REM Sleep Measures and REM Vagal Activity Predict Extinction Recall in Trauma-Exposed Individuals.

Accumulating evidence suggests that rapid eye movement sleep (REM) supports the consolidation of extinction memory. REM is disrupted in PTSD, and REM abnormalities after traumatic events increase the risk of developing PTSD. Therefore, it was hypothesized that abnormal REM in trauma-exposed individuals may pave the way for PTSD by interfering with the processing of extinction memory. In addition, PTSD patients display reduced vagal activity. Vagal activity contributes to the strengthening of memories, including fear extinction memory, and recent studies show that the role of vagus in memory processing extends to memory consolidation during sleep. Therefore, it is plausible that reduced vagal activity during sleep in trauma-exposed individuals may be an additional mechanism that impairs extinction memory consolidation. However, to date, the contribution of sleep vagal activity to the consolidation of extinction memory or any emotional memory has not been investigated. To test these hypotheses, we examined the association of extinction memory with REM characteristics and REM vagal activity (indexed as high-frequency heart rate variability; HF-HRV) in a large sample of trauma-exposed individuals (n=113). Consistent with our hypotheses, REM sleep characteristics (increased REM density and shortened REM latency) were associated with poorer physiological and explicit extinction memory. Furthermore, higher HF-HRV during REM was associated with better explicit extinction memory. These findings support the notion that disrupted REM may contribute to PTSD by impairing the consolidation of extinction memory and indicate the potential utility of interventions that target REM sleep characteristics and REM vagal activity in fear-related disorders.

Rapid eye movement sleep parasympathetic activity predicts wake hyperarousal symptoms following a traumatic event.

Heart rate variability (HRV) can be used to assess changes in output of the parasympathetic nervous system (PNS). Considering that patients with post-traumatic stress disorder (PTSD) often experience disturbances in sleep, arousal, and autonomic functioning, we sought to explore the association of PNS activity during sleep with hyperarousal symptoms of PTSD. Because a broad literature supports the importance of rapid eye movement (REM) sleep in PTSD, REM-sleep features were specifically examined as predictors of PTSD symptom severity. A total of 90 participants, primarily civilian and female, aged 18-40 years who had experienced a traumatic event in the last 2 years, underwent an ambulatory polysomnography (PSG) acclimation night followed by a second PSG night from which sleep physiological measures were computed. Participants underwent an ambulatory polysomnography (PSG) acclimation night followed by a second PSG night from which sleep physiological measures were computed. PTSD severity was measured using the PTSD Checklist for the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (PCL-5). Dependent variables were total PCL-5 score as well as its hyperarousal symptom subscore. Predictors included REM latency, percentage, density, segment length, and an index of parasympathetic tone (root mean square of the successive differences in the R-R interval or RMSSD). Hierarchical regression models were conducted to analyse the association of REM features with PCL-5 total and hyperarousal subscales. Using hierarchical regression, REM-sleep RMSSD accounted for a significant proportion of the variation in outcome variables, even when accounting for other REM-sleep features. The present findings support hypothesised relationships between PTSD symptomatology and REM-sleep physiology and, specifically, that lowered parasympathetic tone in REM may be an important associate of the hyperarousal symptom cluster in PTSD.

Autonomic activity, posttraumatic and nontraumatic nightmares, and PTSD after trauma exposure.

