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.

Pierre Janet on obsessive-compulsive disorder (1903). Review and commentary.

Pierre Janet's classic contribution to the understanding of obsessive-compulsive disorder, Obsessions and Psychasthenia (1903), remains untranslated as well as unappreciated by American psychiatry, despite increasing recognition of the importance of this mental health problem. Herein the work is summarized and discussed. Although it tends to be remembered for its theoretical ideas, most of which have become dated, the most valuable aspect of Obsessions and Psychasthenia is its clinical discoveries. These include the important role played in the disorder by symptoms that are closely related to, but yet cannot properly be called, obsessions and compulsions (the "forced agitations"); the underlying psychasthenic mental state; and the obsessive-compulsive person's specific failure to adapt to reality. Despite the passage of nearly a century, these observations, and Janet's suggestions regarding treatment, are as timely now as when they were made.

Psychophysiologic assessment of posttraumatic stress disorder imagery in Vietnam combat veterans.

This study utilized psychophysiologic techniques to assess emotional arousal during imagery of psychologically traumatic experiences. All subjects were medication-free Vietnam combat veterans, classified on the basis of DSM-III-R criteria into groups with posttraumatic stress disorder (PTSD, n = 18) and no mental disorder (control, n = 15), which did not differ in extent of combat or in the judged severity of the traumatic experiences reported. "Scripts" describing each subject's combat experiences as well as other experiences were read to them in the laboratory, and they were instructed to imagine the events the scripts portrayed, while heart rate, skin conductance, and frontalis electromyogram were recorded. The PTSD subjects' physiologic responses to their combat scripts were markedly higher than the controls'. The combined physiologic variables identified PTSD subjects with a specificity of 100% and a sensitivity of 61%. The results demonstrate exaggerated physiologic arousal during recollection of traumatic experiences in PTSD.

Physiologic responses to loud tones in Israeli patients with posttraumatic stress disorder.

Orbicularis oculi (eye blink) electromyogram, skin conductance, and heart rate responses to 15 consecutive 95-dB, 500-millisecond, 1000-Hz tones with 0-millisecond rise and fall times were measured in 14 patients with posttraumatic stress disorder, 14 patients with other anxiety disorders, 15 mentally healthy subjects with past traumatic experiences, and 19 mentally healthy subjects with no trauma history. The patients with posttraumatic stress disorder showed significantly larger skin conductance and heart rate responses and a trend toward larger electromyogram responses to the tones than every other group. These effects were not explained by subjective anxiety, resting physiologic arousal, physiologic arousal preceding the tone trials, or initial physiologic responsivity. The group with posttraumatic stress disorder was the only one that failed to show habituation of skin conductance responses.

Naloxone-reversible analgesic response to combat-related stimuli in posttraumatic stress disorder. A pilot study.

We tested the hypothesis that exposure to a stimulus resembling the original traumatic event would induce naloxone-reversible analgesia in patients with posttraumatic stress disorder (PTSD). Eight medication-free Vietnam veterans with PTSD and eight veterans without PTSD, matched for age and combat severity, viewed a 15-minute videotape of dramatized combat under naloxone hydrochloride and placebo conditions in a randomized double-blind crossover design. In the placebo condition, the subjects with PTSD showed a 30% decrease in reported pain intensity ratings of standardized heat stimuli after the combat videotape. No decrease in pain ratings occurred in the subjects with PTSD in the naloxone condition. The subjects without PTSD did not show a decrease in pain ratings in either condition. The results are consistent with the induction of opioid-mediated stress-induced analgesia in the patients with PTSD.

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.

A prospective study of heart rate response following trauma and the subsequent development of posttraumatic stress disorder.

BACKGROUND: Physiological arousal during traumatic events may trigger the neurobiological processes that lead to posttraumatic stress disorder (PTSD). This study prospectively examined the relationship between heart rate and blood pressure recorded immediately following a traumatic event and the subsequent development of PTSD. METHODS: Eighty-six trauma survivors who presented at the emergency department of a general hospital were followed up for 4 months. Heart rate and blood pressure were recorded on arrival at the emergency department. Heart rate, anxiety, depression, and PTSD symptoms were assessed 1 week, 1 month, and 4 months later. The clinician-administered PTSD scale defined PTSD status at 4 months. RESULTS: twenty subjects (23%) met PTSD diagnostic criteria at the 4-month assessment (PTSD group), and 66 (77%) did not (non-PTSD group). Subjects who developed PTSD had higher heart rates at the emergency department (95.5+/-13.9 vs 83.3+/-10.9 beats per minute, t=4.4, P<.001) and 1 week later (77.8+/-11.9 vs 72.0+/-9.5 beats per minute, t=2.25, P<.03), but not after 1 and 4 months. The groups did not differ in initial blood pressure measurement. Repeated-measures analysis of variance (ANOVA) for heart rate showed a significant group effect (P<.02), time effect (P<.001), and group x time interaction (P<.001). The time effect and group x time interaction remained significant when adjusted for sex, age, trauma severity, immediate response, and dissociation during the traumatic event. CONCLUSION: Elevated heart rate shortly after trauma is associated with the later development of PTSD.

