|Year : 2019 | Volume
| Issue : 1 | Page : 33-39
Post-traumatic stress disorder: Relationship to traumatic brain injury and approach to forensic psychiatry evaluation
Ye-Fei Chen1, Hu Zhao2
1 Faculty of Forensic Medicine, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China
2 Faculty of Forensic Medicine; Guangdong Province Translational Forensic Medicine Engineering Technology Research Center; Guangdong Province Key Laboratory of Brain Function and Disease, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China
|Date of Web Publication||28-Mar-2019|
Dr. Hu Zhao
Faculty of Forensic Medicine, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, Guangdong
Source of Support: None, Conflict of Interest: None
Posttraumatic stress disorder (PTSD) has an important and complex relationship with traumatic brain injury (TBI). The prevalence of comorbid PTSD and TBI is increasing in both military and civilian populations. Moreover, TBI has emerged as an important risk factor for the development and manifestation of PTSD. Meanwhile, PTSD is also a significant mediator of the negative sequelae of TBI. PTSD and TBI, especially mild TBI (mTBI), have overlapping neural substrates and neuroanatomical functional features. Given that comorbid PTSD and TBI remain a challenge for forensic psychiatry evaluation, we review the relationship between the two disorders and discuss special considerations during evaluation of the condition.
Keywords: Forensic psychiatry evaluation, neural mechanism, posttraumatic stress disorder, traumatic brain injury
|How to cite this article:|
Chen YF, Zhao H. Post-traumatic stress disorder: Relationship to traumatic brain injury and approach to forensic psychiatry evaluation. J Forensic Sci Med 2019;5:33-9
|How to cite this URL:|
Chen YF, Zhao H. Post-traumatic stress disorder: Relationship to traumatic brain injury and approach to forensic psychiatry evaluation. J Forensic Sci Med [serial online] 2019 [cited 2019 Aug 25];5:33-9. Available from: http://www.jfsmonline.com/text.asp?2019/5/1/33/255130
| Introduction|| |
Posttraumatic stress disorder (PTSD) and traumatic brain injury (TBI) are both common conditions that affect individuals who have experienced mental or physical injuries. There has been significant controversy surrounding the complex relationship between these two disorders for decades., Indeed, TBI has emerged as an important risk factor for the development of PTSD, while PTSD may also be a significant mediator of the negative sequelae of TBI., In addition, individuals with PTSD or TBI, especially combat veterans, have a high rate of criminal violence, substance abuse, and suicidal behavior, which can create difficulties in forensic psychiatry evaluation.,
In this review, we begin with a brief description and definition of PTSD and TBI, followed by an analysis of the epidemiology of the two disorders. Next, we briefly review the complex and controversial relationship between TBI and PTSD based on characteristics of the overlapping neural substrates and neuroanatomical functional features, paying particular attention to the role of TBI as a risk factor for PTSD. Finally, we discuss special considerations in evaluating individuals with comorbid PTSD and TBI in forensic psychiatry contexts.
| Description and Definitions of Posttraumatic Stress Disorder and Traumatic Brain Injury|| |
According to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, PTSD is defined as an anxiety disorder that requires a history of exposure to a traumatic event with symptoms from each of the following four symptom clusters: (1) exposure to or witnessing of an event that is threatening to one's well-being; (2) symptoms of re-experiencing, such as intrusive memories, nightmares, a sense of reliving the trauma, or psychological and physiological distress when reminded of the trauma; (3) avoidance of thoughts, feelings, or reminders of the trauma, and inability to recall parts of the trauma, withdrawal, and emotional numbing; and (4) arousal, manifesting as sleep disturbance, irritability, difficulty concentrating, hypervigilance, or heightened startle response.
Traumatic events that can result in PTSD fall into several categories, including military combat, rape, physical assault, natural disaster, and witnessing violence. Since the beginning of the conflicts in Iraq and Afghanistan, it has become clear that PTSD has an important and complex relationship with TBI. Both disorders are common in Iraq and Afghanistan veterans,, whereas among civilian populations, the comorbidity is most common as a result of motor vehicle accidents.
The most common form of TBI is mild TBI or concussion, and it has multiple definitions derived from various sources. In particular, mild TBI is considered a “silent epidemic” because many of the acute and enduring alterations in cognitive, motor, and somatosensory functions may not be readily apparent to external observers. The Glasgow Coma Scale (GCS) score, which measures the level of consciousness, has been the primary clinical tool for assessing initial brain injury severity in mild (GCS 13–15), moderate (GCS 9–12), or severe (GCS <8) cases. Concussion is a frequent occurrence in contact sports, and there is increasing evidence that athletes may sustain multiple concussions throughout their career.,, Another significant population is soldiers suffering from blast-related injuries, with one in six Iraq veterans meeting the criteria for concussion. Two primary complications of concussion are postconcussion syndrome and second impact syndrome.
