Prospective Measurement of Skin Conductance Response during Trauma Interview Predicts Future PTSD Severity in Trauma Exposed Children.

Previous cross-sectional studies have shown that sympathetic nervous system (SNS) arousal is positively associated with posttraumatic stress disorder (PTSD) symptoms in children with trauma exposure. One of the ways that SNS activity is measured is through skin conductance response (SCR), which has been shown to predict future PTSD severity in adults. In this study, we explored the utility of a novel, low-cost mobile SCR device, eSense, to predict future PTSD symptom severity in trauma exposed children. We recruited children (N=43, age 9 years at initial visit) for a longitudinal study in which SCR was recorded at baseline visit, and PTSD symptoms were assessed two years later. Results indicated an interaction between SCR and trauma exposure, such that children with lower trauma exposure who demonstrated greater SCR reported higher PTSD severity two years later. This association remained significant even after controlling for baseline PTSD symptoms. Children with higher levels of trauma exposure did not show this association, potentially due to ceiling effects of PTSD symptoms. Together these findings suggest the utility of SCR as a biomarker for predicting trauma related disorders in children, and that it may be a valuable tool in clinical interventions targeting sympathetic arousal.

Resting heart rate associations with violence exposure and posttraumatic stress symptoms: sex differences in children.

BACKGROUND: Traumatic events experienced in childhood can lead to increased risk of cardiovascular disorders in adulthood. Black Americans are disproportionately affected, as they are at increased risk for experiencing childhood trauma and cardiovascular diseases in adulthood. One of the hypothesized mechanisms of this association is through long-lasting dysregulation of the autonomic nervous system, a hallmark physiological biomarker of posttraumatic stress disorder (PTSD), which is twice as prevalent in women compared to men. METHODS: Ninety-one, majority Black American children, aged 9 were recruited to be a part of our longitudinal study of child development at research centers in Atlanta, GA and Detroit, MI. Resting HR was measured through a electrocardiogram (ECG) recording using the Biopac MP150. Self-report measures of violence exposure and PTSD symptoms were administered by research staff. RESULTS: Children with more violence exposure reported increased PTSS as well as lower resting HR. Regression analysis showed evidence of sex modifying this relationship, (B = -0.64, p < 0.05), such that the association between resting HR and PTSS was stronger in girls than in boys. In our exploratory analysis with standard clinical cutoffs of resting HR, the normative HR group was found to significantly moderate the relationship between violence exposure and PTSS in boys, (B = -2.14, p < 0.01), but not girls (B = -0.94, p = 0.27). CONCLUSION: In our sample of primarily Black urban children, we found that violence exposure was associated with slower, more adult-like HR, that girls showed greater PTSS associated with slower HR while boys did not, and that girls with lower than normative HR showed significantly higher PTSS compared to girls with normative HR. Our sample's demonstration of psychological consequences in addition to the physiological implications could provide new information about a psychobiological sequelae of violence exposure.

Experiencing traumatic events in childhood can lead to increased risk of heart disease in adulthood. One of the ways this might happen is through long-lasting changes of the autonomic nervous system. This system is dysregulated in posttraumatic stress disorder (PTSD), which is twice as common in women compared to men. We explored whether resting heart rate (HR), a measure of autonomic functioning was associated with violence exposure in children, and whether this relationship was different in boys and girls. We also explored whether categorizing our sample into resting HR groups based off standardized norms for HR predicted differing relationships between violence exposure and posttraumatic stress symptoms (PTSS). Because childhood trauma and heart disease impact Black Americans at greater rates, we recruited our sample of 92 nine-year-old children from research centers in Atlanta, GA and Detroit, MI. We measured their resting HR, exposure to violence, and PTSS. We found that violence exposure was associated with lower HR overall, that girls showed greater PTSS associated with lower HR when compared to boys, and that boys with lower than normative HR showed a stronger association between violence exposure and PTSS compared to boys with normative HR. Future studies should examine potential mechanisms underlying this sex difference to best understand the long-term cardiovascular consequences for sex-related health disparities. Specifically, longitudinal studies may be able to help researchers understand how reduced HR during adolescents might lead to future cardiovascular disease and psychopathology.

