Schizophrenia week 2

This week, I found that both models of schizophrenia presented had promise, but ultimately they left me with more questions than answers.

In Ayhan et al., I thought that modulating DISC1 at different times during the lifespan was very smart. Since schizophrenia has well characterized roots in development, it made a lot of sense to me to look at the timing of mutant DISC1 expression. I thought overall this paper did a good job of re-confirming the behavioral disruptions brought on by this genetic mutation, but I had a difficult time pulling together a ‘big picture’ summary. In particular, they really lost me when they started switching between male-only and female-only analysis based on where there was significance. As I read through the paper, I decided I would give them a pass until I reached their explanation, but I was disappointed to find that they barely touched on the matter, and hadn’t provided a single potential reason for why they saw these differences. While I think it was useful to go through and identify the variability between genders, I think this made their overall model much weaker. I know that there are some sex differences in human schizophrenia expression (such as age of onset and severity), the findings in this paper seemed too random and unexplained to be mapped onto the human phenotype in any meaningful way. Because of this, I couldn’t convince myself that this model could be especially useful in future research, despite the fact that their data was very interesting.

The paper by Burrows et al. seemed much more clear to me, and I thought their model of schizophrenia was very strong. The use of environmental enrichment immediately made me hopeful for the possibility of early intervention and/or preventative treatment in humans. That being said, it seemed fairly obvious that living in a more enriching environment can have a number of beneficial outcomes, and I wasn’t sure if this was necessarily specific to schizophrenia as much as it is a general truth. Still, the ability to improve the cognitive function of mGlu5 KO mice was very promising. I think the ability to improve an animal’s function (and perhaps quality of life) in spite of genetic mutations is an important line of research.