Transcriptomic Biomarkers For Clinical High-Risk Psychosis And The MicroRNA Alteration Of Nucleus Accumbens During Chronic Stress

PART ONE[BACKGROUND]Clinical high risk of psychosis(CHR-P)is currently the research hotspot of early intervention in psychotic disorders.The biomarkers of clinical outcomes of CHR-P is still lacking.[METHOD]We recruited fifty six CHR-P patients at Shanghai Mental Health Center and collected their peripheral bloods as well as SIPS score at both baseline and one-year follow-up time point.We applied RNA sequence the blood samples for both timepoint and conducted paired differential expression analysis.Step regression analysis and F test were performed to select the combination with the most significant correlation and the least number of genes as markers reflecting CHR-P outcome.[RESULT]After controlling for confounding factors such as GC ratio,23 genes were significantly differently expressed in the first year of follow-up of patients in different groups(p <0.001).Stepwise regression found that a model consisting of 11 genes,including PER1,OLIG2,could explain the maximum degree of change in the SIPS-P score(Pearson correlation coefficient 0.72).The model had the lowest F-test p-value.Permutation test,leave-one-out method,and random feature test all confirmed that the model was significantly better than expected(p <0.05).[CONCLUSION]The peripheral blood transcriptome has the potential to reflect the CHR-P outcome process and predict the outcome of CHR-P outcomes.PART TWO[BACKGROUND]The nucleus Accumbens plays an important role in the process of chronic stress,but the molecular mechanism of this role at the small RNA level is not clear.[METHOD]Chronic unpredictable mild stress was performed on rats.Behavioral tests were used to determine chronic stress symptoms.Bilateral nucleus Accumbens were taken for small RNA sequencing,differential expression analysis,target gene prediction,and Pathway analysis.[RESULT]Weight gain and sucrose preference of rats in the chronic stress group were significantly lower than those in the control group.Nineteen small RNAs were significantly differentially expressed between the stress group and the control group,and they had a total of 595 predicted target genes.These target genes are enriched in pathways such as the RAS signaling system and axon guidance.[CONCLUSION]Small RNA disturbances play an important role in the chronic stress pathology of the nucleus Accumbens,which may mediate RAS signal pathway conduction and axonal disturbances.