Mind the Gap: Missing Links in the Understanding of Traumatic Brain Injury and Mental Health

TBI is a leading cause of disability worldwide, with an increasing incidence and an estimated 55 million people living with traumatic brain injury- (TBI-) related disability (1). Disability after TBI appears to be driven largely by the diverse neurobehavioral—or mental health-related—consequences of the injury (2,3). The reviews in this special issue of Biological Psychiatry discuss the current state of knowledge on TBI and mental health, but we cannot introduce them without acknowledging that definitions of TBI and mental health are continually evolving.

Though commonly discussed as a single diagnosis, TBI is an amalgam of conditions comprising myriad pathophysiological features and clinical sequelae. While there is no doubt that injuries resulting in frank unconsciousness and acute neuroimaging findings reflect TBI, the “floor” of the injury spectrum has sunk lower in the past 25 years (4). In particular, clear outward signs of brain injury like unconsciousness are now recognized as not only unnecessary for diagnosis but uncommon after mild TBI (mTBI). The fact that TBI is not always readily identified by clinical signs during routine assessments presents challenges for identifying, treating, and studying this disorder. Exciting advances in detecting TBI through noninvasive (e.g., blood-based and neuroimaging) biomarkers bring hope that the current state of uncertainty about what TBI is and how to identify it will improve in the foreseeable future (5).

Just as definitions of TBI are hotly debated, the construct of mental health and, relatedly, psychiatric disease, lacks a universally agreed-upon definition. Definitions of mental health can emphasize normative cutoffs on psychological health scales, personal characteristics (e.g., positive affect, subjective wellbeing, resilience), and differing end goals (e.g., individual versus societal) and need to be appropriate to the contexts and cultures in which they are to be applied (6). An ambitious international mixed-methods study recently sought to identify the core concepts of mental health as defined by diverse stakeholders from at least 8 countries. The most popular definition of mental health was that of the Public Health Agency of Canada (7): “the capacity of each and all of us to feel, think, and act in ways that enhance our ability to enjoy life and deal with the challenges we face. It is a positive sense of emotional and spiritual well-being that respects the importance of culture, equity, social justice, interconnections and personal dignity.” The study converged on three themes many considered important to mental health: agency, autonomy and control. Reflecting on the components of this definition makes it clear that TBI—which often arises from circumstances outside one’s control and that changes individuals’ emotions, cognitive capacity, and behavior—is inextricably tied to mental health, regardless of how one views either construct.

At the risk of appearing to view an ocean through a porthole, for this special issue we considered topics relevant to the relationship between TBI and mental health that encompassed the traditional neuropsychiatric (e.g., affective, neurocognitive, and behavioral) problems commonly considered by our respective fields of psychology and psychiatry. First, McAllister eloquently summarizes the history of how TBI became recognized as relevant to public health, highlighting how events such as military conflict has increased attention on TBI and its neuropsychiatric sequelae in the past 20 years (8). Next, Howlett et al. (9) and Shahim and Zetterberg (5) provide broad overviews of two topics important to contextualize the more targeted material that appears within the issue: the scope and epidemiology of neuropsychiatric sequelae following TBI and advances in understanding and measuring the human neurobiological response to TBI using biofluid-based biomarkers. Howlett et al. reviews the breadth of neuropsychiatric symptoms and disorders that appear at elevated rates in individuals with TBI across the injury severity spectrum (9), while Shahim and Zetterberg summarize the growing number of objective markers available to detect the axonal, astrocytic, microglial, blood-brain barrier, and other neural changes after brain injury in humans (5). Olsen and Corrigan thoughtfully considers the epidemiological and neuroscientific basis for the question of whether risky substance use, which is a well-established precursor to TBI, can also be caused by TBI (10).

The acute TBI-specific biomarkers emphasized by Shahim and Zetterberg show great promise for contributing to the diagnosis of TBI. As the authors point out, however, it is unclear whether these biomarkers will also show strong predictive value for near- and long-term mental health sequelae. Thus, a broader perspective—one that encompasses other neurobiological systems, as well as psychosocial/contextual factors—is needed to understand the mental health consequences of TBI. Risbrough et al. summarizes the literature on inflammatory pathways triggered by early TBI injury processes, which can be persistently altered and are plausibly related to the chronic psychiatric consequences of injury (11). Traveling a step further down the neurometabolic cascade of brain injury, Meier and Savitz use the kynurenine pathway as an illustration of a downstream physiological consequence of inflammation that has strong preclinical and emerging human research support for a more direct cause of TBI sequelae such as depression (12).

Taking a systems neuroscience perspective, Mayer and Quinn (13) and Weis et al. (14) illustrate the value of neuroimaging for understanding the neuropsychiatric consequences of TBI. Mayer critically evaluates epidemiological and neuroimaging evidence that TBI causes new-onset psychiatric disorders, and Weis discusses how consideration of emotional regulation circuitry can advance understanding of the overlap between TBI and posttraumatic stress disorder. Piantino et al. present a highly novel proposal that glymphatic system dysfunction, which is not yet readily measurable in humans, may combine with sleep disruption to contribute to impaired neural and clinical recovery following mTBI (15).

Two articles within the issue discuss current topics about TBI at the extremes of the lifespan (i.e., in children and older adults). Fischer et al. discuss the widely documented role of family environment in pediatric TBI outcomes, taking an innovative perspective to propose next steps toward pinning down the neural basis for the impact of environmental factors on pediatric TBI outcomes (16). Brett et al. take on the controversial topic of whether and how TBI of all severities causes neurodegenerative disorder (17).

As Fann et al. successfully enumerates (18), despite the many questions that remain about the causes and mechanisms of post-TBI psychiatric problems, numerous evidence-informed treatments are available to lessen these problems and improve the quality of life for individuals with TBI. Moreover, exciting up-and-coming treatment research may lead to truly evidence-based prevention and treatment strategies in the future. Collectively, this issue celebrates the great progress that has been made to recognize and understand the mental health sequelae of TBI while also setting a research agenda to encourage continued progress toward better supporting the mental health of the many individuals affected by TBI.