Diminished medial prefrontal cortex activation during the recollection of stressful events is an acquired characteristic of PTSD.

BACKGROUND: Previous research has shown relatively diminished medial prefrontal cortex activation and heightened psychophysiological responses during the recollection of personal events in post-traumatic stress disorder (PTSD), but the origin of these abnormalities is unknown. Twin studies provide the opportunity to determine whether such abnormalities reflect familial vulnerabilities, result from trauma exposure, or are acquired characteristics of PTSD. METHODS: In this case-control twin study, 26 male identical twin pairs (12 PTSD; 14 non-PTSD) discordant for PTSD and combat exposure recalled and imagined trauma-unrelated stressful and neutral life events using a standard script-driven imagery paradigm during functional magnetic resonance imaging and concurrent skin conductance measurement. RESULTS: Diminished activation in the medial prefrontal cortex during Stressful v. Neutral script-driven imagery was observed in the individuals with PTSD, relative to other groups. CONCLUSIONS: Diminished medial prefrontal cortex activation during Stressful v. Neutral script-driven imagery may be an acquired characteristic of PTSD. If replicated, this finding could be used prospectively to inform diagnosis and the assessment of treatment response.

Decreased regional cerebral blood flow in medial prefrontal cortex during trauma-unrelated stressful imagery in Vietnam veterans with post-traumatic stress disorder.

BACKGROUND: Neuroimaging research has demonstrated medial prefrontal cortex (mPFC) hyporesponsivity and amygdala hyperresponsivity to trauma-related or emotional stimuli in post-traumatic stress disorder (PTSD). Relatively few studies have examined brain responses to the recollection of stressful, but trauma-unrelated, personal events in PTSD. In the current study, we sought to determine whether regional cerebral blood flow (rCBF) abnormalities in mPFC and amygdala in PTSD could be observed during the recollection of trauma-unrelated stressful personal events. METHOD: Participants were 35 right-handed male combat veterans (MCVs) and female nurse veterans (FNVs) who served in Vietnam: 17 (seven male, 10 female) with current military-related PTSD and 18 (nine male, nine female) with no current or lifetime PTSD. We used positron emission tomography (PET) and script-driven imagery to study rCBF during the recollection of trauma-unrelated stressful versus neutral and traumatic events. RESULTS: Voxelwise tests revealed significant between-group differences for the trauma-unrelated stressful versus neutral comparison in mPFC, specifically in the anterior cingulate cortex (ACC). Functional region of interest (ROI) analyses demonstrated that this interaction in mPFC represented greater rCBF decreases in the PTSD group during trauma-unrelated stressful imagery relative to neutral imagery compared to the non-PTSD group. No differential amygdala activation was observed between groups or in either group separately. CONCLUSIONS: Veterans with PTSD, compared to those without PTSD, exhibited decreased rCBF in mPFC during mental imagery of trauma-unrelated stressful personal experiences. Functional neuroanatomical models of PTSD must account for diminished mPFC responses that extend to emotional stimuli, including stressful personal experiences that are not directly related to PTSD.

An fMRI study of anterior cingulate function in posttraumatic stress disorder.

BACKGROUND: Several recent neuroimaging studies have provided data consistent with functional abnormalities in anterior cingulate cortex in posttraumatic stress disorder (PTSD). In our study, we implemented a cognitive activation paradigm to test the functional integrity of anterior cingulate cortex in PTSD. METHODS: Eight Vietnam combat veterans with PTSD (PTSD Group) and eight Vietnam combat veterans without PTSD (non-PTSD Group) underwent functional magnetic resonance imaging (fMRI) while performing the Emotional Counting Stroop. In separate conditions, subjects counted the number of combat-related (Combat), generally negative (General Negative), and neutral (Neutral) words presented on a screen and pressed a button indicating their response. RESULTS: In the Combat versus General Negative comparison, the non-PTSD group exhibited significant fMRI blood oxygenation level-dependent signal increases in rostral anterior cingulate cortex, but the PTSD group did not. CONCLUSIONS: These findings suggest a diminished response in rostral anterior cingulate cortex in the presence of emotionally relevant stimuli in PTSD. We speculate that diminished recruitment of this region in PTSD may, in part, mediate symptoms such as distress and arousal upon exposure to reminders of trauma.

Multivariate assessment of explicit memory function in combat veterans with posttraumatic stress disorder.

