Tsai Tsung Han, Wu Cheng Ying, Chang Cheng Chen, Lin Ta Tsung, Liu Chin San, Chen Po See
Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
School of Medicine, Chung Shan Medical University, Taichung, Taiwan.
Kaohsiung J Med Sci. 2025 Jan;41(1):e12914. doi: 10.1002/kjm2.12914. Epub 2024 Nov 23.
Persistent cognitive challenges in bipolar disorder (BD) may be tied to insulin resistance, which crucially affects both metabolism and brain health. Additionally, mitochondrial DNA (mtDNA) copy number has emerged as an indicator of cognitive performance and response to treatment in BD. However, it remains unclear whether and how this indicator might serve as a bridge between metabolic dysfunction and cognitive capacity. In 68 study participants with euthymic BD, insulin resistance was assessed according to fasting glucose and insulin levels. mtDNA copy number was quantified from leukocytes, and executive function was measured with the Wisconsin card-sorting test (WCST). Mediation models were applied to explore the statistical relationship between insulin resistance, mtDNA copy number, and executive function. Both linear regression and Poisson distribution approaches with robust bootstrap simulations were used for significance testing. The results indicated that insulin resistance indirectly affects executive function via mtDNA copy number. This mediation relationship was statistically significant for both preservation errors and completion of categories in the WCST, although there were no significant direct effects of insulin resistance on the executive functions. We therefore concluded that insulin resistance is associated with reduced mtDNA copy number in blood, which may negatively impact executive functions in patients with euthymic BD. Further work is warranted to determine if improving metabolic and mitochondrial health may lead to better cognitive outcomes in BD.
双相情感障碍（BD）中持续存在的认知挑战可能与胰岛素抵抗有关，胰岛素抵抗对代谢和大脑健康都有着至关重要的影响。此外，线粒体DNA（mtDNA）拷贝数已成为BD患者认知表现和治疗反应的一个指标。然而，该指标是否以及如何在代谢功能障碍和认知能力之间架起一座桥梁仍不清楚。在68名处于心境正常的BD研究参与者中，根据空腹血糖和胰岛素水平评估胰岛素抵抗。从白细胞中定量mtDNA拷贝数，并用威斯康星卡片分类测验（WCST）测量执行功能。应用中介模型来探索胰岛素抵抗、mtDNA拷贝数和执行功能之间的统计关系。采用线性回归和泊松分布方法以及稳健的自助模拟进行显著性检验。结果表明，胰岛素抵抗通过mtDNA拷贝数间接影响执行功能。尽管胰岛素抵抗对执行功能没有显著的直接影响，但这种中介关系在WCST中的保持错误和分类完成方面均具有统计学意义。因此，我们得出结论，胰岛素抵抗与血液中mtDNA拷贝数减少有关，这可能会对心境正常的BD患者的执行功能产生负面影响。有必要进一步开展研究，以确定改善代谢和线粒体健康是否会使BD患者获得更好的认知结果。