BACKGROUND: Nightmares are a hallmark symptom of posttraumatic stress disorder (PTSD). This strong association may reflect a shared pathophysiology in the form of altered autonomic activity and increased reactivity. Using an acoustic startle paradigm, we investigated the interrelationships of psychophysiological measures during wakefulness and PTSD diagnosis, posttraumatic nightmares, and nontraumatic nightmares. METHODS: A community sample of 122 trauma survivors were presented with a series of brief loud tones, while heart rate (HRR), skin conductance (SCR), and orbicularis oculi electromyogram (EMGR) responses were measured. Prior to the tone presentations, resting heart rate variability (HRV) was assessed. Nightmares were measured using nightmare logs. Three dichotomous groupings of participants were compared: (1) current PTSD diagnosis (n = 59), no PTSD diagnosis (n = 63), (2) those with (n = 26) or without (n = 96) frequent posttraumatic nightmares, and (3) those with (n = 22) or without (n = 100) frequent nontraumatic nightmares. RESULTS: PTSD diagnosis was associated with posttraumatic but not with nontraumatic nightmares. Both PTSD and posttraumatic nightmares were associated with a larger mean HRR to loud tones, whereas nontraumatic nightmare frequency was associated with a larger SCR. EMGR and resting HRV were not associated with PTSD diagnosis or nightmares. CONCLUSIONS: Our findings suggest a shared pathophysiology between PTSD and posttraumatic nightmares in the form of increased HR reactivity to startling tones, which might reflect reduced parasympathetic tone. This shared pathophysiology could explain why PTSD is more strongly related to posttraumatic than nontraumatic nightmares, which could have important clinical implications.

Exaggerated amygdala activation to ambiguous facial expressions is a familial vulnerability factor for posttraumatic stress disorder.

OBJECTIVE: Previous research has reported hyperresponsivity in the amygdala and hyporesponsivity in ventral portions of the medial prefrontal cortex to threat-related stimuli in posttraumatic stress disorder (PTSD). Whether such findings generalize to more ambiguous stimuli and whether such brain activation abnormalities reflect familial vulnerabilities, trauma-exposure, or acquired characteristics of PTSD remain unclear. In this study, we measured brain responses to emotionally ambiguous stimuli (i.e., surprised facial expressions) in identical twin pairs discordant for trauma exposure to elucidate the origin of brain activation abnormalities. METHODS: Participants with PTSD (n = 12) and their trauma-unexposed identical cotwins (n = 12), as well as trauma-exposed participants without PTSD (n = 15) and their trauma-unexposed identical cotwins (n = 15), passively viewed surprised and neutral facial expressions during functional magnetic resonance imaging (fMRI). Afterward, participants labeled and rated each facial expression on valence and arousal. RESULTS: Amygdala activation to Surprised and Neutral facial expressions (versus Fixation) was greater in the participants with PTSD and their trauma-unexposed identical cotwins without PTSD, compared to the control twin pairs. In contrast, medial frontal gyrus (MFG) activation to Surprised facial expressions (versus Fixation) was diminished in the PTSD group relative to the other three groups. CONCLUSIONS: Amygdala hyperresponsivity to emotionally ambiguous facial expressions may be a familial vulnerability factor that increases the likelihood of developing PTSD after experiencing a traumatic event. In contrast, MFG hyporesponsivity may be an acquired characteristic of the disorder.

Associations of sleep measures with neural activations accompanying fear conditioning and extinction learning and memory in trauma-exposed individuals.

STUDY OBJECTIVES: Sleep disturbances increase risk of posttraumatic stress disorder (PTSD). Sleep effects on extinction may contribute to such risk. Neural activations to fear extinction were examined in trauma-exposed participants and associated with sleep variables. METHODS: Individuals trauma-exposed within the past 2 years (N = 126, 63 PTSD) completed 2 weeks actigraphy and sleep diaries, three nights ambulatory polysomnography and a 2-day fMRI protocol with Fear-Conditioning, Extinction-Learning and, 24 h later, Extinction-Recall phases. Activations within the anterior cerebrum and regions of interest (ROI) were examined within the total, PTSD-diagnosed and trauma-exposed control (TEC) groups. Sleep variables were used to predict activations within groups and among total participants. Family wise error was controlled at p < 0.05 using nonparametric analysis with 5,000 permutations. RESULTS: Initially, Fear Conditioning activated broad subcortical and cortical anterior-cerebral regions. Within-group analyses showed: (1) by end of Fear Conditioning activations decreased in TEC but not PTSD; (2) across Extinction Learning, TEC activated medial prefrontal areas associated with emotion regulation whereas PTSD did not; (3) beginning Extinction Recall, PTSD activated this emotion-regulatory region whereas TEC did not. However, the only between-group contrast reaching significance was greater activation of a hippocampal ROI in TEC at Extinction Recall. A greater number of sleep variables were associated with cortical activations in separate groups versus the entire sample and in PTSD versus TEC. CONCLUSIONS: PTSD nonsignificantly delayed extinction learning relative to TEC possibly increasing vulnerability to pathological anxiety. The influence of sleep integrity on brain responses to threat and extinction may be greater in more symptomatic individuals.

