L12 - schizophrenia and antipsychotics Flashcards
describe the pathology of schizophrenia
- reduction in cortical grey matter - supporting degeneration within cortex
- post mortem analysis shows that cortical pyramidal cells had reduced dendritic length and spine density
- reduced synapses especially in pre-frontal cortex
describe the pathology of schizophrenia
- reduction in cortical grey matter - supporting degeneration within cortex
- post mortem analysis shows that cortical pyramidal cells had reduced dendritic length and spine density
- reduced synapses especially in pre-frontal cortex
how was reduced synapses in schizophrenia identiifed?
PET scanning using tracer that binds to synaptic protein SV2A
does loss of synapses correlate with intensity of schizophrenia symptoms? what can be concluded from this
no
suggests synapse loss occurs at early stage of disease
supports the neurodevelopmental hypothesis for schizophrenia
it doesnt worsen with the progression of loss of synapses
list possible causes of schizophrenia
genetic
environmental
neurodevelopmental
expand on genetic cause for schizophrenia
50% risk of schizophrenia if individual has affected twin
many gene association studies concluded that singular genes have little impact on schizophrenia developmeny, but a combination of several of these genes may do
expand on environmental causeof schizophrenia
- cannabis exposure
- maternal factors (events during pregnancy eg malnutrition / infection)
- urban living and stress of adolescence
expand on neurodevelopmental hypothesis for schizophrenia
suggests the cause could either be
- a trigger in the gestational period that leads to schizophrenia development (possibly infection or malnutrition)
evidence is that individuals with schizophrenia have abnormal fingerprint ( which is developed in the 14th - 22 week gestational period) - in adolecence fine tuning of synapses could be affected (by genetics/environmental disturbance) that leads to the impairment of this fine tuning and development of schizophrenia
evidence that supports this is reduced no. of synapses
what are the 3 categories of Schizophrenia symptoms and define them
positive -> exaggeration of normal behaviour
negative -> suppression of normal behaviour
different patients will experience different symptoms
cognitive symptoms
give some examples of positive symotoms of schizophrenia
- delusions -> fixed inaccurate self belief such as delusions of grandeur
- hallucinations
- delusions
- thought disorders (irrational thoughts)
- abnormal behaviour (agression, repetitive, purposless
give some examples of negative symptoms of schizophrenia
- social withdrawal
- Flattened emotions
- Lack of drive
- Disorganised speech (alogia)
give some examples of cognitive symptoms of schizophrenia
- attention deficits
- Learning and memory issues
- Decision making
what is the dopamine hypothesis of schizophrenia
DA hyperactivity is responsible for positive symptoms of schizophrenia
list evidence that supports the DA hypothesis of schizophrenia
- Amphetamine (which increases [DA]) induces stereotypical psychotic like symptoms in patients (paranoia, visual&auditory hallucinations)
- L-DOPA can induce psychosis in patients with Parkinson’s
- Genetic associations between genes of dopaminergic system and schizophrenia
- D2/D3 receptor genes
- BDNF (brain derived neurotrophic factor) which supports growth and survival of dopaminergic neurones
- COMT (catecho-O-methyl transferase) enzyme involved in dopamine metabolism
- Increased numbers of D2 dopamine receptors in brain post mortem (more receptors indicates more firing and over activity)However some have argued that this could be as a result of treatment - blocking receptors may cause the brain to upregulate their expression
- Effective anti-psychotic drugs block brain dopamine D2 receptors
- Affinity of drug for D2 receptors directly correlates with clinical potency of drugs
describe the genetic evidence that supports the DA hypothesis of schizophrenia
Genetic associations between genes of dopaminergic system and schizophrenia
- D2/D3 receptor genes - BDNF (brain derived neurotrophic factor) which supports growth and survival of dopaminergic neurones - COMT (catecho-O-methyl transferase) enzyme involved in dopamine metabolism
polymmorphisms in these associated with schizophrenia
what could the increased numbers of D2 DA receptors in schizophrenia patients be due to rather than the disease itself?
However some have argued that this could be as a result of treatment - blocking receptors may cause the brain to upregulate their expression
what are the two classes of antipsychotics
typical
atypical / 2nd generation
where else do typical antipsychotics act as antagonists
a adrenoreceptors
D1 receptors
5-HT2 & mACh
histamine H1
where do atypical antipsychotics act as antagonists
same as typical, but have highest affinity for 5-HT2 receptors
also have a higher affinity for D4 receptors over D2 receptors
