Multiple genes encoding mitochondrial ribosomes are downregulated in brain and blood samples of individuals with schizophrenia.

Objectives: 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.

Methods: 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).

Results: 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.

Conclusions: 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.