Sleep Power Spectral Density and Spindles in PTSD and Their Relationship to Symptom Severity.

Sleep disturbances are common in post-traumatic stress disorder (PTSD), although which sleep microarchitectural characteristics reliably classify those with and without PTSD remains equivocal. Here, we investigated sleep microarchitectural differences (i.e., spectral power, spindle activity) in trauma-exposed individuals that met (n = 45) or did not meet (n = 52) criteria for PTSD and how these differences relate to post-traumatic and related psychopathological symptoms. Using ecologically-relevant home sleep polysomnography recordings, we show that individuals with PTSD exhibit decreased beta spectral power during NREM sleep and increased fast sleep spindle peak frequencies. Contrary to prior reports, spectral power in the beta frequency range (20.31-29.88 Hz) was associated with reduced PTSD symptoms, reduced depression, anxiety and stress and greater subjective ability to regulate emotions. Increased fast frequency spindle activity was not associated with individual differences in psychopathology. Our findings may suggest an adaptive role for beta power during sleep in individuals exposed to a trauma, potentially conferring resilience. Further, we add to a growing body of evidence that spindle activity may be an important biomarker for studying PTSD pathophysiology.

Fear extinction memory is negatively associated with REM sleep in insomnia disorder.

STUDY OBJECTIVES: Formation and maintenance of fear-extinction memories are disrupted in post-traumatic stress disorder (PTSD) and anxiety disorders. Sleep contributes to emotional memory consolidation and emotion regulation. Insomnia disorder (ID) is characterized by persistent sleep disturbance as well as rapid eye movement (REM) sleep abnormalities and often precedes or develops in parallel with PTSD and anxiety disorders. Here, we explore the impact of chronic poor sleep and sleep immediately following fear conditioning and extinction learning on preservation of extinction memories. METHODS: Twenty-four ID age- and sex-matched to 24 healthy, good sleeper controls (GS) completed up to 2 weeks of habitual sleep monitoring with daily sleep-wake diaries and actigraphy, and then participated in a two-session fear conditioning, extinction learning and extinction recall procedure. Fear Conditioning and Extinction Learning occurred during session 1, followed by Extinction Recall approximately 24 hours later. Skin-conductance responses (SCR) and shock expectancies were recorded throughout all experimental phases to evaluate associative learning and memory. Overnight sleep between sessions 1 and 2 was recorded using ambulatory polysomnography. RESULTS: ID showed greater physiological reactivity during Fear Conditioning. REM sleep physiology was associated with poorer extinction memory in ID but better extinction memory in GS. CONCLUSION: REM sleep physiology may differentially support emotional memory retention and expression in ID and GS. In the former, REM may enhance retention of fear memories, while in the later, REM may enhance the expression of extinction memories.

In Trauma-Exposed Individuals, Self-reported Hyperarousal and Sleep Architecture Predict Resting-State Functional Connectivity in Frontocortical and Paralimbic Regions.

