Solis et al. (2016) found that the lower levels of cortisol seen in patients with MD were independent of periodontal status. One study concluded that the association between periodontal disease and depressive symptoms is not mediated by systemic inflammation (Nascimento et al., 2019). The activation of proinflammatory immune parameters (IL-1β, IL-6, MMP-8) in periodontal damage was found to be independent of depression in a predictive (hypothetical) model among humans (Rodriguez Franco et al., 2020). This evidence concerns the gene MMP8 and major depressive disorder.