title: 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.
authors.affiliation: Stress, Psychiatry, and Immunology Laboratory (SPI-Lab), Department of Psychological Medicine, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, United Kingdom.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Horowitz
authors.affiliation: Stress, Psychiatry, and Immunology Laboratory (SPI-Lab), Department of Psychological Medicine, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, United Kingdom.
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Zunszain
mesh_terms: D000818:Animals; D016207:Cytokines / Q000097:blood; D003863:Depression / Q000503:physiopathology*; D003865:Major Depressive Disorder / Q000276:immunology / Q000503:physiopathology*; D005938:Glucocorticoids / Q000378:metabolism; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007113:Immunity, Innate / Q000276:immunology; D007249:Inflammation / Q000276:immunology; D015213:Neuroimmunomodulation / Q000276:immunology; D009490:Neurosecretory Systems / Q000276:immunology / Q000503:physiopathology*; D015398:Signal Transduction; D013315:Stress, Psychological / Q000276:immunology / Q000503:physiopathology*
chemical_list: D016207:Cytokines; D005938:Glucocorticoids; D006854:Hydrocortisone
keywords: HPA axis; cytokines; glucocorticoid resistance; inflammation; stress