BACKGROUND: Symptoms of posttraumatic stress disorder (PTSD) reflect abnormalities in large-scale brain networks. In individuals with recent trauma exposure, we examined associations of seed-based resting-state functional connectivity (rs-FC) with posttraumatic symptoms and sleep. We hypothesized that more severe PTSD symptoms and poorer sleep quality would predict 1) greater rs-FC between fear-related seeds and other fear-related regions and 2) lesser rs-FC between fear-related seeds and emotion-regulatory regions. METHODS: Seventy-four participants who had experienced a DSM-5 criterion A stressor within the past 2 years and ranged from asymptomatic to fully meeting criteria for PTSD diagnosis underwent 14 days of actigraphy and sleep diaries, a night of ambulatory polysomnography, and a functional magnetic resonance imaging resting-state scan at 3T. rs-FC measures of 5 fear-related seeds and 1 emotion regulatory seed with regions of the anterior cerebrum were correlated with PTSD symptoms, objective and subjective habitual sleep quality, and sleep architecture. RESULTS: Longer objective habitual sleep onset latency was associated with greater connectivity between fear-related seeds and other regions of the salience network. Greater PTSD symptoms were associated with less connectivity between fear-related seeds and anterior emotion regulatory regions, whereas greater percent slow wave sleep was associated with more connectivity between these regions. However, other objective and subjective measures reflecting better habitual sleep quality were associated with less rs-FC between these regions. CONCLUSIONS: Longer sleep onset latency predicted greater rs-FC among fear-related areas. More severe PTSD symptoms predicted less rs-FC between fear and fear regulatory regions reflecting putatively reduced top-down fear regulation. Some (e.g., percent slow wave sleep), but not all sleep indices predicted greater top-down fear regulation.

Effects of post-exposure naps on exposure therapy for social anxiety.

Exposure therapy for social anxiety disorder (SAD) utilizes fear extinction, a memory process enhanced by sleep. We investigated whether naps following exposure sessions might improve symptoms and biomarkers in response to social stress in adults undergoing 5-week exposure-based group SAD therapy. Thirty-two participants aged 18-39 (18 females) with SAD were randomized. Before and after treatment, participants completed the Liebowitz Social Anxiety Scale (LSAS) and underwent a Trier Social Stress Test with psychophysiological monitoring (mpTSST) that included skin conductance (SCL), electromyographic (EMG) and electrocardiographic recording, and an auditory startle procedure while anticipating the social stressor. At sessions 3 and 4, exposure was followed by either a 120-min polysomnographically monitored sleep opportunity (Nap, N = 17) or wakefulness (Wake, N = 15). Primary hypotheses about SAD symptom change (LSAS) and EMG blink-startle response failed to differ with naps, despite significant symptom improvement (LSAS) with therapy. Some secondary biomarkers, however, provided preliminary support for enhanced extinction learning with naps, with trend-level Time (pre-, post-treatment) × Arm interactions and significant reduction from pre- to post treatment in the Nap arm alone for mpTSST SCL and salivary cortisol rise. Because of the small sample size and limited sleep duration, additional well-powered studies with more robust sleep interventions are indicated.

Skin Conductance Responses and Neural Activations During Fear Conditioning and Extinction Recall Across Anxiety Disorders.

