F. Don Nidiffer, PhD, Austin Errico, PhD, Tina M. Trudel, PhD, and Jeffrey T. Barth, PhD

Individual reactions to being exposed to trauma vary greatly. Factors that influence such reactions include age, gender, history of previous exposure, personality predispositions, and nature of the trauma [1]. For most people, being exposed to trauma on any given day is fortunately of low probability. For others, such as those in military combat, trauma is a part of daily life. The experience of trauma in daily life is more frequent than one may think. Children and spouses who are frequently exposed to violence at home know what it’s like to live in an unsafe situation, and can develop “stress disorders” that can include mood disorders, anxiety disorders and somatoform disorders [2]. Military personnel who are exposed to severe training conditions in readiness for deployment to active duty are also familiar with living under extremely stressful circumstances. Stress related disorders often result in physiological distress and concomitant cognitive and behavioral problems. Traumatic events that are capable of causing a brain injury also may cause stress reactions and/or can further complicate pre-existing anxiety disorders. A stress related disorder can interfere with and significantly impede the treatment and recovery from traumatic brain injury (TBI).

Stress and Post traumatic Stress Disorder (PTSD)

Evolution requires that a species adapt or become extinct. One basic adaptation is known as the “fight or flight” response. Whether choosing to fight or escape from danger, autonomic changes are rapid and intense. Changes include blood pressure elevation, increased cardiac output, increased bronchial dilation, increase in blood glucose, elevation in basal metabolic rate and increased central nervous system excitability. By the same token, physiological systems that are not needed to address an acute threat are spared. These include decreased immune response, decrease in blood flow to the digestive systems, etc. Essentially, attention to the threat and assessment of the immediate surroundings become the primary focus. Such responses place a strain on many organ systems, including the heart, lung, and endocrine system, etc. All of these biological responses are adaptive and increase the possibility of survival by increasing the readiness of the organism to effectively cope with the impending threat. When the threat disappears, for most people, so do the physiological responses that prepared them to survive. However, when the threat occurs for longer periods of time or the possibility exists that the threat may return, the result is an inability to relax and return to a homeostatic physiological state. Unfortunately, no physiological difference may exist between actual or anticipated threat when it comes to wear and tear on the body. Continued exposure to threat, whether actual or perceived, can over time, damage, the same organ systems that prepared the person for survival.

The Diagnostic and Statistical Manual used by professionals in mental health has an explicit definition of PTSD noted in Table 1. As indicated in the table, characteristics this anxiety disorder include are four major criteria and three basic symptom clusters. In evaluating someone for the first time, it is important to note duration of symptoms, as should symptoms persist for more than one month, the early diagnosis of Acute Stress Disorder becomes PTSD, a more chronic and persistent anxiety condition.

Prevalence of PTSD in the general civilian population ranges from 2% to 20%. An estimated 5% of men will develop PTSD at some point in their lifetime. Estimates for women are 10% [3]. In addition, women are four times more likely to develop PTSD than men who are exposed to the same trauma. Events that are perceived as unpredictable or uncontrollable, by definition, are experienced by the organism as stressful. These events, when severe, are capable of precipitating the development of PTSD. Examples of such traumatic events include physical and emotional abuse, motor vehicle accidents, gunshot wounds, burns, witnessing abuse of others, natural disasters and continuous exposure to life-threatening conditions such as combat. This article will focus on the co-occurrence of PTSD and TBI in the military population.

Predictors of PTSD Development

When someone is exposed to a traumatic event, he/she is at risk for developing PTSD. Whether PTSD develops or not depends upon a number of factors [1, 4]. People who are already depressed, anxious, or have a history of PTSD are more likely to develop PTSD symptoms following a traumatic event [5]. Other risk factors include use of an avoidant coping style [6], history of chronic pain; history of substance abuse and/or an inordinate fear of death. Moreover, persons who externalize blame for their problems or experience a loss of control during a traumatic event are more likely to present with symptoms.

