Wk 10.1 Schizophrenia Flashcards
What are the clinical features of Schizophrenia?
- Common major psychosis
- Affects 0.5-1% of adult population
- 40% are hospitalised
-Peak in late teens to early 20s
-40% risk of offspring having condition if both parents are affected
-10% if one parent is affected
What are some symptoms?
-Delusions
-Hallucinations}- Linked to hyperactive DA pathway to FB
-Anhedonia
-Social withdrawal
-Depression/ anxiety
What causes schizophrenia?
The cause is unknown, but many factors have been implicated:
-Genetic factors
-Neurochemical changes (GABA, GLU, DA??)
-Neurophysiological changes
-Brain structural changes (evidence from patients and animal models)
How many stages of schizophrenia are there and what are the names?
-2
-Positive (1) or negative (2) - some ppl can have both
- Positive symptoms= D & H
- Negative symptoms= A,SW and alogia
What is difference between healthy and schizophrenic brain during an MRI scan?
-Ventricular enlargement - tissue absence adjacent to frontal cortex
-Bigger space- less tissue surrounding
- Reduced cortical tissue volume in Schizo
What does scan also show?
- Pink shows the maximal loss of neurone tissue over time
-Young people brain is still under development - so it could be an issue if neurodevelopmental failure and partial failure as well as neuronal loss of tissue
What is the difference between neurodevelopment on normal and schizophrenia?
-Under 25yrs brain is still somewhat developing
Normal: Child and early adulthood that the prefrontal excitatory synapsis will die off
No inhibitory synapse as a child comes in late teens and early adult phase
When old the inhibitory tends to predominate
Schizophrenia
-Slower rate
-Prefrontal synapse pruning other the years happens at different rate compared to normal brain
What are the gentic link or causation?
-NR1 and NR2C- are genes that encoded subunits for NMDA receptors
- Monozygotic twins and homozygous carrier parents indicate strong hereditary link
-NT receptor and ion channel genes (DRD4, DRD2, NR1, NR2C, KCNH3.1) -some evidence
-Knockout
- Neurodevelopmental genes- dvl1
What is Disheveled (dvl1) and Dsh how does it work?
-Dvl1 is Example of a knockout
-Dvl1 is found in humans, mice and flies which are used as models to look at what happens when knocking out or in a particular gene
-Dvl1 encodes Dsh protein
-Dsh is a protein found found in the Wnt and it critical to CNS development
-Dvl1 (-/-) mice -abnormalities that may correlate with schizophrenia
What is limited in dvl and what does it lead to?
-Dvl-/- may have limited ability to traffic NMDArs to GLU synapses
-Is dvl1 isn’t working leading to synapse not forming correctly
-This leads to effects on the glutamate pathways and other pathways
Information on DISC1?
-Linked to schizophrenia / depression phenotype in this family
-Protein has important role in neuro-development and acts as ‘scaffold’ or ‘interactome
-If DISC1 doesn’t work properly the normal protein interactions will not happen appropriately.
In hDISC1 which one has more dendrites?
Control so it it good for connections with other cells
