Differences in cognitive impairment and its correlation with circulating cell-free mitochondrial DNA in medication-free depression and bipolar depression patients

Objective: This study aimed to investigate whether there are differences in cognitive impairment between medication-free patients with bipolar depression (BD) and major depressive disorder (MDD) and whether these differences are related to circulating cell-free mtDNA (ccf-mtDNA).

Methods: For this cross-sectional study, 76 outpatients with BD, 86 outpatients with MDD and 70 healthy controls (HCs) were enrolled. Sociodemographic and clinical data were collected. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and the Stroop Color-Word Test were used to assess cognitive function. Plasma ccf-mtDNA levels were measured via qPCR.

Results: BD and MDD patients had similar scores for immediate memory, language, attention, delayed memory, the RBANS total score, Stroop color, Stroop word, and Stroop total score, which were significantly lower than the HCs. The visuospatial/constructive scores of the BD patients were significantly lower than those of the HCs (p < 0.001) and MDD patients (p = 0.008), but there was no difference between the HCs and MDD patients. The ccf-mtDNA levels in the BD and MDD patient groups were significantly higher than those in the HC group, and those in the MDD group were higher than those in the BD group (p = 0.016). Multiple stepwise regression analysis showed that ccf-mtDNA was negatively correlated with language in patients with depression (t = -2.11, p = 0.039).

Conclusion: There were differences in specific cognitive dimensions between patients with BD and MDD. Increased ccf-mtDNA levels were found in BD and MDD patients, suggesting ccf-mtDNA may be involved in the pathophysiology of MDD and BD.