Screening And Identification Of Specific Long Noncoding RNAs In The Peripheral Blood With Major Depressive Disorder

Objective: Major depressive disorder(MDD) is one of the most common psychiatric disorders with high levels of morbidity, mortality, disability and low levels of efficiency for clinical treatment. While the pathogenesis and pathphysiology are currently unknown. Recently, the regulation of noncoding RNAs(nc RNAs) has become a fruitful area of research in MDD as one of epigenetic mechanisms. Lnc RNAs are one of the most highly expressed classes of nc RNAs in the brain and have broad spectrum functions in the normal brain development and function maintenance. Moreover, a body of study has showed that lnc RNAs play a direct role in the regulation of genes involved in neural plasticity and cognitive function. Indeed, an increasing number of studies have shown that lnc RNAs are associated with several neurodegenerative and psychiatric disorders. Therefore, it is possible to determinate the underlying mechanisms in the development of MDD. Following important results were obtained in this study. Methods: The whole study was performed in three stages. In the first stage, we used a microarray analysis profiling to identify genome-wide lnc RNAs and m RNAs expression in the peripheral blood of 10 MDD patients and 10 contols. And the expression of some lnc RNAs in all subjects included in this study was measured by real-time PCR. Then, we further constructed gene-lnc RNA co-expression networks to determine interaction patterns among genes with their related co-expressed lnc RNAs, and identified the specific lnc RNAs associated with MDD. Finally, a total 27 drug-free patients who fulfilled 8 weeks treatment with SSRIs antidepressant and achieved remission were enrolled. The expression of the specific lnc RNAs was detected in their peripheral blood and the relationships were analyzed with the clinical characters. Results: 1. From the lnc RNA expression profiles, we found that 2007 lnc RNAs and 1667 m RNAs were differentially expressed, consisting of 1556 upregulated lnc RNAs and 441 down-regulated lnc RNAs. Among these, 1799 lnc RNAs were antisense RNA. Meanwhile, 1766 differentially expressed m RNAs were found with comparisons between MDD patients and controls, which consisted of 759 up-regulated m RNAs and 1007 downregulated m RNAs. We examined the expression of these four lnc RNAs(upregulated: FR344886, chr21:39641845-39641964, chr17:78355675-78355935, chr17:78354412-78354623) in two sets using q PCR. These data supported a strong consistency between the q PCR result and microarray data. 2. The analysis of the co-expression network of lnc RNAs and m RNAs indicated significantly different patterns in the MDD group compared to the control group. In the MDD-derived network, there were a greater number of nodes and connections than that in the control-derived network. The lnc RNAs located at chr10:874695-874794, chr10:75873456-75873642, and chr3:47048304-47048512 may be important factors regulating the expression of m RNAs as they have previously been reported associations with MDD. Gene Ontology(GO) and pathway analyses of differentially expressed m RNAs indicated that the biological functions of differentially expressed m RNAs were related to fundamental metabolic processes and neurodevelopment diseases. 3. We found that the lnc RNA chr10:874695-874794 in the peripheral blood was down-regulated expression in the MDD patient(P = 0.0001). Interestingly, it was greatly increase after drug treatment(P = 0.001), showing a negative relation between its level and HAMD score before and after treatment(r =-0.588, P = 0.001; r =-0.552,P = 0.003) and positive relation with attention function before treatment. The lnc RNA chr10:75873456-75873642 was only up-regulated expression after treatment and has a positive relation with immediate memory. Conclusion: In conclusion, we report here for the first time that circulating lnc RNAs are differentially expressed in MDD patients compared to demographically-matched controls. The lnc RNAs chr10:874695-874794 was detected as potential regulatory factors in MDD, most likely through interactions with coding transcripts. Further work is needed to understand the biological functions and molecular.