Steven Crane Compiled Section Handouts. Human Behavioral Biology 2012

Use brain imaging instead

Study unmedicated schizophrenics (esp. early on in the disease)

Study close relatives of schizophrenics who might have the same changes but to a lesser extent.

• Also clues you in to the genetics.

But regardless, what are the big findings in terms of the differences?

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  Larger ventricles (atrophied brain tissue)
  
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  Small loss of neurons in the hippocampus
  
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  Hippocampal neurons are oriented in the wrong direction
  
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  Frontal cortex has neuronal loss and structural atrophy
  
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    Loss of GABA neurons (perhaps explains enhanced dopamine signaling)
    
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    Remember that frontal cortex is still maturing ages 18-25 and that's also where you get schizophrenia
    
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  Glia distribution abnormalities
  
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  Reelin protein has abnormal levels: it helps neurons migrate appropriately
  
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  Some evidence for thalamus atrophy
  

What are the genetics of schizophrenia?

What do classical behavioral genetics approaches tell us?

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  Gotta remember Kety's study of schizophrenia in Denmark. Biological/adoptive parent associations and the synergistic event of schizophrenogenic environment and genes.
  
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  Standard approaches (with standard caveats) show schizophrenia has genetic links: more concordance with closer relatives.
  
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  Standard approaches also show schizophrenia has environmental components: DZ twins have higher concordance for the disease than non-twin full siblings.
  

What have we learned from molecular genetics about schizophrenia?

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  Inconsistent genetic markers, probably because it's a heterogeneous disease.
  
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  COMT variant is associated with schizophrenia with a tiny effect.
  
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    Interestingly, the version that broke down dopamine MORE efficiently was associated with HIGHER levels of schizophrenia, complicating our earlier take on COMT and dopamine.
    
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  DISC-1 (disrupted in schizophrenia 1) is a gene that is, unsurprisingly, associated with schizophrenia. But also tied to depression and bipolar disease too.
  
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  MHC genes seem to be disrupted in schizophrenia. (see below with viral infection connection)
  
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  Various genes show abnormal copy number variants in schizophrenia.