Persistent and reversible consequences of combat stress on the mesofrontal circuit and cognition

Wingen, Guido van; Geuze, Elbert; Caan, Matthan W.A.; Kozicz, Tamás; Olabarriaga, Sílvia D.; Denys, Damiaan; Vermetten, Eric; Fernández, Guillén

doi:10.1073/pnas.1206330109

Cited by 65 publications

(49 citation statements)

References 52 publications

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“…These inconsistencies in cingulum FA are likely due to differences in study design (eg, cross-sectional, no control group), or inclusion of non-deployed controls. These differences, along with the observation that deployment has been shown to reduce white matter microstructure integrity in the brainstem (Van Wingen et al, 2012), suggest that future studies aimed at understanding the neurobiology of PTSD in combat-deployed PTSD patients must include a combatexposed control group.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, whole-brain analyses were performed to provide a comprehensive unrestricted survey of potential treatment-related white matter differences. We included a deployed, trauma-exposed comparison group to control for the effects of time and deployment (Van Wingen et al, 2012). Using treatment outcome as an indicator, patients with remitted PTSD were compared with patients who still had a PTSD diagnosis after treatment (persistent PTSD), and with combat controls.…”

Section: Introductionmentioning

confidence: 99%

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Treatment Outcome-Related White Matter Differences in Veterans with Posttraumatic Stress Disorder

Kennis

Rooij

Tromp

et al. 2015

Neuropsychopharmacol

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Posttraumatic stress disorder (PTSD) is a debilitating disorder that has been associated with brain abnormalities, including white matter alterations. However, little is known about the effect of treatment on these brain alterations. To investigate the course of white matter alterations in PTSD, we used a longitudinal design investigating treatment effects on white matter integrity using diffusion tensor imaging (DTI). Diffusion tensor and magnetization transfer images were obtained pre-and posttreatment from veterans with (n = 39) and without PTSD (n = 22). After treatment, 16 PTSD patients were remitted, and 23 had persistent PTSD based on PTSD diagnosis. The dorsal and hippocampal cingulum bundle, stria terminalis, and fornix were investigated as regions of interest. Exploratory whole-brain analyses were also performed. Groups were compared with repeated-measures ANOVA for fractional anisotropy (FA), and magnetization transfer ratio. Persistently symptomatic PTSD patients had increasing FA of the dorsal cingulum over time, and at reassessment these FA values were higher than both combat controls and the remitted PTSD group. Group-by-time interactions for FA were found in the hippocampal cingulum, fornix, and stria terminalis, posterior corona radiata, and superior longitudinal fasciculus. Our results indicate that higher FA of the dorsal cingulum bundle may be an acquired feature of persistent PTSD that develops over time. Furthermore, treatment might have differential effects on the hippocampal cingulum, fornix, stria terminalis, posterior corona radiata, and superior longitudinal fasciculus in remitted vs persistent PTSD patients. This study contributes to a better understanding of the neural underpinnings of PTSD treatment outcome.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Treatment Outcome-Related White Matter Differences in Veterans with Posttraumatic Stress Disorder

Kennis

Rooij

Tromp

et al. 2015

Neuropsychopharmacol

Self Cite

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“…Previous research has indicated that survival training and battlefield stress impairs working memory, reaction time, and visual-spatial capacity which can lead to operational or battlefield errors [1] [7]. Combat stress has also been shown to affect midbrain activity and attention, including reduced functional connectivity between the prefrontal cortex and midbrain, which persisted at an 18 month follow-up [3]. Surging military rates of PTSD [8] and suicide in the wake of the US military operations in the Middle East [9], illustrate the need for training to prepare individuals to recognize and cope with severe stress both during performance and in the aftermath.…”

Section: Introductionmentioning

confidence: 97%

“…While exposure to moderate, acute stress is associated with improved performance, long-term severe stress can reduce fine motor performance [1], attention [2], and cognitive function [3] due to biological and neural mechanisms. Unmitigated stress is associated with a number of disease states including cardiovascular disease, depression, and cancer [4], and with a significant reduction in productivity [5].…”

