PTSD in the Emergency Setting

Aug 01, 2006

The following 3 cases illustrate the diagnostic challenges related to differentiating brain injury and posttraumatic stress disorder (PTSD) in patients presenting to the emergency department (ED) in the acute period following a traumatic injury. Such patients pose a dilemma for ED clinicians because of the interplay between head injury and PTSD in the clinical presentation of cognitive impairments in the aftermath of trauma.


A 30-year-old woman sustained a closed head injury as a result of a motor vehicle accident (MVA). She was in the process of making a left turn when her vehicle was struck twice by a drunk driver, causing her car to hit a brick wall and her head to be struck twice in the left occipital region. According to her husband's report, the patient did not lose consciousness. However, she did report 10 minutes of anterograde amnesia.

The patient was transported to a major medical center's ED by ambulance 10 to 15 minutes after the MVA for medical evaluation. Her medical records showed cervical strain, head contusion, and anxiety secondary to the accident. CT and MRI scans demonstrated no remarkable findings.

In the weeks after her accident, the patient complained of daily intense headaches localized to her left occipital region that often averaged an 8 on a 0-to-10 pain scale. Her cognitive symptoms included frequent forgetfulness that disrupted her occupational functioning and overall daily activities and memory impairment. She also reported increased fatigue. The patient's husband noted that she had difficulty in remembering her activities.

In addition, the patient experienced depressed mood, anxiety, and confusion. She blamed herself for the accident, no longer enjoyed driving, and refused to drive after dark. She reported reexperiencing the accident while driving, during which she would feel intense psychological distress, would feel increased physiologic arousal, and would repeatedly "see the accident occurring in her head." Therefore, she attempted to avoid thinking about the event and avoided driving. She also had recurrent nightmares about the accident and lost interest in activities that were once important to her. She said she felt like a different person and that she did not have the same caring feelings for people; her husband confirmed this.

Problems with the quality and duration of this patient's sleep emerged after the MVA; she often self-medicated with generic over-the-counter antihistamines. She easily awakened on hearing a noise and generally maintained a heightened awareness of her surroundings. She was easily fatigued and irritable on a daily basis, had headaches, and had trouble concentrating. These symptoms made it difficult for her to work and impaired her social relationships.

Escitalopram was prescribed to help manage her anxiety, but she reported a lack of interest in taking it or any other psychiatric medication. The patient's medical history was significant for hysterectomy and right breast cyst removal.

Neuropsychological evaluation, performed approximately 5 months after the MVA, demonstrated mild impairments in verbal attention and moderate to severe impairments in both verbal and visuospatial memory. The patient particularly maintained deficits in initial encoding of presented materials. She met criteria for PTSD, based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, and her results on the Minnesota Multiphasic Personality Inventory-2 (MMPI-2) revealed that she was highly phobic at the time of her testing and may have had a predisposition to stress reactions.


A common complicating factor in patients who present to the ED with stress symptoms is possible brain injury. Although there is consensus that PTSD can occur in the aftermath of brain injury, estimates of the actual prevalence vary widely (0% to 58%).1,2 This case illustrates the dilemma of diagnosing PTSD in the presence of mild head injury and loss of memory of the accident.

Diagnostic criteria for PTSD indicate that a person must experience the event with "intense fear, horror, or helplessness."3 But is it possible to encode a traumatic memory if there is no conscious memory of the event because of head injury? Previously it was argued that PTSD was not possible with head injury if there was no explicit memory of the event. However, there is growing consensus that this is not the case.2,4 For example, Bryant2 has argued that trace memories from accidents can exist that form the core of the memory that leads to PTSD, even if no explicit memory of the event exists.

A number of studies of PTSD have been performed in patients presenting to the ED with head injury. One study of 120 persons who presented with mild traumatic brain injury (TBI) and were hospitalized found that PTSD developed in 14% of the patients at 6 months.5 PTSD was more likely to develop in patients who remembered the event primarily because of more reexperiencing of symptoms.

