Basal and LPS-stimulated inflammatory markers and the course of anxiety symptoms

Wessel A Van Eeden,Ebtisam El Filali,Albert M Van Hemert,Ingrid V.E Carlier,Brenda W.J.H Penninx,Femke Lamers,Robert Schoevers,Erik J Giltay

doi:10.1016/j.bbi.2021.09.001

Abstract

A cross-sectional relationship between low-grade inflammation –characterized by increased blood levels of C-reactive protein (CRP) and pro-inflammatory cytokines– and anxiety has been reported, but the potential longitudinal relationship has been less well studied. We aimed to examine whether basal and lipopolysaccharide (LPS-)induced levels of inflammatory markers are associated with anxiety symptom severity over the course of nine years.We tested the association between basal and LPS-induced inflammatory markers with anxiety symptoms (measured with the Beck’s Anxiety Inventory; BAI, Fear Questionnaire; FQ and Penn’s State Worry Questionnaire; PSWQ) at 5 assessment waves over a period up nine years. We used multivariate-adjusted mixed models in up to 2867 participants of the Netherlands Study of Depression and Anxiety (NESDA).At baseline, 43.6% of the participants had a current anxiety disorder, of which social phobia (18.5%) was most prevalent. Our results demonstrated that baseline inflammatory markers were significantly associated with several outcomes of anxiety at baseline over nine subsequent years. BAI subscale of somatic (arousal) symptoms of anxiety, and FQ subscale of agoraphobia demonstrated the strongest effects with standardized beta-coefficients of up to 0.14. The associations were attenuated by 25%-30% after adjusting for the presence of (comorbid) major depressive disorder (MDD), but remained statistically significant.In conclusion, we found that participants with high levels of inflammatory markers have on average high levels of anxiety consisting of physical arousal and agoraphobia, which tended to persist over a period of nine years, albeit with small effect sizes. These associations were partly driven by co-morbid depression.

Highlights

Anxiety is regarded as a psychobiological state or reaction that, amongst others, consists of unpleasant subjective feelings of tension, nervousness and worry, often accompanied by physiological manifes tations such as increased heart rate and blood pressure, and irregularity of breathing (Pitsavos et al, 2006)
Our study is the first to examine the relationship between basal as well as LPS-induced inflammatory markers with longitudinal measures of anxiety symptom severity over a period of up to nine years
Our re sults demonstrated that participants with elevated inflammatory markers at baseline had on average higher levels of anxiety at baseline, which persisted during the course of nine years follow-up

Summary

Introduction

Anxiety is regarded as a psychobiological state or reaction that, amongst others, consists of unpleasant subjective feelings of tension, nervousness and worry, often accompanied by physiological manifes tations such as increased heart rate and blood pressure, and irregularity of breathing (Pitsavos et al, 2006). Anxiety can be induced by an external stressor (Trier social stress test), resulting in the characteristic physiological changes, as well as the biochemical response of cortisol and catechol amines release (Foley & Kirschbaum, 2010). This activated inflammatory pathways in peripheral mononuclear cells through the transcription factor-ƙB (NF-ƙB), leading to increased levels of circulating pro-inflammatory cytokines such as interleukin-6 (Bier haus et al, 2003; Pace et al, 2006). These symptoms could be prevented when patients were pretreated with selective serotonin reuptake inhibitors (SSRIs) before the start of IFN-α administration, indicating that these inflammation-related symptoms may in part be mediated through se rotonin (Musselman et al, 2001)

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