Citation

Mondelli V, Vernon AC. Clin. Exp. Immunol. 2019; 197(3): 319-328.

Affiliation

MRC Centre for Neurodevelopmental Disorders, King's College London.

Copyright

(Copyright © 2019, John Wiley and Sons)

DOI

10.1111/cei.13351

PMID

31319436

Abstract

Increased peripheral levels of cytokines and central microglial activation have been reported in patients with psychiatric disorders. The degree of both innate and adaptive immune activation is also associated with worse clinical outcomes and poor treatment response in these patients. Understanding the possible causes and mechanisms leading to this immune activation is therefore an important and necessary step for the development of novel and more effective treatment strategies for these patients. In this manuscript, we review the evidence of literature pointing to childhood trauma as one of the main causes behind the increased immune activation in patients with psychiatric disorders. We then discuss the potential mechanisms linking the experience of early-life adversity (ELA) to innate immune activation. Specifically, we focus on the innervation of the bone marrow from sympathetic nervous system (SNS) as new and emerging mechanism that has the potential to bridge the observed increases in both central and peripheral inflammatory markers in patients exposed to ELA. Experimental studies in laboratory rodents suggest that SNS activation following early-life stress exposure causes a shift in the profile of innate immune cells, with an increase in pro-inflammatory monocytes. In turn, these cells traffic to the brain and influence neural circuitry, which manifests as increased anxiety and other relevant-behavioral phenotypes. To date however, very few studies have been conducted to explore this candidate mechanism in humans. Future research is also needed to clarify whether these pathways could be partially reversible to improve prevention and treatment strategies in the future. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

Language: en

Keywords

childhood trauma; cytokine; depression; early adversity; inflammation; microglia; psychosis; sympathetic nervous system