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Schizophrenia, Ayhan & Burrows

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The papers by Ayhan et al and Burrows et al focused on mouse models of schizophrenia and possible mechanisms that underlie its pathology. I really appreciate that both of these papers included female and male mice in their studies since schizophrenia in humans does not seem to be sex-specific. Ayhan et al focused on the effects of the mutant human DISC1 gene (hDISC1) seen in schizophrenic patients, whereas Burrows et al mainly studied the role of metabotropic glutamate receptor 5 (mGlu5) in schizophrenia.

The Ayhan paper immediately makes me think of the long-standing debate of “nature vs. nurture.” Their data indicate that different effects on both neuroanatomy and behavior depending on when the hDISC1 protein is expressed. This is especially relevant in light of the discovery of epigenetics, where some genes can preferentially express in individuals depending on their experiences. Therefore, I am interested to know how environmental factors, such as maternal care and absolute “mouse poverty” could affect those specifically with the hDISC1 gene. Are the same behavioral effects seen in hDISC1 mutants with enriched upbringings the same as those seen in hDISC1 mutants brought up under adverse conditions? In my opinion, that would make their study much more translatable to humans, especially to the groups who are identified to have the DISC1 gene mutation, since human upbringings can substantially affect one’s health in adulthood. Additionally, if no significant effects were seen in the experiments testing environmental factors, it would strengthen the Ayhan paper’s argument that hDISC1 expression itself causes the effects seen in schizophrenia. I acknowledge that this is much easier said than done.

The Burrows paper addresses the possibility of environmental factors contributing to schizophrenia and its associated symptoms. However, they identify mGlu5 as a mediator of behavioral impairments seen in schizophrenia. These results, along with the results from the Ayhan paper, highlight the complexity of schizophrenia as a neurological disorder. I would be very interested to see how environmental enrichment from the Burrows paper affected the hDISC1 mice from the Ayhan paper. Can environmental enrichment truly act as a therapeutic treatment for schizophrenia and counteract the effects of genetic mutations? Or are these beneficial effects of enrichment only sufficient when symptoms of schizophrenia are induced by dysregulation of NMDAR’s?

The Ayhan and Burrows papers certainly elucidate possible causes that underlie the pathology of schizophrenia. I think it’s extremely important for readers to critically think about the results regarding such complex disorders so that neither genetic nor environmental factors are discounted as possible contributors to the symptoms of schizophrenia. As always, more research is needed to paint a clearer picture of schizophrenia as a human disorder.

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