**2. Definitions**

The lack of consistent definitions and assessments of mTBI and PTSD complicates the ability to capture accurate statistics for each condition. We focus on mild traumatic brain injury, as this is both the most common traumatic brain injury in civilian [28] and military populations [29], and is also the most likely to co-occur with PTSD [30]. Additionally, as mTBI is often the hardest to diagnose, the pursuit of biomarkers with clinical utility is of great importance. However, when it comes to describing what constitutes an mTBI, a large amount of ambiguity becomes apparent. What is clear is that for a diagnosis of mTBI, two things need to occur: (1) An external force must be exerted to the head; and (2) there must be a temporary change of mental status and/or other evidence of brain injury. Of course, for a traumatic brain injury to be classified as mild, there also needs to be an upper limit for the severity. This includes: (1) a loss of consciousness that does not exceed 30 minutes; and (2) posttraumatic amnesia that does not exceed 24 hrs. These criteria are largely accepted on a global scale [31–33] and will be used for this chapter as well.

Formal methods for the diagnosis of PTSD currently exist, making the definitions regarding the psychiatric condition somewhat consistent. In general, PTSD is characterized by four symptom clusters that develop in response to a traumatic event. The traumatic event must involve exposure to actual or perceived death, serious injury, or sexual violation. Furthermore, the event must be directly

experienced or witnessed by the individual, or indirectly experienced by subsequently learning about the event after it happened to a close family member or friend. Specific clinical criteria include: (1) intrusive symptoms related to re-experiencing the trauma; (2) avoidance of the traumatic memory or cues; (3) negative mood and thoughts including emotional numbing and anhedonia; and (4) altered arousal including hypervigilance, irritability, aggression, and sleep disturbances [7, 34]. Additionally, symptoms result in significant social, personal, and vocational impairment [7]. PTSD is commonly comorbid with other anxiety or mood disorders, further complicating diagnosis, and is also associated with increased risk for numerous negative behavioral and health conditions, including substance use disorder, type II diabetes, and Alzheimer's disease [35–38], significantly expanding the costs of treatment. Although the criteria for diagnosing PTSD are rather straightforward, this does not mean that PTSD is a static phenomenon without gradation. It is known that PTSD symptoms appear on a continuum and can fluctuate in terms of their functional impact and presence across time. Furthermore, although the precipitating traumatic event is a critical component of PTSD, it is how an individual responds to that trauma that is essential in the diagnosis. An identical traumatic event for one individual may result in PTSD, whereas another person experiencing an identical event may not. Therefore, it is as much about the symptoms and functional impairment as it is about the event itself.
