The Impact of MIR137 on Dorsolateral Prefrontal–Hippocampal Functional Connectivity in Healthy Subjects

A recent mega-analysis combining genome-wide association study data revealed that a variant of microRNA 137 (MIR137) exhibits the most significant association with schizophrenia. Other biological evidence also consistently suggests that MIR137 may have a pivotal role in the pathogenesis of schizophrenia. However, the underlying neural mechanism remains unclear. As the disrupted dorsolateral prefrontal cortex (DLPFC) coupling with the hippocampal formation (HF) has been widely observed in schizophrenia patients, DLPFC-HF dysconnectivity can therefore be thought of as a pivotal intermediate phenotype that links genetic variants of psychiatric risk genes to schizophrenia. This study used resting-state functional magnetic resonance imaging to test whether the MIR137 variant (rs1625579) impacts DLPFC-HF functional connectivity and cognitive performance in 290 young, healthy Han Chinese individuals. To identify functional connectivity between DLPFC and HF, a seed-based functional connectivity analysis was used. The association between DLPFC-HF connectivity and working memory performance was further examined in individuals with different MIR137 genotypes. The individuals who are homozygous for the MIR137 risk allele (TT), which confers a high risk for schizophrenia, exhibited significantly different DLPFC-HF functional connectivity compared with TG individuals. Moreover, the DLPFC-HF connectivity could predict the working memory performance in MIR137 TG individuals, but not in TT individuals. The current findings obtained in a large sample of healthy participants identified potential neural mechanisms linking MIR137 with the risk of developing schizophrenia via the intermediate phenotype of DLPFC-HF connectivity.