the psychotic brain Flashcards
what are the symptoms of schizophrenia?
positive symptoms:
• hallucinations
• dellusions
• racing thoughtd
cognitive symptoms: • issues in working memory • issues in attention • issues in executive function • disorganised thoughts
negative symptoms: • withdrawal • blunted affect • loss of motivation • apathy
what pathology underlines schizophrenia?
very little underlying pathology
scans mainly done to rule out other diseases
in schizophrenia:
• ventricle enlargement
• decreased cortical volume - particularly temporal
• volume loss in thalamus
what post-mortem changes are observed in schizophrenics?
absence of gliosis
altered synaptic connectivity
loss of cortical asymmetry
decreased spine density, dendritic length, number of terminals in pyramidal neurons
does schizophrenia have a genetic component?
yes, known from family studies that schizophrenia has a genetic component
contribution of many small genes:
– neuregulin → regulates synaptic plasticity
– dysbindin
– DISC1 → encodes important protein
– RGS4
genes have structural variations which have small contribution to schizophrenia
accumulation of copy number variants leads to schizophrenia
what is the schizophrenic energy metabolism hypothesis?
energy metabolism is disordered in schizophrenics
mitochondrial dysfunction = ketone bodies used as energy source instead of glucose
what is the schizophrenic dopamine hypothesis?
is there any evidence which contradicts this hypothesis?
hyperactivity of D2 receptor in limbic systems contributes to positive symptoms of SZ
hypoactivity of D1 receptor in the prefrontal cortex contributes to negative symptoms
SUPPORTING EVIDENCE:
increased density of the dopamine D2 receptor in postmortem brain tissue of schizophrenia sufferers
CONTRADICTING EVIDENCE:
– no primary DA abnormalities
– prolactin levels normal
– many patients unresponsive despite complete DA blockade
which receptor is commonly blocked by psychostimulants?
many psychostimulants block NMDA receptors which are heavily involved with glutamate
give 6 examples of psychostimulants
PCP ketamine cocaine THC D-amphetamine MK-801
what is the schizophrenic glutamate hypothesis?
disrupted mechanisms of glutamate signalling
blocked NMDA receptors stop GABAergic interneurons from detecting excitation
interneurons think there is no excitation and don’t release GABA = over-excitation (positive symptoms)
what is the schizophrenic neurodevelopmental hypothesis?
genetic and non-genetic factors impact on the orderly cascade of brain development, leaving the affected offspring susceptible to adult-onset schizophrenia
risk factors: – infection in early life – nutrition in early life – foetal hypoxia – cannabis – stress – born in winter or spring
what are the 7 domains of cognition?
- attention/vigilance
- speed of processing
- reasoning and problem solving
- verbal learning and memory
- visual learning and memory
- working memory
- social cognition
how is pre-pulse inhibition tested in animals?
how is pre-pulse inhibition effected in schizophrenics?
the acoustic startle system is used to assess pre-pulse inhibition in animals
based on a startle response after exposure to a sudden noise
in normal animals, the addition of a softer noise, or pre-pulse, immediately before the loud startle stimulus, can lead to a significant inhibition of the subsequent startle response
deficits in pre-pulse inhibition are seen with schizophrenia and other neuropsychiatric disorders
how is pre-pulse inhibition modulated?
pre-pulse inhibition modulated by dopamine, glutamate, GABA in various brain regions
how is attention measured in the continuous performance test?
a series of stimuli are presented one at a time for several minutes
subjects instructed to press key when target is presented
– single target version (X)
– cue-target version (A-X)
measurements:
– reaction time
– number of hits
– errors of omission (failing to respond to a target)
– errors of commission (responding to stimuli other than the target)
