This set of papers read differently compared to the other papers covered in class so far. In the past the papers we have read have focused on investigating a new aspect of anxiety or depression based on pre-established models. This week however, the focus of Moore et al. was the creation of a rodent model of schizophrenia, while Kellendock et al. focused on D2 receptor overexpression.
After reading Kellendock et al. my first impression was “The researchers still don’t know anything definitive about the etiology of the cognitive symptoms. They just know a polymorphism in the D2 receptor gene increased D2 ligand binding.” I was definitely convinced that the dopamine system is implicated in the pathology of schizophrenia, but I still was not sure how; I had trouble seeing the big picture. The authors mentioned in their introduction that “the genetics of most mental illness is polygenic and complex” as opposed to the genetics of neurological illness.” Consequently, the researchers decided to focus on a very specific aspect of the disease, in this case the link between dysfunction of dopamine D2 transmission and deficits in working memory and behavioral flexibility. In my Clinical Neuroscience class I noticed a trend, whenever we studied a different disease we would learn that there was some abnormality in the patient’s brain, but we would never learn in which direction the implications of said abnormality leaned. All the researchers knew was something was different, but did not know specifically how said differences affected the patient. I found that trend to be present when reading this paper. The researchers had all of these findings such as D2 mice having altered glucose metabolism, or D2Rs in the striatum affected D1R activation in the mPFC, but said finding seemed isolating and did not integrate well into the overall narrative of the paper.
To be fair, I also feel that had I had a stronger background in schizophrenia research this paper may have read more smoothly. If that had been the base I may have been able to see connections between the etiology of the disease and the corresponding finding in the paper. The same can be said for the Moore paper. Based on my limited knowledge of schizophrenia it seemed like the researchers had created a successful rodent model, but without further background knowledge it is difficult to be critical.