Schizophrenia Flashcards
What are the 3 types of schizophrenia symptoms?
- Positive - Delluisons, hallucinations, etc
- Negative - Self-neglact, apathy, social withdrawal
- Cognitive (dementia?)
(Able to treat poitive not negative symp (Heterogeneous))
What is schizophrenia?
- Twice as prevalent as Alzheimer’s disease
- Relapsing, remitting or chronic progressive
- Strong but not invariable hereditary componen
- Early environmental risk factors important
What pathways are important in Schizophrenia?
- Hyper-activity of mesolimbic dopamine neurons (positive symptoms)
- Hypo-activity of mesocortical dopamine neurons (Negative symptoms)
What else is involved in schizophrenia and how is LE effected?
- Changes in post-syn dopamine D2&D3 receptors
- Cortical glutamate hypo-function & loss of GABAergic interneurons in striatum (Cognitive)
- Dysfunctional dev of frontal cortex
- LE decreased by 2 decades
- Only 1in7 recover
What are the anatomical characteristics of Schizophrenia?
- Brain structure abnormalities present at onset of psychosis, not progressive
- Suggests dev rather than degen
- Vol 6-10% red
- Enlarged ventricles + red temporal lobe
What are the genetic factors for schizophrenia?
- Family high risk (1 parent 12% risk) and 50% risk in identical twins
- Genome wide associaton study- 8 rare copy number variants of strong effect are associated but not disease specific.
What are the environmental factors of Schizophrenia?
- Early lesion hypothesis
* Foetal or perinatal event, that effects normal development - Late lesion hypothesis
* Deviation in neuronal maturation during adolescence
How does maternal immune activation affect schizophrenia development?
- 2X increase in risk of schizophrenia for babies born in winter
- Possibly due to maternal infection during pregnancies
- Disruption of neurogenesis at mid-pregnancy shows the development of positive symptoms
- Disruption of synaptogenesis at late pregnancy shows the development of negative symptoms
What pathways and areas of the brain are affected in Schizophrenia?
- Mesocortical pathways
- Mesolimbic pathways (Ventral tegmental area)
(Other 2 dopamine pathways, Nigrostriatal and tuberoinfundibular unaltered)
- Brain areas involved are Frontal cortex and Nuc acc and ventral striatum
What is the evidence for dopamine and schizophrenia?
- Amphetamine: Psychosis (positive-like symp) in schizophrenia
2.Amphetamine: Increases DA levels in the brain
3.Effects of amphetamine antagonised by anti-schizophrenic drugs called antipsychotics or neuroleptic drugs
- Antipsychotic drugs are dopamine D2 receptor antagonists
Explain link D2 receptors and schizophrenia?
- a-Flupenthixol - Blocks only D2 rec - clin effective
- b-Flupenthixol - Not active clin and not D2 ant
- D2 rec number incd in schizophrenia - Caused by treatment??
- D2 rec antagonism essential for antipsychotic effects
What is chloropromazine?
- Benefits: Apathy, red initiative
- Red emotion: D2 antagonist
- Red aggression (mesolimbic)
- Neuroendocrine effects: D2 antagonist
- Problem: Extrapyrimidal (striatum) effects: D2 antagonist
1. Acute parkinson’s
2. Long-term tardive dyskinesia
What are the extrapyrimidal side effects?
What are side effects of anti-psychotics?
- Actute dystonia - 1-5 days
- Parkinsonism - 5-30 days
- Akthisia - 5-60 days
- Tardive Dyskinesia - Months-Years
What causes these side effects?
(antipsychotics)
- Block of postsyn D2 receptors
- Acute dystonia, Akathisia - Basal ganglion
- Parkinsonism - Lack of striatal dop
- Tardive Dyskinesia - Long term dopa excess in striatum