Neurobehavioral symptoms are commonly reported in TBI. However, the symptoms vary in type and duration and may manifest as somatic or neuropsychiatric symptoms. Neuropsychiatric sequelae after TBI comprise cognitive deficits and behavioral disorders and are identified in almost all TBI patients for up to 3 months, with a small percentage exhibiting persistent symptoms for months or years.
The sequelae of TBI and psychological trauma exposure may be difficult to distinguish, especially at lower levels of TBI severity. In addition to confusing diagnostic decisions, their shared attributes and associated features can potentially complicate forensic evaluation of each disorder. For example, TBI sequelae and PTSD may each be associated with an elevated risk of substance abuse and suicidal behavior, as well as with symptoms of irritability, anxiety, depression, cognitive impairment, and sleep disturbance.
| Does Traumatic Brain Injury Protect Against Posttraumatic Stress Disorder?|| |
Prior to the Iraq and Afghanistan conflicts, comorbid PTSD and TBI received relatively little attention and was considered to be a rare phenomenon. In particular, it was argued that impairment or loss of consciousness, which occurs with severe TBI, may prevent PTSD by interfering with the encoding of trauma-related memories., Indeed, some researchers have argued that limited awareness at the time of trauma makes it less likely that traumatic memories can be encoded and that, as a result, these memories remain unavailable for the mediation of re-experiencing symptoms. It was also suggested that amnesia regarding the traumatic event minimizes the possibility that any cognitive representations of the trauma will be established. Other researches indicate that PTSD is in fact rare among road-accident survivors with TBI. An additional study involving 188 road-accident victims who sustained loss of consciousness reports that none exhibited symptoms of PTSD compared with road-accident survivors without TBI.
However, as summarized by Jones et al., there are several mitigating factors that allow PTSD to develop in the context of amnesia for the event. These are as follows: (1) affective responses and sensory-perceptual experiences associated with the trauma may be encoded at an implicit (i.e., unconscious) level that influences subsequent physiological, behavioral, and emotional responses; (2) amnesia may only be partial, with some aspects of the trauma preserved in conscious memory; (3) reconstruction of memory from secondary sources such as family, friends, or other observers may influence the development of PTSD symptoms; and (4) the circumstances of the trauma and peritraumatic events are psychologically traumatic in and of themselves and therefore may lead to PTSD.
Moreover, a computed tomography (CT) study of brain lesions in veterans of the Vietnam War found that damage to either the amygdala or ventromedial prefrontal cortex protects against PTSD. However, while this result does suggest that damage to one of the two specific regions of the brain, which are critically involved in the pathogenesis of PTSD, can reduce the occurrence of PTSD, it fails to explain the complex relationship between TBI and PTSD.
| Can Traumatic Brain Injury and Posttraumatic Stress Disorder Coexist?|| |
Early epidemiological studies of veterans of the Iraq and Afghanistan conflicts observed high rates of comorbid PTSD and TBI and reported that TBI is in fact an important risk factor for PTSD. Moreover, research of Iraq veterans reported that 4.9% reported an injury with loss of consciousness, and an additional 10.3% reported an injury with altered mental status but without loss of consciousness. The study found a strong association between TBI and PTSD: of those who reported loss of consciousness, 43.9% developed PTSD, and of those who reported altered mental status, 27.3% developed PTSD. In contrast, among those with an injury without loss of consciousness or altered mental status, the rate of PTSD was 16.2%, and in those without an injury, it was 9.1%. Another study of Iraq and Afghanistan veterans reported that 11% screened positive for PTSD and 12% reported a history consistent with mild TBI. Moreover, mild TBI was associated with a 2.37-fold increase in the prevalence of PTSD. Furthermore, among veterans with mild TBI, 34% also met criteria for PTSD. An investigation of veterans performed by the RAND Corporation found that 19.5% of returned service members had sustained a probable TBI, and of these, about 34% were affected by probable PTSD.
These studies generally indicate that both PTSD and acute stress disorder can coexist with TBI, even following a single incident in which the patient lost consciousness. PTSD has been documented in cases of moderate and severe TBI. However, several studies have suggested that PTSD is more likely to occur in the context of mild TBI (mTBI) rather than severe TBI, which is of particular relevance to veterans. Consistent with this, a longitudinal study of patients with mTBI documented an inverse relationship between the severity of re-experiencing symptoms at 3-month follow-up and the duration of posttraumatic amnesia. The results suggest that the strength with which trauma memories are encoded may in part determine whether PTSD develops, with clearer memories of the trauma associated with a greater likelihood of developing PTSD.
