Abstract
Major depression is a debilitating disease. To date, the development of biomarkers of major depressive disorder (MDD) remains a challenge. Recently, alterations in the expression of microRNAs (miRNAs) from post-mortem brain tissue and peripheral blood have been linked to MDD. The goals of this study were to detect the differential miRNAs in cerebrospinal fluid (CSF) and serum of MDD patients. First, the relative expression levels of 179 miRNAs (relative high levels in serum) were analyzed by miRNA PCR Panel in the CSF of MDD patients. Then, the differentially altered miRNAs from CSF were further assessed by qRT-PCR in the serum of the same patients. Finally, the serum differentially altered miRNAs were further validated by qRT-PCR in the serum of another MDD patients. The CSF-results indicated that 11 miRNAs in MDD patients were significantly higher than these in control subjects, and 5 miRNAs were significantly lower than these in control subjects. The serum-results from the same patients showed that 3 miRNAs (miR-221-3p, miR-34a-5p, and let-7d-3p) of the 11 miRNAs were significantly higher than these in control subjects, and 1 miRNA (miR-451a) of 5 miRNAs was significantly lower than these in control subjects. The up-regulation of miR-221-3p, miR-34a-5p, let-7d-3p and down-regulation of miR-451a was further validated in another 32 MDD patients. ROC analysis showed that the area under curve of let-7d-3p, miR-34a-5p, miR-221-3p and miR-451a 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 miRNAs are involved in affecting some important genes and pathway related to MDD. Our results suggested that differentially altered miRNAs in CSF might be involved in MDD, and serum miR-221-3p, miR-34a-5p, let-7d-3p, and miR-451a might be able to serve as biomarkers for MDD.
Highlights
Major depressive disorder (MDD) is a common chronic mood illness, resulting in heavy social and economic burdens [1, 2]
Our results showed that cerebrospinal fluid (CSF) miRNAs from MDD patients could be detected
We should seriously consider how to look for serum specific miRNAs as biomarker for MDD because the change of CSF miRNAs was poorly related to the alteration of serum miRNAs for CNS diseases[13]
Summary
Major depressive disorder (MDD) is a common chronic mood illness, resulting in heavy social and economic burdens [1, 2]. There is no reliable biological marker from blood or cerebrospinal fluid that can be used for the diagnosis of MDD. MicroRNAs (miRNAs) are small noncoding RNA molecules that regulate the stability and/ or the translational efficiency of target messenger RNAs [3] and can influence the activity of approximately 50% or more of all protein-coding genes in mammals [4, 5], and several studies have reported that miRNAs are very important regulatory factors in the normal developmental, physiological and disease states, including cancer, mental disorders and cardiovascular diseases [6,7,8]. Alterations in miRNAs expression from post-mortem brain tissues and peripheral blood samples have been linked to MDD [9,10]. Recent studies have found that the diseased tissues of heart or brain can release miRNAs into the circulatory blood or CSF, and these miRNAs may be new biological markers of cardiovascular and cerebral diseases [11,12]
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