Physiologic responses to sudden,loud tones in monozygotic twins discordant for combat exposure: association with posttraumatic stress disorder

BACKGROUND: Larger heart rate responses to sudden, loud (startling) tones represent one of the best-replicated psychophysiologic markers for posttraumatic stress disorder (PTSD). This abnormality may be a pretrauma vulnerability factor, ie, it may have been present prior to the event's occurrence and increased the individual's likelihood of developing PTSD on traumatic exposure. Alternately, it may be an acquired PTSD sign, ie, it may have developed after the traumatic exposure, along with the PTSD. Studying identical twins discordant for traumatic exposure offers an opportunity to resolve these competing origins. METHODS: Subjects included pairs of Vietnam combat veterans and their non-combat-exposed, monozygotic twins. Combat veterans were diagnosed as having current PTSD (n = 50) or non-PTSD (ie, never had) (n = 53). All subjects listened to a series of 15 sudden, loud tone presentations while heart rate, skin conductance, and orbicularis oculi electromyogram responses were measured. RESULTS: Consistent with previous reports, averaged heart rate responses to the tones were larger in Vietnam combat veterans with PTSD. These larger responses were not shared by their non-combat-exposed co-twins, whose responses were similar to those of the non-PTSD combat veterans and their non-combat-exposed co-twins. This result remained significant after adjusting for a number of potentially confounding factors. CONCLUSIONS: The results suggest that larger heart rate responses to sudden, loud tones represent an acquired sign of PTSD rather than a familial vulnerability factor.     

Somatic manifestations in women with generalized anxiety disorder. Psychophysiological responses to psychological stress

Generalized anxiety disorder is associated with symptoms that suggest heightened muscular tension and autonomic arousal. Since self-reports of physiological states in patients with anxiety disorder are frequently unreliable, we compared 20 female patients with generalized anxiety disorder with a matched group of nonanxious controls on a battery of psychophysiological assessments (skin conductance, heart interbeat interval, blood pressure, respiration, and forehead and gastrocnemius electromyographic activity). We found that during baseline patients with generalized anxiety disorder differed from controls on electromyographic, but not on autonomic, measures. During psychological stress tasks, patients with generalized anxiety disorder showed a weaker mean skin conductance response with a narrower range in both skin conductance and heart rate than controls. These findings suggest that sympathetic inhibition, rather than enhancement, occurs in patients with generalized anxiety disorder during performance stress.     

Psychophysiologic assessment of aversive conditioning in posttraumatic stress disorder.

BACKGROUND: The objective of this study was to evaluate the acquisition, generalization, and extinction of conditioned physiologic responses to aversive stimuli in posttraumatic stress disorder (PTSD). METHODS: Thirty-six PTSD patients, 20 individuals with past trauma and no current PTSD, and 30 mentally healthy individuals without exposure to major trauma underwent a differential aversive conditioning experiment. Bursts of 105 dB white noise were used as unconditioned stimuli (UCSs), and 35x24 mm slides of different colors served as either CS+ (paired) or CS- (unpaired) stimuli. Heart rate (HR) and nondominant palm skin conductance (SC) were measured at rest and between 1 and 4 sec following each CS presentation. RESULTS: The PTSD group showed higher levels of resting SC and resting HR, larger SC responses to the initial presentation of unpaired CSs, larger HR responses following paired CS+ stimuli, larger SC responses to unpaired CS- during acquisition and extinction, and larger SC and HR responses to CS+ during extinction. The group differences in responses to CS+ during extinction remained statistically significant after controlling for age, resting physiologic levels, and initial responsivity. CONCLUSIONS: PTSD is associated with elevated autonomic responses to both innocuous and aversive stimuli, with larger responses to unpaired cues and with reduced extinction of conditioned responses.     

Auditory startle response in trauma survivors with posttraumatic stress disorder: a prospective study

OBJECTIVE: Previous studies have shown elevated autonomic responses to startling tones in trauma survivors with chronic posttraumatic stress disorder (PTSD). The origin of these abnormal responses is obscure. The present study attempted to clarify this issue by prospectively evaluating responses to sudden, loud tones in individuals who arrived at a hospital emergency room after psychologically traumatic events. METHOD: By using a previously established protocol, autonomic and muscular responses to the tones were evaluated at 1 week, 1 month, and 4 months after the traumatic event. Structured diagnostic interviews performed at 4 months classified subjects into groups with (N=36) and without (N=182) PTSD, which were further subdivided according to the presence or absence of major depressive disorder as follows: neither PTSD nor depression (N=166), depression alone (N=16), PTSD alone (N=21), and both PTSD and depression (N=15). RESULTS: The groups showed comparable physiological responses to the tones at 1 week posttrauma. However, at 1 and 4 months posttrauma, the subjects with PTSD showed a greater heart rate response and required more stimulus trials to reach the criteria of skin conductance and orbicularis oculi electromyogram nonresponse. These findings were not significantly influenced by comorbid depression and were not explained by the severity of the traumatic event or by the intensity of the initial symptoms. CONCLUSIONS: Differences in physiological response to startling tones develop along with PTSD in the months that follow a traumatic event. This pattern supports the theories that associate PTSD with progressive neuronal sensitization.     