The fear that remains: Associations between trauma, related psychopathology, and fear-potentiated startle in youth resettled as refugees.

Fear-potentiated startle (FPS) can be used to measure fear and safety learning-behaviors affected by trauma that may map onto posttraumatic stress disorder (PTSD). Therefore, FPS could be a candidate biomarker of trauma-related psychopathology and a potential identifier of trauma-exposed youth in need of focused treatment. We enrolled n = 71 (35 females, Mage  = 12.7 years) Syrian youth exposed to civilian war trauma. Eyeblink electromyogram (EMG) data from a differential conditioning FPS paradigm were obtained 2.5 years after resettlement. Youth provided self-report of trauma exposure (Harvard Trauma Questionnaire) and PTSD symptoms (UCLA PTSD Reaction Index). While FPS during conditioning was not associated with symptoms, associations with psychopathology emerged in fear extinction. Probable PTSD was associated with FPS in the last block of extinction, such that FPS to threat cue was significantly greater in the PTSD+ group compared to the PTSD- group at the end of extinction (F = 6.25, p = .015). As with adults, we observed a deficit in extinction learning but not fear conditioning in youth with PTSD. These results support the use of trauma-informed cognitive behavioral therapy based on the learning principles of extinction in youth with PTSD.

Structural inequities contribute to racial/ethnic differences in neurophysiological tone, but not threat reactivity, after trauma exposure.

Considerable racial/ethnic disparities persist in exposure to life stressors and socioeconomic resources that can directly affect threat neurocircuitry, particularly the amygdala, that partially mediates susceptibility to adverse posttraumatic outcomes. Limited work to date, however, has investigated potential racial/ethnic variability in amygdala reactivity or connectivity that may in turn be related to outcomes such as post-traumatic stress disorder (PTSD). Participants from the AURORA study (n = 283), a multisite longitudinal study of trauma outcomes, completed functional magnetic resonance imaging and psychophysiology within approximately two-weeks of trauma exposure. Seed-based amygdala connectivity and amygdala reactivity during passive viewing of fearful and neutral faces were assessed during fMRI. Physiological activity was assessed during Pavlovian threat conditioning. Participants also reported the severity of posttraumatic symptoms 3 and 6 months after trauma. Black individuals showed lower baseline skin conductance levels and startle compared to White individuals, but no differences were observed in physiological reactions to threat. Further, Hispanic and Black participants showed greater amygdala connectivity to regions including the dorsolateral prefrontal cortex (PFC), dorsal anterior cingulate cortex, insula, and cerebellum compared to White participants. No differences were observed in amygdala reactivity to threat. Amygdala connectivity was associated with 3-month PTSD symptoms, but the associations differed by racial/ethnic group and were partly driven by group differences in structural inequities. The present findings suggest variability in tonic neurophysiological arousal in the early aftermath of trauma between racial/ethnic groups, driven by structural inequality, impacts neural processes that mediate susceptibility to later PTSD symptoms.

Associations among civilian mild traumatic brain injury with loss of consciousness, posttraumatic stress disorder symptom trajectories, and structural brain volumetric data.

Posttraumatic stress disorder (PTSD) is prevalent and associated with significant morbidity. Mild traumatic brain injury (mTBI) concurrent with psychiatric trauma may be associated with PTSD. Prior studies of PTSD-related structural brain alterations have focused on military populations. The current study examined correlations between PTSD, acute mTBI, and structural brain alterations longitudinally in civilian patients (N = 504) who experienced a recent Criterion A traumatic event. Participants who reported loss of consciousness (LOC) were characterized as having mTBI; all others were included in the control group. PTSD symptoms were assessed at enrollment and over the following year; a subset of participants (n = 89) underwent volumetric brain MRI (M = 53 days posttrauma). Classes of PTSD symptom trajectories were modeled using latent growth mixture modeling. Associations between PTSD symptom trajectories and cortical thicknesses or subcortical volumes were assessed using a moderator-based regression. mTBI with LOC during trauma was positively correlated with the likelihood of developing a chronic PTSD symptom trajectory. mTBI showed significant interactions with cortical thickness in the rostral anterior cingulate cortex (rACC) in predicting PTSD symptoms, r = .461-.463. Bilateral rACC thickness positively predicted PTSD symptoms but only among participants who endorsed LOC, p < .001. The results demonstrate positive correlations between mTBI with LOC and PTSD symptom trajectories, and findings related to mTBI with LOC and rACC thickness interactions in predicting subsequent chronic PTSD symptoms suggest the importance of further understanding the role of mTBI in the context of PTSD to inform intervention and risk stratification.