Declarative memory impairment is a frequent complaint of patients suffering from posttraumatic stress disorder (PTSD). We assessed memory, attention, visual spatial skills, and executive function in Vietnam combat veterans with (n = 19) and without (n = 13) PTSD. Although PTSD subjects demonstrated a "generalized impairment" relative to non-PTSD subjects on a majority of tasks, only attention and memory provided unique and independent prediction of PTSD versus non-PTSD status. Our findings suggest that memory functioning represents a neurocognitive domain of specific relevance to the development of PTSD in trauma-exposed individuals, which can be distinguished from generalized attentional impairment as well as the effects of trauma exposure severity, IQ, comorbid depression, history of alcohol use, and history of developmental learning problems.

Psychophysiologic assessment of posttraumatic stress disorder in Vietnam nurse veterans who witnessed injury or death.

This study examined whether witnessing death and injury could produce psychophysiologically responsive posttraumatic stress disorder (PTSD). Participants consisted of medication-free female Vietnam nurse veterans with a diagnosis of current PTSD (n = 17) and who never had PTSD (n = 21), related to their military service. Individualized scripts describing personal traumatic military nursing events, a standard military nursing event, and other life events were tape recorded and played back to the participant while heart rate, skin conductance, and facial electromyograms were recorded. Nurses with PTSD showed significantly larger physiologic responses than non-PTSD nurses only during imagery of military-related nursing events. The groups' self-reported emotional responses did not differ during imagery. Psychophysiologic results support the proposition that witnessing death and serious injury to others is sufficiently stressful to cause PTSD.

De novo conditioning in trauma-exposed individuals with and without posttraumatic stress disorder.

Differential conditioning was assessed in 15 medication-free individuals meeting Diagnostic and Statistical Manual of Mental Disorders (4th ed.; American Psychiatric Association, 1994) criteria for chronic posttraumatic stress disorder (PTSD) and 18 trauma-exposed individuals who never developed PTSD (non-PTSD). Conditioned stimuli (CSs) were colored circles, and the unconditioned stimulus was a "highly annoying" electrical stimulus. Individuals with PTSD had higher resting heart rate (HR) and skin conductance (SC) levels and produced larger SC orienting responses. During conditioning, the PTSD group showed larger differential SC, HR, and electromyogram responses to the reinforced vs. nonreinforced stimuli (CS+ vs. CS-) compared with the non-PTSD group. Only PTSD participants continued to show differential SC responses to CS+ vs. CS- during extinction trials. Results suggest that individuals with PTSD have higher sympathetic nervous system arousal at the time of conditioning and are more conditionable than trauma-exposed individuals without PTSD.

Exaggerated amygdala response to masked facial stimuli in posttraumatic stress disorder: a functional MRI study.

BACKGROUND: Converging lines of evidence have implicated the amygdala in the pathophysiology of posttraumatic stress disorder (PTSD). We previously developed a method for measuring automatic amygdala responses to general threat-related stimuli; in conjunction with functional magnetic resonance imaging, we used a passive viewing task involving masked presentations of human facial stimuli. METHODS: We applied this method to study veterans with PTSD and a comparison cohort of combat-exposed veterans without PTSD. RESULTS: The findings indicate that patients with PTSD exhibit exaggerated amygdala responses to masked-fearful versus masked-happy faces. CONCLUSIONS: Although some previous neuroimaging studies of PTSD have demonstrated amygdala recruitment in response to reminders of traumatic events, this represents the first evidence for exaggerated amygdala responses to general negative stimuli in PTSD. Furthermore, by using a probe that emphasizes automaticity, we provide initial evidence of amygdala hyperresponsivity dissociated from the "top-down" influences of medial frontal cortex.

Neurologic soft signs in chronic posttraumatic stress disorder.

