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

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.

Bruton’s tyrosine kinase drives neuroinflammation and anxiogenic behavior in mouse models of stress

“…A growing body of evidence indicates a significant association between peripheral proinflammatory markers such as plasma IL1β in stress and trauma-related disorders [ 39 , 41 , 115 , 116 ]. PBMCs isolated from subjects with PTSD also exhibit significantly higher spontaneous production of IL1β and other proinflammatory cytokines, which correlate well with the severity of the PTSD symptoms [ 40 ].…”

“…Identification of transcripts with overlapping expression profile between blood and brain in stress disorders suggests the importance of peripheral inflammation in stress disorders [ 115 , 117 ]. Recent studies have shown that increased peripheral inflammation can predict altered functional connectivity in the major brain regions related to anxiety in the depression and PTSD [ 116 , 118 ]. Through there is a wide consensus that a few of the inflammatory markers, especially IL1β, are enhanced in blood following stress, however, bi-directional relationship, i.e., if peripheral inflammation contributes to stress disorders is not well understood [ 11 , 119 , 120 ].…”

COVID-19 y salud mental

“…Sin embargo, el estrés crónico origina una respuesta inflamatoria sostenida perjudicial. La inflamación, por tanto, actúa como elemento beneficioso y perjudicial para el organismo, ya que es un componente esencial de la inmunovigilancia y la defensa del huésped, mientras que un estado inflamatorio crónico de bajo grado, entendido como la presencia crónica de factores proinflamatorios que pueden surgir de factores estresantes persistentes en el cuerpo, incluido un mayor estrés oxidativo y psicosocial, es característico de una amplia gama de enfermedades crónicas como el síndrome metabólico, la esteatosis hepática no alcohólica, la diabetes mellitus tipo 2 o la arterioesclerosis 9 , así como de enfermedades neuropsiquiátricas y neurocognitivas, incluidos los trastornos neurodegenerativos, la depresión, la psicosis, el autismo, el abuso de sustancias, en especial, el alcohol, los trastornos del sueño y la epilepsia 4 , 5 .…”

P2X7 Receptor-Related Genetic Mouse Models – Tools for Translational Research in Psychiatry

“…In line with the immunometabolic hypothesis, studies have shown that genetic polymorphisms in inflammatory genes such as interleukin 1 beta (IL-1β), tumor necrosis factor alpha (TNFα) and C-reactive protein, influence depression incidence, severity, and treatment response ( Barnes et al, 2017 ; de Kluiver et al, 2019 , 2021 ; Draganov et al, 2019 ; Kappelmann et al, 2021 ). Meanwhile, psychosocial stress, the main environmental risk factor for depression, was linked to changes in adenosine triphosphate (ATP) mediated P2X7 receptor (P2X7R) signaling and related to neuroinflammation ( Kendler et al, 1999 ; Iwata et al, 2013 ; Rohleder, 2014 ; Calcia et al, 2016 ; Nelson et al, 2017 ; Maydych, 2019 ; Ribeiro et al, 2019 ; Kim et al, 2020 ). Therefore, innate, and adaptive immunity involving P2X7R is currently deemed a key player in stress-induced depression ( Wohleb et al, 2016 ; Leday et al, 2018 ; Giollabhui et al, 2020 ; Illes et al, 2020 ; Troubat et al, 2020 ; von Muecke-Heim et al, 2021 ).…”