In a military population, combat exposure can result in the development of PTSD [7,8]. Hoge and colleagues (2004) studied military personnel who had been deployed to Iraq. They reported that the incidence of PTSD increased as a function of the number of firefights a person experienced during deployment. PTSD was found in 4.5% of the Iraq deployed military personnel who had no exposure to firefights, 9.3% for one to two firefights, 12.7% for three to five firefights, and 19.3% for more than five firefights. In addition, criteria were met for major depression, generalized anxiety or PTSD in 15.6% to 17.1% of the military personnel after duty in Iraq and 11.2% after duty in Afghanistan. Interestingly, 9.3% of the military personnel in the same study were found to have one of these diagnoses prior to deployment, however rates of PTSD increased more than any other condition from pre- to post-deployment periods.

Rona et al., (2005) discussed the problems associated with screening for psychological conditions in the military. Acceptability of this approach, confidentiality, stigma associated with reporting problems, validity of screening instruments, and the evaluation of treatments were identified as obstacles in attempting to screen military personnel for mental health problems. The authors suggested that the focus should be upon a conservative approach to screening, improving support systems and improving recognition and management of health problems while maintaining confidentiality [9].

Neurophysiological Studies of PTSD

Brain imaging studies on individuals diagnosed with PTSD (e.g., Bremner, 2002) have largely focused on the hippocampal region of the brain. Such studies have found that veterans with PTSD have a smaller hippocampus than veterans without PTSD[10]. Moreover, the hippocampal size was specific to the effects of PTSD versus anxiety in general. This finding has been replicated with survivors of childhood abuse, demonstrating an inverse relationship between the level of abuse and the size of the hippocampus. PET scans of these individuals revealed low activity levels (glucose uptake) in the hippocampal region as well [11]. Hippocampal functioning is critical in the consolidation of new learning for long term memory, a cognitive function commonly affected after TBI.

The Hypothalamic –Pituitary –Adrenal (HPA) Axis plays a central role in the physiological preparation of an organism to address an acute stressor. In brief, corticotrophin releasing factor (CRF) is produced and released by the hypothalamus during times of stress. CRF travels down the hypophyseal stalk on route to its target organ, the pituitary gland. The pituitary gland, in response to CRF, produces a hormone call Adrenocorticotropic Hormone (ACTH). ACTH, in turns, travels through the bloodstream toward its target organ, the adrenal cortex. The adrenal cortex, in response to ACTH, produces the glucocorticoid, cortisol. Elevated levels of cortisol serve to decrease the secretion of CRF, resulting in feedback inhibition of ACTH production. CRF production is also inhibited through neuronal pathways between the hypothalamus and the hippocampus.

Cortisol has a number of adaptive functions in response to acute stress including the increase in blood glucose through the process of gluconoegenesis and the increase in blood pressure. As stated above, the HPA axis provides an adaptive function to the organism during times of acute stress. Maladaptive effects can arise, however, when the HPA axis, is stimulated for long periods of time in response to chronic stressors [12]. In these incidences, cortisol can cause destruction to the immune system, a decrease in muscle mass, thinning of the skin and damage to cells in the hippocampus Recall that the hippocampus has an inhibitory effect on the release of CRF. Therefore, a reduction in hippocampal neurons would result in greater amounts of CRF being available, and this has been noted in cerebrospinal fluid [10].

Recall that high cortisol levels secondary to chronic stress are associated with damage to hippocampal neurons, especially in the CA3 region. Cortisol disrupts cellular metabolism and increases vulnerability of hippocampal neurons to glutamate, an excitatory amino acid. While the hippocampus is capable of regenerating neurons, chronic stress inhibits this process. Both the hippocampus and prefrontal cortex (PFC) have demonstrated decreased activation (PET scans) upon provocation of PTSD symptoms in veterans and women abused as children [10]. Animal studies have supported the finding that glucocorticoid-mediated elevation occurs with PTSD and result in PFC impairment affecting aspects of memory and amygdale restraint [13]. The prefrontal cortex modulates emotional responsiveness and conditioned fear responses through inhibition of amygdala. Through this mechanism, the prefrontal cortex is theorized to underlie pathological emotional responses in PTSD. This PFC is also one of the regions most vulnerable to the effects of traumatic brain injury.

