PURPOSE. Post-traumatic stress disorder (PTSD) is associated with inflammatory-related medical conditions. This review examines studies of immune function in individuals with PTSD to determine if excessive inflammation is associated with PTSD. CONCLUSIONS. Current studies suggest an excess of inflammatory actions of the immune system in individuals with chronic PTSD. High levels of inflammatory cytokines have also been linked to PTSD vulnerability in traumatized individuals. There is also evidence that excessive inflammation is in part due to insufficient regulation by cortisol. PRACTICE IMPLICATIONS. An excess of inflammatory immune activity may contribute to health declines in individuals with PTSD, and treating PTSD symptoms may reduce these risks.

Traumatic brain injury (TBI) is recognized as the signature injury in military personnel deployed for combat operations in Operation Enduring Freedom and Operation Iraqi Freedom. Combat injuries and injuries in nondeployed settings have resulted in more than 300 000 TBI cases, with many experiencing multiple TBIs.¹ While most of these TBIs are mild and individuals show good recovery, TBIs place military personnel at risk for chronic neurological and psychological symptoms, including postconcussive disorder (PCD), posttraumatic stress disorder (PTSD), and depression, and for the development of chronic traumatic encephalopathy.^2-6

Objectives To determine whether a panel of blood-based biomarkers can discriminate between patients with suspected mild traumatic brain injury (mTBI) with and without neuroimaging findings (CT and MRI). Methods Study participants presented to the emergency department with suspected mTBI (n = 277) with a CT and MRI scan and healthy controls (n = 49). Plasma concentrations of tau, glial fibrillary acidic protein (GFAP), ubiquitin carboxyl-terminal hydrolase L1, and neurofilament light chain (NFL) were measured using the single-molecule array technology. Results Concentrations of GFAP, tau, and NFL were higher in patients with mTBI, compared with those of controls (p9s < 0.01). GFAP yielded an area under the curve (AUC) of 0.93 (95% confidence interval [CI] 0.90–0.96), confirming its discriminatory power for distinguishing mTBI from controls. Levels of GFAP, tau, and NFL were higher in patients with trauma-related intracranial findings on CT compared with those with normal CT, with the only significant predictor being GFAP (AUC 0.77, 95% CI 0.70–0.84). Among patients with mTBI, tau, NFL, and GFAP differentiated subjects with and without MRI abnormalities with an AUC of 0.83, with GFAP being the strongest predictor. Combining tau, NFL, and GFAP showed a good discriminatory power (AUC 0.80, 95% CI 0.69–0.90) for detecting MRI abnormalities, even in patients with mTBI with a normal CT. Conclusion Our study confirms GFAP as a promising marker of brain injury in patients with acute mTBI. A combination of various biomarkers linked to different pathophysiologic mechanisms increases diagnostic subgroup accuracy. This multimarker strategy may guide medical decision making, facilitate the use of MRI scanning, and prove valuable in the stratification of patients with brain injuries in future clinical trials. Classification of evidence Class I evidence that blood concentrations of GFAP, tau, and NFL discriminate patients with mTBI with and without neuroimaging findings.

Objective: Identify biomarkers in peripheral blood that relate to chronic post-concussive and behavioural symptoms following traumatic brain injuries (TBIs) to ultimately improve clinical management. Research design: We compared military personnel with mild TBIs (mTBIs) (n = 42) to those without TBIs (n = 22) in concentrations of tau, amyloid-beta (Aβ42) and cytokines (tumour necrosis factor alpha (TNFα, interleukin (IL)-6 and -10) in neuronal-derived exosomes from the peripheral blood. We utilized nanosight technology coupled with ultra-sensitivity immunoassay methods. We also examined the impact of post-concussive and behavioural symptoms including depression and post-traumatic stress disorder (PTSD) on these neuronal-derived markers. Results: We report that concentrations of exosomal tau (F_1, 62 = 10.50), Aβ42 (F_1, 61 = 5.32) and IL-10 (F_1, 59 = 4.32) were elevated in the mTBI group compared to the controls. Within the mTBI group, regression models show that post-concussive symptoms were most related to exosomal tau elevations, whereas exosomal IL-10 levels were related to PTSD symptoms. Conclusions: These findings suggest that chronic post-concussive symptoms following an mTBI relate to altered exosomal activity, and that greater tau pathology may underlie chronic post-concussive symptoms that develop following mTBIs. It also suggests that central inflammatory activity contributes to PTSD symptoms following an mTBI, providing necessary insights into the role of inflammation in chronic PTSD symptoms.

Objective: To determine whether tau changes after sport-related concussion (SRC) relate to return to play (RTP). Methods: Collegiate athletes underwent preseason plasma sampling and cognitive testing and were followed. After a SRC (n = 46), athletes and controls (n = 37) had sampling at 6 hours, and at 24 hours, 72 hours, and 7 days after SRC. A sample of 21 nonathlete controls were compared at baseline. SRC athletes were grouped by long (>10 days, n = 23) and short (≤10 days, n = 18) RTP. Total tau was measured using an ultrasensitive immunoassay. Results: Both SRC and athlete controls had significantly higher mean tau at baseline compared to nonathlete healthy controls (F_101,3 = 19.644, p < 0.01). Compared to SRC athletes with short RTP, those with long RTP had higher tau concentrations overall, after controlling for sex (F_39,1 = 3.59, p = 0.022), compared to long RTP athletes, at 6 (p < 0.01), 24 (p < 0.01), and 72 hours (p = 0.02). Receiver operator characteristic analyses showed that higher plasma tau 6 hours post-SRC was a significant predictor of RTP >10 days (area under the curve 0.81; 95% confidence interval 0.62–0.97, p = 0.01). Conclusions: Elevated plasma tau concentration within 6 hours following a SRC was related to having a prolonged RTP, suggesting that tau levels may help inform RTP.