Associations between children's trauma-related sequelae and skin conductance captured through mobile technology.

Although many children experience trauma, few receive diagnoses and subsequent care despite experiencing trauma-related sequelae. At age nine (M = 9.11), children (N = 62; female = 46.4%) who predominantly identified as Black (78.7%) were enrolled in this first study examining how skin conductance as captured by mobile technology, eSense, related to children's traumatic experiences and trauma-related symptoms. Skin conductance measures were associated with degree of trauma exposure and PTSD hyperarousal symptoms. These findings suggest that physiological responses in addition to self-report measures may be easily used to assess children's trauma exposure and symptoms. Given eSense's ease-of-use, this technology could assist clinics and research institutions assess children's trauma-related needs.

Acute Posttraumatic Symptoms Are Associated With Multimodal Neuroimaging Structural Covariance Patterns: A Possible Role for the Neural Substrates of Visual Processing in Posttraumatic Stress Disorder.

BACKGROUND: Although aspects of brain morphology have been associated with chronic posttraumatic stress disorder (PTSD), limited work has investigated multimodal patterns in brain morphology that are linked to acute posttraumatic stress severity. In the present study, we utilized multimodal magnetic resonance imaging to investigate if structural covariance networks (SCNs) assessed acutely following trauma were linked to acute posttraumatic stress severity. METHODS: Structural magnetic resonance imaging data were collected around 1 month after civilian trauma exposure in 78 participants. Multimodal magnetic resonance imaging data fusion was completed to identify combinations of SCNs, termed structural covariance profiles (SCPs), related to acute posttraumatic stress severity collected at 1 month. Analyses assessed the relationship between participant SCP loadings, acute posttraumatic stress severity, the change in posttraumatic stress severity from 1 to 12 months, and depressive symptoms. RESULTS: We identified an SCP that reflected greater gray matter properties of the anterior temporal lobe, fusiform face area, and visual cortex (i.e., the ventral visual stream) that varied curvilinearly with acute posttraumatic stress severity and the change in PTSD symptom severity from 1 to 12 months. The SCP was not associated with depressive symptoms. CONCLUSIONS: We identified combinations of multimodal SCNs that are related to variability in PTSD symptoms in the early aftermath of trauma. The identified SCNs may reflect patterns of neuroanatomical organization that provide unique insight into acute posttraumatic stress. Furthermore, these multimodal SCNs may be potential candidates for neural markers of susceptibility to both acute posttraumatic stress and the future development of PTSD.

A prospective examination of sex differences in posttraumatic autonomic functioning.

BACKGROUND: Cross-sectional studies have found that individuals with posttraumatic stress disorder (PTSD) exhibit deficits in autonomic functioning. While PTSD rates are twice as high in women compared to men, sex differences in autonomic functioning are relatively unknown among trauma-exposed populations. The current study used a prospective design to examine sex differences in posttraumatic autonomic functioning. METHODS: 192 participants were recruited from emergency departments following trauma exposure (Mean age = 35.88, 68.2% female). Skin conductance was measured in the emergency department; fear conditioning was completed two weeks later and included measures of blood pressure (BP), heart rate (HR), and high frequency heart rate variability (HF-HRV). PTSD symptoms were assessed 8 weeks after trauma. RESULTS: 2-week systolic BP was significantly higher in men, while 2-week HR was significantly higher in women, and a sex by PTSD interaction suggested that women who developed PTSD demonstrated the highest HR levels. Two-week HF-HRV was significantly lower in women, and a sex by PTSD interaction suggested that women with PTSD demonstrated the lowest HF-HRV levels. Skin conductance response in the emergency department was associated with 2-week HR and HF-HRV only among women who developed PTSD. CONCLUSIONS: Our results indicate that there are notable sex differences in autonomic functioning among trauma-exposed individuals. Differences in sympathetic biomarkers (BP and HR) may have implications for cardiovascular disease risk given that sympathetic arousal is a mechanism implicated in this risk among PTSD populations. Future research examining differential pathways between PTSD and cardiovascular risk among men versus women is warranted.

