SCIZOPHRENIA Flashcards
positive symptoms
hallucinations
delusions
negative symptoms
blunted emotional responses
withdrawal from social interactions
lack of motivation
behave eccentrically
poverty of speech
poor attention spam
cognitive symptoms
disorganised life > long term disability
no treatment
can be found to some degree before the positive symptoms appeared
hallucinations
- precepts that occur in the absence of appropriate sensory stimuli
- auditory hallucinations
delusions
firm beliefs that are not realistic and not explained by the patient’s culture
periods of florid psychosis
accompanied by markedly disordered thinking and abnormalities in the regulation of emotion
interspersed with periods of residual symptoms
treatement for schizophrenia
antipsychotics > most effective at diminishing positive symptoms
aetiology of schizophrenia
genetically heterogeneous
may genes associated are expressed during neurodevelopment, therefore a neurodevelopmental disorder
2 forms of genetic variation in schizophrenia
variations in single nucleotide bases
large chromosomal deletions, duplications, or translocations
22q11.2
chromosomal translocation in sz
chromosomes 1 and 11
inactivates a gene (DISC-1)
DISC-1
- important for brain development
- disrupted in schizophrenia-1
- DISC-1 must interact with other genes and non-genetic factors to determine the final phenotype
amino acid neurotransmitters
glutamate
GABA
biogenic amines neurotransmitters
histamine
serotonin
catecholamine (noradrenaline, adrenaline, dopamine)
acetylcholine
neuropeptide neurotransmitters
orexin
oxytocin
structural abnormalities
- thinning of specific areas of the prefrontal, temporal and parietal cerebral cortex
- prefrontal cortex > the most pronounced area > dorsolateral prefrontal cortex (working memory, cognitive function)
- temporal lobe > loss of grey matter in > the superior temporal gyrus, temporal pole, amygdala (may be limited to males), hippocampus
cellular and synaptic level - grey matter
loss of grey matter in the cerebral cortex
- due to network dysfunction
- not the result of cell death
- a reduction in dendritic, axonal and synaptic processes
cellular and synaptic level - smaller thalamus
- may be explained by cell death
- may be loss of cell bodies in the mediodorsal nucleus of the thalamus
- loss of axonal terminals in the DLPFC
- contribute to the reduction of cortical dendrites and the dendritic spines
when are the abnormalities observed in sz
diagnosed in late teen years/early 20s
cortical abnormalities and ventricular enlargement are generally observed at the time of first diagnosis
adolescent (healthy) brain
- early adulthood is an important period of brain development
- ‘synaptic pruning’ - circuit refinement
- may be particularly important in the PFC
- pruning coincides with major changes in dopaminergic neurotransmission during late adolescence
1st generation antipsychotics in sz
- all act on dopaminergic pathways
- chlorpromazine (originally an anti-histamine)
- reducing positive symptoms such as hallucinations and delusions
- less impact on the negative symptoms and little/no impact on cognitive deficits
- produced Parkinson-like side effects
2nd generation antipsychotics in sz
- clozapine has the best efficacy
- lower affinity for D2 receptors
- some also block the serotonin 5-HT 2A receptors
clozapine in sz
- atypical drug
- affinity: D1, D2, 5HTRs, others
chlorpromazine in sz
- ‘dirty’ drug
- acting on many receptors
haloperidol in sz
- typical drug
- high affinity for D2 receptors
olanzapine in sz
- atypical drug
- affinity for 5-HT 2A receptors > D2 receptors
risperidone for sz
- qualitatively atypical drug
- more pronounced serotonin antagonism than dopamine antagonism
D1 and D5 dopamine receptors
- coupled to stimulatory G proteins that activate adenylyl cyclase
- striatum, cerebral cortex and hippocampus
D2, D3 and D4 dopamine receptors
- coupled to inhibitory G protein that inhibits adenylyl cyclase
- striatum, cerebral cortex, amygdala and hippocampus
