Saliva cell-free mitochondrial DNA (cf-mtDNA) as a dynamic biomarker of stress and emotion in daily life: Evidence from two independent repeated-measures studies.

The present study analyzes the impact of naturalistic stress and emotions on saliva cell-free mitochondrial DNA (cf-mtDNA) in daily life across two independent cohorts with different temporal resolutions. Study 1 examined the interaction between daily stress and major depressive disorder (MDD) on cf-mtDNA in young adults (n = 18, 8 MDD, 10 controls). Across four days, participants provided 4 saliva samples and nightly stress inventories. Among individuals with MDD, cf-mtDNA concentrations were 68% lower on days with reported stress exposure compared with days without reported stress exposure. Among stress-exposure days, a greater number and higher severity of stressors were associated with 24-27% lower cf-mtDNA concentrations. Study 2 extended this framework by implementing a finer temporal resolution in healthy young adults (n = 25), measuring saliva and momentary affective states with hourly ecological momentary assessments, up to 20 times per day for 2 days. Higher positive affect was associated with higher cf-mtDNA; however, this relationship weakened as negative affect increased. Exploratory analyses of individual emotions showed that cf-mtDNA tended to be higher during positive emotional states and lower during negative emotional states; however, person-specific models indicated that these associations, particularly for happiness and stress, varied substantially across participants. Overall, cf-mtDNA did not exhibit a uniform stress response in daily life; rather, the dynamics were dependent on diagnostic status and stress exposure timing in Study 1, and on momentary emotional context in Study 2. Accordingly, cf-mtDNA should be conceptualized as a dynamic biobehavioral signal rather than a static indicator of between-person differences.