Role of Inflammation in Traumatic Brain Injury-Associated Risk for Neuropsychiatric Disorders: State of the Evidence and Where Do We Go From Here

In the past decade, there has been an increasing awareness that traumatic brain injury (TBI) and concussion substantially increase the risk for developing psychiatric disorders. Even mild TBI increases the risk for depression and anxiety disorders such as posttraumatic stress disorder by two- to threefold, predisposing patients to further functional impairment. This strong epidemiological link supports examination of potential mechanisms driving neuropsychiatric symptom development after TBI. One potential mechanism for increased neuropsychiatric symptoms after TBI is via inflammatory processes, as central nervous system inflammation can last years after initial injury. There is emerging preliminary evidence that TBI patients with posttraumatic stress disorder or depression exhibit increased central and peripheral inflammatory markers compared with TBI patients without these comorbidities. Growing evidence has demonstrated that immune signaling in animals plays an integral role in depressive- and anxiety-like behaviors after severe stress or brain injury. In this review, we will 1) discuss current evidence for chronic inflammation after TBI in the development of neuropsychiatric symptoms, 2) highlight potential microglial activation and cytokine signaling contributions, and 3) discuss potential promise and pitfalls for immune-targeted interventions and biomarker strategies to identify and treat TBI patients with immune-related neuropsychiatric symptoms.

Automated summary

In the past decade, there has been increasing awareness of the elevated risk for developing psychiatric disorders such as depression and anxiety after traumatic brain injury (TBI) and concussion. One potential mechanism for increased neuropsychiatric symptoms after TBI is through inflammatory processes, where central nervous system inflammation can persist for years. Emerging evidence suggests that TBI patients with comorbid posttraumatic stress disorder or depression exhibit higher levels of central and peripheral inflammatory markers compared to those without these conditions. Immune signaling has also been found to play a role in depressive- and anxiety-like behaviors after severe stress or brain injury. This review discusses the evidence for chronic inflammation after TBI in the development of neuropsychiatric symptoms, potential contributions of microglial activation and cytokine signaling, and the promise and challenges of immune-targeted interventions and biomarkers in identifying and treating TBI patients with immune-related neuropsychiatric symptoms.