In general, PTSD and TBI can coexist, and PTSD is more likely to develop in association with mTBI. Evidence also suggests that PTSD may be inversely related to TBI severity and potentially to the strength with which trauma memories are consolidated.
| Does Traumatic Brain Injury Act as an Additional Risk of Posttraumatic Stress Disorder Development?|| |
Physical injury of any type, even if not involving the brain, is a risk factor for PTSD. However, TBI may confer additional risk of adverse mental health outcomes, including PTSD, following psychological trauma exposure. In Operation Enduring Freedom/Operation Iraqi Freedom veterans, PTSD is more prevalent among those who report mTBI compared with both veterans who suffered no injury and those who suffered injuries not involving the head. Moreover, the Vietnam Experience Study, which enrolled Vietnam-era veterans, reported that the presence of mTBI increased the risk of current PTSD experienced at an average of 16 years after military discharge.
| Neural Substrates Underlying Traumatic Brain Injury and Posttraumatic Stress Disorder|| |
Mild neuropsychological impairment, such as dysfunction of attention, learning and memory, and executive functioning, can often characterize both PTSD and TBI. While there is significant overlap in these neuropsychological domains, their manifestations are potentially different in each disorder. A meta-analytic research has indicated that most measurable neuropsychological deficits associated with mTBI resolve within a few weeks of the injury, returning to baseline within 1–3 months. In contrast, PTSD symptoms and neuropsychological deficits associated with PTSD more often persist years after psychological trauma exposure.
The potentially transient nature of cognitive sequelae in most mTBI cases and the neuropsychological consequences of mTBI might be relevant to PTSD for several reasons. First, heterogeneity in injury attributes across cases classified as mTBI partly reflected variability in recovery from mTBI. Furthermore, individual differences, such as premorbid psychological factors and subsequent life stressors, might be more important in predicting recovery. Moreover, genetic vulnerability is also being explored as a potential determinant of outcomes. At least 17 genes have been reported to be associated with PTSD. These genes are also reported to be critical in modulating neurotransmitters and neuromodulators.,,,,,,,,, It has been argued that there is a particularly increased risk of PTSD and depression with postconcussive symptoms following war-zone mTBI. However, a study of Vietnam-era veterans reported that mTBI and PTSD contributed independently to variance in residual somatic, cognitive, and emotional complaints experienced years after injury/psychological trauma exposure, suggesting that the effects of mTBI and PTSD on postconcussive symptoms may be additive.
Second, neuropsychological deficits associated with mTBI always occur during the period relevant to the formation of trauma memories. Short-term consolidation allows for the formation of memory traces within 24 h, and this period is critical to the consolidation and integration of the trauma memory. TBI-related deficits are most likely to surface shortly after the event. Similarly, emotional responses to psychological aspects of the event during or shortly after exposure have been found to be one of the strongest predictors of subsequent PTSD and emotional symptoms.,,, It is noteworthy that, even in the absence of demonstrable cognitive deficits, mTBI may be associated with an increased risk of developing anxiety and depression symptoms more generally, especially in the context of multiple concussions.,,, These deficits are thought to reflect reduced information-processing capacity, either in terms of speed of processing or the amount of information that can be handled simultaneously, and may affect the course of PTSD.
| Overlapping Neuroanatomical Functional Features Underlying Posttraumatic Stress Disorder and Traumatic Brain Injury|| |
Neural circuitry models and neuroimaging data suggest several key frontal and limbic structures, including the prefrontal cortex, the amygdala, and the hippocampus, as critical for PTSD development.,,,, These results suggest that the amygdala response underlies a heightened responsivity to potential threat, whereas both the hippocampus and medial prefrontal cortex are thought to be critical for appropriate contextual tagging of fear responses. Our team found that right-handed patients with PTSD are more vulnerable to left than right hippocampal damage.
Enduring pathophysiological effects are evident in mTBI. This damage is often not visible with conventional CT and magnetic resonance imaging. However, it can be seen with diffusion tensor imaging, which measures the functional integrity of white matter, as well as in postmortem brain studies. The primary pathology associated with mTBI is traumatic axonal injury, caused by shearing and tensile forces that result from sudden deceleration and rotation of the head. Shearing effects may lead to the tearing and disconnection of axons and primarily affect deep frontal white-matter and subcortical structures, with white-matter projections to the frontal cortex. Shearing may also disrupt small veins, resulting in microhemorrhagic lesions in the frontal and temporal regions. The hippocampus is especially vulnerable to axonal damage and may be affected indirectly by the damaging effects of trauma-induced release of excitatory neurotransmitters.
