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Circulating cell-fr...
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Blalock, Zachary N.University of California, San Francisco
(author)
Circulating cell-free mitochondrial DNA levels and glucocorticoid sensitivity in a cohort of male veterans with and without combat-related PTSD
- Article/chapterEnglish2024
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LIBRIS-ID:oai:lup.lub.lu.se:07137567-e5b3-40ec-9de7-921c46ceb269
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https://lup.lub.lu.se/record/07137567-e5b3-40ec-9de7-921c46ceb269URI
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https://doi.org/10.1038/s41398-023-02721-xDOI
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Language:English
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Summary in:English
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Subject category:art swepub-publicationtype
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Subject category:ref swepub-contenttype
Notes
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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.
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Wu, Gwyneth W.Y.University of California, San Francisco
(author)
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Lindqvist, DanielLund University,Lunds universitet,Psykiatri, Lund,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,LU profilområde: Proaktivt åldrande,Lunds universitets profilområden,Psychiatry (Lund),Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine,LU Profile Area: Proactive Ageing,Lund University Profile areas(Swepub:lu)med-del
(author)
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Trumpff, CarolineColumbia University
(author)
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Flory, Janine D.Icahn School of Medicine at Mount Sinai,Veterans Health Administration
(author)
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Lin, JueUniversity of California, San Francisco
(author)
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Reus, Victor I.University of California, San Francisco
(author)
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Rampersaud, RyanUniversity of California, San Francisco
(author)
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Hammamieh, RashaUS Army Medical Research and Materiel Command
(author)
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Gautam, AartiUS Army Medical Research and Materiel Command
(author)
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Ressler, Kerry J.Harvard Medical School
(author)
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Yang, RuotingUS Army Medical Research and Materiel Command
(author)
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Muhie, SeidUS Army Medical Research and Materiel Command
(author)
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Daigle, Bernie J.University of Memphis
(author)
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Bierer, Linda M.Icahn School of Medicine at Mount Sinai,Veterans Health Administration
(author)
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Hood, LeroyInstitute for Systems Biology, Seattle
(author)
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Wang, KaiInstitute for Systems Biology, Seattle
(author)
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Lee, InyoulInstitute for Systems Biology, Seattle
(author)
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Dean, Kelsey R.Harvard John A. Paulson School of Engineering and Applied Sciences
(author)
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Somvanshi, Pramod R.Harvard John A. Paulson School of Engineering and Applied Sciences
(author)
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Doyle, Francis J.Harvard John A. Paulson School of Engineering and Applied Sciences
(author)
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Marmar, Charles R.NYU Grossman School of Medicine
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Jett, MartiUS Army Medical Research and Materiel Command
(author)
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Yehuda, RachelVeterans Health Administration,Icahn School of Medicine at Mount Sinai
(author)
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Wolkowitz, Owen M.University of California, San Francisco(Swepub:lu)ow2624wo
(author)
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Mellon, Synthia H.University of California, San Francisco
(author)
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University of California, San FranciscoPsykiatri, Lund
(creator_code:org_t)
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In:Translational Psychiatry14:12158-3188
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Blalock, Zachary ...
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Wu, Gwyneth W.Y.
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Lindqvist, Danie ...
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Trumpff, Carolin ...
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Flory, Janine D.
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Lin, Jue
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Reus, Victor I.
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Rampersaud, Ryan
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Hammamieh, Rasha
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Gautam, Aarti
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Ressler, Kerry J ...
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Yang, Ruoting
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Muhie, Seid
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Daigle, Bernie J ...
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Bierer, Linda M.
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Hood, Leroy
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Wang, Kai
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Lee, Inyoul
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Dean, Kelsey R.
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Somvanshi, Pramo ...
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Doyle, Francis J ...
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Marmar, Charles ...
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