Hippocampal activation during contextual fear inhibition related to resilience in the early aftermath of trauma.

BACKGROUND: Impaired contextual fear inhibition is often associated with posttraumatic stress disorder (PTSD). Our previous work has demonstrated that more hippocampal activation during a response inhibition task after trauma exposure was related to greater resilience and fewer future PTSD symptoms. In the current study, we sought to extend our previous findings by employing a contextual fear conditioning and extinction paradigm to further determine the role of the hippocampus in resilience and PTSD in the early aftermath of trauma. METHODS: Participants (N = 28) were recruited in the Emergency Department shortly after experiencing a traumatic event. A contextual fear inhibition task was conducted in a 3 T MRI scanner approximately two months post-trauma. Measures of resilience (CD-RISC) at time of scan and PTSD symptoms three months post-trauma were collected. The associations between hippocampal activation during fear conditioning and during the effect of context during extinction, and post-trauma resilience and PTSD symptoms at three-months were assessed. RESULTS: During fear conditioning, activation of the bilateral hippocampal region of interest (ROI) correlated positively with resilience (r = 0.48, p = 0.01). During the effect of context during extinction, greater bilateral hippocampal activation correlated with lower PTSD symptoms three months post-trauma after controlling for baseline PTSD symptoms, age and gender (r=-0.59, p=0.009). CONCLUSIONS: Greater hippocampal activation was related to post-trauma resilience and lower PTSD symptoms three months post-trauma. The current study supports and strengthens prior findings suggesting the importance of hippocampus-dependent context processing as a mechanism for resilience versus PTSD risk, which could be a potential mechanistic target for novel early interventions.

Case Series: Unilateral Amygdala Ablation Ameliorates Post-Traumatic Stress Disorder Symptoms and Biomarkers.

BACKGROUND: Post-traumatic stress disorder is a severe psychobiological disorder associated with hyperactivity of the amygdala, particularly on the right side. Highly selective laser ablation of the amygdalohippocampal complex is an effective neurosurgical treatment for medically refractory medial temporal lobe epilepsy that minimizes neurocognitive deficits relative to traditional open surgery. OBJECTIVE: To examine the impact of amygdalohippocampotomy upon symptoms and biomarkers of post-traumatic stress disorder. METHODS: Two patients with well-documented chronic post-traumatic stress disorder who subsequently developed late-onset epilepsy underwent unilateral laser amygdalohippocampotomy. Prospective clinical and neuropsychological measurements were collected in patient 1. Additional prospective measurements of symptoms and biomarkers were collected pre- and post-surgery in patient 2. RESULTS: After laser ablation targeting the nondominant (right) amygdala, both patients experienced not only reduced seizures, but also profoundly abated post-traumatic stress symptoms. Prospective evaluation of biomarkers in patient 2 showed robust improvements in hyperarousal symptoms, fear potentiation of the startle reflex, brain functional magnetic resonance imaging responses to fear-inducing stimuli, and emotional declarative memory. CONCLUSION: These observations support the emerging hypothesis that the right amygdala particularly perpetuates the signs and symptoms of post-traumatic stress disorder and suggests that focal unilateral amydalohippocampotomy can provide therapeutic benefit.

Increased Skin Conductance Response in the Immediate Aftermath of Trauma Predicts PTSD Risk.