The c-Jun N-terminal kinases (JNKs) are a subfamily of mitogen-activated protein kinases that play important roles in the central nervous system, in both physiological and pathological conditions. JNK activation has been observed in both neurons and axons in experimental models of TBI, as well as in humans. The disruption of axonal transport appeared to be mediated by the neuron-specific JNK3 isoform, which may explain the observed protective effect of genetic deletion of the JNK3 isoform after axotomy of dopaminergic neurons.,
| Dual Challenges: Posttraumatic Stress Disorder and Traumatic Brain Injury in Forensic Psychiatry Evaluation|| |
Posttraumatic stress disorder, traumatic brain injury, and aggression
A crucial question in forensic psychiatry evaluation is whether PTSD and/or TBI is associated with a neuropsychiatric profile that diminishes culpability, either by interfering with the ability to appreciate the wrongfulness of one's actions or by reducing the ability to conform to one's behavior to the requirements of the law. The Aspen Neurobehavioral Conference Consensus Statement notes that all human behaviors are variably governed by the interaction of numerous factors, including genes, early life experience, acquired brain damage, learned behavioral patterns, and situational contingencies. PTSD and TBI appear to cause neurobiological dysfunction that impairs an individual's capacity to inhibit violent behavior. Nonetheless, it is crucial to appreciate that illness is not destiny, and that many preinjury and postinjury psychosocial factors are at play in any individual who exhibits violent behavior toward others.
Organic aggressive syndrome is characterized by aggression that is reactive (provoked by seemingly trivial stimuli), nonreflective (unplanned), nonpurposeful (serves no clear aim or objective), explosive (occurs suddenly and without any apparent buildup), periodic (prolonged periods of relative calm punctuated by aggressive outbursts), and ego-dystonic (the individual feels bad about the behavior). This type of posttraumatic aggression is relatively uncommon and is generally observed among individuals who are severely neurologically compromised. In such instances, causative relationships between injury and behavior are relatively straightforward. Impulsive violence, wherein unplanned aggressive behavior is directed at a specific person in response to a perceived threat, is far more common among neurobehaviorally impaired patients with PTSD and TBI survivors. It is particularly observed among those with generalized impairments of impulse control (i.e., disinhibited behavior) and those with comorbid severe cognitive impairments, depression, mania, anxiety, or psychosis.
However, aggression of any kind may also arise in the absence of such neuropsychiatric conditions. Indeed, it may be a function of problems that bear no direct relation to a neuropsychiatric injury per se, including states of intoxication, premorbid personality traits and disorders (especially antisocial, borderline, and narcissistic), or as a premeditated, purposeful, instrumental violent act. Attribution of aggressive behavior to PTSD or TBI (i.e., impaired impulse control resulting from neuropsychiatric illness) rather than to purposeful, instrumental violence must be undertaken with caution and only after careful consideration of all circumstances surrounding such acts. This includes (but is not limited to) specific details of the neuropsychiatric condition, psychosocial factors in existence before and after the event, the context in which the particular violent act occurred, potential precipitants, and possible objectives.
| Posttraumatic Stress Disorder, Traumatic Brain Injury, and Criminal Responsibility|| |
Another crucial question in forensic psychiatry evaluation is how traumatic exposure may lead to impaired emotionality and cognition that may offer a basis for legal defenses. The defense of insanity, impaired legal capacity, and sentence mitigation have always been a controversial issue., In general, both PTSD- and TBI-induced concussion syndrome and brain contusion syndrome are not psychiatric disorders. It is cautioned that assessment cannot be based solely on self-reported traumatic exposure, a lesson learned by forensic evaluators of veterans from earlier eras., Bryant and Harvey found that the qualitative features of trauma memories that had been continuously recalled were largely indistinguishable from those of inaccurate “memories” that were reconstructed following severe TBI. This finding highlights that it is difficult to determine the historical accuracy of a memory on the basis of the respondent's subjective experience. These various findings converge on the conclusion that reported memories of events that occurred during periods of impaired consciousness need to be interpreted as reflections of a narrative truth rather than historical truth.,
| Posttraumatic Stress Disorder, Traumatic Brain Injury, and Compensation Medicine|| |
Within judicial practice, cases of mental disability caused by traumatic events or brain injury are increasing. The susceptibility to and chronic course of PTSD are often controversial issues in court. It can be questioned why only a few people develop PTSD despite similar or identical stressful environments. Moreover, most patients with PTSD can recover from stressful conditions after treatment. Why are some patients unable to recover, with their condition evolving into chronic illness and mental disability? When PTSD patients have comorbid TBI, does TBI increase or decrease the susceptibility to and chronicity of PTSD? The possibility of malingering is another consideration in PTSD and TBI litigation. Because judicial identification of mental injury still relies on traditional mental examination, neuroimaging, and psychological testing, it is necessary to establish more objective identification techniques in the future.