Section: Introductionmentioning

confidence: 99%

Examination of the Impact of Condensed Biofeedback Training on Acute Stress Responses

Carroll¹,

Winslow²

2017

JBBS

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The objective of this study was to measure the effects of a condensed 90 minute Biofeedback Training (BFT) method on stress response and decision making performance under stress. Forty one novice male participants received either BFT training, which incorporated diaphragmatic breathing with Stress Inoculation Training (SIT), or a control training task. Participants completed pre-and post-training assessments which incorporated a socio evaluative stress induction method followed immediately by performance of a simulation-based decision making under stress scenario. Stress was assessed using real-time physiological measures of the Autonomic Nervous System (ANS) response and cortisol measures of the Hypothalamic-Pituitary-Adrenal (HPA) axis stress response. Perceived stress was measured using the state portion of the State Trait Anxiety Inventory and decision making performance was assessed during scenario performance. Results showed that participants in the BFT condition experienced a significant reduction in cortisol from pre-training to post-training, while the control group did not. However, BFT participants did not experience statistically significant reductions in ANS stress response or in perceived stress compared to the control group. Participants in the biofeedback group experienced greater improvements in performance from pre-training to post-training compared to the control group; however, these results only approached statistical significance (p = 0.09). These results suggest that the condensed BFT method has the potential to impart the knowledge and skills necessary to implement the biofeedback-based coping mechanisms; however, it may require additional practice time to allow the technique to be utilized more effectively.

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“…Mounting evidence suggests that many differences in brain structure may actually represent risk factors for the development of PTSD rather than consequences of the disorder (Gilbertson et al, 2002;Pitman et al, 2006). However, two groups conducting studies before and following deployment or combat exposure demonstrated changes in brain structure, function, and functional connectivity following war zone deployment (Admon et al, 2009(Admon et al, , 2013avan Wingen et al, 2011van Wingen et al, , 2012, although not directly due to the development of PTSD. Exploratory analyses to evaluate the robustness of our results demonstrate the level of heterogeneity present in the data.…”

Section: Limitations and Future Directionsmentioning

confidence: 99%

Contrasting Effects of Posttraumatic Stress Disorder and Mild Traumatic Brain Injury on the Whole-Brain Resting-State Network: A Magnetoencephalography Study

et al. 2017

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The aim of this study was to evaluate alterations in whole-brain resting-state networks associated with posttraumatic stress disorder (PTSD) and mild traumatic brain injury (mTBI). Networks were constructed from locations of peak statistical power on an individual basis from magnetoencephalography (MEG) source series data by applying the weighted phase lag index and surrogate data thresholding procedures. Networks representing activity in the alpha bandwidth as well as wideband activity (DC-80 Hz) were created. Statistical comparisons were adjusted for age and education level. Alpha network results demonstrate reductions in network structure associated with PTSD, but no differences associated with mTBI. Wideband network results demonstrate a shift in connectivity from the alpha to theta bandwidth in both PTSD and mTBI. Also, contrasting alterations in network structure are noted, with increased randomness associated with PTSD and increased structure associated with mTBI. These results demonstrate the potential of the analysis of MEG resting-state networks to differentiate two highly comorbid conditions. The importance of the alpha bandwidth to resting-state connectivity is also highlighted, while demonstrating the necessity of considering activity in other bandwidths during network construction.

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Persistent and reversible consequences of combat stress on the mesofrontal circuit and cognition

Cited by 65 publications

References 52 publications

Treatment Outcome-Related White Matter Differences in Veterans with Posttraumatic Stress Disorder

Treatment Outcome-Related White Matter Differences in Veterans with Posttraumatic Stress Disorder

Examination of the Impact of Condensed Biofeedback Training on Acute Stress Responses

Contrasting Effects of Posttraumatic Stress Disorder and Mild Traumatic Brain Injury on the Whole-Brain Resting-State Network: A Magnetoencephalography Study

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