Associations of circulating cell-free DNA, C-reactive protein, and cardiometabolic risk among low-active smokers with elevated depressive symptoms

Teresa E Daniels; Emily K Zitkovsky; Zachary J Kunicki; Destiny J Price; Abigail L Peterson; Phyllis A Dennery; Hung-Teh Kao; Lawrence H Price; Audrey R Tyrka; Ana M Abrantes

doi:10.1016/j.bbih.2022.100519

Associations of circulating cell-free DNA, C-reactive protein, and cardiometabolic risk among low-active smokers with elevated depressive symptoms

Brain Behav Immun Health. 2022 Sep 19:25:100519. doi: 10.1016/j.bbih.2022.100519. eCollection 2022 Nov.

Authors

Teresa E Daniels^{1

2

3}, Emily K Zitkovsky^{1

4}, Zachary J Kunicki², Destiny J Price⁵, Abigail L Peterson⁶, Phyllis A Dennery^{6

7}, Hung-Teh Kao², Lawrence H Price^{1

2}, Audrey R Tyrka^{1

2

3}, Ana M Abrantes^{2

8}

Affiliations

¹ Mood Disorders Research Program and Laboratory for Clinical and Translational, Neuroscience, Butler Hospital, 345 Blackstone Boulevard, Providence, RI, 02906, USA.
² Department of Psychiatry and Human Behavior, Warren Alpert Medical School of Brown University, 345 Blackstone Boulevard, Providence, RI, 02906, USA.
³ Initiative on Stress, Trauma, and Resilience (STAR), Department of Psychiatry and Human Behavior, Warren Alpert Medical School, Brown University, Providence, RI, USA.
⁴ Warren Alpert Medical School of Brown University, Providence, RI, USA.
⁵ Department of Psychiatry, New York State Psychiatric Institute and Columbia University Irving Medical Center, 1051 Riverside Dr, New York, NY, 10032, USA.
⁶ Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, RI, USA.
⁷ Department of Pediatrics, Warren Alpert Medical School of Brown University, 593 Eddy St, Providence, RI, 02903, USA.
⁸ Behavioral Medicine and Addictions Research Department, Butler Hospital, 345 Blackstone Boulevard, Providence, RI, 02906, USA.

Abstract

Background and aims: Cell-free DNA (cfDNA) is elevated in several disease states. Metabolic syndrome is a constellation of factors associated with poor cardiometabolic outcomes. This study examined associations of cfDNA from the nucleus (cf-nDNA) and mitochondria (cf-mtDNA), C-reactive protein (CRP), and metabolic syndrome risk, in low-active smokers with depressive symptoms.

Methods: Participants (N = 109; mean age 47) self-reported medical history. Physical activity was determined by accelerometry and anthropometrics were measured. Blood was collected and analyzed for cf-nDNA, cf-mtDNA, CRP, triglycerides, high-density lipoprotein, hemoglobin A1c. A continuous metabolic syndrome composite risk score was calculated. Relationships of cf-nDNA, cf-mtDNA, CRP, and cardiometabolic risk were examined with correlations and linear regression.

Results: CRP and cf-nDNA were significantly associated with metabolic syndrome risk (r = .39 and r = .31, respectively), cf-mtDNA was not (r = .01). In a linear regression, CRP and cf-nDNA significantly predicted the metabolic syndrome risk score, findings that remained significant controlling for age, gender, nicotine dependence, and physical activity.

Conclusions: Associations of cf-nDNA with both CRP and metabolic risk suggest a role for cf-nDNA in inflammatory processes associated with metabolic syndrome. The negative findings for cf-mtDNA suggest distinct roles for cf-nDNA and cf-mtDNA in these processes.

Keywords: C-reactive protein; CES-D, Center for Epidemiologic Studies Depression Scale; Cardiometabolic risk; Cell-free DNA; DAMP, damage-associated molecular pattern; FTND, Fagerström Test for Nicotine Dependence; Inflammation; Metabolic syndrome; NET, neutrophil extracellular trap; cf-mtDNA, cell-free mitochondrial DNA; cf-nDNA, cell-free nuclear DNA; cfDNA, cell-free DNA.

Abstract

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