Affective dysregulation and dissociative experience in female patients with borderline personality disorder: a startle response study

Affective dysregulation and dissociation are currently discussed as core features of borderline personality disorder (BPD). Affective dysregulation is hypothesized to be correlated with increased amygdala functioning and dissociation is linked to inhibited processing on the amygdala and dampened autonomic output, according to the corticolimbic disconnection model of dissociation from Sierra and Berrios [Biological Psychiatry 44 (1998) 898]. We assessed startle response, which is mainly mediated by the amygdala, to investigate the relationship between affective dysregulation and dissociation. We hypothesized that patients with BPD would reveal enhanced responses to startling tones, but that these would be lessened by the presence of state dissociative experiences. 21 unmedicated female patients with BPD and 21 healthy female controls listened to 15 startling tones (95-dB, 500-ms, 1000-Hz) while heart rate, skin conductance and orbicularis oculi electromyogram responses were measured. Covariance analysis showed that the BPD group had a significantly higher startle response in the electromyogram as compared to controls. Furthermore, present-state dissociative experiences significantly influenced the startle response. Patients with low dissociative experiences revealed enhanced startle responses whereas patients with high dissociative experiences showed reduced responses. Our data support affective dysregulation in BPD as well as the corticolimbic disconnection model of dissociation, at least for EMG. Furthermore, it highlights the importance of assessing present-state dissociation in basic research as well as psychotherapy.     

Situational reactivity of autonomic functions in schizophrenic patients

In a study designed to evaluate the state of arousal and the autonomic reactivity to experimental conditions in schizophrenic patients, 12 acute, unmedicated schizophrenic patients with paranoid hallucinatory symptomatology and 63 healthy normal control subjects were administered four standardized tasks: cold pressor test, noise, mental arithmetic, and active relaxation. Biochemical (norepinephrine and cortisol) and physiological (electromyogram, electroencephalogram, skin conductance response, skin conductance level, finger pulse amplitude, finger temperature, heart rate, respiratory volume, pulse wave velocity, and electrogastrogram) parameters were measured simultaneously. Schizophrenic patients showed elevated levels of cortisol and norepinephrine, as well as heightened responsivity on measures of electromyographic activity, skin conductance level, and heart rate, throughout the trial, and reduced responsivity to conditions of stress. It is concluded that schizophrenic patients show higher nonspecific activation and reduced ability to react to external stimulation, perhaps induced by lack of inhibition of the reticular formation by the limbic system.     

Autonomic responses and neural-cardiac coupling during individually tailored symptom provocation in obsessive-compulsive disorder

Elevated anxiety in obsessive-compulsive disorder (OCD) has been linked to cortico-limbic hyperactivation, whereas hyperarousal of the autonomous nerve system (ANS) has inconsistently been found. We investigate ANS functioning during symptom provocation with individually tailored OCD-relevant pictures in 14 unmedicated patients and 14 controls and link it to activation in brain areas involved in ANS regulation. In addition to OCD-triggers, aversive and neutral control stimuli were included. Both groups showed increased skin conductance and heart rate changes to aversive control stimuli, whereas only patients demonstrated augmented skin conductance responses to OCD-triggers. Overall ANS hyperarousal in patients relative to controls was found at trend level. Activity in limbic and paralimbic areas in OCD patients was increased to both generally aversive and OCD-relevant stimuli, whereas dorsolateral prefrontal cortex (DLPFC) hyperactivation, covarying with cardiac responses in patients but not in controls, was present for disorder-relevant triggers only. Despite the small study group, these preliminary findings suggest ANS hyperactivity during OCD symptom provocation that could reflect arousal to the perceived threatening value of OCD-triggers and might mediate elevated anxiety.     