Importance: The fear conditioning and extinction neurocircuitry has been extensively studied in healthy and clinical populations, with a particular focus on posttraumatic stress disorder. Despite significant overlap of symptoms between posttraumatic stress disorder and anxiety disorders, the latter has received less attention. Given that dysregulated fear levels characterize anxiety disorders, examining the neural correlates of fear and extinction learning may shed light on the pathogenesis of underlying anxiety disorders. Objectives: To investigate the psychophysiological and neural correlates of fear conditioning and extinction recall in anxiety disorders and to document how these features differ as a function of multiple diagnoses or anxiety severity. Design, Setting, and Participants: This investigation was a cross-sectional, case-control, functional magnetic resonance imaging study at an academic medical center. Participants were healthy controls and individuals with at least 1 of the following anxiety disorders: generalized anxiety disorder, social anxiety disorder, specific phobia, and panic disorder. The study dates were between March 2013 and May 2015. Exposures: Two-day fear conditioning and extinction paradigm. Main Outcomes and Measures: Skin conductance responses, blood oxygenation level-dependent responses, trait anxiety scores from the State Trait Anxiety Inventory-Trait Form, and functional connectivity. Results: This study included 21 healthy controls (10 women) and 61 individuals with anxiety disorders (36 women). P values reported for the neuroimaging results are all familywise error corrected. Skin conductance responses during extinction recall did not differ between individuals with anxiety disorders and healthy controls (ηp2 = 0.001, P = .79), where ηp2 is partial eta squared. The anxiety group had lower activation of the ventromedial prefrontal cortex (vmPFC) during extinction recall (ηp2 = 0.178, P = .02). A similar hypoactive pattern was found during early conditioning (ηp2 = 0.106, P = .009). The vmPFC hypoactivation was associated with anxiety symptom severity (r = -0.420, P = .01 for conditioning and r = -0.464, P = .004 for extinction recall) and the number of co-occuring anxiety disorders diagnosed (ηp2 = 0.137, P = .009 for conditioning and ηp2 = 0.227, P = .004 for extinction recall). Psychophysiological interaction analyses revealed that the fear network connectivity differed between healthy controls and the anxiety group during fear learning (ηp2 range between 0.088 and 0.176 and P range between 0.02 and 0.003) and extinction recall (ηp2 range between 0.111 and 0.235 and P range between 0.02 and 0.002). Conclusions and Relevance: Despite no skin conductance response group differences during extinction recall, brain activation patterns between anxious and healthy individuals differed. These findings encourage future studies to examine the conditions longitudinally and in the context of treatment trials to improve and guide therapeutics via advanced neurobiological understanding of each disorder.

Association of Resting Metabolism in the Fear Neural Network With Extinction Recall Activations and Clinical Measures in Trauma-Exposed Individuals.

OBJECTIVE: Exposure-based therapy, an effective treatment for posttraumatic stress disorder (PTSD), relies on extinction learning principles. In PTSD patients, dysfunctional patterns in the neural circuitry underlying fear extinction have been observed using resting-state or functional activation measures. It remains undetermined whether resting activity predicts activations during extinction recall or PTSD symptom severity. Moreover, it remains unclear whether trauma exposure per se affects resting activity in this circuitry. The authors employed a multimodal approach to examine the relationships among resting metabolism, clinical symptoms, and activations during extinction recall. METHOD: Three cohorts were recruited: PTSD patients (N=24), trauma-exposed individuals with no PTSD (TENP) (N=20), and trauma-unexposed healthy comparison subjects (N=21). Participants underwent a resting positron emission tomography scan 4 days before a functional MRI fear conditioning and extinction paradigm. RESULTS: Amygdala resting metabolism negatively correlated with clinical functioning (as measured by the Global Assessment of Functioning Scale) in the TENP group, and hippocampal resting metabolism negatively correlated with clinical functioning in the PTSD group. In the PTSD group, dorsal anterior cingulate cortex (dACC) resting metabolism positively correlated with PTSD symptom severity, and it predicted increased dACC activations but decreased hippocampal and ventromedial prefrontal cortex activations during extinction recall. The TENP group had lower amygdala resting metabolism compared with the PTSD and healthy comparison groups, and it exhibited lower hippocampus resting metabolism relative to the healthy comparison group. CONCLUSIONS: Resting metabolism in the fear circuitry correlated with functioning, PTSD symptoms, and extinction recall activations, further supporting the relevance of this network to the pathophysiology of PTSD. The study findings also highlight the fact that chronic dysfunction in the amygdala and hippocampus is demonstrable in PTSD and other trauma-exposed individuals, even without exposure to an evocative stimulus.

Reprint of: "Demographic factors predict magnitude of conditioned fear".

