Jeong Hyunjin, Dimick Mikaela K, Sultan Alysha, Duong Angela, Park Sarah Sohyun, El Soufi El Sabbagh Dana, Goldstein Benjamin I, Andreazza Ana C
Department of Pharmacology and Toxicology, Faculty of Medicine, University of Toronto, Toronto, Canada; Centre for Addiction and Mental Health, Toronto, Canada.
Department of Pharmacology and Toxicology, Faculty of Medicine, University of Toronto, Toronto, Canada; Centre for Youth Bipolar Disorder, Sunnybrook Health Sciences Centre, Toronto, Canada.
J Psychiatr Res. 2020 Apr;123:187-193. doi: 10.1016/j.jpsychires.2020.02.009. Epub 2020 Feb 10.
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.
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).
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.
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.
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.
线粒体功能障碍与双相情感障碍（BD）的病理生理学有关。线粒体氧化磷酸化受阻会导致向无氧呼吸和乳酸生成的转变。BD成年患者中枢神经系统乳酸水平升高表明有必要对外周样本以及BD病程早期的乳酸进行评估。此外，最近有大量研究将循环游离线粒体DNA（ccf-mtDNA）视为一种潜在的生物标志物，因为它们在生理应激、细胞凋亡或生物能量受损时从细胞中释放出来。
比较BD青少年与健康对照青少年（HC）中乳酸和ccf-mtDNA这两种评估线粒体健康和功能的不同方法。
纳入105名青少年（n = 64名BD患者，n = 41名HC）。使用市售比色试剂盒测量血清乳酸水平。使用定量聚合酶链反应从通过市售旋转柱纯化的ccfDNA中测量血清ccf-mtDNA浓度。使用半结构化访谈评估诊断和情绪症状。
BD青少年的血清乳酸水平（1.319±0.444 nmol/uL）高于HC（1.168±0.353 nmol/uL；p = 0.043），但ccf-mtDNA水平无差异。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显著性。在整个样本中，乳酸与ccf-mtDNA呈正相关（ρ = 0.201；p = 0.043）。按诊断进行检查时，这种关联在BD患者中仍然存在（ρ = 0.273；p = 0.032），但在HC中不存在。
这些初步结果表明，即使在BD病程早期的青少年中也观察到乳酸水平升高，乳酸与ccf-mtDNA之间的关联似乎是BD特有的，并且ccf-mtDNA可能与青少年BD的抑郁症状有关。此外，用于治疗BD的精神药物对外周乳酸和ccf-mtDNA的影响需要进一步研究。