Traumatic Brain Injury and Post traumatic Stress Disorder

Estimates of the co-occurrence of PTSD and TBI vary from one study to another. Studies estimate that PTSD symptoms from a brain injury can occur anywhere from 3% to 33% of the time, depending upon the nature of the trauma and the study participants. In a large sample study of persons with TBI from motor vehicle crashes, 48% at three months and 33% at one year presented with PTSD [14]. However, when comparing individuals with TBI to those suffering non-TBI related traumatic injuries, some studies have found lower rates of PTSD among the TBI group [15]. Such studies have led to the belief that the amnesia that commonly occurs with brain injuries may actually serve a protective function in the development of PTSD symptoms. While such amnesia may not completely eliminate the possibility of PTSD development, support exists that post-TBI amnesia may serve to lessen the probability and severity of PTSD, although the evidence is not well established [16,17,18]. Klein et al. (2003) found that when traumatized individuals with brain injuries did recall at least part of the traumatic event, they were five times more likely to develop PTSD. In one of the largest studies in this area involving 993 Cambodian refugees, individuals with TBI had among the highest rates of depression and PTSD of all refugees, second only to those who were victims of torture [19].

When TBI and PTSD do co-exist, the effects are often synergistic. Similar brain regions and functions are frequently impacted. For instance, both TBI and PTSD can impair executive functioning, aspects of memory and emotional regulation. Additionally, memory and attention are impaired both through the primary effects of tissue damage from the physical injury and by the emotional response and obsessive thinking from the psychological disorder. A similar pattern can emerge regarding emotional changes. For instance, during times of war, military personnel may undergo prolonged periods of stress that can exacerbate the stress that is frequently accompanied by TBI. In short, just as PTSD can exacerbate the cognitive impairments that are caused by a TBI, TBI can exacerbate the psychological impairments that are caused by PTSD.

Treatment of TBI and PTSD

The presence of either TBI or PTSD can be devastating, particularly if either is severe. The combination of these two conditions frequently has debilitating effects even on simple tasks of daily living. As such, both conditions are best treated simultaneously. For example, nightmares from PTSD can limit restful sleep and, if frequent, may cause a fear of falling asleep. This, combined with the common fatigue from brain injury, can significantly impede participation in rehabilitation and routine cognitive functions. Treatment approaches that address fatigue with this knowledge are likely to be more successful than those that target the cause as arising exclusively from one condition or another.

Similarly, mood instability from TBI can exacerbate the hyper vigilance often experienced by individuals with PTSD. Inattention and distractibility can arise from either TBI or PTSD with the effects being cumulative in creating functional impairments in daily life. TBI and PTSD also have depression as a shared major feature. Agitation from TBI and emotional over-reactivity from PTSD can further impair daily functioning. All of these problems are better addressed when the rehabilitation team can be sensitive to the multiple etiologies that underlie the targeted symptom.

Treatment approaches include individual, group and family psychotherapy; education on brain injury and psychological syndromes; and pharmacological interventions. Most studies have examined the use of only one of these approaches. Future research should consider the additive benefit from a multi-prong approach, particularly including all of the aforementioned elements.

Practice Guidelines from the International Society for Traumatic Stress Studies have strongly endorsed Cognitive Behavior Therapy (CBT) as the treatment of choice for treating PTSD [20,21]. This approach addresses conditioned fear and cognitive distortions associated with conditioning. CBT effectively treats misperceptions that have occurred from prolonged exposure to trauma by challenging the belief that the world is an inordinately dangerous place and that one is powerless to change their fate. CBT also helps to overcome emotions such as guilt and shame that arise from an inaccurate sense of responsibility attached to the traumatic experiences. Other CBT techniques attempt to extinguish anxiety based responses to situations by having the individual systematically experience presumably threatening circumstances in visualizations or in vivo (often with relaxation therapy) until the anxiety subsides. By doing so, the avoidant responses that arose from unrealistic fear and sustained anxiety will disappear or be better managed[22].

Likewise, psychotherapeutic interventions for survivors of TBI include a gamut of approaches that are often symptom specific or skill based. CBT is again a recommended approach. Problems addressed in psychotherapy can include commonly displayed social skills difficulties arising from impairments in executive functions, such as poor judgment, egocentricity, impulsivity, and lack of reciprocity in interpersonal relationships. Behavioral strategies can focus upon difficulties with initiation or inhibition.

