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Anterior hippocampal dysconnectivity in posttraumatic stress disorder: a dimensional and multimodal approach.

ABSTRACT: The anterior hippocampus (aHPC) has a central role in the regulation of anxiety-related behavior, stress response, emotional memory and fear. However, little is known about the presence and extent of aHPC abnormalities in posttraumatic stress disorder (PTSD). In this study, we used a multimodal approach, along with graph-based measures of global brain connectivity (GBC) termed functional GBC with global signal regression (f-GBCr) and diffusion GBC (d-GBC), in combat-exposed US Veterans with and without PTSD. Seed-based aHPC anatomical connectivity analyses were also performed. A whole-brain voxel-wise data-driven investigation revealed a significant association between elevated PTSD symptoms and reduced medial temporal f-GBCr, particularly in the aHPC. Similarly, aHPC d-GBC negatively correlated with PTSD severity. Both functional and anatomical aHPC dysconnectivity measures remained significant after controlling for hippocampal volume, age, gender, intelligence, education, combat severity, depression, anxiety, medication status, traumatic brain injury and alcohol/substance comorbidities. Depression-like PTSD dimensions were associated with reduced connectivity in the ventromedial and dorsolateral prefrontal cortex. In contrast, hyperarousal symptoms were positively correlated with ventromedial and dorsolateral prefrontal connectivity. We believe the findings provide first evidence of functional and anatomical dysconnectivity in the aHPC of veterans with high PTSD symptomatology. The data support the putative utility of aHPC connectivity as a measure of overall PTSD severity. Moreover, prefrontal global connectivity may be of clinical value as a brain biomarker to potentially distinguish between PTSD subgroups.

SUBMITTER: Abdallah CG

PROVIDER: S-EPMC5545643 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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Anterior hippocampal dysconnectivity in posttraumatic stress disorder: a dimensional and multimodal approach.

Abdallah C G CG Wrocklage K M KM Averill C L CL Akiki T T Schweinsburg B B Roy A A Martini B B Southwick S M SM Krystal J H JH Scott J C JC

Translational psychiatry 20170228 2

The anterior hippocampus (aHPC) has a central role in the regulation of anxiety-related behavior, stress response, emotional memory and fear. However, little is known about the presence and extent of aHPC abnormalities in posttraumatic stress disorder (PTSD). In this study, we used a multimodal approach, along with graph-based measures of global brain connectivity (GBC) termed functional GBC with global signal regression (f-GBCr) and diffusion GBC (d-GBC), in combat-exposed US Veterans with and ...[more]

PMID: 28244983

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Project description:BackgroundSmaller hippocampal volume in patients with posttraumatic stress disorder (PTSD) represents the most consistently reported structural alteration in the brain. Subfields of the hippocampus play distinct roles in encoding and processing of memories, which are disrupted in PTSD. We examined PTSD-associated alterations in 12 hippocampal subfields in relation to global hippocampal shape, and clinical features.MethodsCase-control cross-sectional studies of U.S. military veterans (n = 282) from the Iraq and Afghanistan era were grouped into PTSD (n = 142) and trauma-exposed controls (n = 140). Participants underwent clinical evaluation for PTSD and associated clinical parameters followed by MRI at 3 T. Segmentation with FreeSurfer v6.0 produced hippocampal subfield volumes for the left and right CA1, CA3, CA4, DG, fimbria, fissure, hippocampus-amygdala transition area, molecular layer, parasubiculum, presubiculum, subiculum, and tail, as well as hippocampal meshes. Covariates included age, gender, trauma exposure, alcohol use, depressive symptoms, antidepressant medication use, total hippocampal volume, and MRI scanner model.ResultsSignificantly lower subfield volumes were associated with PTSD in left CA1 (P = 0.01; d = 0.21; uncorrected), CA3 (P = 0.04; d = 0.08; uncorrected), and right CA3 (P = 0.02; d = 0.07; uncorrected) only if ipsilateral whole hippocampal volume was included as a covariate. A trend level association of L-CA1 with PTSD (F4, 221 = 3.32, P = 0.07) is present and the other subfield findings are nonsignificant if ipsilateral whole hippocampal volume is not included as a covariate. PTSD-associated differences in global hippocampal shape were nonsignificant.ConclusionsThe present finding of smaller hippocampal CA1 in PTSD is consistent with model systems in rodents that exhibit increased anxiety-like behavior from repeated exposure to acute stress. Behavioral correlations with hippocampal subfield volume differences in PTSD will elucidate their relevance to PTSD, particularly behaviors of associative fear learning, extinction training, and formation of false memories.

Project description:BackgroundPosttraumatic stress disorder (PTSD) symptoms can develop following acute, life-threatening medical events. This study explores a potential biomarker of PTSD risk that is novel to a medical trauma population: a noninvasive, mobile skin conductance (SC) measurement.MethodsParticipants (N=64) were enrolled in-hospital following a stroke or transient ischemic attack (TIA). Mobile measurement of SC reactivity to recalling the stroke/TIA traumatic event was conducted at hospital bedside in the days following the stroke/TIA. PTSD symptoms that developed in response to the stroke/TIA were measured at 1-month follow-up. We tested the association between SC reactivity and total 1-month PTSD symptoms, as well as PTSD symptom dimensions of fear and dysphoria.ResultsIn unadjusted analyses, there were significant positive associations between in-hospital SC reactivity to recalling the stroke/TIA traumatic event and higher-order fear-related symptoms (r=.30, p=.016), as well as lower-order fear-related symptoms of anxious arousal (r=.27, p=.035) and avoidance (r=.25, p=.043) at 1 month. Associations between SC reactivity and the fear, anxious arousal, and avoidance symptom dimensions remained significant in multivariable regression models that adjusted for relevant covariates including age, gender, stroke severity, medical comorbidity, and psychosocial factors. Although there was a positive association observed between SC reactivity to recalling the stroke/TIA event and total PTSD symptom severity at 1-month follow-up, it did not reach the level of statistical significance (r=.23, p=.070). Further, no significant association was detected for dysphoria-related symptoms (r=.11, p=.393).ConclusionsThis is the first study to test the prospective association of SC reactivity with PTSD symptom development following a medical trauma. The findings indicate that mobile measures of SC reactivity may be useful for in-hospital identification of individuals at risk for fear-related PTSD symptom development following a medical event and highlight the potential mechanisms involved in the development of these symptoms following a medical event.

Dataset Information

Anterior hippocampal dysconnectivity in posttraumatic stress disorder: a dimensional and multimodal approach.

Publications

Anterior hippocampal dysconnectivity in posttraumatic stress disorder: a dimensional and multimodal approach.

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