Schizophrenia: mutant DISC1

Burrows et al. (2015) and Ayhan et al. (2011) emphasize that idea that the neurological pathology of schizophrenia is complex and nuanced. While Ayhan’s team focused on the effect of temporal expression on mutant human DISC1 expression on schizophrenic phenotypes, Burrows and colleagues put forth the idea that environment mediates glutamatergic pathways responsible for schizophrenic phenotypes. Both papers brought forward interesting human parallels and potential future directions in animal models in schizophrenia research.
One finding of note in the paper by Ayhan et al. was prefaced by the fact that “lateral ventricle enlargement is one of the most consistent abnormalities of the brain of patients with schizophrenia.” The team found no significant gender effects on ventricle enlargement after performing MRIs on the mice. The study also found that the Pre&Post and Post-Only groups had significantly larger ventricles and smaller cortical volume compared to the NO group. At the same time, these two groups were flagged as having greater neuronal spine density in certain areas of the brain compared to other groups. This makes sense when taking into account that larger vesicles yield less space for neurons. The authors conclude that post-natal expression of the mutant DISC1 gene was likely responsible for the enlargement of vesicles. I thought this idea was pretty exciting! However I am stuck on an insignificant gender effect. The authors also highlight that these results fall in line with a previous hypothesis that ventricular pathology is related to “post-natal changes”. In human patients, male patients with schizophrenia usually have earlier ages of onset (2) and, more interestingly, abnormally large ventricles are found more commonly (1, 3). Could there be a connection between age of onset and these “post-natal changes?” I find this disconnect to be puzzling and hard to place in the bigger picture of the pathology of schizophrenia.

Sources
(1) Henry A. Nasrallah, Steven B. Schwarzkopf, Stephen C. Olson, Jeffrey A. Coffman; Gender Differences in Schizophrenia on MRI Brain Scans, Schizophrenia Bulletin, Volume 16, Issue 2, 1 January 1990, Pages 205–210, https://doi.org/10.1093/schbul/16.2.205
(2) https://www.nami.org/Learn-More/Mental-Health-Conditions/Schizophrenia
(3) My Abnormal Psych Class notes :)

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