Abstract
Major depressive disorder (MDD) is a chronic condition that affects one in six adults in the US during their lifetime. The current practice of antidepressant medication prescription is a trial-and-error process. Additionally, over a third of patients with MDD fail to respond to two or more antidepressant treatments. There are no valid clinical markers to personalize currently available antidepressant medications, all of which have similar mechanisms targeting monoamine neurotransmission. The goal of this review is to summarize the recent findings of immune dysfunction in patients with MDD, the utility of inflammatory markers to personalize treatment selection, and the potential of targeting inflammation to develop novel antidepressant treatments. To personalize antidepressant prescription, a c-reactive protein (CRP)-matched treatment assignment can be rapidly implemented in clinical practice with point-of-care fingerstick tests. With this approach, 4.5 patients need to be treated for 1 additional remission as compared to a CRP-mismatched treatment assignment. Anti-cytokine treatments may be effective as novel antidepressants. Monoclonal antibodies against proinflammatory cytokines, such as interleukin 6, interleukin 17, and tumor necrosis factor α, have demonstrated antidepressant effects in patients with chronic inflammatory conditions who report significant depressive symptoms. Additional novel antidepressant strategies targeting inflammation include pharmaceutical agents that block the effect of systemic inflammation on the central nervous system. In conclusion, inflammatory markers offer the potential not only to personalize antidepressant prescription but also to guide the development of novel mechanistically-guided antidepressant treatments.
Highlights
Major depressive disorder (MDD) affects one in six adults in the United States during their lifetime [1,2]
This report aims to briefly review the role of inflammation in the pathophysiology of depression along with the recent findings of inflammatory markers moderating antidepressant treatment outcomes and the efficacy of monoclonal antibodies in reducing depressive symptoms in patients with chronic inflammatory conditions
They showed that (1) levels of Th17 cells were higher in brains of rodents that exhibited learned helplessness; (2) infusion of Th17 cells was associated with depression-like behaviors at sub-threshold stimulation; (3) infusion of anti-interleukin 17 (IL-17) antibody or administration of SR1001, an inhibitor of retinoid-related orphan receptor- γT (RORγT, a transcription factor essential for differentiation of naïve CD4+ T cells to Th17 cells) mitigated the effects of Th17 cell infusion; and (4) RORγT knockout mice exhibited marked resistance to learned helplessness paradigm [58]
Summary
Major depressive disorder (MDD) affects one in six adults in the United States during their lifetime [1,2]. MDD has a chronic course that is marked either by persistent symptoms or by repeated depressive episodes interspersed with periods of symptomatic improvement [3]. To reduce the disability and economic burden associated with MDD and to improve the poor clinical outcomes in clinical practice [10], there is an urgent need to parse through the syndromic and etiological heterogeneity of MDD [11]. This report aims to briefly review the role of inflammation in the pathophysiology of depression along with the recent findings of inflammatory markers moderating antidepressant treatment outcomes and the efficacy of monoclonal antibodies in reducing depressive symptoms in patients with chronic inflammatory conditions. A theoretical framework and potential future studies are discussed in order to personalize the prescription of currently available antidepressants and to identify novel treatments
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