In another study, PTSD was also more common in patients with TBI who remembered the event and affected only 3% of those with no memory of the accident.6 Of 43 children with and without TBI who were in an MVA, there were no differences in PTSD rates.7 In a study of 96 patients with severe TBI, PTSD was seen in 27%, of whom only 19% had intrusive memories of the trauma and 96% had emotional reactivity8; patients with more PTSD symptoms had worse health and lower levels of functioning9; 19% had intrusive memories8; 96% showed emotional reactivity8; and those with avoidant coping style had higher levels of PTSD.10

In a study of 307 consecutive admissions to a level I trauma center because of mild TBI, over half of patients had at least partial recall of the event.11 PTSD developed in 10% of patients by 12 months after injury, and there were no differences between traumatized and nontraumatized patients with and without TBI. There were also no differences in PTSD between those with and without amnesia for the event.

A study of 107 persons with and without TBI involved in MVAs showed that patients who lost consciousness had greater impairment on neuropsychological testing of speed and recall of verbal material.12 PTSD was as common in patients with TBI as in patients without TBI. In another study, of 34 patients with TBI, 59% met criteria for PTSD by self-report measure but only 3% had PTSD based on clinician-administered assessment with the Clinician Administered PTSD Scale.13 The authors concluded that the effects of head injury led to discrepancies in diagnosis.

PTSD symptoms were not associated with severity of brain injury in a study of 66 patients with severe TBI.14 Also, patients with amnesia had lower norepinephrine/cortisol ratios and fewer PTSD symptoms than those without amnesia.15

PTSD is possible in patients with head injury even if there is no explicit memory for the actual event.2,4-15 It is possible to encode a traumatic memory (at an implicit level) even if there is no conscious (explicit) recall. For example, patients with hippocampal damage may not be able to spontaneously repeat words that they have seen previously (explicit memory), but if provided with the first few letters of a word, they may be able to fill in the gaps (implicit memory).

A similar situation may occur in trauma patients with amnesia. The event could be encoded in some way that is not available to conscious recall. Some have called this a "body memory," which is some memory trace of the event that has been retained in terms of conditioned responses, physiologic memory, or otherwise. Nonetheless, studies show that PTSD rates are lower in patients with amnesia and that these patients have fewer symptoms in the intrusion category and more symptoms in the hyperarousal category.5,6


A 23-year-old woman was involved in a head-on vehicular collision at about 35 miles per hour, causing her airbag to deploy. A tractor trailer fell on top of her vehicle, trapping her inside. She was extracted from her vehicle after 30 minutes, during which time a family friend died in the seat next to her. She denied any loss of consciousness during the accident but experienced intermittent loss of consciousness while trapped inside her vehicle and on the way to the nearest medical center. The patient was fully alert and oriented when she arrived at the ED, as evidenced by her Glasgow Coma Scale score of 15.

She sustained numerous physical injuries as a result of the accident, including right posterior shoulder pain, right breast numbness, and left shoulder and neck pain. However, CT and MRI scans demonstrated no evidence of brain injury, and she was discharged. Within the next month, she presented to the ED several times with complaints of intractable pain, shortness of breath, and severe headache. A repeated CT scan demonstrated fractured ribs but no changes in the brain, which was supported by an MRI scan. She had at least 3 subsequent ED visits.

Her first subsequent ED visit was for intractable pain, and the second ED visit resulted in a cholecystectomy. An MRI scan obtained 4 months post-MVA revealed an L5-S1 disk protrusion that was treated by laminectomy. She received multiple nerve blocks for lower back and rib pain related to the accident. About 6 months post-MVA, she presented to the ED with severe headache, blurred vision, photophobia, hot flashes, nausea, neck pain, and decreased "short-term memory," all of which began after the accident. Negative findings on a CT scan led to her being discharged without medical treatment. However, she had received a diagnosis of postconcussive syndrome by one physician.

