Cellular Basis of Behavioural Illness

Question 1

What are the general anatomical neuropathic findings in schizophrenia?

Answer 1

decreases in neuron size, number of connections (dendrites and synapses), fewer connections between thalamus and cortex, and changes to cell skeleton

Question 2

Which markers indicate decreases in synapses in schizophrenia?

Answer 2

synapsin, gap43, connexins

Question 3

What are the 3 types of changes that occur in the brain?

Answer 3

Neurochemical, anatomical, and changes in trophic signalling or developmental pathways

Question 4

What are the 3 general risk groups for schizophrenia?

Answer 4

genetic/epigenetic; perinatal (hypoxia during birth); and prenatal (pyrexia and starvation)

Question 5

Schizophrenia is characterized by

Answer 5

excess of dopamine leading to psychotic features such as delusions and hallucinations

Question 6

What neurochemical abnormalities are associated with schizophrenia?

Answer 6

excess dopamine; glutamatergic; GABAergic (ubiquitination where cells get ri of damaged proteins)

Question 7

What signalling and developmental pathways have been implicated in schizophrenia?

Answer 7

neuregulin (NRG1), AKT1, Wnt/GSK

Question 8

What is the importance of the Wnt pathway?

Answer 8

it decideds the fate of a cell - whether it becomes a neuron or not by regulating the cytoskeleton via glycogen synthase kinase 3 beta (GSK3b); expression of many of the components of the pathway are altered in schizophrenia and AD

Question 9

What is the role of glial cells?

Answer 9

Regulation of synaptic activity

Question 10

What affect on glial cells is found in the anterior cingulate (mood and affect) of bipolar disorder, schizophrenia, and major depression?

Answer 10

decreased glial cell density in deeper layers of cortex and decreased neuronal size

Question 11

What affect on glial cells is found in the dorsolateral prefrontal cortex (mood and affect) of bipolar disorder, schizophrenia, and major depression?

Answer 11

decreased glial cell density and neuron volume in all 3 disorders

Question 12

What is observed of glial cells in schizophrenia?

Answer 12

decreased density of cells and reduced neuron volume in deep cortical layers

Question 13

What is the significance of elevated calprotectin in schizophrenic brains?

Answer 13

expressed by microglia, therefore a marker of inflammatory process (upregulation of the genes A8 and A9 for this protein are also upregulated)

Question 14

What is the significance of microglia in OCD?

Answer 14

Hoxb8 gene is expressed only in microglia; Hoxb8-KO mice express OCD behaviour

Question 15

How is autism linked to cortical growth?

Answer 15

Often an overgrowth in the frontal cortex that resolves by 7-8

Question 16

How are microglia implicated in autism?

Answer 16

microglia in autistic DLPFC are enlarged and amoeboid - they look as if activated by inflammation but there are no associated inflammatory cytokines

Question 17

What is observed of microglia in autism with respect to white and grey matter?

Answer 17

increased density in both grey (sig) and white matter; increased somal volume in grey matter (moreso in age <6) and moreso in white matter

Question 18

What is a SNP?

Answer 18

When a single nucleotide differs within a population or individual

Question 19

How are SNPs implicated in autism?

Answer 19

Parents pass on risk or protective SNPs (more protective = better); especially related to GRM5 receptor which dampens microglial activation and is decreased in autism