Francesco Saverio Bersani1, Claire Morley2, Daniel Lindqvist3, Elissa S Epel4, Martin Picard5, Rachel Yehuda6, Janine Flory6, Linda M Bierer6, Iouri Makotkine6, Duna Abu-Amara7, Michelle Coy2, Victor I Reus2, Jue Lin8, Elizabeth H Blackburn8, Charles Marmar7, Owen M Wolkowitz9, Synthia H Mellon10. 1. Department of Psychiatry, University of California San Francisco, San Francisco, CA, USA; Department of Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy. 2. Department of Psychiatry, University of California San Francisco, San Francisco, CA, USA. 3. Department of Psychiatry, University of California San Francisco, San Francisco, CA, USA; Department of Clinical Sciences, Section for Psychiatry, Lund University, Lund, Sweden. 4. Department of Psychiatry, University of California San Francisco, San Francisco, CA, USA; Center for Health and Community, University of California San Francisco, San Francisco, CA, USA. 5. Center for Mitochondrial and Epigenomic Medicine, The Children's Hospital of Philadelphia and University of Pennsylvania, Philadelphia, PA, USA. 6. Department of Psychiatry, MSSM/James J. Peters Veterans Administration Medical Center, New York, NY, USA. 7. Department of Psychiatry, Steven and Alexandra Cohen Veterans Center for Posttraumatic Stress and Traumatic Brain Injury, New York, NY, USA. 8. Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, CA, USA. 9. Department of Psychiatry, University of California San Francisco, San Francisco, CA, USA. Electronic address: Owen.Wolkowitz@ucsf.edu. 10. Department of OB/GYN and Reproductive Science, University of California San Francisco, San Francisco, CA, USA.
Abstract
INTRODUCTION: Mitochondrial abnormalities may be involved in PTSD, although few studies have examined this. Mitochondrial DNA copy number (mtDNAcn) in blood cells is an emerging systemic index of mitochondrial biogenesis and function. The present study assessed mtDNAcn in male combat-exposed veterans with PTSD compared to those without PTSD as well as its correlation with clinical scales. METHODS: mtDNAcn was assessed with a TaqMan multiplex assay in granulocytes of 43 male combat veterans with (n=43) or without (n=44) PTSD. Twenty of the PTSD subjects had co-morbid major depressive disorder (MDD). The Clinician Administered PTSD Scale (CAPS), the Positive and Negative Affect Schedule (PANAS), the Early Trauma Inventory (ETI) and the Beck Depression Inventory II (BDI-II) were used for the clinical assessments. All analyses were corrected for age and BMI. RESULTS: mtDNAcn was significantly lower in subjects with PTSD (p<0.05). Within the PTSD group, those with moderate PTSD symptom severity had relatively higher mtDNAcn than those with mild or severe symptoms (p<0.01). Within the PTSD group, mtDNAcn was positively correlated with PANAS positive subscale ratings (p<0.01) but was not significantly correlated with PANAS negative subscale, ETI or BDI-II ratings. DISCUSSION: This study provides the first evidence of: (i) a significant decrease of mtDNAcn in combat PTSD, (ii) a possible "inverted-U" shaped relationship between PTSD symptom severity and mtDNAcn within PTSD subjects, and (iii) a direct correlation of mtDNAcn with positive affectivity within PTSD subjects. Altered mtDNAcn in PTSD may reflect impaired energy metabolism, which might represent a novel aspect of its pathophysiology.
INTRODUCTION:Mitochondrial abnormalities may be involved in PTSD, although few studies have examined this. Mitochondrial DNA copy number (mtDNAcn) in blood cells is an emerging systemic index of mitochondrial biogenesis and function. The present study assessed mtDNAcn in male combat-exposed veterans with PTSD compared to those without PTSD as well as its correlation with clinical scales. METHODS: mtDNAcn was assessed with a TaqMan multiplex assay in granulocytes of 43 male combat veterans with (n=43) or without (n=44) PTSD. Twenty of the PTSD subjects had co-morbid major depressive disorder (MDD). The Clinician Administered PTSD Scale (CAPS), the Positive and Negative Affect Schedule (PANAS), the Early Trauma Inventory (ETI) and the Beck Depression Inventory II (BDI-II) were used for the clinical assessments. All analyses were corrected for age and BMI. RESULTS: mtDNAcn was significantly lower in subjects with PTSD (p<0.05). Within the PTSD group, those with moderate PTSD symptom severity had relatively higher mtDNAcn than those with mild or severe symptoms (p<0.01). Within the PTSD group, mtDNAcn was positively correlated with PANAS positive subscale ratings (p<0.01) but was not significantly correlated with PANAS negative subscale, ETI or BDI-II ratings. DISCUSSION: This study provides the first evidence of: (i) a significant decrease of mtDNAcn in combat PTSD, (ii) a possible "inverted-U" shaped relationship between PTSD symptom severity and mtDNAcn within PTSD subjects, and (iii) a direct correlation of mtDNAcn with positive affectivity within PTSD subjects. Altered mtDNAcn in PTSD may reflect impaired energy metabolism, which might represent a novel aspect of its pathophysiology.
Authors: Olga Tymofiyeva; Eva Henje Blom; Tiffany C Ho; Colm G Connolly; Daniel Lindqvist; Owen M Wolkowitz; Jue Lin; Kaja Z LeWinn; Matthew D Sacchet; Laura K M Han; Justin P Yuan; Sarina P Bhandari; Duan Xu; Tony T Yang Journal: J Affect Disord Date: 2018-02-17 Impact factor: 4.839
Authors: F Saverio Bersani; Synthia H Mellon; Daniel Lindqvist; Jee In Kang; Ryan Rampersaud; Pramod Rajaram Somvanshi; Francis J Doyle; Rasha Hammamieh; Marti Jett; Rachel Yehuda; Charles R Marmar; Owen M Wolkowitz Journal: Mil Med Date: 2020-01-07 Impact factor: 1.563
Authors: Kathryn K Ridout; Jesse L Coe; Stephanie H Parade; Carmen J Marsit; Hung-Teh Kao; Barbara Porton; Linda L Carpenter; Lawrence H Price; Audrey R Tyrka Journal: Psychoneuroendocrinology Date: 2020-02-20 Impact factor: 4.905
Authors: Kelly J Brunst; Marco Sanchez-Guerra; Yueh-Hsiu Mathilda Chiu; Ander Wilson; Brent A Coull; Itai Kloog; Joel Schwartz; Kasey J Brennan; Michelle Bosquet Enlow; Robert O Wright; Andrea A Baccarelli; Rosalind J Wright Journal: Environ Int Date: 2017-12-15 Impact factor: 9.621