Circulating Cell-Free Mitochondrial DNA and Depressive Symptoms Among Low-Active Adults Who Smoke

Psychosom Med. 2024 Jan 1;86(1):37-43. doi: 10.1097/PSY.0000000000001254. Epub 2023 Sep 29.

Abstract

Objectives: Mitochondrial dysfunction is implicated in the pathophysiology of psychiatric disorders. Levels of circulating cell-free mitochondrial DNA (cf-mtDNA) are observed to be altered in depression. However, the few studies that have measured cf-mtDNA in depression have reported conflicting findings. This study examined cf-mtDNA and depressive symptoms in low-active adults who smoke.

Methods: Participants were adults 18 to 65 years old ( N = 109; 76% female) with low baseline physical activity and depressive symptoms recruited for a smoking cessation study. Self-report measures assessed depression severity, positive and negative affect, and behavioral activation. Blood was collected and analyzed for cf-mtDNA. Relationships between depressive symptoms and cf-mtDNA were examined with correlations and linear regression.

Results: Levels of cf-mtDNA were associated with categorically defined depression (Center for Epidemiologic Studies Depression Scale score >15), lower positive affect, and decreased behavioral activation ( p < .05). Relationships remained significant after adjustment for age, sex, and nicotine dependence. In a linear regression model including all depressive symptom measures as predictors, Center for Epidemiologic Studies Depression Scale group and lower positive affect remained significant.

Conclusions: This work suggests that mitochondrial changes are associated with depressive symptoms in low-active adults who smoke. Higher levels of cf-mtDNA in association with depression and with lower positive affect and decreased behavioral activation are consistent with a possible role for mitochondrial function in depressive symptoms.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Cell-Free Nucleic Acids*
  • DNA, Mitochondrial / genetics
  • Depression / complications
  • Female
  • Humans
  • Male
  • Middle Aged
  • Mitochondria
  • Smoking
  • Tobacco Use Disorder*
  • Young Adult

Substances

  • DNA, Mitochondrial
  • Cell-Free Nucleic Acids