Epigenetics of concussion: a systematic review

Background: Concussion is the most common neurological disorder affecting millions of people globally each year. Identifying epigenetic mechanisms influencing concussion incidence, severity and recovery could provide diagnostic and prognostic insight into this injury. Objectives: This systematic review aims to identify the epigenetic mechanisms underpinning concussion. Methods: Seven electronic databases; PubMed, MEDLINE, CINAHL, Cochrane library, SPORTDiscus, Scopus and Web of Science were searched for studies that investigated the epigenetic mechanisms of concussion and its underlying neuropathology. Results: Based on inclusion and exclusion criteria, 772 titles were independently analysed by two of the authors to a final list of 28 studies that totaled 3042 participants. We observed separate associations between sncRNAs, methylation, histone modification and concussion. Overall, 204 small non-coding RNAs were significantly dysregulated between concussed participants and controls or between concussion participants with no post-concussive symptoms and those with post-concussive symptoms. From these, 37 were reported in more than one study and 23 of these were expressed in a consistent direction with at least one further study. Ingenuity pathway analysis identified 10 miRNAs known to regulate 15 genes associated with human neurological pathologies. Two studies found significant changes in global methylation in concussed participants and one study found a decrease in H3K27Me3 in the context of DNA damage and concussion. Conclusions: The review findings suggest that epigenetic mechanisms may play an important role in the pathophysiological mechanisms that could influence outcome, recovery, and potential long-term consequences of concussion for individuals.