TY - JOUR
T1 - Neuroimmune and neuroendocrine abnormalities in depression
T2 - Two sides of the same coin
AU - Horowitz, Mark A.
AU - Zunszain, Patricia A.
PY - 2015/9/1
Y1 - 2015/9/1
N2 - 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.
AB - 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.
KW - Cytokines
KW - Glucocorticoid resistance
KW - HPA axis
KW - Inflammation
KW - Stress
UR - http://www.scopus.com/inward/record.url?scp=84942079455&partnerID=8YFLogxK
U2 - 10.1111/nyas.12781
DO - 10.1111/nyas.12781
M3 - Article
AN - SCOPUS:84942079455
SN - 0077-8923
VL - 1351
SP - 68
EP - 79
JO - Annals of the New York Academy of Sciences
JF - Annals of the New York Academy of Sciences
IS - 1
ER -