Institute of Clinical Sciences (ICS), Faculty of Medicine, Imperial College London, London, W12 0NN, UK; Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, De Crespigny Park, London, SE5 8AF, UK.
Institute of Clinical Sciences (ICS), Faculty of Medicine, Imperial College London, London, W12 0NN, UK; Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, De Crespigny Park, London, SE5 8AF, UK; H Lundbeck A/s, 3 Abbey View, Everard Close, St Albans, AL1 2PS, UK.
Neurosci Biobehav Rev. 2022 Jan;132:449-464. doi: 10.1016/j.neubiorev.2021.11.047. Epub 2021 Dec 2.
There has been increasing interest in the role of mitochondrial dysfunction in the pathophysiology of schizophrenia. Mitochondrial complex one (MCI) dysfunction may represent a mechanism linking bioenergetic impairment with the alterations in dopamine signalling, glutamatergic dysfunction, and oxidative stress found in the disorder. New lines of evidence from novel approaches make it timely to review evidence for mitochondrial involvement in schizophrenia, with a specific focus on MCI. The most consistent findings in schizophrenia relative to controls are reductions in expression of MCI subunits in post-mortem brain tissue (Cohen's d> 0.8); reductions in MCI function in post-mortem brains (d> 0.7); and reductions in neural glucose utilisation (d= 0.3 to 0.6). Antipsychotics may affect glucose utilisation, and, at least in vitro, affect MC1. The findings overall are consistent with MCI dysfunction in schizophrenia, but also highlight the need for in vivo studies to determine the link between MCI dysfunction and symptoms in patients. If new imaging tools confirm MCI dysfunction in the disease, this could pave the way for new treatments targeting this enzyme.
人们对线粒体功能障碍在精神分裂症病理生理学中的作用越来越感兴趣。线粒体复合物 1（MCI）功能障碍可能代表了一种将生物能量损伤与多巴胺信号、谷氨酸能功能障碍和该疾病中发现的氧化应激改变联系起来的机制。来自新方法的新证据使得及时审查线粒体参与精神分裂症的证据变得很有必要，特别是关注 MCI。与对照组相比，精神分裂症中最一致的发现是死后脑组织中 MCI 亚基表达减少（Cohen's d > 0.8）；死后大脑中 MCI 功能减少（d > 0.7）；以及神经葡萄糖利用率降低（d= 0.3 至 0.6）。抗精神病药可能会影响葡萄糖利用，并且至少在体外会影响 MC1。这些发现总体上与精神分裂症中的 MCI 功能障碍一致，但也强调需要进行体内研究以确定 MCI 功能障碍与患者症状之间的联系。如果新的成像工具确认该疾病中的 MCI 功能障碍，这可能为针对该酶的新治疗方法铺平道路。