There is substantial variability across individuals in the magnitudes of their skin conductance (SC) responses during the acquisition and extinction of conditioned fear. To manage this variability, subjects may be matched for demographic variables, such as age, gender and education. However, limited data exist addressing how much variability in conditioned SC responses is actually explained by these variables. The present study assessed the influence of age, gender and education on the SC responses of 222 subjects who underwent the same differential conditioning paradigm. The demographic variables were found to predict a small but significant amount of variability in conditioned responding during fear acquisition, but not fear extinction learning or extinction recall. A larger differential change in SC during acquisition was associated with more education. Older participants and women showed smaller differential SC during acquisition. Our findings support the need to consider age, gender and education when studying fear acquisition but not necessarily when examining fear extinction learning and recall. Variability in demographic factors across studies may partially explain the difficulty in reproducing some SC findings.

Demographic factors predict magnitude of conditioned fear.

There is substantial variability across individuals in the magnitudes of their skin conductance (SC) responses during the acquisition and extinction of conditioned fear. To manage this variability, subjects may be matched for demographic variables, such as age, gender and education. However, limited data exist addressing how much variability in conditioned SC responses is actually explained by these variables. The present study assessed the influence of age, gender and education on the SC responses of 222 subjects who underwent the same differential conditioning paradigm. The demographic variables were found to predict a small but significant amount of variability in conditioned responding during fear acquisition, but not fear extinction learning or extinction recall. A larger differential change in SC during acquisition was associated with more education. Older participants and women showed smaller differential SC during acquisition. Our findings support the need to consider age, gender and education when studying fear acquisition but not necessarily when examining fear extinction learning and recall. Variability in demographic factors across studies may partially explain the difficulty in reproducing some SC findings.

Pharmacological blockade of memory reconsolidation in posttraumatic stress disorder: three negative psychophysiological studies.

Posttraumatic stress disorder (PTSD) may involve over-consolidated emotional memories of the traumatic event. Reactivation (RP) can return a memory to an unstable state, from which it must be restabilized (reconsolidated) if it is to persist. Pharmacological agents administered while the memory is unstable have been shown to impair reconsolidation. The N-methyl-d-aspartate (NMDA) partial agonist d-cycloserine (DCS) may promote memory destabilization. In the three studies reported here, we investigated whether the ß-adrenergic blocker propranolol or the glucocorticoid (GR) antagonist mifepristone, given at the time of traumatic memory reactivation, could reduce PTSD symptoms and physiological responding during subsequent traumatic imagery. Individuals with PTSD were randomized as follows: Study One: propranolol with memory reactivation (n=10) or without reactivation (n=8); Study Two: reactivation mifepristone (n=13), non-reactivation (NRP) mifepristone (n=15), or double placebo (PL) (n=15); Study Three: reactivation mifepristone plus d-cycloserine (n=16), or two placebos (n=15). Subjects underwent memory retrieval by describing their traumatic event. A week later they engaged in script-driven traumatic mental imagery, while heart rate (HR), skin conductance (SC), and facial electromyogram (EMG) responses were measured. There were no significant group differences in physiological responsivity or change in PTSD symptoms in any of the studies. These results do not support successful blockade of reconsolidation of traumatic memories in PTSD.

Psychophysiological assessment of PTSD: a potential research domain criteria construct.