Education and support-focused groups for soldiers with brain injury and PTSD and their families can help to address misperceptions about alterations in behavior. Greater understanding and broad personal/family coping skills can be developed while focused treatment attempts to target symptoms. Support group models related to TBI and PTSD are common and usually cover the general issues and needs of these disorders. However, areas of importance for education that are at times neglected include the implications of system and symptom overlap between these two conditions, recovery of function versus use of compensatory strategies, maximization of environmental adaptations, a focus on wellness and the need for pacing.

From a psychotropic-pharmacological standpoint, Selective Serotonin Reuptake Inhibitors (SSRIs) are usually the first line of treatment for PTSD. Sertraline and paroxetine have been shown to address the three basic clusters of PTSD symptoms—re-experiencing of the trauma, avoidance/numbing in association with traumatic events, and hyperarousal and hypervigilance to maintain a constant state of readiness. Other medications, such as antiadrenergic agents and anticonvulsants may eventually prove to be even more effective [22]. According to the American Psychiatric Association (see Practice Guidelines for the Treatment of Patients with Acute Stress Disorder and Posttraumatic Stress Disorder, 2004), benzodiazepines have not been found to be useful for PTSD, and this class of medications is minimally used post-TBI due to suppression of neural growth factor which helps recovery after TBI [23]. In general, medication following traumatic brain injury is largely dependent upon the specific symptom that is problematic. For example, Ritalin or other stimulants may be given to help address problems of inattention/concentration that commonly occur following a brain injury. Antidepressants, such as SSRIs, are frequently used for treatment of brain injuries and can be beneficial for PTSD as mentioned previously. Newer types of anticonvulsants that are used in treatment of PTSD (lamotrigine) may already be in place for TBI related seizure management or prevention and may also facilitate mood stabilization.

Summary

The military must maintain a constant state of readiness in order to fulfill their primary purpose of defending the country. In times of combat, prolonged periods of stress can result in physiological changes that may impair cognitive, emotional and behavioral functioning. Traumatic Brain Injury is also common in wartime, and it too results in cognitive, emotional, and behavioral dysfunction. While returning home can be challenging without an injury, the combination of a TBI and PTSD requires even greater effort. The occurrence of TBI and PTSD produces significant challenges for service men and women, their families, and the rehabilitation team. Professionals who recognize the potential synergistic effects of these two conditions are better able to provide education and design treatment approaches that are sensitive to the multiple etiologies that underlie many of the complex symptoms shared by both conditions.

References

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About the Authors

F. Don Nidiffer, PhD is the Co-Principal Investigator of the Virginia NeuroCare DVBIC program and Executive Director of Lakeview Virginia NeuroCare, Dr. Nidiffer is a clinical psychologist with 23 years of experience in the University of Virginia Health System, providing rehabilitation and behavior therapy services across all ages. He completed his post-doctoral fellowship in Behavioral Pediatrics from Johns Hopkins School of Medicine.

Austin Errico, PhD is the Clinical Director of Lakeview NeuroRehabilitation Center in Effingham Falls, NH, where he previously served as neuropsychologist and Director of the APPIC accredited psychology internship program. Dr. Errico received his doctorate in biological psychology from the University of Oklahoma, completed his training in clinical neuropsychology at the University of Virginia and has served as a neuropsychologist in rehabilitation hospital, residential treatment and community integrated settings.

Tina M. Trudel, PhD is the Principal Investigator of the Virginia NeuroCare DVBIC program, and the President/COO of Lakeview Healthcare Systems, Inc., a national provider of rehabilitation and neurobehavioral services. She is an Assistant Professor of Clinical Psychiatry and Neurobehavioral Sciences at the University of Virginia School of Medicine and has published and presented extensively in the field of brain injury.

Jeffrey T. Barth, PhD, ABPP holds the John Edward Fowler Endowed Professorship in Clinical Neuropsychology at the University of Virginia School of Medicine. He is Chief of the Neurobehavioral Study Section and Director of the UVA Brain Injury and Sports Concussion Institute. He also maintains a Senior Scientist position with Lakeview Healthcare Systems and Virginia Neurocare, and has published and presented internationally on topics including neuropsychology, brain injury and rehabilitation.