The somatic common deletion in mitochondrial DNA is decreased in schizophrenia.
The somatic common deletion in mitochondrial DNA is decreased in schizophrenia.
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DOI：
10.1016/j.schres.2014.08.026
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发表时间：
2014-11
影响因子：
4.5
通讯作者：
Vawter, Marquis P.
中科院分区：
文献类型：
--
作者：
Mamdani, Firoza;Rollins, Brandi;Morgan, Ling;Sequeira, P. Adolfo;Vawter, Marquis P.
线粒体DNA(MtDNA)的大量缺失可在氧化应激过程中发生或由氧化应激引起，导致恶性循环，增加活性氧物种(ROS)的损伤，降低线粒体功能，从而导致进一步的氧化应激。本研究的目的是确定与对照组相比，重度抑郁障碍(MDD)、双相情感障碍(BD)和精神分裂症(SZ)患者的体细胞mtDNA共同缺失(4977bp)在疾病特异性脑中是否存在差异。10个脑区(前扣带回皮质、杏仁核、尾状核、背外侧前额叶皮质、海马体、伏隔核、眶前叶皮质、壳核、黑质和丘脑)的mtDNA共同缺失的累积通过定量分析来测量。如前所述，mtDNA缺失与年龄的相关性在不同脑区之间高度显著。在校正了年龄、pH、PMI和性别后，与MDD、BD和对照组相比，SZ受试者中共同缺失的整体累积显著减少。SZ在多巴胺能区的下降幅度最大。抗精神病药物对线粒体的一个潜在副作用是线粒体功能受损，这可能解释了这些发现。脑线粒体DNA共同缺失水平的降低表明，线粒体功能受损，可能是精神分裂症患者整体线粒体功能障碍特征的一部分。
Large deletions in mitochondrial DNA (mtDNA) can occur during or result from oxidative stress leading to a vicious cycle that increases reactive oxygen species (ROS) damage, decreases mitochondrial function, thereby causing further oxidative stress. The objective of this study was to determine if disease specific brain differences of the somatic mtDNA common deletion (4,977 bp) could be observed in major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SZ) compared to a control group. The accumulation of the mtDNA common deletion was measured using a quantitative assay across 10 brain regions (anterior cingulate cortex, amygdala, caudate nucleus, dorsolateral prefrontal cortex, hippocampus, nucleus accumbens, orbitofrontal cortex, putamen, substantia nigra, and thalamus). The correlation with age of the mtDNA deletion was highly significant across brain regions as previously shown. A significant decrease in the global accumulation of common deletion in subjects with SZ compared to MDD, BD, and controls was observed after correcting for age, pH, PMI, and gender. The decreases in SZ were largest in dopaminergic regions. One potential side effect of antipsychotic drugs on mitochondria is the impairment of mitochondria function, which might explain these findings. The decreased global brain mtDNA common deletion levels suggests that mitochondrial function is impaired and might be part of an overall mitochondria dysfunction signature in subjects with schizophrenia.
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发表时间：
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