**1. Introduction**

Highlighted by recent world-conflicts, such as the wars in Afghanistan and Iraq, it has become evident that a better and more comprehensive understanding of the relationship between stress-related psychological disorders and traumatic brain injury is much-needed, in both military and civilian populations. For the purposes of this chapter, we will focus on posttraumatic stress disorder (PTSD) and mild traumatic brain injury (mTBI); however, this is not to underplay the crucial need to better understand the wide range of stress-related psychological conditions and

brain injury. The prevalence rates of PTSD and mTBI in American military personnel returning from Operation Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF) has been reportedly as high as approximately 14 and 20%, respectively [1]. Despite both PTSD and mTBI conditions being "invisible injuries" (injuries not outwardly observable), they are both capable of creating significant disruptions in normal living for individuals. Further, what little we know about the co-occurrence of these conditions suggests that, when combined, they are more difficult to treat and often result in poorer prognoses [2–4]. This understanding is a significant advancement, as it was once thought that the loss of consciousness or altered mental status that is often observed with brain injury offered protection from the development of stress disorders [5]. Although it is recent military engagements that have highlighted the need for a better understanding of concomitant PTSD and mTBI, these conditions are prevalent in both military and civilian contexts and are therefore issues of broad public health on a global scale.

Approximately 3.5–7.0% of adults within the United States develop PTSD every year. When examining military personnel, this number increases to anywhere between 33 and 65% [6]. On the global scale, approximately 25% of the world's population has been affected by PTSD, making it the most prevalent psychiatric disorder [7]. Traumatic brain injuries are also very commonplace, and well over one-million people within the U.S. seek care annually for brain injury [8], with the majority of these being classified as mild [9, 10]. Worldwide, up to 50-million people annually seek treatment [6]. However, this number is likely an underestimation as many individuals who suffer an mTBI do not seek medical care. Furthermore, those that do seek medical attention oftentimes are misdiagnosed or underdiagnosed, especially if symptoms are mild or transient and loss of consciousness is limited to a short period of time [11]. When examining PTSD comorbid with mTBI, it becomes clear that many of those that have been affected by trauma have also experienced mTBI. Within civilian populations, PTSD following accidents such as falls or automotive collisions in which an mTBI occurs, range from approximately 20–36% [12]. Within a military context, this number increases to roughly 34–44% [13, 14]. However, like the reporting of each condition in isolation, the potential for misdiagnosis or underdiagnosis is large.

The prevalence and impact of both mTBI and PTSD (whether it be together or in isolation) result in a high cost of treatment, increased suicide rates, and lost work, all of which place a substantial burden on healthcare systems. Although the true costs are difficult to quantify, estimates for the health services cost associated with an mTBI alone range from \$10,000USD to \$100,000+ per patient depending on severity, length of hospital stay, and costs of rehabilitation [15–19], with a mean cost of \$96,000USD [20]. The numbers are equally startling for the treatment costs associated with PTSD, with annual costs in excess of 200 million USD in US military personnel alone [21], and civilian costs estimated at even greater levels [22–24]. This estimate does not include the loss of productivity associated with this condition, which easily exceeds billions of dollars at a national level [25]. Although both PTSD and mTBI have substantial costs of care in isolation, when combined, healthcare costs are certainly increased, largely due to the complexity of treating comorbid conditions.

Posttraumatic stress disorder and mild traumatic brain injury have overlapping symptomology yet require different therapeutic approaches. In classical diagnoses, detailed information is collected about the onset and progression of symptoms to arrive at a probable diagnosis, which is then further refined. When dealing with an individual that may meet diagnostic criteria for both conditions, this process becomes much more difficult. In theory, a pattern of symptom overlap and divergence could

#### *Current Understanding of Biomarkers in Post Traumatic Stress Disorder and Mild Traumatic… DOI: http://dx.doi.org/10.5772/intechopen.102766*

help differentiate etiologies when dealing with comorbid PTSD and mTBI, however, recent evidence suggests this is not the case. In a 2009 study, eight symptoms that are related to both PTSD and mTBI (fatigue, irritability, concentration problems, memory problems, depression, anxiety, insomnia, and dizziness) were examined and compared between patients who had experienced a recent mTBI or PTSD, revealing substantial overlap between both clinical groups. Although it was found that patients with PTSD had greater overall symptom severity, the degree of overlap prevented differential diagnoses based on the pattern of symptoms reported [26]. A meta-analysis conducted the same year [27] provided some evidence that there are symptoms unique to each when occurring in isolation (PTSD—shame, guilt, re-experiencing symptoms; mTBI—headache, sensitivity to light, dizziness, memory deficits), however, this information does not assist in the diagnosis of those that experience both mTBI and PTSD. Therefore, it remains unclear which aspects of these disorders play significant roles in disease onset following event exposure (whether it be set individual traits, epigenetic changes, alterations to specific brain area structure and function, or a combination of these and other factors), and ultimately which set of symptoms will manifest that are linked to the genuine presence of PTSD, mTBI, or both.

The objective of this chapter is to review our current understanding of comorbid mTBI and PTSD, with an emphasis on reviewing the current state of biomarkers used to diagnose comorbid mTBI and PTSD that offer promise on a single-patient basis. To best accomplish these goals, we will begin with providing definitions of what is meant by the terms PTSD and mTBI. Following, we will review the current understanding of the neurological underpinnings of each condition, with a focus on areas of overlap, and examine currently accepted methods of diagnosis and treatment options. Lastly, we will provide an account of the current researchers utilizing biomarkers for either diagnosis or prognosis of PTSD and mTBI, as well as discuss implications for future research and treatment.
