## 4 Discussion
### Feature Selection  
For the second part of the study, we took an exploratory approach to identify what factors may be contributing to rosuvastatin's action of mood improvement. As previously mentioned, statins have been shown to bring changes in inflammatory responses and in rCBF. To further test the involvement of these factors narrowed down to their components becomes especially important. As a result, we compiled a large amount of information pertaining to these changes. We collected resting-state perfusion data from 45 distinct brain regions, including major gyri in the four major gyri as well as 32 different Brodmann Areas (BA) known to be affected in MDD. In parallel, we performed extensive blood tests to evaluate several circulating markers of inflammation and hemostasis in addition to other standard blood tests. We also tested the subjects' cognitive abilities before and after the study. Using the CANTAB test, we could curate scores representing a wide range of cognitive abilities such as attention, emotional processing, planning, visual processing, verbal memory, and spatial working memory. Using proven tools to handle a large number of variables for a relatively small study cohort, we identified ten unique variables (Table 4) that contributed the most to the differences between both groups. Initially, both the mRMR and Relieff techniques identified LDL cholesterol levels in the blood as the most distinct feature between groups. The Relieff algorithm also identified total cholesterol level as the fourth most distinct feature. This can be expected due to rosuvastatin's target application. Stating are prescribed not only due to their action on hyperlipemia and cholesterol production but also due to their role in diminishing cardiovascular events and stroke. As mentioned in the Results section, due to the expected action of stain use, these factors were excluded a priori, and the best five features were selected after this exclusion. Thus, the most distinct features between groups correspond to rCBF abnormalities in the left temporal lobe, and right BA 6 and right BA 23. Along with perfusion abnormalities in these regions, we found distinct changes between groups in levels of phosphorous and thyroid-stimulating hormone (THS), as well as circulating inflammatory markers such as NAP-2 and sCD40L. Notably, the median latency of response (from stimulus appearance to button press) on congruent trials measured through the CANTAB environment's attention switching task was also found to be distinct between groups. Feature selection tools provide information about the differences between groups, but they do not indicate the direction of these differences. Our analyses observed that there were no significant statistical differences between groups in any of the \(\Delta\) variables. Even so, it is relevant to consider the average \(\Delta\) values for both groups to understand the \"direction\" of the change occurring in these features for both groups. The perfusion \"abnormality\" in the left temporal pole decreased in the rosuvastatin group but increased in the placebo group. On the other hand, perfusion abnormalities increased in both the left middle and inferior temporal gyri as well as BA 6 in the rosuvastatin group, while it decreased in the placebo group. Additionally, perfusion abnormality in BA 23 increased in both groups but more in the placebo group. In one of our previous studies published recently, a significant association between endothelial dysfunction markers and changes in rCBF was observed in another group of MDD patients not taking any specific medication [76]. This suggests that the systematic damage or activation of the endothelium may be contributing to the observed perfusion abnormality. Interestingly, TSH levels in the blood decreased in the rosuvastatin group, while they increased in the placebo group. The same was observed for phosphorous levels in the blood. The significance of this non-metal element in the pathophysiology of MDD is not yet clear.