BACKGROUND Mitochondrial dysfunction has been implicated in the pathophysiology of bipolar disorder (BD). Impediment of mitochondrial oxidative phosphorylation results in a shift toward anaerobic respiration and lactate production. Elevated CNS lactate levels in adults with BD inform the need to evaluate lactate in peripheral samples and early in the course of BD. Furthermore, there exists a recent surge of investigations looking at circulating cell-free mitochondrial DNA (ccf-mtDNA) as a potential biomarker as they are released from cells under physiological stress, apoptosis, or bioenergetic compromise. OBJECTIVES To compare lactate and ccf-mtDNA, two different ways in assessing the mitochondrial health and function, in adolescents with BD versus healthy control adolescents (HC). METHODS One-hundred and five adolescents (n = 64 BD, n = 41 HC) were included. Serum lactate level was measured using a commercially available colorimetric kit. Serum ccf-mtDNA concentration was measured using quantitative polymerase chain reaction from ccfDNA purified by commercially available spin columns. Diagnosis and mood symptoms were evaluated using semi-structured interviews. RESULTS There is an increase in serum lactate level of adolescents with BD (1.319 ± 0.444 nmol/uL) versus HC (1.168 ± 0.353 nmol/uL; p = 0.043), but not ccf-mtDNA. Among BD adolescents, depression symptoms were negatively correlated with ccf-mtDNA levels (ρ = -0.289; p = 0.038) but loses significance when corrected for multiple comparison. Lactate was positively correlated with ccf-mtDNA in the overall sample (ρ = 0.201; p = 0.043). When examined by diagnosis, this association remained in BD (ρ = 0.273; p = 0.032), but not HC. CONCLUSION These preliminary results indicate that elevated lactate is observed even among adolescents early in their course of BD, that the association between lactate and ccf-mtDNA appears to be specific to BD, and that ccf-mtDNA is potentially associated with depression symptoms in adolescent BD. In addition, the effect of psychotropic medications used in the treatment of BD on peripheral lactate and ccf-mtDNA requires further investigation.

中文翻译：

---

患有双相情感障碍的青少年线粒体功能障碍的外周生物标志物。

背景技术线粒体功能障碍已经牵涉到躁郁症（BD）的病理生理中。线粒体氧化磷酸化的障碍导致向厌氧呼吸和乳酸产生的转变。患有BD的成年人中CNS乳酸水平升高，提示需要评估周围样本和BD早期的乳酸。此外，最近有大量研究将循环中的无细胞线粒体DNA（ccf-mtDNA）视为潜在的生物标记，因为它们在生理压力，细胞凋亡或生物能量折衷下从细胞中释放出来。目的比较乳酸和ccf-mtDNA，这是评估BD青春期与健康对照青春期（HC）线粒体健康和功能的两种不同方法。方法一百零五个青少年（n = 64 BD，n = 41 HC）。使用可商购的比色试剂盒测量血清乳酸水平。使用通过市售旋转柱纯化的ccfDNA的定量聚合酶链反应，测量血清ccf-mtDNA的浓度。使用半结构式访谈评估诊断和情绪症状。结果与HC（1.168±0.353 nmol / uL； p = 0.043）相比，BD的青少年血清乳酸水平增加（1.319±0.444 nmol / uL； p = 0.043），而ccf-mtDNA则没有。在BD青少年中，抑郁症状与ccf-mtDNA水平呈负相关（ρ= -0.289； p = 0.038），但在进行多重比较校正后失去了意义。乳酸在整个样本中与ccf-mtDNA正相关（ρ= 0.201； p = 0.043）。当通过诊断检查时，这种关联仍然存在于BD（ρ= 0.273; p = 0.032），但不是HC。结论这些初步结果表明，即使在BD早期的青少年中，乳酸水平也升高，乳酸和ccf-mtDNA之间的联系似乎是BD特有的，而ccf-mtDNA可能与BD青少年抑郁症状相关。此外，用于治疗BD的精神药物对外周乳酸和ccf-mtDNA的作用需要进一步研究。