SZ - Basic Science Flashcards
Which NIMH research domains is SZ studied under?
Cognitive impairment
Anhedonia
Which aspects of SZ can be modelled in rodents?
Locomotor changes Psychomotor agitation Sensory gating abnormality Alteration in NTM levels Changes in cellular function
Describe the speech abnormalities in SZ
Word salad and knights move thinking
Perseveration
Rhyming
What abnormalities in action are seen in SZ?
Difficulty starting or finishing tasks
Bizarre behaviours with lack of purpose
Unpredictable emotional response
Describe frontal lobe activity in SZ?
Low
What is the DISC-1 mutation?
Translocation between chromosome 1 and 11 which truncates and activates the DISC-1 gene
What does the DISC-1 mutation put you at risk of?
SZ, bipolar and depression
What is the normal function of DISC-1?
Required for pyramidal cell migration
Tomita et al 2011
What is observed in DISC-1 KO mice?
Abnormal social behaviour
Reduced staining and abnormal interneuron activity
Pletnikov et al 2008
What does an inducible expression of DISC-1 in mice show?
Hyperactivity
Abnormal social behaviour
Ventricular enlargement
Reduced gamma synchrony
Pletnikov 2008
Give a brief outline of the neurodevelopmental hypothesis of SZ
There is hyperconnectivity between some neurons, and hypoconnectivity between others
Due to the aberrant neuronal migration (seen with the DISC-1 mutation)
This causes synaptic change
Outline the schizophrenia hypothesis of developmental oxidative stress
Oxidative stress damages cortical interneurons
Causing altered parvalbumin staining in the prodromal phase
This leads to E/Iimbalance
Then causing EEG alterations and cognitive defects
What is observed when monitoring rats with early hippocampal lesions?
Hyperactivity Hypersensitivity to stress Working memory deficits Reduced PPI Reduced parvalbumin staining Developmental changes in DA Altered E/I balance
What are endophenotypes?
Simple, quantifiable and heritable biological or behavioural traits
Which segregates an illness
What do endophenotypes need to be?
Heritable
Stable across symptom state
Easily and rapidly measured
Reliable