - negative and cognitive symptoms
What is the main neurotransmitter effected in schizophrenia?
Dopamine - there is a large imbalance of these neurotransmitters throughout different regions of the brain
Mesolimbic - hyperactivity due to reduced reuptake of dopamine
Mesocortical - hypoactivity
SO treat with drugs targeting the dopaminergic pathways and receptors
What are the different dopamine receptor and which do you want to target for schizophrenia?
D1 type - D1, D5
D2 type - D2, D3, D4
The D2 receptors are the major pharmacological target for the treatment of schizophrenia
What is the main drug used to treat schizophrenia?
Chlorpromazine aka. Largactil
DRUGS ARE IN DRUG BANK
DRUGS ARE IN DRUG BANK
What are the adverse effects of antipsychotic drugs?
Parkinsonism Weight gain Dyslipidemia Type 2 diabetes Postural hypotension
These are generally due to the usage of atypicals
What is an effect of long term usage of anti-psychotics?
Tardive dyskinesia - involuntary movements of the lips, jaw, face, grimacing, constant chewing, tongue thrusting
What are the non-pharmacological treatments to treat schizophrenia?
Cognitive behavioural therapy
Family therapy
BUT these should not replace the pharmacological treatment and should be used in conjunction
What is the mesolimbic pathway and what is it’s role?
This is the dopaminergic pathway from the ventral tegmental area to the nucleus accumbens
There is dopaminergic release in the nucleus accumbens for rewarding stimuli
Where is the ventral tegmental area?
Located in the midbrain
Where is the nucleus accumbens?
Part of the basal ganglia - in the basal forebrain
What is the mesocortical pathway and what is it’s role?
Dopaminergic pathway from the ventral tegmental area to the prefrontal cortex
Involved in cognitive control, motivation and emotional responses
What are the three dopaminergic pathways of the CNS that we need to be aware of and what does dysfunction in them result in?
Mesolimbic - Schizophrenia
Mesocortical - Schizophrenia
Nigrostriatal - Parkinson’s disease
What environmental factors can lead to the development of schizophrenia?
Drug and substance abuse - can trigger schizophrenia if you have the genes that predispose you to the disease Unemployment Poor housing conditions Low birthweight Childhood trauma
What are the different targets for the pharmacological treatments of schizophrenia?
Typical antipsychotics - these mainly target D2 receptors BUT these also have an affinity for many other receptors e.g. D1, histamine H1
Atypical antipsychotics - used to mainly target 5-HT receptors (these are the first choice) - antagonistic effects at 5-HT so may potentially be able to also improve cognition
What is the relation of schizophrenia to glutamate receptors?
Post mortem studies have shown that there is a hypoglutamaterigic state in the cortex and schiz is associated with decreased glutamatergic transmission
What type of symptoms is catatonia?
Used to be considered a positive symptom and now considered a negative symptom - either is correct
What are the differential diagnoses for schizophrenia?
Psychosis in other conditions
What is clozapine and when is this used to treat schizophrenia?
Blocks D4 receptors with a high affinity - used if there is no response to any other medication
How can non-compliance of schizoprenia medication be overcome?
Depot injection of the medication
