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.

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.

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.

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.

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.

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.