Re: Inflammation-modulating chemical has AD potential » SLS

> My impression is that inflammation emerges after the onset of depression rather than before.

Based on what I've read, I'm inclined to agree with you, at least to an extent. One factor that I think might account for the reported tendencies toward increased levels of inflammatory markers in patients with depression is the low vitamin D status that's been found to be associated with depression (Parker & Brotchie, 2011). A study that examined the association between vitamin D deficiency and inflammation in older Irish adults (Laird et al., 2014) found that participants with deficient vitamin D levels had significantly higher concentrations of interleukin-6 and C-reactive protein, as well as significantly higher interleukin-6-to-interleukin-10 and C-reactive-protein-to-interleukin-10 ratios, than participants whose vitamin D levels were sufficient. This finding follows reports from "numerous" in vitro studies that have indicated that vitamin D can significantly reduce concentrations of tumor necrosis factor and interleukin-6 and also increase the secretion of interleukin-10 (Laird et al., 2014). Considering that Zhang et al. (2012) found that two forms of vitamin D dose-dependently inhibited lipopolysaccharide-induced increases in interleukin-6, tumor necrosis factor, and p38 phosphorylation in human blood monocytes, there is reason to think that vitamin D might play a causative role in reducing inflammatory markers. Factors other than hypovitaminosis D might account for the associations that have been found between inflammation and depression, but I think that the evidence that I've described here points toward the possibility that low vitamin D levels might play a role in mediating the increased levels of inflammatory markers that tend to be found in patients with depression. Perhaps hypovitaminosis D might play a role in both causing depressive symptoms and in increasing the concentrations of inflammatory markers, or maybe hypovitaminosis D occurs mainly as a consequence of depression and then also contributes to raising inflammatory markers that tend to be increased in depressed patients, but I tend to think that the low vitamin D levels that tend to occur in patients with depression might at least contribute to the increased levels of inflammatory markers that have been found in those with depression.

But even though there is, from my perspective, some reason to think that the increased levels of inflammatory markers that have been found to be associated with depression might not necessarily contribute to the causation of depression, I do think it's interesting that the inflammation-modulating chemical (TPPU) that was the focus of the press release that I posted here seemed to prevent the onset of depression-related behaviors in mice when the chemical was administered to the animals before they were subjected to either inflammation or repeated social-defeat stress. Maybe some methods of reducing inflammation (such as soluble epoxide hydrolase inhibition) might have more antidepressant potential than other methods of reducing inflammation? I don't know. I do think that the findings that were reported in the press release that I posted are quite preliminary, but at the same time, I think that if sEH inhibitors do turn out to possess some antidepressant efficacy that they'd represent a rather unique way of treating depression that might potentially help some patients who aren't being helped by the treatment methods that are currently available.

Laird, E., McNulty, H., Ward, M., Hoey, L., McSorley, E., Wallace, J.M.W., et al. (2014). Vitamin D deficiency is associated with inflammation in older Irish adults. The Journal of Clinical Endocrinology & Metabolism, 99, 0000-0000. Article: http://press.endocrine.org/doi/full/10.1210/jc.2013-3507

Parker, G., & Brotchie, H. (2011). 'D' for depression: Any role for vitamin D? Acta Psychiatrica Scandinavica, 124, 243-249. Abstract: http://www.ncbi.nlm.nih.gov/pubmed/21480836

Zhang, Y., Leung, D.Y.M., Richers, B.N., Liu, Y., Remigio, L.K., Riches, D.W., et al. (2012). Vitamin D inhibits monocyte/macrophage proinflammatory cytokine production by targeting MAPK phosphatase-1. The Journal of Immunology, 188, 2127-2135. Article: http://www.jimmunol.org/content/188/5/2127.full

"Maybe someday
We'll figure all this out
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Try to find a way to just feel better now"

- Rob Thomas

Re: Inflammation-modulating chemical has AD potential » SLS

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