Gene-Environment Interaction of Rims1 and Adolescent Social Isolation on Schizophrenia-Like Behaviors in Mice

Schizophrenia (SCZ) is a severe mental illness influenced by gene-environment interactions (GEI). However, little is known about how GEI mediates SCZ. The present study aimed to examine the underlying mechanism of SCZ mediated by GEI. We found that a single environmental factor (two-week adolescent social isolation) or genetic factor (the heterozygous Rims1 knockout mice) did not induce SCZ-like behaviors. Interestingly, two-week adolescent social isolation successfully caused SCZ-like behaviors in heterozygous Rims1 knockout mice, which can be rescued by anti-SCZ drugs. RNA-seq analysis further revealed that synaptic vesicle-related biological processes and target genes were enriched in the hippocampus of GEI animal model mice, which was accompanied by disturbed excitatory synaptic neurotransmission. Finally, the Nrg1 gene was decreased in our RNA-seq analysis, and supplementation of Nrg1 ameliorated SCZ-like behaviors in heterozygous Rims1 socially isolated mice. Our findings establish a novel GEI animal model and offer a potential therapeutic target in the treatment of SCZ.