The patient reported a number of physical, cognitive, and emotional complaints that she attributed directly to the accident. Cognitively, she had trouble concentrating and was easily distracted. She had difficulty in remembering recent events, future appointments and tasks, and the location of objects. She reported word-finding difficulties and comprehension difficulties for both spoken and written information, as well as new problems with spelling. She had subjective difficulty in performing multiple activities concurrently, planning ahead, and managing her time effectively. These problems persisted for 6 months after the accident and significantly reduced her functional status.

The patient's emotional status included severe anxiety and depression. Both the patient and her parents noted a change in her personality since the accident. She reported emotional lability, disrupted sleep, passive suicidal ideations, and compulsive behavior. She was irritable and became very angry when things were not done in a certain way. She also had recurrent thoughts of the accident; had nightmares relevant to her trauma; and felt very anxious and aroused when driving, especially around tractor trailers. The patient had panic attacks, became extremely anxious in automobiles, and felt considerable guilt about surviving the incident, given the death of the family friend in the seat next to her.

She continued to drive after the accident, although only occasionally, and reported considerable anxiety when doing so. She became withdrawn, had disrupted social relations, and avoided things that would remind her of the accident. Before her neuropsychological evaluation, PTSD was diagnosed, at which time sertraline was prescribed. However, she discontinued the medication for unclear reasons.

She was administered the MMPI-2, and the Gass correction factor was used to control for cognitive and physical symptoms commonly associated with brain injuries. Her profile revealed a poor tolerance for frustration and limited coping mechanisms for dealing with stress. A neuropsychological evaluation revealed several areas of impairment, including mildly to moderately impaired attention; moderate impairment on select spatial perceptual tasks; and impaired ability to acquire new information, which contributed to her poor memory performance.

Her health history included polycystic ovarian disease and diabetes. She was a nonsmoker who rarely drank alcohol and denied substance use. Although the patient denied any history of mental illness, her records indicated childhood sexual abuse that continued to affect some aspects of her life. For example, she refused a gynecologic examination during her post-MVA ED visit.


This case illustrates memory impairment in the aftermath of a car accident that may be attributable to a mild head injury or to PTSD. Patients often present to the ED with symptoms of memory disturbance or cognitive dysfunction, which are often attributed to a brain injury, whether or not there is evidence of such. However, these memory problems could be related to early presentation of PTSD.

Patients with PTSD exhibit a broad range of problems with memory, including gaps in memory, problems with declarative memory, attentional biases to trauma-related information, and intrusive memories. Many ED clinicians may not appreciate that memory impairment can be associated with PTSD in the absence of head injury.

Stress in the absence of physical injury can be associated with changes in memory and brain structures that mediate memory. The hippocampus is an area of the brain that plays a critical role in memory and is sensitive to stress. Studies in animals exposed to stress showed deficits in hippocampal-based memory function16 and alterations in hippocampal morphology.17,18 More specifically, stress can interfere with long-term potentiation.16,19 Mechanisms in the hippocampus proposed for these findings include elevated levels of glucocorticoids released during stress,20 stress-related inhibition of brain-derived neurotrophic factor,21 changes in serotonergic function,22 and inhibition of neurogenesis.23

Neuropsychological testing as a probe of brain function has been used to better understand PTSD. Several review studies have demonstrated verbal declarative memory deficits in patients with PTSD24-27 using a variety of measures (including the Wechsler Memory Scale, visual and verbal components of the Buschke Selective Reminding Test, Rey Auditory Verbal Learning Test, California Verbal Learning Test, and Rivermead Behavioral Memory Test). These studies looked at PTSD related to combat, rape, early childhood abuse, and childhood trauma. However, other studies found no evidence of memory impairments related to PTSD.28,29

Women with PTSD had verbal declarative memory deficits specifically associated with PTSD that were not a nonspecific effect of trauma exposure.30 Other memory disturbance studies in PTSD in both men and women have shown gaps in memory for everyday events (dissociative amnesia),31 deficits in autobiographical memory,32 false recall of material,33 an attentional bias for trauma-related material,34 and frontal lobe-related impairments.35

