Schizophrenia Flashcards
What are some endocrine factors that could cause disturbances of thought?
1) Pituitary: tumor (hallucinations, acromegaly) or hypo (personality changes, sleep distrubances, memory loss)
2) Thyroid: hyper (cognitive dysfunction, depression then anxiety) or hypo (cognitive dysfunction, depression, encephalopathy
3) Hashimoto’s: encephalopathy- usually progressive decline
4) Parathyroid: hyper (psychosis, cognitive decline) or hypo (delirium and psychosis)
5) Cortisol: Cushing’s (depression, anxiety, psychosis is rare) or Addison’s (depression and behavioural changes)
What are some neurological factors which could cause disturbances of thought?
Epilepsy, Parkinsons, Huntingtons, Traumatic Brain injury, Neoplasm, infection, tumor, ischaemia, haemorrhage
What are some other factors which could cause disturbances of thought?
Pain, dehydration, electrolyte imbalance, infection, fever, hypothermia,
What are the 4 main biochemical hypothesises of schizoprenia?
Dopamine (excess in mesolimbic and decrease in mesocortical); serotonin (stimulation of 5HT 2a receptors causes psychosis); glutamate (decreased glutamate combines with serotonin to disable ‘gate’); GABA (decreased gabaergic in hippocampus gives loss of regulatory effects on dopaminergic)
What is the dopamine theory of schizophrenia?
Based on response to medications. An increase in mesolimbic gives positive sx and a decrease in the mesocortical system accounts for negatives.
There is also proposed overactivity of D2 receptors and also reduced activity of dopamine at D1 in the prefrontal cotrex implicated in working deficits
Some problems with this hypothesis such as relative ineffectivness of dopamine blocking drugs
What is the serotonin hypothesis of schizophrenia?
Pathways originate in midbrain dorsal and median raphe nuclei and project to cortex, striatum, hippocampus and other limbic regions.
LSD (an agonist/antagonist) produces similar symptoms as well as drugs like risperidone which are agonists at D2 and serotonin receptors.
Antagonist activity of atypical at 5HT is thought to account for the low liability of extrapyramidal sx and increased negative sx control of these drugs
What is the glutamate hypothesis of schizophrenia?
Decreased glutamate causes psychosis.
NMDA antagonists produced psychotic sx and decreased plasma concentration and receptor densities have been reported in post mortem brains.
Suggested that glutamate and domapmine exert excitatory and inhibitory effects respectively on GABA ergic striatal neurons that project tot he thalamus and constitute a sensory ‘gate’. Decreased glutamate and increased dopaminergic disables this gate and allows uninhibited sensory input to reach cortex.
What is the GABA hypothesis of schizophrenia?
Loss of gabaergic neurons in hippocampus causes loss of regulatory effect on dopamine activity and this causes hyperactivity of dopaminergic neurons
What are the strong risk factors for schizophrenia?
Family hx (closer to the pt the higher the risk) Substance use (cannabis etc)
What are the weak risk factors for schizophrenia?
parent age at birth 35 years Psychological stress Childhood abuse Birth time Geographic location (closer to the equator) Migrant status Inflammation Obstetric complications Infections Neurodevelopmental hypothesis
What receptors do antipsychotics supposedly work on?
Dopamine receptors (D1 and D2)
Serotonin (5-HT 2A)
Ach Muscarinic receptors
How do antipsychotics supposedly work on dopamine receptors?
Block mainly D2 eg antagonism of D2 in mesolimbic pathways relieves positive sx.
Doesn’t discriminate receptors in distinct brain areas so you get:
Nigrostraital: involved in movement (EPS, tardive dyskinesia)
Mesolimbic: Causes positive sx
Mesocortical: Negative sx
Tubulo-Infundibular: hypoprolactinaemia in untreated
How do antipsychotics supposedly work on serotonin receptors?
Receptor activation causes neuronal inhibition. Receptors in nigrostriatal pathway can control DA release and therefore antagonist enchance DA release in the striatum by inhibiting inhibitory effects of serotonin.
In the mesolimbic the combined effects of D2 and serotonin antagonist are thought to countaract the increased dopamine that gives the positive sx
How do antipsychotics supposedly work on ach muscarinic receptors?
In the striatum, dopaminergic nerve terminals are thought to innervate cholinergic interneurons which express inhibitory D2.
Blocking D2 in the striatum will then enhance Ach release and produce EPS.
A D2 receptor blocker with muscarinic antagonist activity will counteract this (SE: dry mouth, constipation and blurred vision)
What are the basic properties of typical antipsychotics?
Strong antagonism at D2 and some D1
Weak antagonism at 5-HT
Have efficiency against positive symptoms
Have many side effects- EPS, increased prolactin levels, sedation, hypotension,
