Increased circulating cell-free mitochondrial DNA in plasma of first-diagnosed drug-naïve bipolar disorder patients: A case-control and 4-week follow-up study

Background The study of clinical biological indicators in bipolar disorder (BD) is important. In recent years, basic experiments have associated the pathophysiological mechanism of BD is related to mitochondrial dysfunction, but few clinical studies have confirmed this finding. Object The present study aimed to evaluate whether plasma circulating cell-free mitochondrial DNA (ccf-mtDNA) levels, which can represent the degree of mitochondrial damage in vivo, are altered in patients with BD in early onset and during treatment compared with controls. Method A total of 75 first-diagnosed drug-naive patients with BD and 60 HCs were recruited and followed up for 1 month. The clinical symptoms were assessed using HAMD, HAMA, and YMRS, and ccf-mtDNA levels were measured by qPCR before and after drug treatment in BD. Result (1) The plasma ccf-mtDNA levels in first-diagnosed drug-naive patients with BD increased compared with those in HCs (p = 0.001). (2) Drug treatment for 1 month can decrease the expression of ccf-mtDNA in BD (p < 0.001). (3) No significant correlation was observed between the changes in ccf-mtDNA levels and the improvement of clinical symptoms in BD after drug treatment. Conclusion The plasma ccf-mtDNA level was increased in BD, and decreased after pharmacological treatment. These outcomes suggested that plasma ccf-mtDNA level is likely to be sensitive to the drug response in BD, and mitochondrial pathway is a potential target for further therapy.