Neuroimaging studies showed alterations in the hippocampus in patients with PTSD. MRI scans showed smaller volume of the hippocampus in patients with PTSD, particularly decreases in right hippocampal volume that were associated with deficits in short-term memory.36 Findings of smaller hippocampal volume and/or a reduction in N-acetylaspartate (NAA) in the hippocampus (a marker of neuronal integrity) in adults with chronic PTSD have been replicated in the literature.37-39 Studies of pediatric40,41 and new-onset PTSD (including patients presenting to the ED)42,43 did not find hippocampal volume reduction, although reduced levels of NAA--indicating loss of neuronal integrity--were found in the medial prefrontal cortex in children with PTSD.44

Findings of a meta-analysis revealed smaller hippocampal volume for both the left and the right sides, equally in adult men and women with chronic PTSD, and no change in children.45 Patients with PTSD also had deficits in hippocampal activation while performing a verbal declarative memory task.39,46


A 42-year-old woman was exposed to carbon monoxide while working at a retail store. She recalled headache, dizziness, blurred vision, jitteriness, nausea, and vomiting prior to losing consciousness. She regained consciousness and was transported via ambulance to a nearby hospital, during which time she again lost consciousness. Upon admittance, the patient's carboxyhemoglobin level was elevated to 25.6%. She was transported by helicopter to another hospital where she received 2 courses of hyperbaric oxygen therapy, which resulted in significant symptom reduction. She was discharged 3 days later. Her records indicate that electroencephalography, MRI, and chest radiography demonstrated unremarkable findings and both her initial and follow-up examinations were unremarkable. Thus, she was cleared for return to work.

However, the patient reported numerous physical and cognitive complaints following the event, including photosensitivity, severe headache, daily nausea, myospasm, myalgia, and constant pain in her chest, legs, and joints. Cognitively, she complained of difficulty in concentrating and memory deficits for recent events and information. She underwent neuropsychological evaluation several months after the event, at which time fexofenadine, carisoprodol, guaifenesin/dextromethorphan/phenylephrine, duloxetine, tizanidine, escitalopram, and celecoxib were prescribed. Her medical history was significant for tubal ligation, and she denied any previous loss of consciousness or head injuries and tobacco, alcohol, or illicit drug use.

The patient reported a number of mood and behavioral changes since the event and had nightmares that related to her trauma. She returned to her job for approximately 1 week after being discharged but could not continue working because of anxiety, fatigue, and psychological distress and increased arousal related to being in the workplace. She avoided returning to work, was less socially active, went to church less often, stopped volunteering for various organizations, and would stay in bed for several days each week.

She felt a restricted range of affect--what she described as being mentally dull. Her startle response was exaggerated, and she was more emotionally labile, irritable, and jumpy. The patient had difficulty in falling asleep and often woke in the middle of the night when having nightmares that related to her trauma and could not return to sleep. She also had panic attacks and increased anxiety. She reported having difficulty in concentrating and was easily distracted. She acknowledged passive suicidal ideations once while driving but denied current thoughts or plans.

During the neuropsychological examination, the patient was tearful. She found the memory tests particularly difficult and commented that she was "smarter" before the event. Her examination revealed a mild decrease in visual processing span and in the mental manipulation of such information. She showed mild reductions in her ability to learn visuospatial material and severe deficits in her retention of this information over time. She also demonstrated mild deficits in immediate verbal recall, but her performance was average when verbal material was presented in a meaningful context. In addition, she tended to confuse the verbal contents of her memory.

The MMPI-2 was administered, and findings revealed an overall highly elevated clinical profile. Her results indicated that she was overwhelmed by her internal distress, and she endorsed items that reflected a high number of atypical sensory experiences, a loss of a sense of control over her own mental and physical operations, and a general sense of alienation from others.

This patient was treated with an antidepressant with little improvement in symptoms of PTSD.


