Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
Department of Pharmacology & Toxicology, University of Toronto, Toronto, Ontario, Canada.
Sci Rep. 2018 Apr 18;8(1):6216. doi: 10.1038/s41598-018-24355-6.
Alterations in mitochondrial function have been implicated in the etiology of schizophrenia. Most studies have investigated alterations in mitochondrial function in patients in which the disorder is already established; however, whether mitochondrial dysfunction predates the onset of psychosis remains unknown. We measured peripheral mitochondrial complex (I-V) function and lactate/pyruvate levels in 27 antipsychotic-naïve individuals at clinical high risk for psychosis (CHR) and 16 healthy controls. We also explored the association between mitochondrial function and brain microglial activation and glutathione levels using a translocator protein 18 kDa [F]FEPPA PET scan and H-MRS scan, respectively. There were no significant differences in mitochondrial complex function and lactate/pyruvate levels between CHR and healthy controls. In the CHR group, mitochondrial complex III function (r = -0.51, p = 0.008) and lactate levels (r = 0.61, p = 0.004) were associated with prodromal negative symptoms. As previously reported, there were no significant differences in microglial activation and glutathione levels between groups, however, mitochondrial complex IV function was inversely related to microglial activation in the hippocampus in CHR (r = -0.42, p = 0.04), but not in healthy controls. In conclusion, alterations in mitochondrial function are not yet evident in CHR, but may relate to the severity of prodromal symptoms, particularly negative symptoms.
线粒体功能的改变与精神分裂症的病因有关。大多数研究都调查了已经患有该疾病的患者中线粒体功能的改变；然而，线粒体功能障碍是否先于精神病发作仍然未知。我们测量了 27 名未经抗精神病药物治疗的处于精神病高危状态（CHR）的个体和 16 名健康对照者的外周线粒体复合物（I-V）功能和乳酸/丙酮酸水平。我们还分别使用转位蛋白 18kDa [F]FEPPA PET 扫描和 H-MRS 扫描，探索了线粒体功能与脑小胶质细胞激活和谷胱甘肽水平之间的关系。CHR 和健康对照组之间线粒体功能复合体和乳酸/丙酮酸水平没有显著差异。在 CHR 组中，线粒体复合物 III 功能（r=-0.51，p=0.008）和乳酸水平（r=0.61，p=0.004）与前驱阴性症状相关。如前所述，两组之间的小胶质细胞激活和谷胱甘肽水平没有显著差异，但是，CHR 中海马体中线粒体复合物 IV 功能与小胶质细胞激活呈负相关（r=-0.42，p=0.04），而在健康对照组中则没有。总之，线粒体功能的改变在 CHR 中尚未显现，但可能与前驱症状的严重程度有关，尤其是阴性症状。
