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      Military deployment correlates with smaller prefrontal gray matter volume and psychological symptoms in a subclinical population

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          Abstract

          Research investigating the effects of trauma exposure on brain structure and function in adults has mainly focused on post-traumatic stress disorder (PTSD), whereas trauma-exposed individuals without a clinical diagnoses often serve as controls. However, this assumes a dichotomy between clinical and subclinical populations that may not be supported at the neural level. In the current study we investigate whether the effects of repeated or long-term stress exposure on brain structure in a subclinical sample are similar to previous PTSD neuroimaging findings. We assessed 27 combat trauma-exposed individuals by means of whole-brain voxel-based morphometry on 3 T magnetic resonance imaging scans and identified a negative association between duration of military deployment and gray matter volumes in ventromedial prefrontal cortex (vmPFC) and dorsal anterior cingulate cortex (ACC). We also found a negative relationship between deployment-related gray matter volumes and psychological symptoms, but not between military deployment and psychological symptoms. To our knowledge, this is the first whole-brain analysis showing that longer military deployment is associated with smaller regional brain volumes in combat-exposed individuals without PTSD. Notably, the observed gray matter associations resemble those previously identified in PTSD populations, and concern regions involved in emotional regulation and fear extinction. These findings question the current dichotomy between clinical and subclinical populations in PTSD neuroimaging research. Instead, neural correlates of both stress exposure and PTSD symptomatology may be more meaningfully investigated at a continuous level.

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          Most cited references36

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          Emotional processing in anterior cingulate and medial prefrontal cortex.

          Negative emotional stimuli activate a broad network of brain regions, including the medial prefrontal (mPFC) and anterior cingulate (ACC) cortices. An early influential view dichotomized these regions into dorsal-caudal cognitive and ventral-rostral affective subdivisions. In this review, we examine a wealth of recent research on negative emotions in animals and humans, using the example of fear or anxiety, and conclude that, contrary to the traditional dichotomy, both subdivisions make key contributions to emotional processing. Specifically, dorsal-caudal regions of the ACC and mPFC are involved in appraisal and expression of negative emotion, whereas ventral-rostral portions of the ACC and mPFC have a regulatory role with respect to limbic regions involved in generating emotional responses. Moreover, this new framework is broadly consistent with emerging data on other negative and positive emotions. Published by Elsevier Ltd.
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            Cognitive and emotional influences in anterior cingulate cortex.

            Bush, Luu, Posner (2000)
            Anterior cingulate cortex (ACC) is a part of the brain's limbic system. Classically, this region has been related to affect, on the basis of lesion studies in humans and in animals. In the late 1980s, neuroimaging research indicated that ACC was active in many studies of cognition. The findings from EEG studies of a focal area of negativity in scalp electrodes following an error response led to the idea that ACC might be the brain's error detection and correction device. In this article, these various findings are reviewed in relation to the idea that ACC is a part of a circuit involved in a form of attention that serves to regulate both cognitive and emotional processing. Neuroimaging studies showing that separate areas of ACC are involved in cognition and emotion are discussed and related to results showing that the error negativity is influenced by affect and motivation. In addition, the development of the emotional and cognitive roles of ACC are discussed, and how the success of this regulation in controlling responses might be correlated with cingulate size. Finally, some theories are considered about how the different subdivisions of ACC might interact with other cortical structures as a part of the circuits involved in the regulation of mental and emotional activity.
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              Neurobiological basis of failure to recall extinction memory in posttraumatic stress disorder.

              A clinical characteristic of posttraumatic stress disorder (PTSD) is persistently elevated fear responses to stimuli associated with the traumatic event. The objective herein is to determine whether extinction of fear responses is impaired in PTSD and whether such impairment is related to dysfunctional activation of brain regions known to be involved in fear extinction, viz., amygdala, hippocampus, ventromedial prefrontal cortex (vmPFC), and dorsal anterior cingulate cortex (dACC). Sixteen individuals diagnosed with PTSD and 15 trauma-exposed non-PTSD control subjects underwent a 2-day fear conditioning and extinction protocol in a 3-T functional magnetic resonance imaging scanner. Conditioning and extinction training were conducted on day 1. Extinction recall (or extinction memory) test was conducted on day 2 (extinguished conditioned stimuli presented in the absence of shock). Skin conductance response (SCR) was scored throughout the experiment as an index of the conditioned response. The SCR data revealed no significant differences between groups during acquisition and extinction of conditioned fear on day 1. On day 2, however, PTSD subjects showed impaired recall of extinction memory. Analysis of functional magnetic resonance imaging data showed greater amygdala activation in the PTSD group during day 1 extinction learning. During extinction recall, lesser activation in hippocampus and vmPFC and greater activation in dACC were observed in the PTSD group. The magnitude of extinction memory across all subjects was correlated with activation of hippocampus and vmPFC during extinction recall testing. These findings support the hypothesis that fear extinction is impaired in PTSD. They further suggest that dysfunctional activation in brain structures that mediate fear extinction learning, and especially its recall, underlie this impairment.
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                Author and article information

                Journal
                Transl Psychiatry
                Transl Psychiatry
                Translational Psychiatry
                Nature Publishing Group
                2158-3188
                February 2017
                14 February 2017
                1 February 2017
                : 7
                : 2
                : e1031
                Affiliations
                [1 ]Max Planck Institute for Human Development, Center for Lifespan Psychology , Berlin, Germany
                [2 ]Charité University Medicine, Campus Charité Mitte, Clinic for Psychiatry and Psychotherapy , Berlin, Germany
                [3 ]Psychotrauma Center of the German Military, Military Hospital Berlin, Berlin, Germany
                [4 ]European University Institute, Department of Political and Social Sciences, Badia Fiesolana , San Domenico di Fiesole, Italy
                [5 ]Max Planck UCL Centre for Computational Psychiatry and Ageing Research , Berlin, Germany
                [6 ]University Clinic Hamburg-Eppendorf, Clinic and Policlinic for Psychiatry and Psychotherapy , Hamburg, Germany
                Author notes
                [* ]Max Planck Institute for Human Development, Center for Lifespan Psychology , Lentzeallee 94, Berlin 14195, Germany. E-mail: butler@ 123456mpib-berlin.mpg.de
                Article
                tp2016288
                10.1038/tp.2016.288
                5438025
                28195568
                d2a04f8d-bde2-418f-bd02-d9c67c577bc5
                Copyright © 2017 The Author(s)

                This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

                History
                : 12 September 2016
                : 26 October 2016
                : 13 November 2016
                Categories
                Original Article

                Clinical Psychology & Psychiatry
                Clinical Psychology & Psychiatry

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