Integration of neural and epigenetic contributions to posttraumatic stress symptoms: The role of hippocampal volume and glucocorticoid receptor gene methylation

M Windy McNerney, Tong Sheng, Jordan M Nechvatal, Alex G Lee, David M Lyons, Salil Soman, Chun-Ping Liao, Ruth O'Hara, Joachim Hallmayer, Joy Taylor, J Wesson Ashford, Jerome Yesavage, Maheen M Adamson, M Windy McNerney, Tong Sheng, Jordan M Nechvatal, Alex G Lee, David M Lyons, Salil Soman, Chun-Ping Liao, Ruth O'Hara, Joachim Hallmayer, Joy Taylor, J Wesson Ashford, Jerome Yesavage, Maheen M Adamson

Abstract

Many Veterans exposed to physical and psychological trauma experience symptoms of posttraumatic stress disorder (PTSD). As the etiology of PTSD symptoms is complex, a better understanding of the underlying biological mechanisms may improve preventative care and treatment for PTSD. Recent findings from the fields of neuroimaging and epigenetics offer important insights into the potential brain structures and biochemical pathways of modified gene expression associated with PTSD. We combined neuroimaging and epigenetic measures to assess current PTSD symptoms by measuring overall hippocampal volume and methylation of the glucocorticoid receptor (GR) gene (promoter region). Multiple regression analyses indicated that the hippocampal volume/GR methylation interaction was a predictor of PTSD symptoms. Our findings suggest that neuroimaging and epigenetic measures contribute interactively to PTSD symptoms. Incorporation of these metrics may aid in the identification and treatment of PTSD patients.

Conflict of interest statement

Competing Interests: The views expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the Department of the Veterans Affairs or the U.S. government. M. Windy McNerney, Tong Cheng, Jodan M. Nechvatal, Chun-Ping Liao, Ruth O'Hara, Joachim Hallmayer, Joy Taylor, J. Wesson Ashford, Jerome Yesavage, and Maheen Adamson are employees of the U.S. Government. This work was prepared as part of their official duties. Title 17 U.S.C. §105 provides that ‘Copyright protection under this title is not available for any work of the United States Government.’ Title 17 U.S.C. §101 defines a US Government work as a work prepared by a military Service Member or employee of the US Government as part of that person’s official duties.

Figures

Fig 1. Map of the NR3C1 -1F…
Fig 1. Map of the NR3C1-1F region.
This was quantified for methylation in comparison to previous studies (8, 26), indicating canonical and noncanonical binding regions.
Fig 2. The relationship between GR methylation…
Fig 2. The relationship between GR methylation and hippocampal volumes for participants who are likely to have met diagnostic criteria for PTSD and those who likely do not.
In patients who scored above the PCL-C cut-off of 50, no relationship was found, while a positive relationship was found for those who scored below.

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