BACKGROUND: Subtle neurologic impairment has been reported in several mental disorders. The goals of the present study were to evaluate neurologic status in patients of both sexes with chronic posttraumatic stress disorder (PTSD) from different traumatic experiences. METHODS: Twenty-one adult women who were sexually abused as children (12 with PTSD, 9 without) and 38 male Vietnam War combat veterans (23 with PTSD, 15 without) underwent examination for 41 neurologic soft signs, which were scored by the examiner as well as a blind rater observing videotapes. Subject history was obtained with special attention to neurodevelopmental problems. Psychometrics included the Wender Utah Rating Scale for symptoms of childhood attention-deficit/hyperactivity disorder and the Michigan Alcoholism Screening Test. Veterans also completed the Combat Exposure Scale and subtests of the Wechsler Adult Intelligence Scale-Revised. RESULTS: Average neurologic soft sign scores (interrater reliability = 0.74) of women with PTSD owing to sexual abuse in childhood (mean [SD], 0.77 [0.32]) and veteran men (0.72 [0.20]) with combat-related PTSD were comparable and significantly (P<.001) higher than those of women sexually abused as children (0.42 [0.10]) and combat veteran men (0.43 [0.17]) without PTSD. This effect could not be explained by a history of alcoholism or head injury. Subjects with PTSD reported more neurodevelopmental problems and more childhood attention-deficit/hyperactivity disorder symptoms and had lower IQs, all of which were significantly correlated with neurologic soft signs. CONCLUSION: Neurologic compromise is evident from subject history and findings from physical examination in both women and men with chronic PTSD who had experienced different kinds of traumatic events in childhood and adulthood.

Five-year follow-up study of eye movement desensitization and reprocessing therapy for combat-related posttraumatic stress disorder.

This study reports the results of a 5-year follow-up evaluation of 13 Vietnam combat veterans with chronic posttraumatic stress disorder (PTSD) who participated in a study of eye movement desensitization and reprocessing (EMDR) therapy previously reported in this journal. Pretreatment and follow-up psychometric outcome measures were compared with those of a demographically matched control group of 14 combat veterans with chronic PTSD who did not receive EMDR. Analysis of variance showed that the modest to moderate therapeutic benefits that were manifest immediately following EMDR were lost at the 5-year follow-up evaluation, and there was an overall worsening of PTSD symptomatology over the 5-year period in both EMDR-treated and nontreated control subjects.

Physiologic reactivity to startling tones in women with posttraumatic stress disorder.

Autonomic and eyeblink reactivity to startling tones were investigated in women with histories of childhood sexual abuse (CSA). Twenty-one women with current posttraumatic stress disorder (PTSD), 23 with lifetime but not current PTSD, and 13 women who never had PTSD listened to 15 95-dB, 500-ms, 1000-Hz tones with a 0-ms rise time while heart rate (HR), skin conductance (SC), and orbicularis oculi electromyogram (EMG) responses were measured. Participants in the current and lifetime PTSD groups produced larger HR responses across tones and showed slower absolute habituation of SC response magnitude compared with the never PTSD group. EMG response magnitudes did not differ among groups. Women with CSA-related PTSD showed increased autonomic reactivity and slower habituation to high-intensity tones similar to that observed in primarily male, combat PTSD samples. This suggests that heightened autonomic responsivity to startling stimuli in PTSD is not gender or event specific.

Regional cerebral blood flow during script-driven imagery in childhood sexual abuse-related PTSD: A PET investigation.

OBJECTIVE: The purpose of this study was to determine whether anterior limbic and paralimbic regions of the brain are differentially activated during the recollection and imagery of traumatic events in trauma-exposed individuals with and without posttraumatic stress disorder (PTSD). METHOD: Positron emission tomography (PET) was used to measure normalized regional cerebral blood flow (CBF) in 16 women with histories of childhood sexual abuse: eight with current PTSD and eight without current PTSD. In separate script-driven imagery conditions, participants recalled and imagined traumatic and neutral autobiographical events. Psychophysiologic responses and subjective ratings of emotional state were measured for each condition. RESULTS: In the traumatic condition versus the neutral control conditions, both groups exhibited regional CBF increases in orbitofrontal cortex and anterior temporal poles; however, these increases were greater in the PTSD group than in the comparison group. The comparison group exhibited regional CBF increases in insular cortex and anterior cingulate gyrus; increases in anterior cingulate gyrus were greater in the comparison group than in the PTSD group. Regional CBF decreases in bilateral anterior frontal regions were greater in the PTSD group than in the comparison group, and only the PTSD group exhibited regional CBF decreases in left inferior frontal gyrus. CONCLUSIONS: The recollection and imagery of traumatic events versus neutral events was accompanied by regional CBF increases in anterior paralimbic regions of the brain in trauma-exposed individuals with and without PTSD. However, the PTSD group had greater increases in orbitofrontal cortex and anterior temporal pole, whereas the comparison group had greater increases in anterior cingulate gyrus.

Directed forgetting of trauma cues in adult survivors of childhood sexual abuse with and without posttraumatic stress disorder.

