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Video: The Underlying Mechanisms of Depression

While it’s likely that there may be more going on with depression than just inflammation by itself, it could be an incredibly useful lens through which to look at promising avenues to potentially treat or prevent it, since controlling systemic inflammation shows promise as being both important for longevity and health in general. Moreover, inflammation can be clinically monitored by well-known biomarkers for systemic inflammation, making it amenable to potentially tracking therapeutic success: the risk of major depression has been shown to increase by 44% for each standard deviation increase in log c-reactive protein.

The immune system and the pathogenesis of depression

During chronic infections and other chronic medical conditions associated with intense immune activation, the sickness behaviour syndrome can develop into a depressive episode. Studies have found that certain cancer and hepatitis c therapies, which often involve the use of cytokines, have been associated with the development of flu-like depressive symptoms. The causal role of the cytokines has been established by the fact that the depressive symptoms appear almost immediately after cytokine administration and disappear shortly after cytokine treatment is terminated.

The immune system and the pathogenesis of depression

There is bidirectional communication between the HPA axis and the immune system. Cytokines activate the HPA axis and thus lead to the release of cortisol, the stress hormone, which ordinarily suppresses the immune response. Cortisol also inhibits its own release and thus the body is able to maintain a stable immune response through a tightly regulated feedback inhibition system. This regulation mechanism seems to be dysfunctional in depressive disorders and is thought to occur because of cytokine mediated receptor resistance to cortisol, thus impairing feedback inhibition. This essentially means that cytokines make cortisol unable to act on the receptors that would inhibit its release. Long story short — the HPA axis is hyperactive because of cytokines, leading to a chronic stress response because cytokines impair the body’s ability to regulate it — thus leading to depressive symptoms.

Probiotic Shot May Alleviate Brain Stress | GEN

“Given the evidence for reduced immunoregulation and chronic low-grade inflammation in anxiety and trauma-related disorders, microbial interventions that increase Treg, promote immunoregulation, and increase anti-inflammatory signaling may have value in the prevention or treatment of these disorders,” the authors suggest. M. vaccae has previously been shown to increase induction of Treg production and anti-inflammatory cytokines. A previous study by CU Boulder scientists showed that mice given injections of a heat-killed M. vaccae preparation and then placed in housing with an aggressive male exhibited less anxiety-like behavior and were less likely to suffer colitis or peripheral inflammation than control animals. These findings suggest that immunoregulatory and anti-inflammatory treatments can “buffer against the proinflammatory effects of stress,” the researchers point out.  What hasn’t been studied before is whether M. vaccae has a direct impact on stress-induced neuroinflammation.

Dark chocolate consumption reduces stress and inflammation: Data represent first human trials examining the impact of dark chocolate consumption on cognition and other brain functions -- ScienceDaily

"This is the first time that we have looked at the impact of large amounts of cacao in doses as small as a regular-sized chocolate bar in humans over short or long periods of time, and are encouraged by the findings. These studies show us that the higher the concentration of cacao, the more positive the impact on cognition, memory, mood, immunity and other beneficial effects."