Circulating Plasma Micro RNAs in Patients with Major Depressive Disorder Treated with Antidepressants: A Pilot Study

Abstract

ObjectiveSignificant progress was made in the understanding etiopathogenic factors related to MDD, including through research on the role of micro RNAs (miRs). We investigated plasma miRs as potential markers for MDD in patients treated with antidepressants.MethodsAt the initiation and at the end of twelve weeks of treatment, blood samples were collected and a structured diagnostic interview and a standardized depression rating scale for the presence and severity of major depression were done. The average decrease in HAMD score was 76.89%. Plasma miR expression profiling was performed by real time PCR. The lists of up-regulated (cut-off=2) and down-regulated miRs were imported into the miRWalk2.0 algorithm and used for target predictions. KEGG database pathways analysis was used to retrieve the pathways significantly targeted by at least two of the miRs.ResultsOf the 222 miRs detected in plasma samples of MDD patients, 40 were differentially expressed after treatment. Twenty-three miRs were significantly overexpressed with fold changes between 1.85 and 25.42, and 17 miRs were significantly downregulated with fold changes from 0.28 to 0.68. Pathway analysis revealed a list of 29 pathways for up-regulated miRs, and 20 pathways for down-regulated miRs. Six dysregulated miRs are common to all the top five pathways (Wnt signaling, Cancer, Endocytosis, Axon guidance, MAPK signaling): miR-146a-5p, miR-146b-5p, miR-221-3p, miR-24-3p, miR-26a-5p.ConclusionOverall, our miRWalk analysis of changes in plasma microRNAs after treatment of patients with major depression might open a new avenue for the understanding of Escitalopram mode of action and for its side effects.

Peripheral blood microRNAandVEGFAmRNAchanges following electroconvulsive therapy: implications for psychotic depression

“…miR‐126‐3p, which is expressed in endothelial cells, has been identified as a key regulator of angiogenesis, vascularisation and inflammatory and immune responses . It has previously been found to be downregulated following escitalopram treatment in a small study, but it is not clear whether any of those patients suffered from psychotic depression . miR‐106a‐5p has been implicated in several cancers, including glioma, where increases in brain levels of miR‐106a‐5p in glioma patients were mirrored in plasma, supporting the utility of exploring miRNA changes in peripheral blood .…”

“…The strengths of this study include the use of deep sequencing technology whereas other miRNA studies in depression have used a microarray approach . In general, there is very little overlap between the miRNAs identified in studies to date.…”

Blood biomarkers and treatment response in major depression

“…Blood samples were collected at baseline and after 12 weeks of escitalopram treatment and, among the 222 miRNAs detected in blood, the authors identified 40 potentially dysregulated miRNAs, which were modulated by antidepressant treatment. Interestingly, these miRNAs were involved in the regulation of pathways such as Wnt signaling, Axon guidance and MAPK signaling that have been suggested to contribute to the mechanism of action of antidepressant drugs [87].…”

MiR-221 is involved in depression by regulating Wnt2/CREB/BDNF axis in hippocampal neurons

“…To determine which miRNA was associated with depression, we detected the levels of miR-221, miR-126, miR-223, miR-652, miR-744 and miR-151-3p in CSF and serum in MDD patients according to the references [12][13][14][15][16]. Compared with the control patients, the expressions of miR-221, miR-223 and miR-151-3p were all increased in CSF, and the increase of miR-221 expression was more obvious (Figure 1(a)).…”