Adolescent anorexia nervosa patients have a discrepancy between neurophysiological responses and self-reported emotional arousal to psychosocial stress

In both clinical practice and research, eating disorder patients are reported to have difficulties in identifying and describing their feelings. They are often described as being unaware of the linkage between their feelings and their behavior. The present study experimentally induced emotions in adolescent anorexia nervosa (AN) patients to examine both self-reported emotional arousal and neurophysiological responses. A group of 10 AN patients and a group of 22 healthy controls (HC) were compared with respect to changes in self-reported emotional arousal and neurophysiological responses, heart rate (HR) and HPA-axis response (cortisol in saliva) during a public speaking test inducing anxious stress. The AN group reported higher levels of anxiety, as a result of stress, but this was not reflected in their HR or cortisol response. By contrast, in the HC group higher levels of self-reported anxiety coincided with clear increases in HR and cortisol. The data indicate that AN patients, in contrast to healthy individuals, show a discordance between self-reported emotional and neurophysiological arousal during psychosocial stress.     

Somatic symptoms and physiologic responses in generalized anxiety disorder and panic disorder: an ambulatory monitor study

BACKGROUND: Physiologic responses of patients with anxiety disorders to everyday events are poorly understood. OBJECTIVE: To compare self-reports and physiologic recordings in patients with panic disorder (PD), patients with generalized anxiety disorder (GAD), and nonanxious controls during daily activities. DESIGN: Participants underwent four 6-hour recording sessions during daily activities while wearing an ambulatory monitor. Physiologic and subjective data were recorded every 30 minutes and during subject-signaled periods of increased anxiety or tension or panic attack. SETTING: Participants' everyday environment. PARTICIPANTS: Twenty-six patients with PD and 40 with GAD, both without substantial comorbidity, and 24 controls. INTERVENTIONS: Recordings obtained during everyday activities. MAIN OUTCOME MEASURES: Recordings of heart interbeat intervals, skin conductance levels, respirations, motion, and ratings of subjective somatic symptoms and tension or anxiety. RESULTS: Patients with anxiety disorders rated higher on psychic and somatic anxiety symptoms than did controls. Common to both anxiety disorders was diminished autonomic flexibility that manifested itself throughout the day, accompanied by less precise perception of bodily states. The main differences between patients with PD and GAD were a heightened sensitivity to body sensations and more frequent button presses. There also was a trend toward heightened basal arousal in patients with PD, manifesting itself in a faster heart rate throughout the day. CONCLUSIONS: Patients with PD or GAD are more sensitive to bodily changes than nonanxious individuals, and patients with PD are more sensitive than those with GAD. Patients with PD experience more frequent distress than those with GAD and controls, but their physiologic responses are comparable in intensity. The findings suggest that the perception of panic attacks reflects central rather than peripheral responses. The diminished autonomic flexibility observed in both anxiety conditions may result from dysfunctional information processing during heightened anxiety that fails to discriminate between anxiety-related and neutral inputs.     

Electrodermal activity in young adults at genetic risk for affective disorder

Low electrodermal activity has been proposed as a trait marker for affective disorder. We attempted to determine if low electrodermal activity could be a genetic marker by testing subjects at genetic risk for affective disorder. High-risk subjects, 22 offspring of a parent with bipolar affective disorder, and 27 low-risk controls 15 to 25 years old had skin conductance recorded bilaterally during rest periods, presentation of 10 nonsignal tones, and performance of reaction-time and mental arithmetic tasks. There were no significant differences in skin conductance levels under any condition or in the frequency or amplitude of orienting responses to nonsignal tones. During task periods high-risk subjects showed significantly greater electrodermal activity that was lateralized to the left hand. Self-rated depression was higher in the high-risk group during task periods. The results show that low electrodermal activity is not a likely genetic marker for affective disorder but suggest that autonomic hyperresponsivity, atypically lateralized information processing, and depressive affect occur during mild stress in persons at risk for the development of affective disorder.     

Eye tracking and physiological reactivity to threatening stimuli in posttraumatic stress disorder

This study tested the vigilance-avoidance model of anxiety and attention bias in posttraumatic stress disorder (PTSD). This study used eye tracking technology to record initial fixations, pupil dilation, fixation time and concurrent skin conductance response to examine initial orienting towards threat stimuli and subsequent fixations. Twenty-one traumatized participants (11 diagnosed with PTSD and 10 trauma-exposed participants without PTSD) viewed 32 stimuli (with four words in each quadrant). Sixteen trials contained a trauma-relevant word in one quadrant and 16 had four neutral words. PTSD patients reported significantly greater number of initial fixations to trauma words, and a greater number of skin conductance responses to initial threat fixations. There were no significant differences in subsequent fixations to trauma words between groups. Although this study provides evidence of attentional bias towards threat that is accompanied by specific autonomic arousal, it does not indicate subsequent avoidance of threat stimuli in PTSD.     

