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. 2017 May;27(5):515-525.
doi: 10.1016/j.euroneuro.2017.02.010. Epub 2017 Mar 6.

Cortical thickness reduction in combat exposed U.S. veterans with and without PTSD

Kristen M Wrocklage  1 , Lynnette A Averill  1 , J Cobb Scott  2 , Christopher L Averill  1 , Brian Schweinsburg  3 , Marcia Trejo  1 , Alicia Roy  1 , Valerie Weisser  1 , Christopher Kelly  1 , Brenda Martini  1 , Ilan Harpaz-Rotem  1 , Steven M Southwick  1 , John H Krystal  1 , Chadi G Abdallah  4
Affiliations

Cortical thickness reduction in combat exposed U.S. veterans with and without PTSD

Kristen M Wrocklage et al. Eur Neuropsychopharmacol. 2017 May.

Abstract

We investigated the extent of cortical thinning in U.S. Veterans exposed to combat who varied in the severity of their posttraumatic stress disorder (PTSD) symptoms. In addition, we explored the neural correlates of PTSD symptom dimensions and the interactive effects of combat exposure and PTSD upon cortical thickness. Sixty-nine combat exposed Veterans completed high-resolution magnetic resonance imaging (MRI) scans to estimate cortical thickness. The Clinician Administered PTSD Scale (CAPS) and Combat Exposure Scale (CES) assessments were completed to measure current PTSD and historical combat severity, respectively. PTSD symptom dimensions (numbing, avoidance, reexperiencing, anxious arousal, and dysphoric arousal) were studied. Vertex-wise whole cerebrum analyses were conducted. We found widespread negative correlations between CAPS severity and cortical thickness, particularly within the prefrontal cortex. This prefrontal correlation remained significant after controlling for depression severity, medication status, and other potential confounds. PTSD dimensions, except anxious arousal, negatively correlated with cortical thickness in various unique brain regions. CES negatively correlated with cortical thickness in the left lateral prefrontal, regardless of PTSD diagnosis. A significant interaction between CES and PTSD diagnosis was found, such that CES negatively correlated with cortical thickness in the non-PTSD, but not in the PTSD, participants. The results underscore the severity of cortical thinning in U.S. Veterans suffering from high level of PTSD symptoms, as well as in Veterans with no PTSD diagnosis but severe combat exposure. The latter finding raises considerable concerns about a concealed injury potentially related to combat exposure in the post-9/11 era.

Keywords: Combat; Cortical thickness; Neuroimaging; PTSD; Veteran.

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Conflict of interest statement

Conflict of Interest

Dr. Krystal has served as a scientific consultant to the following companies (the Individual Consultant Agreements listed are <$10,000 per year): Aisling Capital, Astellas Pharma Global Development, AstraZeneca Pharmaceuticals, Biocortech, Brintnall & Nicolini, Easton Associates, Gilead Sciences, GlaxoSmithKline, Janssen Pharmaceuticals, Lundbeck Research USA, Medivation, Merz Pharmaceuticals, MK Medical Communications, Hoffmann–La Roche, SK Holdings, Sunovion Pharmaceuticals, Takeda Industries, and Teva Pharmaceutical Industries. He is on the Scientific Advisory Board for the following companies: Abbott Laboratories, Bristol-Myers-Squibb, Eisai, Eli Lilly, Forest Laboratories, Lohocla Research Corporation, Mnemosyne Pharmaceuticals, Naurex, Pfizer Pharmaceuticals, and Shire Pharmaceuticals. He holds <$150 in exercisable warrant options with Tetragenex Pharmaceuticals. He is on the Board of Directors of the Coalition for Translational Research in Alcohol and Substance Use Disorders. He was the principal investigator of a multicenter study in which Janssen Research Foundation provided drug and some support to the Department of Veterans Affairs. He is Editor of Biological Psychiatry. He has a patent on dopamine and noradrenergic reuptake inhibitors in treatment of schizophrenia (patent number 5447948) and is a coinventor on a filed patent application by Yale University related to targeting the glutamatergic system for the treatment of neuropsychiatric disorders (PCTWO06108055A1). He has a patent pending on intranasal administration of ketamine to treat depression. Dr. Abdallah has served as a consultant or on advisory boards for Genentech and Janssen. He also serves as editor for the journal Chronic Stress published by SAGE Publications, Inc. All other authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Correlation between cortical thickness and PTSD severity. PTSD symptom severity as measures by CAPS showed a widespread negative correlation with cortical thickness (blue clusters), but not positive correlation. CAPS = Clinician Administered PTSD Scale.
Figure 2
Figure 2
Correlation between cortical thickness and the 5 dimensions of PTSD symptoms. Four dimensions showed negative correlation with cortical thickness (blue clusters), but no positive correlations. The 5th dimension, anxious arousal, did not correlate with cortical thickness.
Figure 3
Figure 3
Correlation between cortical thickness and combat exposure severity. Historical self-report measure of combat exposure severity negatively correlated with cortical thickness in the left lateral prefrontal cortex (blue cluster), after controlling for age and PTSD status. There were no positive correlations between cortical thickness and combat exposure severity.
Figure 4
Figure 4
Interaction between combat exposure severity (CES) and PTSD diagnosis. Five clusters showed a significant interaction between CES and PTSD status (red-yellow clusters; A). Post-hoc analyses revealed significant negative association between CES and cortical thickness in the combat control group (B–E). There was no significant association between CES and cortical thickness in the PTSD group.
See this image and copyright information in PMC

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