Effects of Antidepressant Treatment on Peripheral Biomarkers in Patients with Major Depressive Disorder (MDD).

Anna Mosiołek,Agata Szulc,Natalia Zborowska,Sławomir Jakima,Jadwiga Mosiołek,Aleksandra Pięta

doi:10.3390/jcm10081706

Abstract

Major depressive disorder (MDD) is one of the most prevalent mental illness and a leading cause of disability worldwide. Despite a range of effective treatments, more than 30% of patients do not achieve remission as a result of conventional therapy. In these circumstances the identification of novel drug targets and pathogenic factors becomes essential for selecting more efficacious and personalized treatment. Increasing evidence has implicated the role of inflammation in the pathophysiology of depression, revealing potential new pathways and treatment options. Moreover, convergent evidence indicates that MDD is related to disturbed neurogenesis and suggests a possible role of neurotrophic factors in recovery of function in patients. Although the influence of antidepressants on inflammatory cytokines balance was widely reported in various studies, the exact correlation between drugs used and specific cytokines and neurotrophins serum levels often remains inconsistent. Available data suggest anti-inflammatory properties of selective serotonin reuptake inhibitors (SSRIs), selective serotonin and noradrenaline inhibitors (SNRIs), and tricyclic antidepressants (TCAs) as a possible additional mechanism of reduction of depressive symptoms. In this review, we outline emerging data regarding the influence of different antidepressant drugs on a wide array of peripheral biomarkers such as interleukin (IL)-1ß, IL-2, IL-5, IL-6, IL-8, IL-10, C-reactive protein (CRP), or interferon (IFN)-γ. Presented results indicate anti-inflammatory effect for selected drugs or lack of such effect. Research in this field is insufficient to define the role of inflammatory markers as a predictor of treatment response in MDD.

Highlights

Depression is the most commonly diagnosed psychiatric disorder
Studies confirm that depressive disorders, in the absence of other physical comorbidities, are associated with increased levels of various pro-inflammatory cytokines, including tumor necrosis factor alpha (TNF-α) and interleukins (ILs)
Cytokines are most commonly classified according to their effects on inflammation into cytokines that stimulate the development of inflammation, i.e., pro-inflammatory cytokines (e.g., interferon (IFN)-γ, Tumour Necrosis Factor (TNF), IL-1, IL-2, IL5, IL-8) and those that suppress inflammation, i.e., anti-inflammatory cytokines (e.g., IL-1β, IL-6, TNF-α, IL-10, IL-19, IL-20, IL-22, IL-24, IL-26, IL-28, IL-29)

Summary

Introduction

Depression is the most commonly diagnosed psychiatric disorder. It has a multifactorial etiology and the various hypotheses of depression are complementary to one another. Studies suggest that depression is associated with elevated levels of both pro-inflammatory and anti-inflammatory cytokines, e.g., IL-1β, IL-6, IFN-γ, TNF-α, and C-reactive protein (CRP). Pro-inflammatory cytokines may cause hypothalamic–pituitary–adrenal (HPA) axis hyperactivity by interfering with the negative feedback of the HPA axis and corticosteroids (CS) and may reduce serotonin (5-HT) levels by decreasing the availability of its precursor, tryptophan (TRP), through the activation of a TRP-metabolizing enzyme, indoleamine 2,3-dioxygenase (IDO) [3,4,8,14,15,16,17]. Excessive HPA-axis activity and immune dysregulation lead to abnormal function of the kynurenine pathway responsible for tryptophan conversion to two key compounds involved in mood regulation: serotonin and melatonin [16]. Depression is associated with neuro–immuno–metabolic interactions and immunometabolic dysregulation

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