Visual imagery and perception in posttraumatic stress disorder. A positron emission tomographic investigation.

BACKGROUND: Relative regional cerebral blood flow (rCBF) changes were measured in Vietnam combat veterans with and without posttraumatic stress disorder (PTSD) during exposure to combat-related stimuli. METHODS: Positron emission tomography was used to measure rCBF in 7 combat veterans with PTSD (PTSD group) and 7 healthy combat veterans (control group) who viewed and generated visual mental images of neutral, negative, and combat-related pictures. RESULTS: Unlike control subjects, subjects with PTSD had increased rCBF in ventral anterior cingulate gyrus and right amygdala when generating mental images of combat-related pictures; when viewing combat pictures, subjects with PTSD showed decreased rCBF in Broca's area. CONCLUSIONS: Results suggest that ventral anterior cingulate gyrus and right amygdala play a role in the response of combat veterans with PTSD to mental images of combat-related scenes. Reexperiencing phenomena of PTSD, which often involve emotional visual mental imagery, may be likewise associated with increased rCBF in these regions.

A symptom provocation study of posttraumatic stress disorder using positron emission tomography and script-driven imagery.

BACKGROUND: Previous studies have used symptom provocation and positron emission tomography to delineate the brain systems that mediate various anxiety states. Using an analogous approach, the goal of this study was to measure regional cerebral blood flow changes associated with posttraumatic stress disorder (PTSD) symptoms. METHODS: Eight patients with PTSD, screened as physiologically responsive to a script-driven imagery symptom provocation paradigm, were exposed sequentially to audiotaped traumatic and neutral scripts in conjunction with positron emission tomography. Heart rate and subjective measures of emotional state were obtained for each condition. Statistical mapping techniques were used to determine locations of significant brain activation. RESULTS: Increases in normalized blood flow were found for the traumatic as compared with control conditions in right-sided limbic, paralimbic, and visual areas; decreases were found in left inferior frontal and middle temporal cortex. CONCLUSIONS: The results suggest that emotions associated with the PTSD symptomatic state are mediated by the limbic and paralimbic systems within the right hemisphere. Activation of visual cortex may correspond to the visual component of PTSD reexperiencing phenomena.

Animal models of compulsive behavior.

A convergence of clinical and pathological evidence points to the basal ganglia as the site of disturbance in compulsive disorders. However, the limbic system may be implicated as well. This article draws upon various lines of animal research in an attempt to explain how disturbances in one or another of these systems may produce compulsive behavior. Possible models include stimulation of the reinforcement mechanism, manipulation of the striatal "comparator" function, production and blockade of displacement behavior, and interference with the hippocampus' modulation of the stereotypy-inducing effect of reward. The common denominator of these models is a relative excess of dopaminergic activity in the basal ganglia. However, this does not necessarily implicate a primary dopaminergic disturbance in all human compulsive behavior.

Eye-head synkinesia in schizophrenic adults during a repetitive visual search task.

This study investigated the role of head movements in the functional visual field of three groups of schizophrenics and a normal control group during the performance of a repetitive visual search task. The experimental apparatus consisted of a semicircular panel with six columns of lights extending up to 90 degrees to the right of the subject's initial visual fixation point. The task involved identifying which column contained an extra light by pressing the appropriate response key. A string connected to a potentiometer measured head movements. All schizophrenic groups showed an excess of head movements in comparison to controls, reflecting abnormal coupling of head and eye movements. These results confirm previous anecdotal reports in schizophrenic adults and extend findings in schizophrenic children, which have been interpreted as reflecting maturational lag of the nervous system.

Physiologic responses to loud tones in Israeli veterans of the 1973 Yom Kippur War.

