COMT Val158Met polymorphism moderates the association between PTSD symptom severity and hippocampal volume

COMT Val158Met polymorphism moderates the association between PTSD symptom severity and hippocampal volume

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J Psychiatry Neurosci 2017;42(2):95-102

Jasmeet P. Hayes, PhD; Mark W. Logue, PhD; Andrew Reagan, MA; David Salat, PhD; Erika J. Wolf, PhD; Naomi Sadeh, PhD; Jeffrey M. Spielberg, PhD; Emily Sperbeck, BA; Scott M. Hayes, PhD; Regina E. McGlinchey, PhD; William P. Milberg, PhD; Mieke Verfaellie, PhD; Annjanette Stone, BS; Steven A. Schichman, MD, PhD; Mark W. Miller, PhD

Abstract

Background: Memory-based alterations are among the hallmark symptoms of posttraumatic stress disorder (PTSD) and may be associated with the integrity of the hippocampus. However, neuroimaging studies of hippocampal volume in individuals with PTSD have yielded inconsistent results, raising the possibility that various moderators, such as genetic factors, may influence this association. We examined whether the catechol-O-methyltransferase (COMT) Val158Met polymorphism, which has previously been shown to be associated with hippocampal volume in healthy individuals, moderates the association between PTSD and hippocampal volume.

Methods: Recent war veterans underwent structural MRI on a 3 T scanner. We extracted volumes of the right and left hippocampus using FreeSurfer and adjusted them for individual differences in intracranial volume. We assessed PTSD severity using the Clinician-Administered PTSD Scale. Hierarchical linear regression was used to model the genotype (Val158Met polymorphism) × PTSD severity interaction and its association with hippocampal volume.

Results: We included 146 white, non-Hispanic recent war veterans (90% male, 53% with diagnosed PTSD) in our analyses. A significant genotype × PTSD symptom severity interaction emerged such that individuals with greater current PTSD symptom severity who were homozygous for the Val allele showed significant reductions in left hippocampal volume.

Limitations: The direction of proposed effects is unknown, thus precluding definitive assessment of whether differences in hippocampal volume reflect a consequence of PTSD, a pre-existing characteristic, or both.

Conclusion: Our findings suggest that the COMT polymorphism moderates the association between PTSD and hippocampal volume. These results highlight the role that the dopaminergic system has in brain structure and suggest a possible mechanism for memory disturbance in individuals with PTSD.


Submitted Nov. 9, 2015; Revised May 20, 2016; Accepted July 5, 2016; Early-released Jan. 31, 2017

Acknowledgements:This research was supported in part by National Institute of Mental Health grant R21MH102834, VA SPiRe award I21RX001594, and the Translational Research Center for TBI and Stress Disorders (TRACTS), a VA Rehabilitation Research and Development Traumatic Brain Injury Center of Excellence (B9254-C). This work was also supported by a Career Development Award to E.J. Wolf from the United States Department of Veterans Affairs, Clinical Sciences Research and Development Program. M. Verfaellie is supported by the Department of Veterans Affairs Clinical Science Research and Development Service. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the United States government.

Affiliations: From the National Center for PTSD, VA Boston Healthcare System, Boston, Mass. (Hayes, Reagan, Wolf, Sadeh, Miller); the Department of Psychiatry, Boston University School of Medicine, Boston, Mass. (Hayes, Wolf, Sadeh, Spielberg, Sperbeck, Hayes, Verfaellie, Miller); the Neuroimaging Research for Veterans Center, VA Boston Healthcare System, Boston, Mass. (Hayes, Salat, Spielberg, Hayes); the Research Service, VA Boston Healthcare System, Boston, Mass. (Logue); the Biomedical Genetics, Boston University School of Medicine, Boston, Mass. (Logue); the Department of Biostatistics, Boston University School of Public Health, Boston, Mass. (Logue); the Memory Disorders Research Center, VA Boston Healthcare System, Boston, Mass. (Hayes, Verfaellie); the Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard University, Boston, Mass. (Salat); the Harvard Medical School, Harvard University, Boston, Mass. (Salat); the Translational Research Center for TBI and Stress Disorders and Geriatric Research, Educational and Clinical Center, VA Boston Healthcare System, Boston, Mass. (McGlinchey, Milberg); the Department of Psychiatry, Harvard Medical School, Boston, Mass. (McGlinchey, Milberg); the Pharmacogenomics Analysis Laboratory, Research Service, Central Arkansas Veterans Healthcare System, USA (Stone, Schichman).

Competing interests: None declared.

Contributors: J. Hayes, M. Logue, R. McGlinchey, W. Milberg and M. Miller designed the study. D. Salat, R. McGlinchey, W. Milberg and M. Miller acquired the data, which J. Hayes, M. Logue, A. Reagan, E. Wolf, N. Sadeh, J. Spielberg, E. Sperbeck, S. Hayes, M. Verfaellie, A. Stone, S. Schichman and M. Miller analyzed. J. Hayes, M. Logue and A. Reagan wrote the article, which all authors reviewed and approved for publication.

DOI: 10.1503/jpn.150339

Correspondence to: J.P. Hayes, National Center for PTSD (116B-2), VA Boston Healthcare System, 150 S. Huntington Ave., Boston MA 02130; jphayes@bu.edu