Involvement of inflammatory gene expression pathways in depressed patients with hyperphagia

Rick Jansen,Hilde De Kluiver,Yuri Milaneschi,Brenda W J H Penninx

doi:10.1038/s41398-019-0528-0

Rick Jansen, Hilde De Kluiver + Show 2 more

Open Access

https://doi.org/10.1038/s41398-019-0528-0

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Abstract

The pathophysiology of major depressive disorder (MDD) is highly heterogeneous. Previous evidence at the DNA level as well as on the serum protein level suggests that the role of inflammation in MDD pathology is stronger in patients with hyperphagia during an active episode. Which inflammatory pathways differ in MDD patients with hyperphagia inflammatory pathways in terms of gene expression is unknown. We analyzed whole-blood gene expression profiles of 881 current MDD cases and 331 controls from the Netherlands Study of Depression and Anxiety (NESDA). The MDD patients were stratified according to patients with hyperphagia (characterized by increased appetite and/or weight, N = 246) or hypophagia (characterized by decreased appetite and/or weight, N = 342). Using results of differential gene expression analysis between controls and the MDD subgroups, enrichment of curated inflammatory pathways was estimated. The majority of the pathways were significantly (FDR < 0.1) enriched in the expression profiles of MDD cases with hyperphagia, including top pathways related to factors responsible for the onset of inflammatory response (‘caspase’, ‘GATA3’, ‘NFAT’, and ‘inflammasomes’ pathways). Only two pathways (‘adaptive immune system’ and ‘IL-8- and CXCR2-mediated signaling’) were enriched in the MDD with hypophagia subgroup, these were also enriched in the total current MDD group and the group with hyperphagia. This confirms the importance of inflammation in MDD pathology of patients with hyperphagia, and suggests that distinguishing more uniform MDD phenotypes can help in finding their pathophysiological basis.

Highlights

Major depressive disorder (MDD) is one of the leading causes of morbidity worldwide with a high socioeconomic burden[1,2]
Stratification of the current MDD group according to change in appetite and/or weight during a major depressive episode resulted in 246 participants with MDD hyperphagia and 341 participants with MDD with hypophagia
This study evaluated enrichment of inflammatory pathways among mean gene expression profiles of two MDD subgroups that can be distinguished based on the direction of appetite and/or weight change during an episode, compared to controls

Summary

Introduction

Major depressive disorder (MDD) is one of the leading causes of morbidity worldwide with a high socioeconomic burden[1,2]. MDD is a heterogeneous disorder for which many etiological factors have been suggested, for instance low-grade inflammatory activation[3,4]. Meta-analyses of peripheral inflammatory marker studies report elevated levels of C-reactive protein (CRP), interleukin(IL)-6, tumor necrosis factor (TNF)-α, the soluble IL-2 receptor and lowered levels of interferon(IFN)-γ in MDD patients[5,6,7,8] compared to controls. Large between-study heterogeneities and small to moderate effect sizes were observed in these meta-analyses, which may partially be attributable to the phenotypic heterogeneity of MDD. Recent results from the Netherlands Study of Depression and Anxiety (NESDA) on

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