| Conclusion|| |
Comorbid PTSD and TBI is a common and challenging forensic and clinical situation that requires attention to develop better strategies for assessment and treatment. Accumulating evidence has supported TBI as an important risk factor for PTSD. However, the causal relationship between TBI and PTSD remains unclear, although neurological factors may be involved. Furthermore, significant overlap in the symptoms of PTSD and TBI leads to difficulties in differential diagnosis. Multiple studies have shown that PTSD is associated with postconcussive symptoms, creating debate over whether these symptoms are related to neurological injury, psychological stress, or both. The evaluation of comorbid PTSD and TBI in forensic psychiatry may be complicated by several considerations. For instance, diagnosis might be interfered with by these overlapping symptoms, as well as the cognitive and other sequelae of TBI. Therefore, further studies are needed to clarify these issues.
We thank Rhianna Goozee, PhD, from Edanz Group (www.edanzediting.com/ac) for editing a draft of this manuscript.
Financial support and sponsorship
This work was supported by the National Key Technology R&D Program of China (2012BAK16B03), Science and Technology Projects of Guangdong Province, China (2013B022000054).
Conflicts of interest
There are no conflicts of interest.
| References|| |
Howlett JR, Stein MB. Post-traumatic stress disorder: Relationship to traumatic brain injury and approach to treatment. In: Laskowitz D, Grant G, editors. Translational Research in Traumatic Brain Injury. Boca Raton (FL): CRC Press/Taylor and Francis Group; 2016.
Schneiderman AI, Braver ER, Kang HK. Understanding sequelae of injury mechanisms and mild traumatic brain injury incurred during the conflicts in Iraq and Afghanistan: Persistent postconcussive symptoms and posttraumatic stress disorder. Am J Epidemiol 2008;167:1446-52.
Bryant RA. Posttraumatic stress disorder and traumatic brain injury: Can they co-exist? Clin Psychol Rev 2001;21:931-48.
Stonesifer LD. Mild traumatic brain injury in U.S. Soldiers returning from Iraq. N Engl J Med 2008;358:2178.
Elliott TR, Hsiao YY, Kimbrel NA, Meyer EC, DeBeer BB, Gulliver SB, et al
. Resilience, traumatic brain injury, depression, and posttraumatic stress among Iraq/Afghanistan war veterans. Rehabil Psychol 2015;60:263-76.
Merten T, Friedel E, Stevens A. Insufficient cooperativeness in forensic neuropsychiatric assessment: Prevalence estimates of negative response bias. Versicherungsmedizin 2006;58:19-21.
Reynolds K, Pietrzak RH, Mackenzie CS, Chou KL, Sareen J. Post-traumatic stress disorder across the adult lifespan: Findings from a nationally representative survey. Am J Geriatr Psychiatry 2016;24:81-93.
Maguen S, Hoerster KD, Littman AJ, Klingaman EA, Evans-Hudnall G, Holleman R, et al
. Iraq and Afghanistan veterans with PTSD participate less in VA's weight loss program than those without PTSD. J Affect Disord 2016;193:289-94.
Magruder KM, Goldberg J, Forsberg CW, Friedman MJ, Litz BT, Vaccarino V, et al
. Long-term trajectories of PTSD in Vietnam-era veterans: The course and consequences of PTSD in twins. J Trauma Stress 2016;29:5-16.
Othieno CJ, Okoth R, Peltzer K, Pengpid S, Malla LO. Traumatic experiences, posttraumatic stress symptoms, depression, and health-risk behavior in relation to injury among university of Nairobi students in Kenya. Int J Psychiatry Med 2015;50:299-316.
Teasdale G, Jennett B. Assessment of coma and impaired consciousness. A practical scale. Lancet 1974;2:81-4.
Kriz PK, Stein C, Kent J, Ruggieri D, Dolan E, O'Brien M, et al.
Physical maturity and concussion symptom duration among adolescent ice hockey players. J Pediatr 2016;171:234-90.
Walter KD, Halstead ME. Concussion in teenage athletes. Adolesc Med State Art Rev 2015;26:39-52.
Iverson GL, Silverberg ND, Mannix R, Maxwell BA, Atkins JE, Zafonte R, et al
. Factors associated with concussion-like symptom reporting in high school athletes. JAMA Pediatr 2015;169:1132-40.
Nelson NW, Davenport ND, Sponheim SR, Anderson CR. Blast-related mild traumatic brain injury: Neuropsychological evaluation and findings. In: Kobeissy FH, editor. Brain Neurotrauma: Molecular, Neuropsychological, and Rehabilitation Aspects. Boca Raton (FL): CRC Press/Taylor & Francis; 2015.