Preclinical studies show that there is a window during which modification of traumatic memories may affect long-term outcome. In animals that have encoded a traumatic memory, lesions of the hippocampus within the first month will cancel the memory. After a month, hippocampal lesions have no effect on the memory. These studies suggest that there is a critical window of memory consolidation during which memories are stored within the hippocampus and are susceptible to memory consolidation; after this period, memories are stored in the cerebral cortex and are indelible and no longer susceptible to modification.47 Thus, early interventions are important to prevent the development of indelible memories that will maintain chronic PTSD. However, there is not enough evidence to support specific acute therapies for PTSD.

The early period after trauma exposure is a window of time that is very different from chronic phases of PTSD. Therefore, it cannot be assumed that the same treatments will be effective. Animal studies suggest that early interventions may prevent the development of indelible traumatic memories that are resistant to treatment.48 However, not all treatments of early trauma responses will necessarily be effective. Given this situation, it is important to determine whether early interventions are working.

Few studies have examined treatment efficacy in the acute aftermath of trauma. One study showed that cognitive behavioral therapy resulted in improvement in 58% of acute trauma victims versus 8% for supportive therapy.1 For years, military psychiatrists have relied on anecdotal evidence and treated acutely traumatized soldiers with benzodiazepines or chlorpromazine on the battlefield and have kept them close to the front lines. They knew from experience that if you removed a soldier from the front lines, it would be almost impossible to get him to go back. These military psychiatrists were, in effect, practicing a form of desensitization therapy. In other words, exposure to the front lines promoted extinction of fear responses to the traumatic stimulus--in this case, reminders of combat.

Studies of pharmacotherapy for chronic PTSD, although limited, are more advanced than research in the area of acute trauma. These studies, as well as preclinical studies of the neurobiology of stress and treatment response, may help guide thinking about pharmacotherapy for acute trauma. These findings should be applied with caution to acute trauma, since one cannot assume that efficacy for chronic PTSD will translate into effectiveness in prevention of the development of psychopathology in acute trauma survivors.


The dynamic between brain injury and PTSD in patients presenting to the ED is complicated. Cognitive problems can arise from either brain injury or PTSD. Mild cognitive deficits are part of PTSD even without known brain injury. In patients with blows to the head in whom brain injury is not seen on MRI scans, it is difficult, if not impossible, to determine whether the cognitive deficits are due to PTSD, the head injury, or both. *



1. Bryant RA, Moulds M, Guthrie R, Nixon RD. Treating acute stress disorder following mild traumatic brain injury.

Am J Psychiatry.

2003;160:585-587.2. Bryant RA. Posttraumatic stress disorder and mild brain injury: controversies, causes and consequences.

J Clin Exp Neuropsychol.

2001;23:718-728.3. American Psychiatric Association.

Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (Text Revision)

. Washington, DC: American Psychiatric Press; 2000.4. Harvey AG, Brewin CR, Jones C, Kopelman MD. Coexistence of posttraumatic stress disorder and traumatic brain injury: towards a resolution of the paradox.

J Int Neuropsychol Soc.

2003;9:663-676.5. Gil S, Caspi Y, Ben-Ari IZ, et al. Does memory of a traumatic brain event increase the risk for posttraumatic stress disorder in patients with traumatic brain injury? A prospective study.

Am J Psychiatry.

2005;162:963-969.6. Glaesser J, Neuner F, Lutgehetmann R, et al. Posttraumatic stress disorder in patients with traumatic brain injury.

BMC Psychiatry.

2004;4:5.7. Mather FJ, Tate RL, Hannan TJ. Post-traumatic stress disorder in children following road traffic accidents: a comparison of those with and without mild traumatic brain injury.

Brain Inj.

2003;17:1077-1087.8. Bryant RA, Marosszeky JE, Crooks J, Gurka JA. Posttraumatic stress disorder after severe traumatic brain injury.

Am J Psychiatry.

2000;157:629-631.9. Bryant RA, Marosszeky JE, Crooks J, et al. Posttraumatic stress disorder and psychosocial functioning after severe traumatic brain injury.

