Different aspects of schizophrenia

The two papers differed in their takes on how to go about the alterations in brain function in schizophrenia. While Moore focused more on the lesions and abnormal development of the brain, Kellendonk’s group explored the efficacy of dopamine receptor over-expression in mice. While I felt that both of these papers did an exceptional job with their thorough examination, I found myself questioning what is really the best example of schizophrenia? Kellendonk’s work found some interesting results using the tTa system with dox that gave a nice parallel (a 15% higher receptor binding capacity vs the 12 seen in humans). Kellendonk also had some interesting results regarding executive functioning with working memory and planning that has some weight in that schizophrenic patients often have a difficult time with this task. They showed that D2R mice showed significantly more errors and took more trails to reach criterion. These, I believe, are nice results but I don’t think that they have extreme significance in solely schizophrenia. At the end of the paper, the authors propose that more research is needed to be conducted and that a very small percentage of schizophrenic patients actually exhibit these psychopathologies. What I found to be most promising in the Kellendonk paper was looking at the prefrontal cortex and how the D2 receptors secondarily affect the D1 receptors in the PFC. They found that there was an increase in dopamine levels and a decrease in the DOPAC/ HVA amount in the PFC. Since schizophrenia results in a lot of executive function deficits, I think noting the effects of dopamine receptor increase in areas and its resulting effects in the PFC are extremely important.

A discrepancy I found interesting was the PPI difference between papers. In Kellendonk’s paper, they noted that there were no effects from increasing D2 receptors after prefacing that it is typical of schizophrenic patients to have sensorimotor gating issues, and something one may expect in a dopamine intervention. In Moore’s paper, there was a significant difference between the all dB and msec levels in their “version” of the schizophrenic rodents. Also, there seemed to be a marked discrepancy between ataxia in MAM animals even without PCP. There seems to be ataxia found in many people with schizophrenia, but like most mental disorders like schizophrenia, there are many without, therefore there is no “better” answer to the question of which paper shows this correctly.

As both papers noted and as we know, there is a lot of difficulty targeting the right place for schizophrenia in animal models. While I think that the dopamine paper may hold a more conclusive ending, the MAM paper seems to hold a lot of weight and something more novel in the use of genetic variability, something I would like to see used with dopamine as well. Comparing the families of people with schizophrenia gives a lot of insight in how genetics play a part in predisposition and I think it would be interesting to see that being used with not just morphological differences (which I interesting in the dopamine paper- no real morphological differences) but also behavioral differences passed down.

As a side note, I was a little confused about the use of PCP (ie. why) with the paper and am open to hearing peoples ideas about the drug choices!