The Fiery Landscape of Depression

I am the second author of this review article published in Pakistan Journal of Medical Sciences.

Ali Madeeh Hashmi, Muhammad Awais Aftab, Nauman Mazhar, Muhammad Umair, Zeeshan Butt


The purpose of this article is to review the evidence linking depression with inflammation, to examine the bi-directional relationship between the neuro-humeral circuitry of depression and the inflammatory response, and point out new treatment implications of these ideas. The evidence available is in areas of genetic links, association of depression with raised inflammatory markers such as Tumour Necrosis Factor (TNF)-alpha, Interleukin (IL)-1, IL-6, co-morbidity of depression with inflammatory medical illnesses, administration of cytokines leading to depression, and the recognition that anti-depressants have anti-inflammatory and neuro-protective properties. Inflammatory response and mood regulation constitute a system of bi-directional communication such that inflammatory cytokines can penetrate the CNS and influence behavior. Activation of the CNS cytokine network leads to a cascade of effects such as disturbed metabolism of amino acids, neurotoxicity, diminished neurotrophic support, decreased neurogenesis, impaired negative feedback regulation of HPA axis function and glucocorticoid resistance. Treatment implications include strategies to screen for patients with increased inflammatory activity, possible treatment with anti-inflammatory agents, and the recognition of new target areas for antidepressant medications.