McAllister TW. Neurobehavioral sequelae of traumatic brain injury: Evaluation and management. World Psychiatry 2008;7:3-10.
Bigler ED. Neuropathology of mild traumatic brain injury: Correlation to neurocognitive and neurobehavioral findings. In: Kobeissy FH, editor. Brain Neurotrauma: Molecular, Neuropsychological, and Rehabilitation Aspects. Boca Raton (FL): CRC Press/Taylor & Francis; 2015.
von Wild KRH. Münster TBI Study Council. Posttraumatic rehabilitation and one year outcome following acute traumatic brain injury (TBI): Data from the well defined population based German prospective study 2000-2002. Acta Neurochir Suppl 2008;101:55-60.
Wilk JE, Herrell RK, Wynn GH, Riviere LA, Hoge CW. Mild traumatic brain injury (concussion), posttraumatic stress disorder, and depression in U.S. Soldiers involved in combat deployments: Association with postdeployment symptoms. Psychosom Med 2012;74:249-57.
O'Brien M. Psychiatric consequences of road traffic accidents. Loss of memory is protective. BMJ 1993;307:1283.
Mayou R, Bryant B, Duthie R. Psychiatric consequences of road traffic accidents. BMJ 1993;307:647-51.
Sbordone RJ, Liter JC. Mild traumatic brain injury does not produce post-traumatic stress disorder. Brain Inj 1995;9:405-12.
Tokutomi T, Hirohata M, Miyagi T, Abe T, Shigemori M. Posttraumatic edema in the corpus callosum shown by MRI. Acta Neurochir Suppl 1997;70:80-3.
Ursano RJ, Fullerton CS, Epstein RS, Crowley B, Kao TC, Vance K, et al
. Acute and chronic posttraumatic stress disorder in motor vehicle accident victims. Am J Psychiatry 1999;156:589-95.
Jones C, Harvey AG, Brewin CR. Traumatic brain injury, dissociation, and posttraumatic stress disorder in road traffic accident survivors. J Trauma Stress 2005;18:181-91.
Koenigs M, Huey ED, Raymont V, Cheon B, Solomon J, Wassermann EM, et al
. Focal brain damage protects against post-traumatic stress disorder in combat veterans. Nat Neurosci 2008;11:232-7.
Webster J, Taylor A, Balchin R. Traumatic brain injury, the hidden pandemic: A focused response to family and patient experiences and needs. S Afr Med J 2015;105:195-8.
DePalma RG. Combat TBI: History, epidemiology, and injury modes. In: Kobeissy FH, editor. Brain Neurotrauma: Molecular, Neuropsychological, and Rehabilitation Aspects. Boca Raton (FL): CRC Press/Taylor & Francis; 2015.
Bryant RA, Felmingham K, Whitford TJ, Kemp A, Hughes G, Peduto A, et al
. Rostral anterior cingulate volume predicts treatment response to cognitive-behavioural therapy for posttraumatic stress disorder. J Psychiatry Neurosci 2008;33:142-6.
Vasterling JJ, Verfaellie M, Sullivan KD. Mild traumatic brain injury and posttraumatic stress disorder in returning veterans: Perspectives from cognitive neuroscience. Clin Psychol Rev 2009;29:674-84.
Larrabee GJ, Binder LM, Rohling ML, Ploetz DM. Meta-analytic methods and the importance of non-TBI factors related to outcome in mild traumatic brain injury: Response to Bigler et al
. (2013). Clin Neuropsychol 2013;27:215-37.
Moran GM, Fletcher B, Feltham MG, Calvert M, Sackley C, Marshall T. Fatigue, psychological and cognitive impairment following transient ischaemic attack and minor stroke: A systematic review. Eur J Neurol 2014;21:1258-67.
Bailie JM, Kennedy JE, French LM, Marshall K, Prokhorenko O, Asmussen S, et al
. Profile analysis of the neurobehavioral and psychiatric symptoms following combat-related mild traumatic brain injury: Identification of subtypes. J Head Trauma Rehabil 2016;31:2-12.
Figueroa XA, Wright JK. OK, doc. What do I really have? Posttraumatic stress disorder versus traumatic brain injury. J Spec Oper Med 2015;15:59-66.
Smoller JW. The genetics of stress-related disorders: PTSD, depression, and anxiety disorders. Neuropsychopharmacology 2016;41:297-319.
Wilker S, Schneider A, Conrad D, Pfeiffer A, Boeck C, Lingenfelder B, et al
. Genetic variation is associated with PTSD risk and aversive memory: Evidence from two trauma-exposed African samples and one healthy European sample. Transl Psychiatry 2018;8:251.
