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Ayhan and Burrows

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In their paper, Ayhan et al. (2011) discuss the importance timing plays in the expression of the protein hDISC1 during neurodevelopment, and how this contributes to the manifestation (or lack thereof) of Schizophrenia-like phenotypes. Burrows et al. (2015) explore the role of environmental enrichment in mGlu5 KO mice, and discover robust effects in restoration of spatial learning as well as amelioration of Schizophrenia-like behavioral phenotypes.
There are a few things I found notably interesting in both papers. In Burrows et al., there were no sex differences seen within the experimental group. On the other hand, Ayhan et al. reported sex-specific effects of mutant hDISC1 both in behaviorally and neurally. I thought this brought up an interesting point regarding the etiology and sex-specific nature of Schizophrenia, and whether the sex differences can be more attributed to temporal expression of protein as opposed to gene-environment interactions, or whether this is presumptous or simply incorrect. I would be curious to see a follow-up study by Ayhan et al. where they further explore these behavioral sex-differences in the mutant hDISC1 what that could mean on a more translational level.

I particularly enjoyed the developmental aspect of the Ayhan et al. paper. Although early onset Schizophrenia is not typical among children or adolescents, the aberrant developmental trajectory of the brain is established during gestation, long before clinical symptoms of the disease appear in early adult life. It brought me to thinking about the environmental enrichment model in Burrows et al., and whether we need to start directing more of our focus to exploring early intervention models for major psychiatric disorders like Schizophrenia. I believe a comprehensive characterization model of hDISC1 throughout pre and postnatal development into adolescence and adulthood would be a start, and then creating novel environment enrichment behavioral assays based on these differential patterns of expression. In either case, there is still a tremendous amount of research that would need to be done, but I certainly see a future clinical application for (time and maybe even sex-specific) catered enrichment intervention models.

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