Meechan DW, Tucker ES, Maynard TM, Lamantia AS.
Diminished dosage of 22q11 genes disrupts neurogenesis and cortical development in a mouse model of 22q11 deletion/DiGeorge syndrome. Proc Natl Acad Sci U S A.
2009 Sep 22
Comments on News and Primary Papers
Comment by: Brian Morris
Submitted 5 October 2009
Posted 5 October 2009
The dramatically increased risk of schizophrenia associated with velocardiofacial/DiGeorge syndromes (VCFS/DGS) can potentially provide us with a unique insight into the causes of the disease. This study is interesting in that it provides further evidence that reduced levels of expression of the genes encoded in this short region of chromosome 22 are sufficient to cause neurodevelopmental impairments in cerebrocortical neurons. It is worth remembering, as noted above, and as emphasized by the authors, that VCFS/DGS are associated with increased risk of a number of mental health problems with a neurodevelopmental component, not just schizophrenia. In fact, the cortical abnormality reported in this paper that can be specifically associated with schizophrenia (altered parvalbumin neuron distribution) is really subtle. Nevertheless, the study suggests that reduced expression of these few genes on chromosome 22 may be sufficient to cause cortical parvalbumin neuron dysfunction. In turn, this provides some support for the theory that cortical GABA interneuron impairments are an early event in the etiology of schizophrenia, and not simply a consequence of the cortical dysfunction arising from other causes.
The number of genes in the VCFS/DGS deletion region is small, and studies using gene-specific knockouts can provide further insight into the mechanisms leading to altered cortical function in schizophrenia.
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