Shi L, Chen SJ, Deng JH, Que JY, Lin X, Sun Y, et al
. ADRB2 gene polymorphism modulates the retention of fear extinction memory. Neurobiol Learn Mem 2018;156:96-102.
Zhou H, Cheng Z, Bass N, Krystal JH, Farrer LA, Kranzler HR, et al
. Genome-wide association study identifies glutamate ionotropic receptor GRIA4 as a risk gene for comorbid nicotine dependence and major depression. Transl Psychiatry 2018;8:208.
Guillén-Burgos HF, Gutiérrez-Ruiz K. Genetic advances in post-traumatic stress disorder. Rev Colomb Psiquiatr 2018;47:108-18.
Lind MJ, Marraccini ME, Sheerin CM, Bountress K, Bacanu SA, Amstadter AB, et al
. Association of posttraumatic stress disorder with rs2267735 in the ADCYAP1R1 gene: A meta-analysis. J Trauma Stress 2017;30:389-98.
Schür RR, Boks MP, Rutten BP, Daskalakis NP, de Nijs L, van Zuiden M, et al
. Longitudinal changes in glucocorticoid receptor exon 1F
methylation and psychopathology after military deployment. Transl Psychiatry 2017;7:e1181.
Ramikie TS, Ressler KJ. Stress-related disorders, pituitary adenylate cyclase-activating peptide (PACAP) ergic system, and sex differences. Dialogues Clin Neurosci 2016;18:403-13.
Kulenovic AD, Agani F, Avdibegovic E, Jakovljevic M, Babic D, Kucukalic A, et al
. Molecular mechanisms of posttraumatic stress disorder (PTSD) as a basis for individualized and personalized therapy: Rationale, design and methods of the South Eastern Europe (SEE)-PTSD study. Psychiatr Danub 2016;28:154-63.
Liu Y, Garrett ME, Dennis MF, Green KT; VA Mid-Atlantic MIRECC Registry Workgroup, Ashley-Koch AE, et al
. An examination of the association between 5-HTTLPR, combat exposure, and PTSD diagnosis among U.S. Veterans. PLoS One 2015;10:e0119998.
Kimbrel NA, Hauser MA, Garrett M, Ashley-Koch A, Liu Y, Dennis MF, et al
. Effect of the apoe ε4 allele and combat exposure on PTSD among IRAQ/Afghanistan-ERA veterans. Depress Anxiety 2015;32:307-15.
Hoge CW, Goldberg HM, Castro CA. Care of war veterans with mild traumatic brain injury-flawed perspectives. N Engl J Med 2009;360:1588-91.
Vanderploeg RD, Belanger HG, Curtiss G. Mild traumatic brain injury and posttraumatic stress disorder and their associations with health symptoms. Arch Phys Med Rehabil 2009;90:1084-93.
Biester RC, Krych D, Schmidt MJ, Parrott D, Katz DI, Abate M, et al
. Individuals with traumatic brain injury and their significant others' perceptions of information given about the nature and possible consequences of brain injury: Analysis of a national survey. Prof Case Manag 2016;21:22-33.
Franke LM, Czarnota JN, Ketchum JM, Walker WC. Factor analysis of persistent postconcussive symptoms within a military sample with blast exposure. J Head Trauma Rehabil 2015;30:E34-46.
Mysliwiec V, McGraw L, Pierce R, Smith P, Trapp B, Roth BJ, et al
. Sleep disorders and associated medical comorbidities in active duty military personnel. Sleep 2013;36:167-74.
Booth-Kewley S, Highfill-McRoy RM, Larson GE, Garland CF, Gaskin TA. Anxiety and depression in marines sent to war in Iraq and Afghanistan. J Nerv Ment Dis 2012;200:749-57.
Sherer M, Sander AM, Nick TG, Melguizo MS, Tulsky DS, Kisala P, et al
. Key dimensions of impairment, self-report, and environmental supports in persons with traumatic brain injury. Rehabil Psychol 2015;60:138-46.
Kraal AZ, Waldron-Perrine B, Pangilinan PH, Bieliauskas LA. Affect and psychiatric symptoms in a veteran polytrauma clinic. Rehabil Psychol 2015;60:36-42.
Williams MW, Rapport LJ, Millis SR, Hanks RA. Psychosocial outcomes after traumatic brain injury: Life satisfaction, community integration, and distress. Rehabil Psychol 2014;59:298-305.
Di Battista A, Godfrey C, Soo C, Catroppa C, Anderson V. Depression and health related quality of life in adolescent survivors of a traumatic brain injury: A pilot study. PLoS One 2014;9:e101842.
Mueller SG, Ng P, Neylan T, Mackin S, Wolkowitz O, Mellon S, et al
. Evidence for disrupted gray matter structural connectivity in posttraumatic stress disorder. Psychiatry Res 2015;234:194-201.
