The cell cycle-related genes as biomarkers for schizophrenia

• Published in: Progress in neuro-psychopharmacology & biological psychiatry 2016-10, Vol.70, p.85-91
• Main Authors: Okazaki, Satoshi, Boku, Shuken, Otsuka, Ikuo, Mouri, Kentaro, Aoyama, Shinsuke, Shiroiwa, Kyoichi, Sora, Ichiro, Fujita, Aiko, Shirai, Yutaka, Shirakawa, Osamu, Kokai, Masahiro, Hishimoto, Akitoyo
• Format: Article
• Language: English
• Subjects: Acute Disease; Adult; Aged; Antipsychotic Agents - therapeutic use; Biomarker; Biomarkers - metabolism; CDK4; Cell cycle; Cell Cycle - genetics; Cell Cycle - physiology; Chronic Disease; Cohort Studies; Cyclin-Dependent Kinase 4 - metabolism; DNA Copy Number Variations; DNA Methylation; Female; Humans; Logistic Models; Male; MCM7; Middle Aged; Minichromosome Maintenance Complex Component 7 - metabolism; Real-Time Polymerase Chain Reaction; RNA, Messenger - metabolism; Schizophrenia; Schizophrenia - drug therapy; Schizophrenia - genetics; Schizophrenia - metabolism
• ISSN: 0278-5846; 1878-4216
• DOI: 10.1016/j.pnpbp.2016.05.005

Recent studies suggest that genomic abnormalities such as single nucleotide polymorphisms (SNPs) and copy number variations (CNVs) may elevate the risk of schizophrenia. Such genomic abnormalities often occur during chromosomal DNA replication in the S phase of cell cycle. In addition, several studies showed that abnormal expressions of several cell cycle-related genes are associated with schizophrenia. Therefore, here we compared mRNA expression levels of cell cycle-related genes in peripheral blood cells between patients with schizophrenia and healthy controls. mRNA expression levels of cell cycle-related genes in peripheral blood cells from patients with schizophrenia and healthy controls were measured with quantitative reverse transcription polymerase chain reaction (Q-RT-PCR). The discovery, replication and intervention studies with Q-RT-PCR were performed as follows: discovery (40 cases and 20 controls), replication (82 cases and 74 controls) and intervention (22 cases and 18 controls). Nine genes were identified in the discovery and replication stages as schizophrenia-associated genes. Moreover, the combination of mRNA expression levels of CDK4, MCM7 and POLD4 was identified as a potential biomarker for schizophrenia with multivariate logistic regression analysis. The intervention stage revealed that the mRNA expression levels of these three genes were significantly decreased in the acute state of schizophrenia, and CDK4 was significantly recovered in the remission state of schizophrenia. The combination of mRNA expression levels of three cell cycle-related genes such as CDK4, MCM7 and POLD4 is expected to be a candidate for useful biomarkers for schizophrenia. Especially, the mRNA expression changes of CDK4 may be potential as both trait and state markers for schizophrenia. •A mRNA expression study focused on cell cycle-related genes with Q-RT-PCR was performed.•Nine genes; CDK10, CDK4, MCM3, MCM4, MCM5, MCM6, MCM7, POLD2 and POLD4 were decreased in patients with schizophrenia.•By multivariate logistic regression analysis, CDK4, MCM7 and POLD4 were identified as potential biomarkers for schizophrenia.