J Nerv Ment Dis.

2001;189:109-113.10. Bryant RA, Marosszeky JE, Crooks J, et al. Coping style and post-traumatic stress disorder following severe traumatic brain injury.

Brain Inj.

2000; 14:175-180.11. Creamer M, O'Donnell ML, Pattison P. Amnesia, traumatic brain injury, and posttraumatic stress disorder: a methodological inquiry.

Behav Res Ther.

2005;43:1383-1389.12. Hickling EJ, Gillen R, Blanchard EB, et al. Traumatic brain injury and posttraumatic stress disorder: a preliminary investigation of neuropsychological test results in PTSD secondary to motor vehicle accidents.

Brain Inj.

1998;12:265-274.13. Sumpter RE, McMillan TM. Misdiagnosis of post-traumatic stress disorder following severe traumatic brain injury.

Br J Psychiatry.

2005;186:423-426.14. Williams WH, Evans JJ, Needham P, Wilson BA. Neurological, cognitive and attributional predictors of posttraumatic stress symptoms after traumatic brain injury.

J Trauma Stress.

2002;15:397-400.15. Flesher MR, Delahanty DL, Raimonde AJ, Spoonster E. Amnesia, neuroendocrine levels and PTSD in motor vehicle accident victims.

Brain Inj.

2001;15:879-889.16. Luine V, Villegas M, Martinez C, McEwen BS. Repeated stress causes reversible impairments of spatial memory performance.

Brain Res.

1994;639: 167-170.17. Uno H, Tarara R, Else JG, et al. Hippocampal damage associated with prolonged and fatal stress in primates.

J Neurosci.

1989;9:1705-1711.18. Sapolsky RM, Uno H, Rebert CS, Finch CE. Hippocampal damage associated with prolonged glucocorticoid exposure in primates.

J Neurosci.

1990;10:2897-2902.19. Diamond DM, Fleshner M, Ingersoll N, Rose GM. Psychological stress impairs spatial working memory: relevance to electrophysiological studies of hippocampal function.

Behav Neurosci.

1996;110: 661-672.20. Sapolsky RM. Why stress is bad for your brain.


1996;273:749-750.21. Smith MA, Makino S, Kvetnansky R, Post RM. Stress and glucocorticoids affect the expression of brain-derived neurotrophic factor and neurotrophin-3 mRNAs in the hippocampus.

J Neurosci.

1995;15: 1768-1777.22. McEwen BS, Angulo J, Cameron H, et al. Paradoxical effects of adrenal steroids on the brain: protection versus degeneration.

Biol Psychiatry.

1992;31:177-199.23. Fowler CD, Liu Y, Ouimet C, Wang Z. The effects of social environment on adult neurogenesis in the female prairie vole.

J Neurobiol.

2002;51:115-128.24. Buckley TC, Blanchard EB, Neill WT. Information processing and PTSD: a review of the empirical literature.

Clin Psychol Rev.

2000;28:1041-1065. 25. Elzinga BM, Bremner JD. Are the neural substrates of memory the final common pathway in posttraumatic stress disorder (PTSD)?

J Affect Disord.

2002;70:1-17.26. Brewin CR. A cognitive neuroscience account of posttraumatic stress disorder and its treatment.

Behav Res Ther.

2001;39:373-393.27. Golier J, Yehuda R. Neuroendocrine activity and memory-related impairments in posttraumatic stress disorder.

Dev Psychopathol.

1998;10:857-869.28. Stein MB, Hanna C, Vaerum V, Koverola C. Memory functioning in adult women traumatized by childhood sexual abuse.

J Trauma Stress.

1999;12: 527-534.29. Zalewski C, Thompson W, Gottesman II. Comparison of neuropsychological test performance in PTSD, generalized anxiety disorder, and control Vietnam veterans.


1994;1:133-142.30. Bremner JD, Vermetten E, Afzal N, Vythilingam M. Deficits in verbal declarative memory function in women with childhood sexual abuse-related posttraumatic stress disorder.