Eyeblink and autonomic components of the acoustic startle response were evaluated in a community sample of Israeli veterans of the Yom Kippur war. Individuals were solicited by mail and telephone to participate in the study; they were not seeking treatment or compensation. Nineteen Israeli veterans with current posttraumatic stress disorder (PTSD) and 74 veterans without PTSD were exposed to 15 consecutive 95-dB, 500-msec, 1000-Hz tones with 0-msec rise and fall times, while orbicularis oculi electromyogram, skin conductance, and heart rate responses were measured. Individuals with PTSD produced larger averaged heart rate responses, and a slower decline in skin conductance responses, across the 15 tone presentations compared to non-PTSD subjects. There was no group difference in the magnitude of the averaged electromyogram response. Results of this study replicate previous findings of increased autonomic responses to loud tone stimuli in this disorder.

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.

Predictors of cortisol and 3-methoxy-4-hydroxyphenylglycol responses in the acute aftermath of rape.

BACKGROUND: Prospective studies of trauma survivors can provide information about the relationship between rape characteristics and the development of subsequent symptoms. METHODS: The present study examined the relationship of prior assault, rape severity, posttraumatic stress disorder (PTSD) symptoms following rape, and subsequent PTSD diagnosis, to the acute cortisol and 3-methoxy-4-hydroxyphenylglycol (MHPG) response to this traumatic event in 20 women. RESULTS: Women with a history of prior physical or sexual assault showed a significantly attenuated cortisol response to the acute stress of rape compared to women without such a history. MHPG appeared to be associated with injury-related rape characteristics, and symptoms of active avoidance, but not prior history. PTSD status at the 3-month follow-up was predicted by both a prior history of assault and high injury rape, but was not directly predicted by either cortisol or MHPG levels. MHPG and cortisol were not correlated in the sample as a whole, but were correlated among individuals who did not subsequently develop PTSD (p = .04) CONCLUSIONS: The results suggest that different neuroendocrine systems may mediate different components of the response to traumatic stress.

Activation of anterior paralimbic structures during guilt-related script-driven imagery.

BACKGROUND: Several recent neuroimaging studies have examined the neuroanatomical correlates of normal emotional states, such as happiness, sadness, fear, anger, anxiety, and disgust; however, no previous study has examined the emotional state of guilt. METHODS: In the current study, we used positron emission tomography and the script-driven imagery paradigm to study regional cerebral blood flow (rCBF) during the transient emotional experience of guilt in eight healthy male participants. In the Guilt condition, participants recalled and imagined participating in a personal event involving the most guilt they had ever experienced. In the Neutral condition, participants recalled and imagined participating in an emotionally neutral personal event. RESULTS: In the Guilt versus Neutral comparison, rCBF increases occurred in anterior paralimbic regions of the brain: bilateral anterior temporal poles, anterior cingulate gyrus, and left anterior insular cortex/inferior frontal gyrus. CONCLUSIONS: These results, along with those of previous studies, are consistent with the notion that anterior paralimbic regions of the brain mediate negative emotional states in healthy individuals.

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.

Anger in healthy men: a PET study using script-driven imagery.

BACKGROUND: An understanding of the neurobiological basis of normal emotional processing is useful in formulating hypotheses regarding the pathophysiology of psychiatric illnesses. METHODS: This study examined the mediating functional neuroanatomy of anger in eight healthy men. Narrative scripts were developed from autobiographical information to induce anger and neutral states. The subjects imagined the content of the narrative scripts to induce anger during positron emission tomography to measure normalized regional cerebral blood flow (rCBF). Psychophysiologic responses and subjective ratings of emotional state were measured for each condition. Statistical parametric maps were constructed to reflect the Anger versus Neutral state contrast. RESULTS: Anger was associated with activation of the left orbitofrontal cortex, right anterior cingulate cortex affective division, and bilateral anterior temporal poles. CONCLUSIONS: These results suggest that the subjective experience of anger is associated with rCBF increases in anterior paralimbic regions of the brain.

Diazepam-induced changes in tardive dyskinesia: suggestions for a new conceptual model.

Using an ABA' research design, the effects of a benzodiazepine gamma-aminobutyric acid (GABA)-ergic agent, diazepam, on various aspects of tardive dyskinesia (TD) were investigated in 21 patients. Videotaped recordings of the examinations were rated blind on the Abnormal Involuntary Movements Scale. In nonsedating amounts, diazepam had a significant anti-TD effect, especially in terms of limb dyskinesia. A significant portion of the therapeutic effect persisted after the medication was withdrawn. The results suggest that diazepam has a specific anti-TD action and that in some cases it may be able to produce a somewhat lasting correction of the deranged neurobiological mechanisms in TD. Since the main sites of action of benzodiazepines and the highest concentrations of benzodiazepine-linked GABA receptors are in the limbic and cortical structures that provide principal sources of inputs to the basal ganglia, it is suggested that the supra-striato-pallidal mechanisms of voluntary movement control should be considered in understanding the pathogenesis and treatment of TD.

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.