Linda J. Metzger

Regional Cerebral Blood Flow in the Amygdala and Medial Prefrontal Cortex During Traumatic Imagery in Male and Female Vietnam Veterans With PTSD

CONTEXT Theoretical neuroanatomic models of posttraumatic stress disorder (PTSD) and the results of previous neuroimaging studies of PTSD highlight the potential importance of the amygdala and medial prefrontal regions in this disorder. However, the functional relationship between these brain regions in PTSD has not been directly examined. OBJECTIVE To examine the relationship between the amygdala and medial prefrontal regions during symptom provocation in male combat veterans (MCVs) and female nurse veterans (FNVs) with PTSD. DESIGN Case-control study. SETTING Academic medical center. PARTICIPANTS Volunteer sample of 17 (7 men and 10 women) Vietnam veterans with PTSD (PTSD group) and 19 (9 men and 10 women) Vietnam veterans without PTSD (control group). MAIN OUTCOME MEASURES We used positron emission tomography and the script-driven imagery paradigm to study regional cerebral blood flow (rCBF) during the recollection of personal traumatic and neutral events. Psychophysiologic and emotional self-report data also were obtained to confirm the intended effects of script-driven imagery. RESULTS The PTSD group exhibited rCBF decreases in medial frontal gyrus in the traumatic vs neutral comparison. When this comparison was conducted separately by subgroup, MCVs and FNVs with PTSD exhibited these medial frontal gyrus decreases. Only MCVs exhibited rCBF increases in the left amygdala. However, for both subgroups with PTSD, rCBF changes in medial frontal gyrus were inversely correlated with rCBF changes in the left amygdala and the right amygdala/periamygdaloid cortex. Furthermore, in the traumatic condition, for both subgroups with PTSD, symptom severity was positively related to rCBF in the right amygdala and negatively related to rCBF in medial frontal gyrus. CONCLUSIONS These results suggest a reciprocal relationship between medial prefrontal cortex and amygdala function in PTSD and opposing associations between activity in these regions and symptom severity consistent with current functional neuroanatomic models of this disorder.

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.

Psychophysiology of post-traumatic stress disorder.

In general, the results of psychophysiologic research on PTSD support the presence of a variety of autonomic, sensory, and cognitive processing differences between individuals with and without the disorder. The findings are diverse and include heightened responsiveness to trauma reminders; exaggerated startle; increased conditionability and autonomic responsiveness to aversive, high-intensity stimuli; and elevated tonic or baseline physiologic activity. Increased sensitivity of the central nervous system is suggested by electrophysiologic evidence for a failure to habituate to redundant information, over-responsiveness to novel information, and reduced cortical responsiveness to overstimulation. Cognitive processing abnormalities are suggested by electrophysiologic evidence for a reduced ability to attend to task-relevant information and increased attention to task-irrelevant, trauma-related information in individuals with PTSD. Some findings, such as the heightened physiologic and P300 response amplitude responses to trauma-related stimuli and increased HR response to loud tones, have been highly replicable and appear to be as reliable as any biologic finding in the psychiatric literature. Other findings, such as increased eye-blink startle responses and tonic or baseline physiologic activity, have been less consistently replicated and have led investigators to explore how stressful or threatening experimental contexts might produce phasic alterations in the psychophysiology of individuals with PTSD. We hope that the broad range of psychophysiologic investigations and findings in PTSD will inspire others to consider possible applications of these methodologies to their own clinical and research endeavors.

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.

Clarifying the Origin of Biological Abnormalities in PTSD Through the Study of Identical Twins Discordant for Combat Exposure

Abstract:  A biological abnormality found to be associated with posttraumatic stress disorder (PTSD) may be, among other things, a pretrauma vulnerability factor, that is, it may have been present prior to the events occurrence and increased the individuals likelihood of developing PTSD upon traumatic exposure. Alternately, it may be an acquired PTSD sign, that is, it may have developed after the traumatic exposure, along with the PTSD. We have studied pairs of Vietnam combat veterans and their noncombat‐exposed, identical twins in an effort to resolve these competing origins. Combat veterans were diagnosed as current PTSD or non‐PTSD (i.e., never had). Average heart rate responses (HRRs) to a series of sudden, loud‐tone presentations were larger in Vietnam combat veteran twins with PTSD, but these larger responses were not shared by their noncombat‐exposed cotwins, whose responses were similar to those of the non‐PTSD combat veterans and their noncombat‐exposed cotwins. These results suggest that larger HRRs to sudden, loud tones represent an acquired sign of PTSD. In contrast, increased neurological soft signs (NSSs), diminished hippocampal volume, and presence of abnormal cavum septum pellucidum (CSP) were found in Vietnam combat veteran twins with PTSD and their “high‐risk,” unexposed cotwins compared to Vietnam combat veteran twins without PTSD and their “low‐risk,” unexposed cotwins. These results support the conclusion that the latter abnormalities represent antecedent, familial vulnerability factors for developing chronic PTSD upon exposure to a traumatic event.

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.

PTSD arousal and depression symptoms associated with increased right-sided parietal EEG asymmetry.

Researchers have proposed that depression and particular types of anxiety are associated with unique patterns of regional brain activation. The authors examined the relationship among posttraumatic stress disorder (PTSD), anxiety, and depressive symptoms and frontal, temporal, and parietal EEG alpha asymmetry in female Vietnam War nurse veterans. The results indicate that PTSD arousal symptoms are associated with increased right-sided parietal activation. However, the combination of arousal, depression, and their interaction explain more than twice the variance in parietal asymmetry compared with arousal alone. The results support the contention that the association between anxiety and right-sided posterior activation is specific to the anxious arousal subtype. These findings underscore the importance of isolating, both theoretically and statistically, emotional subcomponents in studies of regional brain activation.

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.

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.