Cellular basis of behavioural illness Flashcards
What is catatonia?
Motor immobility as evidenced by catalepsy or stupor
Excessive motor activity (purposeless, not influenced by external stimuli)
Extreme negativism (motiveless resistance to all instructions or maintenance of a rigid posture against attempts to be moved ) or mutism
Although neuropathology has chnaged significantly over centuries today, what still reminas constant for many diseases?
Clinical diagnoses only
No pathological test
When do most neurodevelopmental and mental disorders arise?
Why?
In late teens to early adulthood
Due to the way the brain is developing at this time
Describe the sequence of maturation of the cortex?
Maturation begins in the occipital lobe
Last part of cortex to mature is frontal lobe
Which brain cells are thought to be responsible for neuropathology?
Probably a mix of neuronal and glial pathology
How much of the adult’s resting metabolic rate is allocated to the brain?
25%
How are synapses implicated in development?
Change dynamically during development
Synaptogenesis and synpatic pruning
How are synapses implicated in neuropathology such as schizophrenia or other disorders in childohhod and adolescence?
Problem with synaptogenesis or synpatic pruning
Describe the differences in connectivity that may occur in neuropathology such as schizophrenia?
Decreased neuronal size
Decreased neuronal connections: between dendrites and synapses, between thalamus and cortex, and decreased molecular markers of synpases
What are the three categories of brain changes?
Neurochemical
Anatomical
Trophic/signalling/developmental
Describe the three risk factor categories for developing schizophrenia?
Genetic/epigenetic
Perinatal - hypoxia
Prenatal - pyrexia, starvation
Which neurochemical chnages may occur to produce neuropathology such as schizophrenia?
Imbalances in dopamine, GABA or glutamate
?ubiquitination
Describe the anatomical abnormalities that may occur to produce neuropathology such as schizophrenia?
Decrease in synpases or dendrites
Decerased GABAergic interneurons (inhibitory)
?glial and microglial changes
Which signalling pathways have been implicated in the development of neuropathology such as schizophrenia?
NRG1
AKT1
Wnt/GSK3b
In which parts of the Wnt signalling pathway are abnromalities present on schizophrenia?
Can be a number of places
How do astrocytes interact with neurons?
Describe how they affect the function of neurons?
Astrocytic prrocess are in contact with synapses
One astrocyte domain encompasses 270,000-2 million synpases
Regulate the activity at synapses
Describe the glial cell changes that are thought to occur in psychiatric disorders?
Decreased glial density, espeically in deeper layers of cortex
Also decreased neuronal size (less active due to loss of glia)
How might microglia play a role in the neuropathology of disorders such as schizophrenia?
Markers of microgila significantly upregulated in schizophrenia
Suggest that inflammatory processes are occurring
Which cell types are thought to be responsible for the OCD-like behaviour seen in autism?
Explain.
Lack of microglia
Hoxb8 knockout mice express behaviour similar to OCD
(Hoxb8 only expressed by microglia)
Mice were rescued by bone marrow transplant from WT mice
How is brain growth thought to be altered in autism?
Early overgrowth of DLPFC
Both grey and white matter affected
Describe the proposed genetic basis behind autism?
SNPs
Distributed autistic and non-autistic individuals based on genetic classifications, and were able to classify with an accuracy of 85% using various SNPs
Thought to involve some protective and some risk factor SNPs