The authors used a directed-forgetting task to investigate whether psychiatrically impaired adult survivors of childhood sexual abuse exhibit an avoidant encoding style and impaired memory for trauma cues. The authors tested women with abuse histories, either with or without posttraumatic stress disorder (PTSD), and women with neither abuse histories nor PTSD. The women saw intermixed trauma words (e.g., molested), positive words (e.g., confident), and categorized neutral words (e.g., mailbox) on a computer screen and were instructed either to remember or to forget each word. Relative to the other groups, the PTSD group did not exhibit recall deficits for trauma-related to-be-remembered words, nor did they recall fewer trauma-related to-be-forgotten words than other words. Instead, they exhibited recall deficits for positive and neutral words they were supposed to remember. These data are inconsistent with the hypothesis that impaired survivors exhibit avoidant encoding and impaired memory for traumatic information.

Lower precombat intelligence is a risk factor for posttraumatic stress disorder.

The authors examined the relation between intelligence and posttraumatic stress disorder (PTSD) by studying the association among precombat intelligence, current intelligence, and self-reported PTSD symptoms. Military aptitude test results were obtained in 59 PTSD and 31 non-PTSD Vietnam combat veterans who had undergone a psychodiagnostic interview and current intelligence testing. People with lower precombat intelligence were more likely to develop PTSD symptoms as assessed by the Clinician-Administered PTSD Scale even after adjustment for extent of combat exposure. The association between current intelligence and PTSD was no longer significant after adjusting for precombat intelligence. These results suggest that lower pretrauma intelligence increases risk for developing PTSD symptoms, not that PTSD lowers performance on intelligence tests.

Psychophysiologic assessment of women with posttraumatic stress disorder resulting from childhood sexual abuse.

Heart rate, skin conductance, and left lateral frontalis and corrugator facial electromyogram responses were measured during script-driven imagery of personal childhood sexual abuse (CSA) and other life experiences among women with and without Diagnostic and Statistical Manual of Mental Disorders (3rd ed., rev., American Psychiatric Association, 1987)--diagnosed posttraumatic stress disorder (PTSD) resulting from CSA. Women with current PTSD (n = 29) showed larger physiologic responses than those who never had PTSD (n = 18) during personal sexual abuse imagery but not during imagery of stressful, nonabuse-related life experiences. Responses of individuals with lifetime, but not current, PTSD (n = 24) fell between the other groups. An a priori discriminant function, derived from physiologic responses of previously studied individuals, correctly classified 66% of women with current PTSD and 78% of women who never had PTSD.

Auditory event-related potentials to tone stimuli in combat-related posttraumatic stress disorder.

This study attempted to replicate findings of abnormal auditory event-related potentials (ERPs) in posttraumatic stress disorder (PTSD) in a sample of Vietnam combat veterans. Veterans with combat-related PTSD, divided into unmedicated (unmed-PTSD, n = 12) and medicated (med-PTSD, n = 22) groups, and veterans without PTSD (non-PTSD, n = 10) completed a three-tone "oddball" target detection task while ERPs were measured. Individuals with comorbid panic disorder (PD) were excluded from the primary analyses. Parietal P3 amplitude to the target tone was significantly smaller in unmed-PTSD compared to med-PTSD and non-PTSD groups. These differences did not remain significant when an adjustment was made for level of depression. Parietal P3 amplitude was also negatively correlated with state anxiety. Secondary analyses within the unmed-PTSD group indicated that participants with comorbid PD (n = 3) had the largest parietal P3 amplitudes to target tones. Results are consistent with attentional or concentration deficits in PTSD and highlight the importance of considering comorbid diagnoses. The absence of ERP differences between med-PTSD and non-PTSD participants suggests that psychotropic medication may normalize these deficits.

Neurological status of combat veterans and adult survivors of sexual abuse PTSD.

We found higher levels of positive soft neurological signs in PTSD participants than in participants who also experienced similar trauma but did not develop PTSD. This finding was replicated in two samples, that is, Vietnam combat veterans and adult female survivors of childhood sexual abuse, despite differences in gender, age, nature of trauma, and period of life when the trauma occurred. Past developmental history of participants and a substance abuse history of first-degree relatives also differentiated PTSD from non-PTSD groups in both combat and sexual abuse samples. Evidence for neurological impairment and compromised developmental history raises the possibility of pretrauma impairment as a risk factor for the development of PTSD.