Investigation The Differentially Expressed MicroRNA In Serum From The Patients Without Insight Schizophrenia

Background: Schizophrenia is the most common chronic braindisease which easily leads to mental disability, onsets in adolescence, hasa persistent course of disease, and it’s a serious threat to human health,causing heavy family and society burden. According to the researchinformation, there was about more than50million patients suffering fromschizophrenia in the world, and lifetime prevalence was about1%, whilethe incidence rate is still increasing year by year. The disease has a widevariety of abnormal clinical symptoms, including cognition, emotion, will,behavior and other mental activity, psychoactivity mismatchedenvironment as the main feature. The most common symptom is a lack ofinsight, and this symptom is the highest clinical diagnostic consistency ineach country. Insight has important clinical and social significance on theaspects of the clinical diagnosis, efficacy evaluation, prognosis,psychotherapy and forensic of the schizophrenia. Although scholarslaunched studies from all aspects of schizophrenia such as genomics andproteomics, the etiology and pathogenesis of schizophrenia remainsunclear. The clinical diagnosis mainly based on its complexity clinicalsymptoms, such as consciousness, emotional, behavioral and othersubjective indicators to judge, but these symptoms and other mentalillnesses often intersect and overlap occur, making the correct diagnosisand treatment observation of schizophrenia for clinical and forensicbecomes a very difficult problem. Therefore, early, rapidly andobjectively to achieve a correct diagnosis of schizophrenia is a majorproblem in the psychiatry research field. Establishing a kind of earlyspecific laboratory diagnosis method for schizophrenia is a topic of current clinical problems to be solved, which will be important clinicalsignificance and practical significance.Recent studies have found that post-transcriptional gene regulationand related non-coding single-stranded small molecule RNA (microRNA,miRNA) may be an important new regulatory factors associated withschizophrenia. MiRNA is very rich in the central nervous system, it canbe used as a novel regulatory factor involved in all stages of the nervoussystem development. This study is to screen serum miRNA differentexpression profile in serum of the onset and clinical cure schizophreniaand healthy control, and analyze the correlation between miRNA andclinical symptoms, specifically no insight symptoms.Objective: To investigate the differentially expressed miRNAprofile and study the correlation between the different miRNA profile andclinical symptoms. Aim to explore a good, simple and fast, highsensitivity, specificity laboratory diagnosis method for schizophrenia, andto provide a new laboratory evidence for disease diagnosis, monitoring,prognosis and personalized medicine.Methods:1. Screening differentially expressed miRNA：Screeningdifferentially expressed miRNAs in serum from the patients with noinsight schizophrenia (the sick group,4cases), remission after treatmentto the without insight schizophrenia (the clinical cure group,3cases) andhealthy subjects (the healthy control group,3cases) by FlashTag Biotin RNA chips and SAM software.2. The screening experimentvalidation: the validation was performed by real-time quantitative reversetranscription polymerase chain reaction (RT-PCR). Sample cases wererespectively30cases,30cases and60cases in diseased group, clinicalcure group and the healthy control group, and statistical analysis of thePCR results through the SPSS17.0software.3. Establishment of the diagnosis model: the schizophrenia serum miRNA artificial neuralnetwork (ANA) diagnostic model was established based on the error backpropagation principle and evaluated its effectiveness.Results:1. Screening results: Six differentially expressed miRNAswere screened, including overexpressed hsa-miR-1281with fold change1.509and5downexpreesed miRNAs: hsa-miR-2861, hsa-miR-638,hsa-miR-320b, hsa-miR-320a, and hsa-miR-1469. Their fold changeswere0.642,0.516,0.437,0.251and0.645respectively.2. Validationresults: The comparative analysis of RT-PCR validation results wasperformed between two groups by SPSS17.0Kruskal Wallis H Test，TheRT-PCR results conformed that hsa-miR-2861, hsa-miR-638,hsa-miR-320b, hsa-miR-320a and hsa-miR-1469were all downexpressed,while hsa-miR-1281was overexpressed. Compared with healthy group,PCR results of the5downexpressed miRNAs were most significantlydifferent (P<0.001), meanwhile there was significantly different (P<0.05)between the sick and the clinical cure group. And hsa-miR-1281wascompared with the healthy subjects and the clinical cure group, there wassignificantly different (P<0.001).3. Diagnosis model results: Itsdiagnostic sensitivity was89.3%, specificity83.3%, and area under theROC curve was0.924.4. Targets predicted results: Hsa-miR-320a,hsa-miR-320b, hsa-miR-1469, hsa-miR-638, hsa-miR-2861and hsa-miR-1281were78,65,251,246,47and31target genes respectively,Conclusion: There are differentially expressed miRNAs in serumfrom the patients with schizophrenia; the aberrant expressed miRNAswere associated with the no insight symptoms; miRNA can serve as aserum marker for laboratory diagnosis of schizophrenia.