Neuroimmune and neuroendocrine abnormalities in depression: two sides of the same coin

Abstract

Major depressive disorder has been linked to alterations in several interacting systems, particularly with respect to neuroendocrine and neuroinflammatory dysfunction. Increased levels of both cortisol and proinflammatory cytokines have regularly been described. This presents an apparent paradox, given the well-known anti-inflammatory properties of glucocorticoids, including inhibition of cytokine release. There are two competing theories to resolve this paradox: one proposes that reduced glucocorticoid signaling, as a result of glucocorticoid resistance, creates a permissive environment for an overactive innate immune system; the other theory focuses on evidence that glucocorticoids can be proinflammatory under some circumstances, depending on context and temporal factors. This review assesses the evidence base and limitations of both theories, discussing animal and clinical data, and preliminary work in human neural cells. Further work to delineate the relationship between neuroimmune and neuroendocrine systems in depression will be critical for understanding the biological perturbations underpinning depression, and therefore, for discerning treatment targets, and we include suggestions for future directions.

Early-life adversity and brain development: Is the microbiome a missing piece of the puzzle?

“…Colonisation later on did not have the same impact. Moreover, bifidobacteria has immunomodulatory properties and hence may be a mechanism through which the bacteria moderate the stress response as has been previously shown (Horowitz and Zunszain, 2015).…”

Depressive-like behavior, its sensitization, social buffering, and altered cytokine responses in rhesus macaques moved from outdoor social groups to indoor housing

“…A reduction in sensitivity to glucocorticoid suppression (i.e., increased glucocorticoid resistance) would have the opposite effect of reduced responsiveness to LPS; that is, it would tend to increase levels of both IL-1β and TNF-α. Increased glucocorticoid resistance has been observed in adolescent girls who have undergone early-life stress (Miller & Chen, 2010) and has been suggested to account for the simultaneously high levels of circulating cortisol and cytokines observed in depressed patients (Horowitz & Zunszain, 2015). …”

Checks and balances: The glucocorticoid receptor and NFĸB in good times and bad

“…Finally, it has recently been proposed that when dysfunctional, glucocorticoids not only signal less effectively, but also exert a pro-inflammatory impact when they do (Horowitz and Zunszain 2015). In particular, glucocorticoid signaling has been demonstrated to enhance inflammation under both stress (Frank, Thompson et al 2012) and conditions of central nervous system injury (Sorrells, Caso et al 2009).…”