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Metabolomic analysis of male combat veterans with post traumatic stress disorder

Mellon, Synthia H. ; Bersani, F. Saverio ; Lindqvist, Daniel LU ; Hammamieh, Rasha ; Donohue, Duncan ; Dean, Kelsey ; Jett, Marti ; Yehuda, Rachel ; Flory, Janine and Reus, Victor I. , et al. (2019) In PLoS ONE 14(3).
Abstract

Posttraumatic stress disorder (PTSD) is associated with impaired major domains of psychology and behavior. Individuals with PTSD also have increased co-morbidity with several serious medical conditions, including autoimmune diseases, cardiovascular disease, and diabetes, raising the possibility that systemic pathology associated with PTSD might be identified by metabolomic analysis of blood. We sought to identify metabolites that are altered in male combat veterans with PTSD. In this case-control study, we compared metabolomic profiles from age-matched male combat trauma-exposed veterans from the Iraq and Afghanistan conflicts with PTSD (n = 52) and without PTSD (n = 51) (‘Discovery group’). An additional group of 31 PTSD-positive and... (More)

Posttraumatic stress disorder (PTSD) is associated with impaired major domains of psychology and behavior. Individuals with PTSD also have increased co-morbidity with several serious medical conditions, including autoimmune diseases, cardiovascular disease, and diabetes, raising the possibility that systemic pathology associated with PTSD might be identified by metabolomic analysis of blood. We sought to identify metabolites that are altered in male combat veterans with PTSD. In this case-control study, we compared metabolomic profiles from age-matched male combat trauma-exposed veterans from the Iraq and Afghanistan conflicts with PTSD (n = 52) and without PTSD (n = 51) (‘Discovery group’). An additional group of 31 PTSD-positive and 31 PTSD-negative male combat-exposed veterans was used for validation of these findings (‘Test group’). Plasma metabolite profiles were measured in all subjects using ultrahigh performance liquid chromatography/tandem mass spectrometry and gas chromatography/mass spectrometry. We identified key differences between PTSD subjects and controls in pathways related to glycolysis and fatty acid uptake and metabolism in the initial ‘Discovery group’, consistent with mitochondrial alterations or dysfunction, which were also confirmed in the ‘Test group’. Other pathways related to urea cycle and amino acid metabolism were different between PTSD subjects and controls in the ‘Discovery’ but not in the smaller ‘Test’ group. These metabolic differences were not explained by comorbid major depression, body mass index, blood glucose, hemoglobin A1c, smoking, or use of analgesics, antidepressants, statins, or anti-inflammatories. These data show replicable, wide-ranging changes in the metabolic profile of combat-exposed males with PTSD, with a suggestion of mitochondrial alterations or dysfunction, that may contribute to the behavioral and somatic phenotypes associated with this disease.

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type
Contribution to journal
publication status
published
subject
in
PLoS ONE
volume
14
issue
3
article number
e0213839
publisher
Public Library of Science
external identifiers
  • scopus:85063274790
  • pmid:30883584
ISSN
1932-6203
DOI
10.1371/journal.pone.0213839
language
English
LU publication?
yes
id
2cab2066-c13c-4df3-aec9-af22ab463a9d
date added to LUP
2019-05-30 14:30:02
date last changed
2020-09-27 07:12:17
@article{2cab2066-c13c-4df3-aec9-af22ab463a9d,
  abstract     = {<p>Posttraumatic stress disorder (PTSD) is associated with impaired major domains of psychology and behavior. Individuals with PTSD also have increased co-morbidity with several serious medical conditions, including autoimmune diseases, cardiovascular disease, and diabetes, raising the possibility that systemic pathology associated with PTSD might be identified by metabolomic analysis of blood. We sought to identify metabolites that are altered in male combat veterans with PTSD. In this case-control study, we compared metabolomic profiles from age-matched male combat trauma-exposed veterans from the Iraq and Afghanistan conflicts with PTSD (n = 52) and without PTSD (n = 51) (‘Discovery group’). An additional group of 31 PTSD-positive and 31 PTSD-negative male combat-exposed veterans was used for validation of these findings (‘Test group’). Plasma metabolite profiles were measured in all subjects using ultrahigh performance liquid chromatography/tandem mass spectrometry and gas chromatography/mass spectrometry. We identified key differences between PTSD subjects and controls in pathways related to glycolysis and fatty acid uptake and metabolism in the initial ‘Discovery group’, consistent with mitochondrial alterations or dysfunction, which were also confirmed in the ‘Test group’. Other pathways related to urea cycle and amino acid metabolism were different between PTSD subjects and controls in the ‘Discovery’ but not in the smaller ‘Test’ group. These metabolic differences were not explained by comorbid major depression, body mass index, blood glucose, hemoglobin A1c, smoking, or use of analgesics, antidepressants, statins, or anti-inflammatories. These data show replicable, wide-ranging changes in the metabolic profile of combat-exposed males with PTSD, with a suggestion of mitochondrial alterations or dysfunction, that may contribute to the behavioral and somatic phenotypes associated with this disease.</p>},
  author       = {Mellon, Synthia H. and Bersani, F. Saverio and Lindqvist, Daniel and Hammamieh, Rasha and Donohue, Duncan and Dean, Kelsey and Jett, Marti and Yehuda, Rachel and Flory, Janine and Reus, Victor I. and Bierer, Linda M. and Makotkine, Iouri and Amara, Duna Abu and Haase, Clare Henn and Coy, Michelle and Doyle, Francis J. and Marmar, Charles and Wolkowitz, Owen M.},
  issn         = {1932-6203},
  language     = {eng},
  month        = {03},
  number       = {3},
  publisher    = {Public Library of Science},
  series       = {PLoS ONE},
  title        = {Metabolomic analysis of male combat veterans with post traumatic stress disorder},
  url          = {http://dx.doi.org/10.1371/journal.pone.0213839},
  doi          = {10.1371/journal.pone.0213839},
  volume       = {14},
  year         = {2019},
}