Major depressive disorder (mdd): emerging immune targets at preclinical level

ABSTRACTBackground Major depressive disorder is a mental health disorder that is characterized by a persistently low mood and loss of interest. MDD is affecting over 3.8% of the global population as a major health problem. Its etiology is complex, and involves the interaction between a number of factors, including genetic predisposition and the presence of environmental stresses.Areas covered The role of the immune and inflammatory systems in depression has been gaining interest, with evidence suggesting the potential involvement of pro-inflammatory molecules like TNF, interleukins, prostaglandins, and other cytokines, among others, has been put forth. Along with this, the potential of agents, from NSAIDs to antibiotics, are being evaluated in therapy for depression. The current review will discuss emerging immune targets at the preclinical level.Expert opinion With increasing evidence to show that immune and inflammatory mediators are implicated in MDD, increasing research toward their potential as drug targets is encouraged. At the same time, agents acting on these mediators and possessing anti-inflammatory potential are also being evaluated as future therapeutic options for MDD, and increasing focus toward non-conventional drugs which can act through these mechanisms is important as regards the future prospects of the use of anti-inflammatory agents in depression.KEYWORDS: DepressionImmune targetsCytokinesInflammationAnti-inflammatory agents Article highlights This article explores the various inflammatory pathways and mechanisms which are thought to be involved in the pathogenesis of major depressive disorder (MDD).An in-depth review of the inflammatory markers that are believed to play a role in the development of depressive symptoms, with a special focus on pro-inflammatory cytokines and prostaglandins, including interleukins 1 and 6 among others, tumor necrosis factor (TNF-α), and also protein kinase C.A discussion of pathways like the NLRP3 inflammasome and the kynurenine pathway which are gaining interest in the etiology of MDD.This article also touches upon the anti-inflammatory effects of conventional antidepressants such as fluoxetine, sertraline, and clomipramine, which may be playing a role in their efficacy.A look at the anti-inflammatory agents targeting the specific pathways mentioned in this paper is also included, along with a discussion about their potential in the therapy of MDD.Declaration of InterestThe authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants, or patents received or pending, or royalties.Reviewer disclosuresPeer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.Additional informationFundingDST-UT project allocated to A Kuhad & R Bhandari is greatly acknowledged