MicroRNAs as biomarkers for major depression: a role for let-7b and let-7c

Abstract

There is a growing emphasis in the field of psychiatry on the need to identify candidate biomarkers to aid in diagnosis and clinical management of depression, particularly with respect to predicting response to specific therapeutic strategies. MicroRNAs are small nucleotide sequences with the ability to regulate gene expression at the transcriptomic level and emerging evidence from a range of studies has highlighted their biomarker potential. Here we compared healthy controls (n=20) with patients diagnosed with major depression (n=40) and who were treatment-resistant to identify peripheral microRNA biomarkers, which could be used for diagnosis and to predict response to electroconvulsive therapy (ECT) and ketamine (KET) infusions, treatments that have previously shown to be effective in treatment-resistant depression (TRD). At baseline and after treatment, blood samples were taken and symptom severity scores rated using the Hamilton Depression Rating Scale (HDRS). Samples were analyzed for microRNA expression using microarray and validated using quantitative PCR. As expected, both treatments reduced HDRS scores. Compared with controls, the baseline expression of the microRNA let-7b was less by ~40% in TRD patients compared with controls. The baseline expression of let-7c was also lower by ~50% in TRD patients who received ECT. Bioinformatic analysis revealed that let-7b and let-7c regulates the expression of 27 genes in the PI3k-Akt-mTOR signaling pathway, which has previously been reported to be dysfunctional in depression. The expression of miR-16, miR-182, miR-451 and miR-223 were similar to that in controls. Baseline microRNA expression could not predict treatment response and microRNAs were unaffected by treatment. Taken together, we have identified let-7b and let-7c as candidate biomarkers of major depression.

Peripheral blood microRNA and VEGFAmRNA changes following electroconvulsive therapy: implications for psychotic depression

“…In this study, the potential role played by miRNAs and their targets in ECT‐treated depression was first investigated by measuring their changes in peripheral blood before and after a course of ECT. To our knowledge, this is the first study using deep sequencing technology to analyse miRNA expression in peripheral blood in depression and only the second to examine miRNA changes following ECT . We found no changes in miRNA levels after a course of ECT in the group as a whole.…”

“…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.…”

MicroRNAs and exosomes in depression: Potential diagnostic biomarkers

“…Deregulation of these molecules could be related with initiation and progression of several diseases such as cancer and mental disorders . It has been showed that deregulation of many miRNAs such as miR‐16, miR‐451, miR‐223, and miR‐182 could be associated with depression condition in different patients . These findings suggested that miRNAs (tissue specific and circulating) could be used as diagnostic and therapeutic biomarkers for patients with depression (Table ).…”

“…It seems that identification of new targets could contribute to better understanding of many cellular and molecular pathways involved in depression pathogenesis and could lead to design new and effective therapeutic platforms . Among several targets, microRNAs (miRNAs) have been emerged as new molecules which could be involved in different physiological events in several diseases such as depression . MiRNAs are known as epigenetic regulators which are able to regulation of various cellular and molecular pathways .…”

“…These studies revealed that miRNAs play key roles in pathogenesis of these diseases which exert their effect via targeting many cellular and molecular pathways . Numerous studies showed that deregulation of various miRNAs could affect on a variety of cellular and molecular targets involved in depression pathogenesis . These findings suggested that miRNAs could be used as effective diagnostic and therapeutic biomarkers for patients with depression.…”