Kellendonk and Moore

Both Kellendonk et al. (2006) and Moore et al. (2006) explored different models for schizophrenia. Kellendonk et al. examined overexpression of dopamine receptors in the striatum and the correlated cognitive deficits, while Moore et al. used methylazoxymethanol  acetate (MAM) at E17 to disrupt corticostriatal circuits and development.

One of the most interesting aspects of both articles was their use of reversal techniques within the experiment. For example, Kellendonk et al. used doxycycline to switch off the expression of dopamine receptors to see if the cognitive deficits were reversed or corrected. The cognitive deficits persisted, however, and could even be exacerbated, suggesting a much more complex pathology. I also found their examination of the circuitry relating to D1 receptors and dopamine turnover interesting as well. This relates to human applications by providing some insight into why some antipsychotics that target dopamine receptors do not improve the cognitive deficits given that treatment usually starts later in life after an episode when it may be too late for physiological affects. Granted, Kellendonk et al. acknowledges the shortcomings in the model of addressing symptoms such as hallucinations.

Moore et al. also focused on the size of different brain regions, especially the PFC, and neuron density. By using the evidence looking at the E17 model, I found their arguments convincing that the post-pubescent approach more accurately reflects the schizophrenia pathology given that the disease usually presents itself in humans in early adulthood.

Personally, I found both of these articles rather difficult to follow, likely because of my very limited neuroanatomical knowledge. While the behavioral and cognitive tests in each seemed to follow a logical progression, they sometimes resulted in inconclusive results or those that conflicted with previous studies. As a first exposure to schizophrenia research, my general impression is that this field seems highly controversial and mysterious. For example, while an increase in dopamine receptors seems to be pertinent, the exact role is controversial. That said, these articles were published ten years ago, and I’m sure many developments have been made since then.