Lecture 6 - Schizophrenia I Flashcards
What is the chance of an identical twin getting schizophrenia if their twin has it and what does this mean?
50% chance so other factors are linked to schizophrenia not just genetics.
What is the highest genetic risk factor for schizophrenia?
Deletion of 30 genes on chromosome 22.
22q11.2 deletion found in about 30% of patients.
What function is disrupted and what does this alter the activity of?
Neuregulin function disrupted and alters the function of AMPA and NMDA receptors.
Describe the changes in the prefrontal cortex in patients with schizophrenia.
Smaller basal dendritic fields.
Dendrites where excitatory synapses come in so less dendrites = less inputs coming in affecting cognitive function and performance.
Decreased spine density in pyramidal cells.
What developmental change happens to the ventricles in schizophrenia?
Enlargement of cerebral ventricles by 20%.
Ventricles involved in the production of CSF and ion regulation in the brain.
Describe the changes in brain gyrification in a patient with schizophrenia.
Increased gyrification initially then reduces.
Describe the changes to the hippocampus in a patient with schizophrenia.
Reduced hippocampus size.
Disorganised organisation of pyramidal cells so the input can’t synapse on the right part of the cell or an input may never reach the cell.
Describe the role of neuroinflammation in schizophrenia patients.
Microglia and astrocytes become active during neuroinflammation and microglia release pro-inflammatory cytokines (when chronic this is bad).
In schizophrenia it is thought there are too many activated microglia leading to the loss of brain tissue.
Many schizophrenic patients have high serum inflammatory markers, correlating the loss of grey matter in the PFC.
Describe the role of dopamine in schizophrenia.
Mesolimbic DA pathway is hyperactive and possibly accounts for positive symptoms.
Mesocortical DA pathway is hypoactive and possible accounts for negative symptoms.
Tuberoinfundibular DA pathway inhibits prolactin, tonic inhibition of lactation which is important for later side effects of treatment.
Describe the role of glutamate in schizophrenia.
Drugs that block NMDA receptors can induce psychosis.
Glutamate hypofunction in schizophrenia.
Abnormalities in NMDA function reduces opportunities for plasticity and normal glutamatergic signalling.
Decreased NR1 protein in PFC in patients with schizophrenia.
Describe the role of GABA in schizophrenia.
Decreased mRNA concentrations for GAD67 (GAD converts glutamate to GABA) and decreased GABA membrane transporter.
Reduction in GAD = less GABA being produced and released into the synapse.
GABA kept around for longer so GAT transporter is down regulated to keep GABA in synaptic cleft.
