Mitochondrial Complex I Deficiency in Schizophrenia and Bipolar Disorder and Medication Influence.
Mitochondrial Complex I Deficiency in Schizophrenia and Bipolar Disorder and Medication Influence.
复制标题
DOI：
10.1159/000484348
复制
发表时间：
2018-02-01
期刊：
影响因子：
--
通讯作者：
Vawter, Marquis P
中科院分区：
文献类型：
--
作者：
Rollins, Brandi L;Morgan, Ling;Vawter, Marquis P
患有精神分裂症（SZ）和双相情感障碍（BD）的受试者显示线粒体复合物I的蛋白质和转录物水平降低。体外结果表明，抗精神病药物和抗抑郁药物可能是负责。我们测量了BD、SZ和对照组中复合物I的活性，以及抗精神病和抗抑郁药物、线粒体DNA（mtDNA）拷贝数和脑中mtDNA“常见缺失”的存在。与对照组相比，SZ的前额叶皮层复合物I活性降低了45%（p = 0.02），而BD无显著差异。与未检测到水平的合并病例相比，合并病例（SZ和BD）中可检测到精神药物和药物的复合物I活性显著降低（p = 0.01）。与发病年龄为成年的受试者相比，发病年龄为青少年且服用精神药物的受试者的复合物I活性降低（p < 0.05）。与对照组相比，SZ组和BD组的mtDNA拷贝数均显著增加（p < 0.05）;然而，共同缺失负荷没有改变。SZ脑组织中发现复合物I缺乏，精神药物可能在线粒体功能障碍中发挥作用。需要对无药物治疗的首发精神病患者进行研究，以阐明线粒体病理生理学是否独立于药物作用而发生。
Subjects with schizophrenia (SZ) and bipolar disorder (BD) show decreased protein and transcript levels for mitochondrial complex I. In vitro results suggest antipsychotic and antidepressant drugs may be responsible. We measured complex I activity in BD, SZ, and controls and presence of antipsychotic and antidepressant medications, mitochondrial DNA (mtDNA) copy number, and the mtDNA "common deletion" in the brain. Complex I activity in the prefrontal cortex was decreased by 45% in SZ compared to controls (p = 0.02), while no significant difference was found in BD. Complex I activity was significantly decreased (p = 0.01) in pooled cases (SZ and BD) that had detectable psychotropic medications and drugs compared to pooled cases with no detectable levels. Subjects with age at onset in their teens and psychotropic medications showed decreased (p < 0.05) complex I activity compared to subjects with an adult age at onset. Both SZ and BD groups displayed significant increases (p < 0.05) in mtDNA copy number compared to controls; however, common deletion burden was not altered. Complex I deficiency is found in SZ brain tissue, and psychotropic medications may play a role in mitochondrial dysfunction. Studies of medication-free first-episode psychosis patients are needed to elucidate whether mitochondrial pathophysiology occurs independent of medication effects.