Identification Of Differential MiRNAs In Cerebrospinal Fluid And Serum Of Patients With Major Depressive Disorder

Background and objective:Major depression is a debilitating, low mood mental illness, resulting in heavy social and economic burdens. Current diagnosis of MDD is mainly based on the patients’ description of symptoms, assessment of mental status and evaluation of clinical behaviors, which increase the chance of misdiagnosis. There is no reliable biological marker from blood or cerebrospinal fluid that can be used for the diagnosis of MDD. Some studies have found that the diseased tissues of heart or brain can release mi RNAs into the circulatory blood or CSF, and some mi RNAs may be new biological markers of cardiovascular and cerebral diseases. The goals of this study were to detect the candidate mi RNAs in cerebrospinal fluid of MDD patients and to investigate these candidate mi RNAs in serum from MDD patients further to provide information about mi RNAs as specific biomarkers for the diagnosis of MDD.Methods:First, the relative expression levels of 179 mi RNAs(relative high levels in serum) were analyzed by LNA- mi RNA PCR Panel in the CSF of MDD patients. Then, the differentially altered mi RNAs from CSF were further assessed by LNA-q RT-PCR in the serum of the same patients. Finally, the serum differentially altered mi RNAs were further validated by LNA-q RT-PCR in the serum of other 32 MDD patients.Results : The CSF results indicated that 11 mi RNAs in MDD patients were significantly higher than in control subjects, and 5 mi RNAs were significantly lower than in control subjects. The serum results from the same patients showed that 3 mi RNAs(mi R-221-3p, mi R-34a-5p, and let-7d-3p) of 11 mi RNAs were significantly higher than in control subjects, and 1 mi RNA(mi R-451a) of 5 mi RNAs was significantly lower than in control subjects. The up-regulation of mi R-221-3p, mi R-34a-5p, let-7d-3p and down-regulation of mi R-451 a was further validated in another 32 MDD patients. ROC analysis showed that the area under curve of let-7d-3p, mi R-34a-5p, mi R-221-3p and mi R-451 a was 0.94, 0.98, 0.97 and 0.94, with specificity of 90.48%, 95.24%, 90.48% and 90.48%, and sensitivity of 93.75%, 96.88%, 90.63% and 84.85%, respectively. In addition, target gene prediction found that the altered mi RNAs are involved in affecting some important genes and pathway related to MDD.Conclusion : Our results suggested that differentially altered mi RNAs in CSF might be involved in MDD, and serum mi R-221-3p, mi R-34a-5p, let-7d-3p, and mi R-451 a might be able to serve as biomarkers for MDD.