Ke J, Zhang L, Qi R, Li W, Hou C, Zhong Y, et al
. A longitudinal fMRI investigation in acute post-traumatic stress disorder (PTSD). Acta Radiol 2016;57:1387-95.
Du MY, Liao W, Lui S, Huang XQ, Li F, Kuang WH, et al
. Altered functional connectivity in the brain default-mode network of earthquake survivors persists after 2 years despite recovery from anxiety symptoms. Soc Cogn Affect Neurosci 2015;10:1497-505.
Meng Y, Qiu C, Zhu H, Lama S, Lui S, Gong Q, et al
. Anatomical deficits in adult posttraumatic stress disorder: A meta-analysis of voxel-based morphometry studies. Behav Brain Res 2014;270:307-15.
Jin C, Qi R, Yin Y, Hu X, Duan L, Xu Q, et al
. Abnormalities in whole-brain functional connectivity observed in treatment-naive post-traumatic stress disorder patients following an earthquake. Psychol Med 2014;44:1927-36.
Shu XJ, Xue L, Liu W, Chen FY, Zhu C, Sun XH, et al
. More vulnerability of left than right hippocampal damage in right-handed patients with post-traumatic stress disorder. Psychiatry Res 2013;212:237-44.
Gardizi E, Millis SR, Hanks R, Axelrod B. Rasch analysis of the postconcussive symptom questionnaire: Measuring the core construct of brain injury symptomatology. Clin Neuropsychol 2012;26:869-78.
Lee JY, Biemond M, Petratos S. Axonal degeneration in multiple sclerosis: Defining therapeutic targets by identifying the causes of pathology. Neurodegener Dis Manag 2015;5:527-48.
Büki A, Povlishock JT. All roads lead to disconnection? – Traumatic axonal injury revisited. Acta Neurochir (Wien) 2006;148:181-93.
Mata-Mbemba D, Mugikura S, Nakagawa A, Murata T, Kato Y, Tatewaki Y, et al
. Intraventricular hemorrhage on initial computed tomography as marker of diffuse axonal injury after traumatic brain injury. J Neurotrauma 2015;32:359-65.
Bauer CA, Brozoski TJ. Gabapentin. Prog Brain Res 2007;166:287-301.
Kuan CY, Whitmarsh AJ, Yang DD, Liao G, Schloemer AJ, Dong C, et al
. A critical role of neural-specific JNK3 for ischemic apoptosis. Proc Natl Acad Sci U S A 2003;100:15184-9.
Ortolano F, Colombo A, Zanier ER, Sclip A, Longhi L, Perego C, et al
. C-jun N-terminal kinase pathway activation in human and experimental cerebral contusion. J Neuropathol Exp Neurol 2009;68:964-71.
Morfini GA, You YM, Pollema SL, Kaminska A, Liu K, Yoshioka K, et al
. Pathogenic huntingtin inhibits fast axonal transport by activating JNK3 and phosphorylating kinesin. Nat Neurosci 2009;12:864-71.
Brecht S, Kirchhof R, Chromik A, Willesen M, Nicolaus T, Raivich G, et al
. Specific pathophysiological functions of JNK isoforms in the brain. Eur J Neurosci 2005;21:363-77.
Filley CM, Price BH, Nell V, Antoinette T, Morgan AS, Bresnahan JF, et al
. Toward an understanding of violence: Neurobehavioral aspects of unwarranted physical aggression: Aspen neurobehavioral conference consensus statement. Neuropsychiatry Neuropsychol Behav Neurol 2001;14:1-4.
Brodaty H, Low LF. Aggression in the elderly. J Clin Psychiatry 2003;64 Suppl 4:36-43.
Li T, Li GR, Jiang HX, Tang CD, Tang JL. Forensic psychiatric cases of 534 mental disorders caused by traumatic brain injury. Fa Yi Xue Za Zhi 2013;29:116-9.
Casartelli L, Chiamulera C. Opportunities, threats and limitations of neuroscience data in forensic psychiatric evaluation. Curr Opin Psychiatry 2013;26:468-73.
Rosen GM, Powel JE. Use of a symptom validity test in the forensic assessment of posttraumatic stress disorder. J Anxiety Disord 2003;17:361-7.
Wortzel HS, Arciniegas DB. A forensic neuropsychiatric approach to traumatic brain injury, aggression, and suicide. J Am Acad Psychiatry Law 2013;41:274-86.
Misic-Pavkov G, Novovic Z, Bozic K, Kolundzija K, Kovacevic SI, Drakip D, et al
. Forensic aspect of late subjective complaints after traumatic brain injury. Eur Rev Med Pharmacol Sci 2012;16:1806-13.