Circulating cell-free mitochondrial DNA levels and glucocorticoid sensitivity in a cohort of male veterans with and without combat-related PTSD
Abstract Circulating cell-free mitochondrial DNA (ccf-mtDNA) is a biomarker of cellular injury or cellular stress and is a potential novel biomarker of psychological stress and of various brain, somatic, and psychiatric disorders. No studies have yet analyzed ccf-mtDNA levels in post-traumatic stres...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2024-01-01
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| Series: | Translational Psychiatry |
| Online Access: | https://doi.org/10.1038/s41398-023-02721-x |
| _version_ | 1797355496948105216 |
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| author | Zachary N. Blalock Gwyneth W. Y Wu Daniel Lindqvist Caroline Trumpff Janine D. Flory Jue Lin Victor I. Reus Ryan Rampersaud Rasha Hammamieh Aarti Gautam SBPBC Francis J. Doyle Charles R. Marmar Marti Jett Rachel Yehuda Owen M. Wolkowitz Synthia H. Mellon |
| author_facet | Zachary N. Blalock Gwyneth W. Y Wu Daniel Lindqvist Caroline Trumpff Janine D. Flory Jue Lin Victor I. Reus Ryan Rampersaud Rasha Hammamieh Aarti Gautam SBPBC Francis J. Doyle Charles R. Marmar Marti Jett Rachel Yehuda Owen M. Wolkowitz Synthia H. Mellon |
| author_sort | Zachary N. Blalock |
| collection | DOAJ |
| description | Abstract Circulating cell-free mitochondrial DNA (ccf-mtDNA) is a biomarker of cellular injury or cellular stress and is a potential novel biomarker of psychological stress and of various brain, somatic, and psychiatric disorders. No studies have yet analyzed ccf-mtDNA levels in post-traumatic stress disorder (PTSD), despite evidence of mitochondrial dysfunction in this condition. In the current study, we compared plasma ccf-mtDNA levels in combat trauma-exposed male veterans with PTSD (n = 111) with those who did not develop PTSD (n = 121) and also investigated the relationship between ccf mt-DNA levels and glucocorticoid sensitivity. In unadjusted analyses, ccf-mtDNA levels did not differ significantly between the PTSD and non-PTSD groups (t = 1.312, p = 0.191, Cohen’s d = 0.172). In a sensitivity analysis excluding participants with diabetes and those using antidepressant medication and controlling for age, the PTSD group had lower ccf-mtDNA levels than did the non-PTSD group (F(1, 179) = 5.971, p = 0.016, partial η 2 = 0.033). Across the entire sample, ccf-mtDNA levels were negatively correlated with post-dexamethasone adrenocorticotropic hormone (ACTH) decline (r = −0.171, p = 0.020) and cortisol decline (r = −0.149, p = 0.034) (viz., greater ACTH and cortisol suppression was associated with lower ccf-mtDNA levels) both with and without controlling for age, antidepressant status and diabetes status. Ccf-mtDNA levels were also significantly positively associated with IC50-DEX (the concentration of dexamethasone at which 50% of lysozyme activity is inhibited), a measure of lymphocyte glucocorticoid sensitivity, after controlling for age, antidepressant status, and diabetes status (β = 0.142, p = 0.038), suggesting that increased lymphocyte glucocorticoid sensitivity is associated with lower ccf-mtDNA levels. Although no overall group differences were found in unadjusted analyses, excluding subjects with diabetes and those taking antidepressants, which may affect ccf-mtDNA levels, as well as controlling for age, revealed decreased ccf-mtDNA levels in PTSD. In both adjusted and unadjusted analyses, low ccf-mtDNA levels were associated with relatively increased glucocorticoid sensitivity, often reported in PTSD, suggesting a link between mitochondrial and glucocorticoid-related abnormalities in PTSD. |
| first_indexed | 2024-03-08T14:12:00Z |
| format | Article |
| id | doaj.art-462b504a442545f2add418e35eab0665 |
| institution | Directory Open Access Journal |
| issn | 2158-3188 |
| language | English |
| last_indexed | 2024-03-08T14:12:00Z |
| publishDate | 2024-01-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Translational Psychiatry |
| spelling | doaj.art-462b504a442545f2add418e35eab06652024-01-14T12:37:29ZengNature Publishing GroupTranslational Psychiatry2158-31882024-01-0114111110.1038/s41398-023-02721-xCirculating cell-free mitochondrial DNA levels and glucocorticoid sensitivity in a cohort of male veterans with and without combat-related PTSDZachary N. Blalock0Gwyneth W. Y Wu1Daniel Lindqvist2Caroline Trumpff3Janine D. Flory4Jue Lin5Victor I. Reus6Ryan Rampersaud7Rasha Hammamieh8Aarti Gautam9SBPBCFrancis J. Doyle10Charles R. Marmar11Marti Jett12Rachel Yehuda13Owen M. Wolkowitz14Synthia H. Mellon15Department of Psychiatry and Behavioral Sciences and Weill Institute for Neurosciences, University of CaliforniaDepartment of Psychiatry and Behavioral Sciences and Weill Institute for Neurosciences, University of CaliforniaUnit for Biological and Precision Psychiatry, Department of Clinical Sciences Lund, Lund UniversityDepartment of