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.

Psychophysiologic assessment of posttraumatic stress disorder in breast cancer patients.

The authors performed psychodiagnostic, psychometric, and psychophysiologic evaluations on 37 patients referred by local surgeons approximately 2 years after tissue diagnosis of Stage I to III breast cancer. The Clinician-Administered Posttraumatic Stress Disorder (PTSD) Scale (CAPS) was used to classify patients into the following groups: "Current PTSD" (n = 5) "Past PTSD" (n = 7), and "Never had PTSD" (n = 25). Individualized "scripts" portraying personal life events were tape recorded and played back to the patients in the laboratory. Current PTSD patients showed significantly higher heart rate, skin conductance, and corrugator electromyogram responses during imagery of their personal breast cancer experiences than Past and Never patients. Physiologic responses were significantly and positively correlated with CAPS scores. These results provide psychophysiologic support for the proposition that a diagnosis of with a life-threatening illness can cause PTSD.

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.

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.

Psychophysiological alterations in post-traumatic stress disorder.

Psychophysiological research in trauma-exposed populations has provided objective data supporting the validity of the post-traumatic stress disorder (PTSD) diagnostic concept. Consistent with a conditioning model, PTSD patients show specific increased peripheral physiological responding to audio-visually and imaginally presented stimuli symbolizing or resembling the etiologic traumatic event. PTSD patients respond to startling stimuli with larger autonomic and electromyographic responses, especially under threat conditions. Electroencephalographic event-related potential (ERP) response abnormalities in PTSD include reduced P2 amplitude at high stimulus intensities, impaired P1 habituation, and attenuated P3 amplitude to target auditory stimuli. However, larger P3 and N1 amplitude responses and shorter P3 and N1 latencies have been reported in PTSD subjects in response to trauma-related stimuli. These ERP findings suggest sensory, cognitive, and affective processing abnormalities in PTSD. Polysomnographic sleep studies have revealed increased awakenings, reduced sleep time, and increased motor activity, or in some cases, paradoxical deepening of sleep. There is also evidence for increased phasic eye movement activity during rapid eye movement (REM) sleep and disrupted REM continuity in PTSD. Psychophysiological studies are offering valuable insights into the pathophysiology of this important neuropsychiatric condition.

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.

Seeking the source of emotional Stroop interference effects in PTSD: a study of P3s to traumatic words.

We investigated the source of emotional Stroop interference effects in posttraumatic stress disorder (PTSD) by measuring reaction times and P3 latencies and amplitudes to personal traumatic, personal positive, and neutral words in a modified Stroop paradigm. Individuals with PTSD were slower to indicate word color, especially for traumatic words, thereby replicating emotional Stroop interference in PTSD. Individuals with PTSD also had significantly reduced and delayed P3 components across word types. Across diagnostic groups, frontal P3 amplitudes were larger to personal positive and traumatic words compared to standard neutral words. However, the absence of Diagnosis x Word Type interactions for P3 measures suggests that individuals with PTSD do not differ from individuals without PTSD in the encoding and recognition of the color of traumatic relative to nontraumatic words, and that Stroop interference does not occur during these early stages of processing.

Physiologic responses to non-startling tones in Vietnam veterans with post-traumatic stress disorder.

We evaluated eyeblink and autonomic reactivity to non-startling acoustic stimuli in a convenience sample of Vietnam combat veterans. Twenty veterans with current PTSD and 19 veterans who never had PTSD were exposed to 15 consecutive 86-dB, 500-ms, 100-Hz tones with 40-ms rise and fall times, while orbicularis oculi electromyogram (EMG), skin conductance (SC) and heart rate (HR) responses were measured. PTSD subjects had higher resting HR levels and produced larger averaged HR responses across the 15 tone presentations compared to non-PTSD subjects. Skin conductance and EMG responses did not differ between the groups. Results suggest that previous findings of larger HR responses to loud tones in PTSD extend to lower intensity, non-startling stimuli, but that the magnitude of the HR response appears smaller to the lower intensity stimuli. Previously observed differences in the magnitude of the eyeblink response and rate of decline of SC responses in PTSD to high intensity stimuli appear to disappear when using non-startling stimuli.

Upper airway and soft tissue structural changes induced by CPAP in normal subjects.

Nasal continuous positive airway pressure (CPAP) is the treatment of choice for adults with obstructive sleep apnea. CPAP is known to increase upper airway size; however, the direct effects of CPAP on soft tissue structures surrounding the upper airway are less well understood. Magnetic resonance imaging was used to study the effect of incremental levels (0, 5, 10, and 15 cm H2O) of CPAP on the upper airway and surrounding soft tissue structures in 10 normal subjects. Progressive increases in CPAP resulted in the following major findings: (1) airway volume and airway area (measured at several different locations [midregion, minimal, maximal]) within the retropalatal and retroglossal regions increased; (2) lateral airway dimensional changes were greater than anterior-posterior changes; (3) lateral upper airway soft tissue structural changes were significantly greater than anterior-posterior changes; (4) lateral pharyngeal wall thickness decreased and the distance between the lateral parapharyngeal fat pads increased. An inverse relationship was demonstrated between CPAP level and pharyngeal wall thickness; (5) minimal changes were noted in the soft palate and tongue. These data suggest that the lateral pharyngeal walls are more "compliant" than the soft palate and tongue. This investigation provides further evidence that the lateral pharyngeal walls play an important role in mediating upper airway caliber.

Upper airway and soft tissue anatomy in normal subjects and patients with sleep-disordered breathing. Significance of the lateral pharyngeal walls.

The geometry and caliber of the upper airway in apneic patients differs from those in normal subjects. The apneic airway is smaller and is narrowed laterally. Examination of the soft tissue structures surrounding the upper airway can lead to an understanding of these apneic airway dimensional changes. Magnetic resonance imaging was utilized to study the upper airway and surrounding soft tissue structures in 21 normal subjects, 21 snorer/mild apneic subjects, and 26 patients with obstructive sleep apnea. The major findings of this investigation in the 68 subjects were as follows: (1) minimum airway area was significantly smaller in apneic compared with normal subjects and occurred in the retropalatal region; (2) airway narrowing in apneic patients was predominantly in the lateral dimension; there was no significant difference in the anterior-posterior (AP) airway dimension between subject groups; and (3) distance between the rami of the mandible was equal between subject groups, and thus the narrowing of the lateral dimension was not explained by differences in bony structure; (4) lateral airway narrowing was explained predominantly by larger pharyngeal walls in apneic patients (the parapharyngeal fat pads were not closer together as one would expect if the airway walls were compressed by fat); and (5) fat pad size at the level of the minimum airway was not greater in apneic than normal subjects. At the minimum airway area, thickness of the lateral pharyngeal muscular walls rather than enlargement of the parapharyngeal fat pads was the predominant anatomic factor causing airway narrowing in apneic subjects.