Zakaria Almuwaqqat1, Matthew T Wittbrodt2, Kasra Moazzami1, Jonathan A Nye3, Bruno B Lima4, Amit J Shah5, Jamil Alkhalaf6, Brad Pearce6, Yan V Sun6, Arshed A Quyyumi4, Viola Vaccarino1, J Douglas Bremner7. 1. Department of Medicine, Division of Cardiology, Emory University School of Medicine, Atlanta, GA, United States of America; Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, United States of America. 2. Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, United States of America. 3. Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA, United States of America. 4. Department of Medicine, Division of Cardiology, Emory University School of Medicine, Atlanta, GA, United States of America. 5. Department of Medicine, Division of Cardiology, Emory University School of Medicine, Atlanta, GA, United States of America; Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, United States of America; Atlanta VA Medical Center, Decatur, Georgia. 6. Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, United States of America. 7. Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, United States of America; Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA, United States of America; Atlanta VA Medical Center, Decatur, Georgia. Electronic address: jdbremn@emory.edu.
Abstract
BACKGROUND: Accelerated biological aging, as indicated by telomere shortening, is associated with CAD pathogenesis. In a cross-sectional study, we investigated neural correlates of acute psychological stress and short telomeres in patients with CAD. METHODS: Individuals with CAD (N = 168) underwent a validated mental stress protocol including public speaking and mental arithmetic. Imaging of the brain with [O-15] water and high-resolution positron emission tomography (HR-PET) was performed during mental stress and control conditions. Blood flow during stressful tasks (average of speech and arithmetic) and control tasks were assessed. Telomere length in peripheral leucocytes was measured by quantitative polymerase chain reaction and expressed as Telomere/Single Copy Gene (T/S) ratio. Voxel-wise regression models were constructed to assess the association between brain areas and activity during rest and mental stress after adjustments for demographic factors and clinical characteristics. RESULTS: The mean (SD) age of the sample was 62 (8) years, and 69% were men. Increased activation with mental stress in the lingual gyrus, cerebellum and superior and inferior frontal gyri were associated with reduced telomere length; 1.6 higher voxel activation of these areas was associated with 0.1 T/S-units reduction in telomere length (P < 0.005). Additionally, during neutral counting and speaking tasks, brain activity in the precentral, middle and superior frontal and middle temporal gyri was inversely associated with telomere length. Results remained consistent after adjustment for demographic and clinical risk factors. CONCLUSION: Increased stress-induced activity in brain areas mediating the stress response was associated with shortened telomere length in CAD patients.
BACKGROUND: Accelerated biological aging, as indicated by telomere shortening, is associated with CAD pathogenesis. In a cross-sectional study, we investigated neural correlates of acute psychological stress and short telomeres in patients with CAD. METHODS: Individuals with CAD (N = 168) underwent a validated mental stress protocol including public speaking and mental arithmetic. Imaging of the brain with [O-15] water and high-resolution positron emission tomography (HR-PET) was performed during mental stress and control conditions. Blood flow during stressful tasks (average of speech and arithmetic) and control tasks were assessed. Telomere length in peripheral leucocytes was measured by quantitative polymerase chain reaction and expressed as Telomere/Single Copy Gene (T/S) ratio. Voxel-wise regression models were constructed to assess the association between brain areas and activity during rest and mental stress after adjustments for demographic factors and clinical characteristics. RESULTS: The mean (SD) age of the sample was 62 (8) years, and 69% were men. Increased activation with mental stress in the lingual gyrus, cerebellum and superior and inferior frontal gyri were associated with reduced telomere length; 1.6 higher voxel activation of these areas was associated with 0.1 T/S-units reduction in telomere length (P < 0.005). Additionally, during neutral counting and speaking tasks, brain activity in the precentral, middle and superior frontal and middle temporal gyri was inversely associated with telomere length. Results remained consistent after adjustment for demographic and clinical risk factors. CONCLUSION: Increased stress-induced activity in brain areas mediating the stress response was associated with shortened telomere length in CAD patients.
Authors: Adam M Staffaroni; Duygu Tosun; Jue Lin; Fanny M Elahi; Kaitlin B Casaletto; Matthew J Wynn; Nihar Patel; John Neuhaus; Samantha M Walters; Elissa S Epel; Elizabeth H Blackburn; Joel H Kramer Journal: Neurobiol Aging Date: 2018-05-08 Impact factor: 4.673
Authors: J Douglas Bremner; Carolina Campanella; Zehra Khan; Majid Shah; Muhammad Hammadah; Kobina Wilmot; Ibhar Al Mheid; Bruno B Lima; Ernest V Garcia; Jonathon Nye; Laura Ward; Michael H Kutner; Paolo Raggi; Brad D Pearce; Amit J Shah; Arshed A Quyyumi; Viola Vaccarino Journal: Psychosom Med Date: 2018 Jul/Aug Impact factor: 4.312
Authors: Jason J Radley; Anne B Rocher; Melinda Miller; William G M Janssen; Conor Liston; Patrick R Hof; Bruce S McEwen; John H Morrison Journal: Cereb Cortex Date: 2005-05-18 Impact factor: 5.357
Authors: Lawrence H Price; Hung-Teh Kao; Darcy E Burgers; Linda L Carpenter; Audrey R Tyrka Journal: Biol Psychiatry Date: 2012-07-24 Impact factor: 13.382
Authors: Ahmed Tawakol; Michael T Osborne; Ying Wang; Basma Hammed; Brian Tung; Tomas Patrich; Blake Oberfeld; Amorina Ishai; Lisa M Shin; Matthias Nahrendorf; Erica T Warner; Jason Wasfy; Zahi A Fayad; Karestan Koenen; Paul M Ridker; Roger K Pitman; Katrina A Armstrong Journal: J Am Coll Cardiol Date: 2019-07-02 Impact factor: 24.094
Authors: Andrew Steptoe; Mark Hamer; Lee Butcher; Jue Lin; Lena Brydon; Mika Kivimäki; Michael Marmot; Elizabeth Blackburn; Jorge D Erusalimsky Journal: Brain Behav Immun Date: 2011-04-23 Impact factor: 7.217
Authors: S Hägg; Y Zhan; R Karlsson; L Gerritsen; A Ploner; S J van der Lee; L Broer; J Deelen; R E Marioni; A Wong; A Lundquist; G Zhu; N K Hansell; E Sillanpää; I O Fedko; N A Amin; M Beekman; A J M de Craen; S Degerman; S E Harris; K-J Kan; C M Martin-Ruiz; G W Montgomery; A N Adolfsson; C A Reynolds; N J Samani; H E D Suchiman; A Viljanen; T von Zglinicki; M J Wright; J-J Hottenga; D I Boomsma; T Rantanen; J A Kaprio; D R Nyholt; N G Martin; L Nyberg; R Adolfsson; D Kuh; J M Starr; I J Deary; P E Slagboom; C M van Duijn; V Codd; N L Pedersen Journal: Transl Psychiatry Date: 2017-04-18 Impact factor: 6.222