Psychiatry, Division of Behavioral Medicine, Columbia University Medical CenterJames J. Peters VA Medical CenterDepartment of Biochemistry and Biophysics, University of CaliforniaDepartment of Psychiatry and Behavioral Sciences and Weill Institute for Neurosciences, University of CaliforniaDepartment of Psychiatry and Behavioral Sciences and Weill Institute for Neurosciences, University of CaliforniaIntegrative Systems Biology, US Army Medical Research and Materiel Command, USACEHR, Fort DetrickIntegrative Systems Biology, US Army Medical Research and Materiel Command, USACEHR, Fort DetrickHarvard John A. Paulson School of Engineering and Applied Sciences, Harvard UniversityDepartment of Psychiatry, New York University Grossman School of MedicineIntegrative Systems Biology, US Army Medical Research and Materiel Command, USACEHR, Fort DetrickJames J. Peters VA Medical CenterDepartment of Psychiatry and Behavioral Sciences and Weill Institute for Neurosciences, University of CaliforniaDepartment of Obstetrics, Gynecology, & Reproductive Sciences, University of CaliforniaAbstract Circulating cell-free mitochondrial DNA (ccf-mtDNA) is a biomarker of cellular injury or cellular stress and is a potential novel biomarker of psychological stress and of various brain, somatic, and psychiatric disorders. No studies have yet analyzed ccf-mtDNA levels in post-traumatic stress disorder (PTSD), despite evidence of mitochondrial dysfunction in this condition. In the current study, we compared plasma ccf-mtDNA levels in combat trauma-exposed male veterans with PTSD (n = 111) with those who did not develop PTSD (n = 121) and also investigated the relationship between ccf mt-DNA levels and glucocorticoid sensitivity. In unadjusted analyses, ccf-mtDNA levels did not differ significantly between the PTSD and non-PTSD groups (t = 1.312, p = 0.191, Cohen’s d = 0.172). In a sensitivity analysis excluding participants with diabetes and those using antidepressant medication and controlling for age, the PTSD group had lower ccf-mtDNA levels than did the non-PTSD group (F(1, 179) = 5.971, p = 0.016, partial η 2 = 0.033). Across the entire sample, ccf-mtDNA levels were negatively correlated with post-dexamethasone adrenocorticotropic hormone (ACTH) decline (r = −0.171, p = 0.020) and cortisol decline (r = −0.149, p = 0.034) (viz., greater ACTH and cortisol suppression was associated with lower ccf-mtDNA levels) both with and without controlling for age, antidepressant status and diabetes status. Ccf-mtDNA levels were also significantly positively associated with IC50-DEX (the concentration of dexamethasone at which 50% of lysozyme activity is inhibited), a measure of lymphocyte glucocorticoid sensitivity, after controlling for age, antidepressant status, and diabetes status (β = 0.142, p = 0.038), suggesting that increased lymphocyte glucocorticoid sensitivity is associated with lower ccf-mtDNA levels. Although no overall group differences were found in unadjusted analyses, excluding subjects with diabetes and those taking antidepressants, which may affect ccf-mtDNA levels, as well as controlling for age, revealed decreased ccf-mtDNA levels in PTSD. In both adjusted and unadjusted analyses, low ccf-mtDNA levels were associated with relatively increased glucocorticoid sensitivity, often reported in PTSD, suggesting a link between mitochondrial and glucocorticoid-related abnormalities in PTSD.https://doi.org/10.1038/s41398-023-02721-x |
| spellingShingle | Zachary N. Blalock Gwyneth W. Y Wu Daniel Lindqvist Caroline Trumpff Janine D. Flory Jue Lin Victor I. Reus Ryan Rampersaud Rasha Hammamieh Aarti Gautam SBPBC Francis J. Doyle Charles R. Marmar Marti Jett Rachel Yehuda Owen M. Wolkowitz Synthia H. Mellon Circulating cell-free mitochondrial DNA levels and glucocorticoid sensitivity in a cohort of male veterans with and without combat-related PTSD Translational Psychiatry |
| title | Circulating cell-free mitochondrial DNA levels and glucocorticoid sensitivity in a cohort of male veterans with and without combat-related PTSD |
| title_full | Circulating cell-free mitochondrial DNA levels and glucocorticoid sensitivity in a cohort of male veterans with and without combat-related PTSD |
| title_fullStr | Circulating cell-free mitochondrial DNA levels and glucocorticoid sensitivity in a cohort of male veterans with and without combat-related PTSD |
| title_full_unstemmed | Circulating cell-free mitochondrial DNA levels and glucocorticoid sensitivity in a cohort of male veterans with and without combat-related PTSD |
| title_short | Circulating cell-free mitochondrial DNA levels and glucocorticoid sensitivity in a cohort of male veterans with and without combat-related PTSD |
| title_sort | circulating cell free mitochondrial dna levels and glucocorticoid sensitivity in a cohort of male veterans with and without combat related ptsd |
| url | https://doi.org/10.1038/s41398-023-02721-x |
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