BACKGROUND: Exposure to a traumatic event leads to posttraumatic stress disorder (PTSD) in 10-20% of exposed individuals. Predictors of risk are needed to target early interventions to those who are most vulnerable. The objective of the study was to test whether a noninvasive mobile device that measures a physiological biomarker of autonomic nervous system activation could predict future PTSD symptoms. METHODS: Skin conductance response (SCR) was collected during a trauma interview in the emergency department within hours of exposure to trauma in 95 individuals. Trajectories of PTSD symptoms over 12 months post-trauma were identified using Latent Growth Mixture Modeling. RESULTS: SCR was significantly correlated with the probability of being in the chronic PTSD trajectory following trauma exposure in the ED (r=0.489, p<0.000001). Lasso regression with elastic net was performed with demographic and clinical measures obtained in the ED, demonstrating that SCR was the most significant predictor of the chronic PTSD trajectory (p<0.00001). CONCLUSIONS: The current study is the first prospective study of PTSD showing SCR in the immediate aftermath of trauma predicts subsequent development of chronic PTSD. This finding points to an easily obtained, and neurobiologically informative, biomarker in emergency departments that can be disseminated to predict the development of PTSD.

The Role of the Hippocampus in Predicting Future Posttraumatic Stress Disorder Symptoms in Recently Traumatized Civilians.

BACKGROUND: Understanding the neurobiological mechanisms that predict posttraumatic stress disorder (PTSD) in recent trauma survivors is important for early interventions. Impaired inhibition of fear or behavioral responses is thought to be central to PTSD symptomatology, but its role in predicting PTSD is unknown. Here we examine whether brain function during response inhibition early after a civilian trauma can predict future PTSD symptoms. METHODS: Participants (original sample, n = 27; replication sample, n = 31) were recruited in the emergency department within 24 hours of trauma exposure. PTSD symptoms were assessed in the emergency department and 1, 3, and 6 months posttrauma. A Go/NoGo procedure in a 3T magnetic resonance imaging scanner was used to measure neural correlates of response inhibition 1 to 2 months posttrauma. Elastic net regression was used to define the most optimal model to predict PTSD symptoms at 3 and 6 months among demographic, clinical, and imaging measures. RESULTS: Less hippocampal activation was a significant predictor in the model predicting PTSD symptoms at 3 months (F11,22 = 4.33, p = .01) and 6 months (F9,19 = 4.96, p = .01). Other significant predictors in the model were race and pain level in the emergency department (3 months), and race and baseline depression symptoms (6 months). Using these predictors in a linear regression in the replication sample again resulted in significant models (3 months [F3,23 = 3.03, p = .05], 6 months [F3,20 = 5.74, p = .007]) with hippocampal activation predicting PTSD symptoms at 3 and 6 months. CONCLUSIONS: Decreased inhibition-related hippocampal activation soon after trauma predicted future PTSD symptom severity. This finding may contribute to early identification of at-risk individuals and reveals potential targets for intervention or symptom prevention in the aftermath of trauma.

Mobile assessment of heightened skin conductance in posttraumatic stress disorder.

BACKGROUND: Increased psychophysiological reactivity is a hallmark intermediate phenotype of posttraumatic stress disorder (PTSD). Individuals with PTSD exhibit greater skin conductance (SC) responses to trauma scripts than trauma survivors without PTSD. However, trauma scripts require time for development and cannot be easily used in a single visit. Thus, there is a need for a low-cost, easy-to-use, SC recording protocol for PTSD assessment. METHODS: Using a mobile device (eSense) connected to a portable tablet computer, we assessed SC reactivity to a standard trauma interview (STI) in 63 participants recruited from Grady Memorial Hospital in Atlanta, GA, approximately 1 year after trauma exposure. SC response (SCR) was calculated by subtracting the SC level (SCL) at the end of the baseline recording from the maximum SCL during the STI. RESULTS: SCL was significantly higher during the STI compared to baseline (P < .001), and individuals with PTSD showed significantly greater SCR than individuals without PTSD (P = .006). Logistic regression using SCR with PTSD diagnosis as the outcome showed an odds ratio of 1.76 (95% CI: 1.11-2.78). Lastly, higher SCR during the STI was also significantly associated with PTSD symptom total score controlling for demographics and trauma severity (b = 0.42, P = .001). CONCLUSIONS: The current study demonstrated feasibility of the use of a mobile device for assessing psychophysiological reactivity in those with PTSD. The use of this low-cost, easy-to-use mobile device to collect objective physiological data in concert with a STI can be easily disseminated in clinical and research settings.