J Nerv Ment Dis.

2004;192: 643-649.31. Bremner JD, Steinberg M, Southwick SM, et al. Use of the Structured Clinical Interview for


Dissociative Disorders for systematic assessment of dissociative symptoms in posttraumatic stress disorder.

Am J Psychiatry.

1993;150:1011-1014. 32. McNally RJ, Litz BT, Prassas A, et al. Emotional priming of autobiographical memory in posttraumatic stress disorder.

Cogn Emot.

1994;8:351-367.33. Bremner JD, Shobe KK, Kihlstrom JF. False memories in women with self-reported childhood sexual abuse: an empirical study.

Psychol Sci.

2000; 11:333-337.34. Constans JI, McCloskey MS, Vasterling JJ, et al. Suppression of attentional bias in PTSD.

J Abnorm Psychology.

2004;113:315-323.35. Beckham JC, Crawford AL, Feldman ME. Trail making test performance in Vietnam combat veterans with and without posttraumatic stress disorder.

J Trauma Stress.

1998;11:811-819.36. Bremner JD, Randall P, Scott TM, et al. MRI-based measurement of hippocampal volume in patients with combat-related posttraumatic stress disorder.

Am J Psychiatry.

1995;152:973-981.37. Villarreal G, Hamilton DA, Petropoulos H, et al. Reduced hippocampal volume and total white matter in posttraumatic stress disorder.

Biol Psychiatry.

2002;15:119-125.38. Schuff N, Neylan TC, Lenoci MA, et al. Decreased hippocampal


-acetylaspartate in the absence of atrophy in posttraumatic stress disorder.

Biol Psychiatry.

2001;50:952-959.39. Bremner JD, Vythilingam M, Vermetten E, et al. MRI and PET study of deficits in hippocampal structure and function in women with childhood sexual abuse and posttraumatic stress disorder.

Am J Psychiatry.

2003;160:924-932.40. Carrion VG, Weems CF, Eliez S, et al. Attenuation of frontal asymmetry in pediatric posttraumatic stress disorder.

Biol Psychiatry.

2001;50:943-951.41. De Bellis MD, Hall J, Boring AM, et al. A pilot longitudinal study of hippocampal volumes in pediatric maltreatment-related posttraumatic stress disorder.

Biol Psychiatry.

2001;50:305-309.42. Bonne O, Brandes D, Gilboa A, et al. Longitudinal MRI study of hippocampal volume in trauma survivors with PTSD.

Am J Psychiatry.

2001;158: 1248-1251.43. Fennema-Notestine C, Stein MB, Kennedy CM, et al. Brain morphometry in female victims of intimate partner violence with and without posttraumatic stress disorder [published correction appears in

Biol Psychiatry

. 2003;53:632].

Biol Psychiatry.

2002;52:1089-1101.44. De Bellis MD, Keshavan MS, Spencer S, Hall J.


-Acetylaspartate concentration in the anterior cingulate of maltreated children and adolescents with PTSD.

Am J Psychiatry.

2000;157:1175-1177.45. Kitayama N, Vaccarino V, Kutner M, et al. Magnetic resonance imaging (MRI) measurement of hippocampal volume in posttraumatic stress disorder: a meta-analysis.

J Affect Disord.

2005;88:79-86.46. Shin LM, Shin PS, Heckers S, et al. Hippocampal function in posttraumatic stress disorder.


2004;14:292-300.47. Bremner JD, Southwick SM, Charney DS. The neurobiology of posttraumatic stress disorder: An integration of animal and human research. In: Saigh P, Bremner JD, eds.

Posttraumatic Stress Disorder: A Comprehensive Text.

New York: Allyn & Bacon; 1999:103-143.48. Charney DS, Nagy LM, Bremner JD, et al. Neurobiological mechanisms of human anxiety. In: Fogel BS, Schiffler RB, Rao SM, eds.

Synopsis of Neuropsychiatry

. Baltimore: Lippincott Williams & Wilkins; 2000:273-288.