Most research on posttraumatic stress disorder (PTSD) relies on clinician-administered interview and self-report measures to establish the presence/absence and severity of the disorder. Accurate diagnosis of PTSD is made challenging by the presence of symptoms shared with other psychopathologies and the subjective nature of patients' descriptions of their symptoms. A physiological assessment capable of reliably "diagnosing" PTSD could provide adjunctive information that might mitigate these diagnostic limitations. In the present study, we examined the construct validity of a potential psychophysiological measure of PTSD, that is, psychophysiological reactivity to script-driven imagery (SDI-PR), as measured against the current diagnostic "gold-standard" for PTSD, the Clinician-Administered PTSD Scale (CAPS). Convergent and predictive validity and stability were examined. Thirty-six individuals completed an SDI-PR procedure, the CAPS, and self-report measures of mental and physical health at their initial visit and approximately 6 months later. SDI-PR and the CAPS demonstrated excellent stability across measurement occasions. SDI-PR showed moderately strong convergent validity with the CAPS. After adjusting for self-reported depression, predictive validity for the CAPS, with regard to health sequelae, was reduced, whereas it remained mostly unchanged for SDI-PR. Findings support SDI-PR as a valid and stable measure of PTSD that captures a pathophysiologic process in individuals with PTSD. Results are discussed with regard to the research domain criteria framework.

Neurological soft signs in individuals with pathological gambling.

Increased neurological soft signs (NSSs) have been found in a number of neuropsychiatric syndromes, including chemical addiction. The present study examined NSSs related to perceptual-motor and visuospatial processing in a behavioral addiction viz., pathological gambling (PG). As compared to mentally healthy individuals, pathological gamblers displayed significantly poorer ability to copy two- and three-dimensional figures, to recognize objects against a background noise, and to orient in space on a road-map test. Results indicated that PG is associated with subtle cerebral cortical abnormalities. Further prospective clinical research is needed to address the NSSs' origin and chronology (e.g., predate or follow the development of PG) as well as their response to therapeutic interventions and/or their ability to predict such a response.

Predicting emotional responses to potentially traumatic events from pre-exposure waking cortisol levels: a longitudinal study of police and firefighters.

There is a large literature demonstrating that individuals who have experienced traumatic events have alterations in the hypothalamic-pituitary-adrenal (HPA) axis. However, the existing literature does not address the extent to which these alterations represent pre-existing risk factors for developing psychopathology upon exposure to a significant stressor. In the current study, we examined the relationship between waking salivary cortisol level and physiological, personality, and psychological measures in 60 firefighters and police trainees during training, and then again after exposure to a highly stressful, potentially traumatic event (PTE). Waking cortisol was negatively associated with neuroticism, but positively associated with physiological reactivity to loud tones and fear conditioning when assessed during training. Longitudinally, there were significant negative correlations between pre-PTE waking cortisol and post-PTE negative mood and anxiety symptoms, but a positive correlation (trend) between pre-PTE waking cortisol and post-PTE physiological reactivity during recollection of the PTE. Thus, waking cortisol level may serve to predict divergent types of emotional sequelae following PTEs.

Predicting post-trauma stress symptoms from pre-trauma psychophysiologic reactivity, personality traits and measures of psychopathology.

BACKGROUND: Most individuals exposed to a traumatic event do not develop post-traumatic stress disorder (PTSD), although many individuals may experience sub-clinical levels of post-traumatic stress symptoms (PTSS). There are notable individual differences in the presence and severity of PTSS among individuals who report seemingly comparable traumatic events. Individual differences in PTSS following exposure to traumatic events could be influenced by pre-trauma vulnerabilities for developing PTSS/PTSD. METHODS: Pre-trauma psychological, psychophysiological and personality variables were prospectively assessed for their predictive relationships with post-traumatic stress symptoms (PTSS). Police and firefighter trainees were tested at the start of their professional training (i.e., pre-trauma; n = 211) and again several months after exposure to a potentially traumatic event (i.e., post-trauma, n = 99). Pre-trauma assessments included diagnostic interviews, psychological and personality measures and two psychophysiological assessment procedures. The psychophysiological assessments measured psychophysiologic reactivity to loud tones and the acquisition and extinction of a conditioned fear response. Post-trauma assessment included a measure of psychophysiologic reactivity during recollection of the traumatic event using a script-driven imagery task. RESULTS: Logistic stepwise regression identified the combination of lower IQ, higher depression score and poorer extinction of forehead (corrugator) electromyogram responses as pre-trauma predictors of higher PTSS. The combination of lower IQ and increased skin conductance (SC) reactivity to loud tones were identified as pre-trauma predictors of higher post-trauma psychophysiologic reactivity during recollection of the traumatic event. A univariate relationship was also observed between pre-trauma heart rate (HR) reactivity to fear cues during conditioning and post-trauma psychophysiologic reactivity. CONCLUSION: The current study contributes to a very limited literature reporting results from truly prospective examinations of pre-trauma physiologic, psychologic, and demographic predictors of PTSS. Findings that combinations of lower estimated IQ, greater depression symptoms, a larger differential corrugator EMG response during extinction and larger SC responses to loud tones significantly predicted higher PTSS suggests that the process(es) underlying these traits contribute to the pathogenesis of subjective and physiological PTSS. Due to the low levels of PTSS severity and relatively restricted ranges of outcome scores due to the healthy nature of the participants, results may underestimate actual predictive relationships.