Twenty-four hour skin conductance in panic disorder

Skin conductance, physical activity, ambient temperature and mood were recorded for 24 h in 22 panic disorder (PD) patients and 29 healthy controls. During the day, subjects performed standardized relaxation tests (ARTs). We hypothesized that tonically elevated anticipatory anxiety in PD during waking and sleeping would appear as elevated skin conductance level (SCL) and greater skin conductance (SC) variability. Mean SCL was higher during both usual waking activities and sleeping in PD, but not during the ARTs. Group SC variability differences did not reach significance, perhaps because of variance unrelated to anxiety. Analyses indicated that in the PD group, antidepressant medication reduced mean SCL whereas state anxiety had the opposite effect during the day. Depressive symptoms reported during the day were related to elevated mean SCL on the night of the recording. The rate and extent of SCL deactivation over the night was equal in the two groups. However, PD patients had more frequent interruptions of deactivation that could have arisen from conditioned arousal in response to threat cues during sleep.     

Psychophysiological reactions in dental phobic patients with direct vs. indirect fear acquisition

Dental phobic patients with reported traumatic experiences at onset of dental anxiety were compared to subjects with an indirect fear acquisition in their psychophysiological responses to video scenes showing dental procedures. It has been suggested that individuals with conditioned fear would respond with higher levels of physiological arousal in response to threat compared to subjects with indirect fear acquisition. Although the overall pattern indicates support for this hypothesis, subjects grouped on the basis of their reported fear-etiology did not statistically differ in recorded muscle tension, heart rate or skin conductance reactions to fear-provoking conditions.     

Auditory startle response in firefighters before and after trauma exposure

OBJECTIVE: Although previous psychophysiological studies have revealed heightened muscular and autonomic responses in individuals with posttraumatic stress disorder (PTSD), these studies have not permitted inferences about whether the abnormal responses are a vulnerability factor or are acquired following trauma. The present study reports the first prospective psychophysiological investigation, to the authors' knowledge, of posttraumatic stress responses by prospectively evaluating the auditory startle response in firefighters before and after trauma exposure. METHOD: Orbicularis oculi (eye blink) electromyograms and skin conductance responses to 15 100-dB acoustic startle stimuli were assessed in 84 trainee firefighters before trauma exposure. After commencement of active duty, 35 firefighters were reassessed within 4 weeks of exposure to a traumatic event, and 36 firefighters were reassessed as a comparison group that was not exposed to trauma. RESULTS: In the trauma-exposed group, pretrauma physiological activity was predictive of posttrauma acoustic startle responses. Pretrauma skin conductance response to startle was also predictive of posttraumatic stress severity. CONCLUSIONS: These results provide initial support for elevated startle response being a vulnerability factor for posttraumatic stress responses.     

How Anxious Do You Think I Am? Relationship Between State and Trait Anxiety in Children With and Without ASD During Social Tasks

Individuals with autism spectrum disorder (ASD) often exhibit increased anxiety, even in non-stressful situations. We investigate general anxiousness (anxiety trait) and responses to stressful situations (anxiety state) in 22 adolescents with ASD and 32 typically developing controls. We measured trait anxiety with standardized self- and parent-reported questionnaires. We used a Biopac system to capture state anxiety via skin conductance responses, mean heart rate and heart rate variability during high- and low-anxiety tasks. Results reveal higher trait anxiety in adolescents with ASD (p?<?0.05) and no group difference in state anxiety. Increased parent-reported trait anxiety may predict decreased state anxiety during high-stress conditions. Together, these findings suggest that higher trait anxiety may result in dampened physical responses to stress.     

Physiological and subjective anxiety responses to caffeine and stress in nonclinical panic

Physiological and subjective anxiety responses to the combination of caffeine and film, cold pressor, and mental arithmetic stressors were examined in 24 healthy females with and without nonclinical panic. Caffeine (3.3 mg/kg) and placebo were administered in a within-subject, double-blind, counterbalanced design on two consecutive days. Repeated measurements of blood pressure, cardiac interbeat interval, skin conductance, and subjective anxiety were obtained during a predrug resting baseline, a postdrug resting baseline, stressor tasks, and a recovery baseline. Panic subjects in the caffeine/placebo drug order exhibited a significantly greater anxiety response on the caffeine day, which combined additively with increases produced by stress. Caffeine and stress also produced additive increases in physiological arousal, although no significant group differences were observed.