Alterations of cellular aging markers in obsessive– compulsive disorder: mitochondrial DNA copy number and telomere length

Alterations of cellular aging markers in obsessive– compulsive disorder: mitochondrial DNA copy number and telomere length

J Psychiatry Neurosci 2021;46(4):E451-E458 | PDF

Jee In Kang, MD, PhD; Chun Il Park, MD; Jue Lin, PhD; Shin Tae Kim, MD; Hae Won Kim, MD, PhD; Se Joo Kim, MD, PhD

Background: The present study examined whether mitochondrial DNA copy number (mtDNAcn) and telomere length — key markers of cellular aging — were altered in male and female participants with obsessive–compulsive disorder (OCD) compared to healthy controls. We also tested for associations between these alterations and OCD-related clinical features and inflammatory index.

Methods: A total of 235 patients with OCD (38.7% female) and 234 healthy controls (41.5% female) were included. We quantified whole-blood mtDNAcn and leukocyte telomere length using quantitative polymerase chain reaction. We also calculated the neutrophil-to-lymphocyte ratio from complete blood cell counts.

Results: Multivariate analysis of covariance showed that OCD status had a significant overall effect on cellular aging markers in men (Wilks λ = 0.889, F2,275 = 17.13, p < 0.001) and women (Wilks λ = 0.742, F2,182 = 31.61, p < 0.001) after controlling for age, body mass index and childhood trauma. In post-hoc comparisons, men with OCD had lower mtDNAcn than controls (p < 0.001), but we found no between-group difference for telomere length (p = 0.55). Women with OCD had a significantly lower mtDNAcn (p < 0.001) and shortened telomere length (p = 0.023) compared to controls. Moreover, the lower mtDNAcn shown in the OCD group was significantly correlated with an increase in systemic inflammation for both sexes, as measured by neutrophil-to-lymphocyte ratio.

Limitations: The present cross‐sectional design did not allow us to infer a causal relationship between OCD disease status and cellular aging markers.

Conclusion: The present study is, to our knowledge, the first to demonstrate alterations in mtDNAcn and telomere shortening in OCD. These results suggest that aging-associated molecular mechanisms may be important in the pathophysiology of OCD.

Submitted Dec. 23, 2020; Revised Feb. 26, 2021; Accepted Mar. 17, 2021

Affiliations: From the Department of Psychiatry and Institute of Behavioural Science in Medicine, Yonsei University College of Medicine, Seoul, South Korea (Kang, S.-T. Kim, S.-J. Kim); the Department of Psychiatry, CHA Bundang Medical Centre, CHA University, Seongnam, Republic of Korea (Park); the Department of Biochemistry and Biophysics, UCSF School of Medicine, San Francisco, CA, USA (Lin); and the Department of Medical Education, Yonsei University College of Medicine, Seoul, South Korea (H.-W. Kim).

Funding: This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (NRF‐2018R1A2B2007714 and NRF-2019R1A2C1084611). The funding source did not influence the study design, data collection, analysis and interpretation of data, writing of the report or the decision to submit the article for publication.

Competing interests: None declared.

Contributors: J.-I. Kang and S.-J. Kim designed the study. C.-I. Park and S.-J. Kim acquired the data, which J. Lin, S.-T. Kim, H.-W. Kim and S.-J. Kim analyzed. J.-I. Kang wrote the article, which C.-I. Park, J. Lin, S.-T. Kim, H.-W. Kim and S.-J. Kim reviewed. All authors approved the final version to be published and can certify that no other individuals not listed as authors have made substantial contributions to the paper.

Content licence: This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BYNC-ND 4.0) licence, which permits use, distribution and reproduction in any medium, provided that the original publication is properly cited, the use is non-commercial (i.e. research or educational use), and no modifications or adaptations are made. See:

DOI: 10.1503/jpn.200238

Correspondence to: S. J. Kim, Department of Psychiatry, Yonsei University College of Medicine, Yonsei-ro 50-1, Seodaemun-gu, Seoul, South Korea, 03722;