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      Cognitive Flexibility Predicts PTSD Symptoms: Observational and Interventional Studies

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          Introduction: Post-Traumatic Stress Disorder (PTSD) is a prevalent, severe and tenacious psychopathological consequence of traumatic events. Neurobehavioral mechanisms underlying PTSD pathogenesis have been identified, and may serve as risk-resilience factors during the early aftermath of trauma exposure. Longitudinally documenting the neurobehavioral dimensions of early responses to trauma may help characterize survivors at risk and inform mechanism-based interventions. We present two independent longitudinal studies that repeatedly probed clinical symptoms and neurocognitive domains in recent trauma survivors. We hypothesized that better neurocognitive functioning shortly after trauma will be associated with less severe PTSD symptoms a year later, and that an early neurocognitive intervention will improve cognitive functioning and reduce PTSD symptoms.

          Methods: Participants in both studies were adult survivors of traumatic events admitted to two general hospitals’ emergency departments (EDs) in Israel. The studies used identical clinical and neurocognitive tools, which included assessment of PTSD symptoms and diagnosis, and a battery of neurocognitive tests. The first study evaluated 181 trauma-exposed individuals one-, six-, and 14 months following trauma exposure. The second study evaluated 97 trauma survivors 1 month after trauma exposure, randomly allocated to 30 days of web-based neurocognitive intervention ( n = 50) or control tasks ( n = 47), and re-evaluated all subjects three- and 6 months after trauma exposure.

          Results: In the first study, individuals with better cognitive flexibility at 1 month post-trauma showed significantly less severe PTSD symptoms after 13 months ( p = 0.002). In the second study, the neurocognitive training group showed more improvement in cognitive flexibility post-intervention ( p = 0.019), and lower PTSD symptoms 6 months post-trauma ( p = 0.017), compared with controls. Intervention- induced improvement in cognitive flexibility positively correlated with clinical improvement ( p = 0.002).

          Discussion: Cognitive flexibility, shortly after trauma exposure, emerged as a significant predictor of PTSD symptom severity. It was also ameliorated by a neurocognitive intervention and associated with a better treatment outcome. These findings support further research into the implementation of mechanism-driven neurocognitive preventive interventions for PTSD.

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          Most cited references 30

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            Training of working memory impacts structural connectivity.

             Hikaru Takeuchi (corresponding) ,  Atsushi Sekiguchi,  Yasuyuki Taki (2010)
            Working memory is the limited capacity storage system involved in the maintenance and manipulation of information over short periods of time. Individual capacity of working memory is associated with the integrity of white matter in the frontoparietal regions. It is unknown to what extent the integrity of white matter underlying the working memory system is plastic. Using voxel-based analysis (VBA) of fractional anisotropy (FA) measures of fiber tracts, we investigated the effect of working memory training on structural connectivity in an interventional study. The amount of working memory training correlated with increased FA in the white matter regions adjacent to the intraparietal sulcus and the anterior part of the body of the corpus callosum after training. These results showed training-induced plasticity in regions that are thought to be critical in working memory. As changes in myelination lead to FA changes in diffusion tensor imaging, a possible mechanism for the observed FA change is increased myelination after training. Observed structural changes may underlie previously reported improvement of working memory capacity, improvement of other cognitive functions, and altered functional activity following working memory training.
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              Fear conditioning, synaptic plasticity and the amygdala: implications for posttraumatic stress disorder.

              Posttraumatic stress disorder (PTSD) is an anxiety disorder that can develop after a traumatic experience such as domestic violence, natural disasters or combat-related trauma. The cost of such disorders on society and the individual can be tremendous. In this article, we review how the neural circuitry implicated in PTSD in humans is related to the neural circuitry of fear. We then discuss how fear conditioning is a suitable model for studying the molecular mechanisms of the fear components that underlie PTSD, and the biology of fear conditioning with a particular focus on the brain-derived neurotrophic factor (BDNF)-tyrosine kinase B (TrkB), GABAergic and glutamatergic ligand-receptor systems. We then summarize how such approaches might help to inform our understanding of PTSD and other stress-related disorders and provide insight to new pharmacological avenues of treatment of PTSD. Copyright © 2011 Elsevier Ltd. All rights reserved.

                Author and article information

                Front Psychiatry
                Front Psychiatry
                Front. Psychiatry
                Frontiers in Psychiatry
                Frontiers Media S.A.
                04 October 2018
                : 9
                1Sagol Brain Institute Tel-Aviv, Wohl Institute for Advanced Imaging, Tel Aviv Sourasky Medical Center , Tel-Aviv, Israel
                2Sagol School of Neuroscience, Tel-Aviv University , Tel-Aviv, Israel
                3Psychological Trauma Care Center, Shaare-Zedek Medical Center , Jerusalem, Israel
                4School of Psychological Sciences, Faculty of Social Sciences, Tel-Aviv University , Tel-Aviv, Israel
                5Department of Psychology, University of Haifa , Haifa, Israel
                6Department of Psychiatry and Behavioral Sciences, Stanford University , Stanford, CA, United States
                7Stanford Neurosciences Institute, Stanford University , Stanford, CA, United States
                8Veterans Affairs Palo Alto Healthcare System, The Sierra Pacific Mental Illness, Research, Education, and Clinical Center (MIRECC) , Palo Alto, CA, United States
                9Trauma Unit and Department of Cardiothoracic Surgery, Shaare-Zedek Medical Center , Jerusalem, Israel
                10Faculty of Medicine, Hebrew University of Jerusalem , Jerusalem, Israel
                11Sackler Faculty of Medicine, Tel-Aviv University , Tel-Aviv, Israel
                12Department of Anesthesiology and Critical Care Medicine, Institute of Pain Medicine, Tel Aviv Sourasky Medical Center , Tel-Aviv, Israel
                13Pain Management and Neuromodulation Centre, Guy's & St Thomas' NHS Foundation Trust , London, United Kingdom
                14Department of Emergency Medicine, Tel Aviv Sourasky Medical Center , Tel-Aviv, Israel
                15Department of Psychiatry, University of Michigan , Ann Arbor, MI, United States
                16Department of Psychiatry, NYU Langone Medical Center , New York, NY, United States
                Author notes

                Edited by: Jutta Lindert, University of Applied Sciences Emden Leer, Germany

                Reviewed by: Andres Ricardo Schneeberger, Albert Einstein College of Medicine, United States; Lawrence T. Lam, University of Technology Sydney, Australia

                *Correspondence: Ziv Ben-Zion zivbenzion@ 123456mail.tau.ac.il

                This article was submitted to Public Mental Health, a section of the journal Frontiers in Psychiatry

                †These authors have contributed equally to this work

                Copyright © 2018 Ben-Zion, Fine, Keynan, Admon, Green, Halevi, Fonzo, Achituv, Merin, Sharon, Halpern, Liberzon, Etkin, Hendler and Shalev.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                Page count
                Figures: 4, Tables: 1, Equations: 0, References: 42, Pages: 9, Words: 6055
                Funded by: National Institute of Mental Health 10.13039/100000025
                Award ID: R01MH 103287
                Award ID: R34MH 102499
                Original Research


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