Association between side effects and blood microRNA expression levels and their targeted pathways in patients with major depressive disorder treated by a selective serotonin reuptake inhibitor, escitalopram: a CAN-BIND-1 report.

TitleAssociation between side effects and blood microRNA expression levels and their targeted pathways in patients with major depressive disorder treated by a selective serotonin reuptake inhibitor, escitalopram: a CAN-BIND-1 report.
Publication TypeJournal Article
Year of Publication2019
AuthorsYrondi A, Fiori LM, Frey BN, Lam RW, Macqueen GM, Milev R, Müller DJ, Foster JA, Kennedy SH, Turecki G
JournalInt J Neuropsychopharmacol
Date Published2019 Dec 10
ISSN1469-5111
Abstract

INTRODUCTION: Antidepressant drugs are effective therapies for Major Depressive Disorder (MDD); however, they are frequently associated with side effects. Although there is some evidence for a relationship between genetic variation and side effects, little is known regarding the role of dynamic molecular factors as moderators of side effect. The aim of this study is to assess microRNA (miRNA) changes associated with side effects during escitalopram treatment, and their downstream effects on target gene expression.METHODS: 160 patients with MDD from the CAN-BIND -1 cohort were included. Side effects were assessed with the Toronto Side Effect Scale after 2 weeks of treatment with escitalopram. We assessed the relationship between side effects and changes in peripheral expression of miRNAs between baseline and week 2. For miRNAs whose expression changed, we used target prediction algorithms to identify putative messenger RNA (mRNA) targets and assessed their expression.RESULTS: Nausea was experienced by 42.5% of patients. We identified 45 miRNAs whose expression changed upon initiation of escitalopram treatment, of which 10 displayed a negative association with intensity of nausea (miR15b-5p, miR17-5p, miR20a-5p, miR20b-5p, miR103a-3p, miR103b, miR106a-5p, miR182-5p, miR185-5p and miR660-5p). Additionally, we found negative associations between 4 miRNAs (miR20a-5p, miR106a-5p, miR185-5p, miR660-5p) and mRNA targets. The expression of the miR185-5p target, CAMK2δ was significantly decreased [log 2 mean= -0.048 (0.233)] between weeks 0 and 2 (p=0.01)].CONCLUSIONS: We identified an overexpression of miR185-5p during escitalopram treatment of MDD, which was negatively associated with intensity of nausea, and identified a potential mRNA target which may mediate this effect.

DOI10.1093/ijnp/pyz066
Alternate JournalInt. J. Neuropsychopharmacol.
PubMed ID31819986