Peripheral Immune Alterations in Major Depression: The Role of Subtypes and Pathogenetic Characteristics.

Frank Euteneuer,Katharina Dannehl,Adriana Del Rey,Winfried Rief,Harald Engler,Manfred Schedlowski

doi:10.3389/fpsyt.2017.00250

Abstract

Depression has been associated with peripheral inflammatory processes and alterations in cellular immunity. Growing evidence suggests that immunological alterations may neither be necessary nor sufficient to induce depression in general, but seem to be associated with specific features. Using baseline data from the Outcome of Psychological Interventions in Depression trial, this exploratory study examines associations between depression subtypes and pathogenetic characteristics (i.e., melancholic vs non-melancholic depression, chronic vs non-chronic depression, age of onset, cognitive-affective and somatic symptom dimensions) with plasma levels of C-reactive protein (CRP), interleukin (IL)-6, IL-10, and numbers of leukocyte subpopulations in 98 patients with major depression (MD) and 30 age and sex-matched controls. Patients with MD exhibited higher CRP levels, higher neutrophil and monocyte counts, lower IL-10 levels, and an increased neutrophil to lymphocyte ratio (NLR) than controls. Patient with later age of onset had higher levels of two inflammatory markers (CRP, NLR) and lower cytotoxic T cell counts after adjusting for sociodemographics, lifestyle factors, and antidepressants. Furthermore, lower anti-inflammatory IL-10 levels were related to more severe somatic depressive symptoms. These results confirm and extend previous findings suggesting that increased levels of CRP are associated with a later onset of depression and demonstrate that also NLR as a subclinical inflammatory marker is related to a later onset of depression.

Highlights

Depression has been associated with peripheral immune alterations, in particular low-grade inflammation [1, 2]
The aim of this report was to examine whether pro- and antiinflammatory cytokines and circulating leukocyte subpopulations are associated with specific subtypes and characteristics in major depression (MD)
Neutrophil counts, monocyte counts, and neutrophil to lymphocyte ratio (NLR) were increased in MD

Summary

Introduction

Depression has been associated with peripheral immune alterations, in particular low-grade inflammation [1, 2]. Longitudinal and experimental studies in humans and animals suggest bidirectional immune-to-brain communications, in which inflammation-associated disorders (e.g., cardiovascular disease, metabolic syndrome) and peripheral inflammatory signals lead to depressive symptoms and vice versa [3,4,5,6,7]. Meta-analyses on depression and inflammation suggest a large heterogeneity across studies [1, 2]. Heterogeneity may reflect that depression is not a “natural kind” but rather a scientific taxonomic category with substantial within-category variation [8]. Confirming this perspective, growing evidence suggests that inflammation may neither be necessary nor sufficient to induce or sustain depression in general, but may be associated with specific subtypes and characteristics of depression, respectively [5]. Other studies indicate that a later age of onset [13] may relate to higher levels of inflammatory markers, while findings for specific depression subtypes are mixed [14,15,16,17,18,19]

Objectives

Methods

Conclusion