Effect of acute posttrauma propranolol on PTSD outcome and physiological responses during script-driven imagery.

INTRODUCTION: Animal and human research suggests that the development of posttraumatic stress disorder (PTSD) may involve the overconsolidation of memories of a traumatic experience. Previous studies have attempted to use pharmaceutical agents, especially the ß-adrenergic blocker propranolol, to reduce this overconsolidation. AIMS: In this randomized, placebo-controlled study of the efficacy of propranolol in reducing the development of PTSD, we optimized dosages and conducted both psychophysiological and clinical assessments 1 and 3 months after the traumatic event. Forty-one emergency department patients who had experienced a qualifying acute psychological trauma were randomized to receive up to 240 mg/day of propranolol or placebo for 19 days. At 4 and 12 weeks post-trauma, PTSD symptoms were assessed. One week later, participants engaged in script-driven imagery of their traumatic event while psychophysiological responses were measured. RESULTS: Physiological reactivity during script-driven traumatic imagery, severity of PTSD symptoms, and the rate of the PTSD diagnostic outcome were not significantly different between the two groups. However, post hoc subgroup analyses showed that in participants with high drug adherence, at the 5-week posttrauma assessment, physiological reactivity was significantly lower during script-driven imagery in the propranolol than in the placebo subjects. CONCLUSIONS: The physiological results provide some limited support for a model of PTSD in which a traumatic conditioned response is reduced by posttrauma propranolol. However, the clinical results from this study do not support the preventive use of propranolol in the acute aftermath of a traumatic event.

Exaggerated activation of dorsal anterior cingulate cortex during cognitive interference: a monozygotic twin study of posttraumatic stress disorder.

OBJECTIVE: Neuroimaging studies have revealed functional abnormalities in the anterior cingulate cortex in posttraumatic stress disorder (PTSD). The goal of this study was to determine whether hyperresponsivity of the dorsal anterior cingulate in PTSD is an acquired characteristic or a familial risk factor. METHOD: Using a case-control twin design, the authors studied combat-exposed veterans with PTSD (N=12) and their identical combat-unexposed co-twins (N=12), as well as combat-exposed veterans without PTSD (N=14) and their identical combat-unexposed co-twins (N=14). Participants underwent functional MRI during completion of the Multi-Source Interference Task, which reliably activates the dorsal anterior cingulate. RESULTS: Combat-exposed veterans with PTSD and their unexposed co-twins had significantly greater activation in the dorsal anterior cingulate and tended to have larger response time difference scores, as compared to combat-exposed veterans without PTSD and their co-twins. Dorsal anterior cingulate activation in the exposed twins was positively correlated with their PTSD symptom severity. Dorsal anterior cingulate activation in the unexposed twins was positively correlated with their combat-exposed co-twins' PTSD symptom severity, but not with depression or alcohol use severity in the combat-exposed co-twins. CONCLUSIONS: Hyperresponsivity in the dorsal anterior cingulate appears to be a familial risk factor for the development of PTSD following psychological trauma.