A double-hit of stress and low-grade inflammation on functional brain network mediates posttraumatic stress symptoms

Jungyoon Kim,Haejin Hong,Eun Hee Lee,Suji Lee,In Kyoon Lyoo,Yoonji Joo,Sujung Yoon,Eunji Ha

doi:10.1038/s41467-020-15655-5

Abstract

Growing evidence indicates a reciprocal relationship between low-grade systemic inflammation and stress exposure towards increased vulnerability to neuropsychiatric disorders, including posttraumatic stress disorder (PTSD). However, the neural correlates of this reciprocity and their influence on the subsequent development of PTSD are largely unknown. Here we investigated alterations in functional connectivity among brain networks related to low-grade inflammation and stress exposure using two large independent data sets. Functional couplings among the higher-order cognitive network system including the salience, default mode, and central executive networks were reduced in association with low-grade inflammation and stress exposure. This reduced functional coupling may also be related to subsequent posttraumatic stress symptom severity. The current findings propose functional couplings among the higher-order cognitive network system as neural correlates of low-grade inflammation and stress exposure, and suggest that low-grade inflammation, alongside with stress, may render individuals more vulnerable to PTSD.

Highlights

Growing evidence indicates a reciprocal relationship between low-grade systemic inflammation and stress exposure towards increased vulnerability to neuropsychiatric disorders, including posttraumatic stress disorder (PTSD)
We investigate the role of altered functional coupling of the largescale brain networks related to both low-grade inflammation and repeated stress exposure in subsequent posttraumatic stress (PTS) symptom severity
Two large independent data sets were used to investigate alterations in internetwork connectivity related to low-grade inflammation and combined influence of stress exposure and low-grade inflammation (Fig. 1)

Summary

Introduction

Growing evidence indicates a reciprocal relationship between low-grade systemic inflammation and stress exposure towards increased vulnerability to neuropsychiatric disorders, including posttraumatic stress disorder (PTSD). Previous neuroimaging studies have identified several brain regions that are sensitive to inflammation, including the prefrontal cortex, insula, anterior cingulate, limbic structures, and basal ganglia[4,5,11,12] These regions are known to undergo functional alteration in response to stress exposure[13,14], and constitute much of the higher-order cognitive network system[15,16]. Little is known about the potential role of these brain regions in the reciprocal interactions between lowgrade inflammation and repeated stress exposure Whether such brain alterations may be directly related to the development of subsequent psychopathology of PTSD remains inconclusive. We investigate the role of altered functional coupling of the largescale brain networks related to both low-grade inflammation and repeated stress exposure in subsequent posttraumatic stress (PTS) symptom severity

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