Modeling Schizophrenia: Ayhan et al. and Burrows et al.

Both of these papers aimed to model schizophrenia in mice models, albeit by very different avenues. The first paper, published in 2011 by Ayhan et al., investigated the role of mutant human DISC1 gene in neurobehavioral abnormalities associated with the disorder by examining the effect of the mutant hDISC1 expression at different timepoints of development. Across these developmental stages of mutant expression, the researchers tested social interaction, depressive-like behaviors, and drug-induced activity. 

I very much appreciated that this paper used both male and female mouse models (which is surprising for a 2011 paper, I think). However, for multiple behavioral tests, the groups of male and female mice exhibited different behaviors, and for some reason this was not addressed in the paper. Specifically, female mice in the “post” group spent more time in immobility compared to the female mice in the “no” group, but “expression of mutant hDISC1 had no effect on these behaviors in male mice of either group.” Also, the male mice in the “pre + post” group exhibited an increase in locomotion with injections of MK-801 and d-amphetamine, but there was no difference among the groups of female mice. Is this not significant? Perhaps I am missing something here, but I would expect an explanation, at the very least, for why the results were different for the male and female mice. Moreover, I found the data from the frontal cortex of the male mice (specifically the decrease in tissue content of DA and DOPAC in the experimental groups when compared to the control) very convincing, but what about the frontal cortex in females? I could not even find this in supplementary. All in all, I did find the data in this paper compelling, but I would have liked an explanation for why the behavioral effects of the mutation were not consistent across the male and female mice.

The second paper, published in 2015 by Burrows et al., used an mGlu5r deficient-model to investigate the interactions between genes and the environment in the context of the development of a schizophrenia phenotype. I believe that this is a very important aspect of all neurological disorders that must be addressed; however, I was shocked to find that their study used only male mice. I feel that it would have been interesting to assess the differential effects of environmental enrichment on male and female mice – can’t we agree that there is possibly a difference in the way that genetics in males and females are modulated by the environment? I would have been much more convinced if this had been addressed in the paper.