The Faculty of Health Sciences, Ben-Gurion University of the Negev, Beersheba, Israel.
Department of Physics of Complex Systems, Weizmann Institute of Science, Rehovot, Israel.
World J Biol Psychiatry. 2023 Nov;24(9):829-837. doi: 10.1080/15622975.2023.2211653. Epub 2023 May 31.
Schizophrenia is a chronic, debilitating mental disorder whose pathophysiology is complex and not fully understood. Numerous studies suggest mitochondrial dysfunction may contribute to the development of schizophrenia. While mitochondrial ribosomes (mitoribosomes) are essential for proper mitochondrial functioning, their gene expression levels have not been studied yet in schizophrenia.
We performed a systematic meta-analysis of the expression of 81 mitoribosomes subunits encoding genes, integrating ten brain samples datasets of patients with schizophrenia compared to healthy controls (overall 422 samples, 211 schizophrenia, and 211 controls). We also performed a meta-analysis of their expression in blood, integrating two blood sample datasets (overall 90 samples, 53 schizophrenia, and 37 controls).
Multiple mitoribosomes subunits were significantly downregulated in brain samples (18 genes) and in blood samples (11 genes) of individuals with schizophrenia, where two showed significant downregulation in both brain and blood, MRPL4 and MRPS7.
Our results support the accumulating evidence of impaired mitochondrial activity in schizophrenia. While further research is needed to validate mitoribosomes' role as biomarkers, this direction has the potential to promote patients' stratification and personalised treatment for schizophrenia.
精神分裂症是一种慢性、使人虚弱的精神障碍，其病理生理学复杂且尚未完全了解。许多研究表明，线粒体功能障碍可能导致精神分裂症的发生。虽然线粒体核糖体（mitoribosomes）对于正常的线粒体功能至关重要，但它们的基因表达水平尚未在精神分裂症中得到研究。
我们对 81 个编码线粒体核糖体亚基的基因的表达进行了系统的荟萃分析，整合了 10 个精神分裂症患者与健康对照的大脑样本数据集（总共有 422 个样本，211 个精神分裂症患者和 211 个健康对照）。我们还对它们在血液中的表达进行了荟萃分析，整合了两个血液样本数据集（总共有 90 个样本，53 个精神分裂症患者和 37 个健康对照）。
精神分裂症患者的大脑样本（18 个基因）和血液样本（11 个基因）中多个线粒体核糖体亚基显著下调，其中两个基因在大脑和血液中均显著下调，即 MRPL4 和 MRPS7。
我们的结果支持线粒体活性受损在精神分裂症中的累积证据。虽然需要进一步的研究来验证线粒体核糖体作为生物标志物的作用，但这一方向有可能促进患者的分层和个性化治疗精神分裂症。
