Correlation between Mild Traumatic Brain Injury-Induced Inflammatory Cytokines and Emotional Symptom Traits: A Systematic Review.

Shazia Malik,Omar Alnaji,Mahnoor Malik,Teresa Gambale,Michel Piers Rathbone

doi:10.3390/brainsci12010102

Abstract

Both mild traumatic brain injuries (mTBI) and systemic injuries trigger a transient neuroinflammatory response that result in similar clinical outcome. The ensuing physical, cognitive, and emotional symptoms fail to subside in approximately 15–20% of the concussed population. Emotional impairments, particularly depression, anxiety, and post-traumatic stress disorder (PTSD), are commonly associated with poor recovery following mTBI. These emotional impairments also have a significant neuroinflammatory component. We hypothesized that the inflammatory cytokines seen in mTBI patients with emotional symptoms would coincide with those commonly seen in patients with emotional symptoms without mTBI. A systematic review was conducted to identify the most common neuroinflammatory cytokines in the mTBI population with psychological symptoms (depression, anxiety, PTSD). The electronic databases EMBASE, MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), PUBMED, and PSYCINFO were searched from data inception to 31 August 2021. A systematic screening approach was employed from screening to data analysis. A total of 994 articles were screened, 108 were selected for full article review, and 8 were selected for data analysis. The included studies consisted of 875 patients of which 81.3% were male. The mean sample size of patients with at least one mTBI was 73.8 ± 70.3 (range, 9–213), with a mean age of 33.9 ± 4.8 years. The most common cytokines associated with poor psychological outcomes involving PTSD and/or depression in the chronic mTBI population were IL-6, TNFα, IL-10, and CRP.

Highlights

Mild traumatic brain injuries, commonly known as concussions, account for approximately 80–90% of all traumatic brain injuries (TBI) [1,2]
This study found evidence supporting the association between upregulated cytokine levels (IL-6, Tumor Necrosis Factor-α (TNF-α), IL-10, C-Reactive Protein (CRP), and IL-1β) and adverse psychological outcomes in Mild traumatic brain injuries (mTBI)
There is a positive correlation between elevated IL-6 and TNF-α levels and post-traumatic stress disorder (PTSD) in chronic mTBI patient population

Summary

Introduction

Mild traumatic brain injuries (mTBI), commonly known as concussions, account for approximately 80–90% of all traumatic brain injuries (TBI) [1,2]. Concussion acutely triggers a cascade of biomolecular changes in the brain [7]. These lead to behavioral changes amongst other symptoms following concussion. It was observed that patients who sustain systemic injuries not involving the brain have the same characteristic symptoms as those who suffer concussions [8]. This raised the possibility that humoral mechanisms triggered by the systemic injury produced the same effect on the brain as a concussive injury to the brain itself [9]

Methods

Results

Discussion

Conclusion