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.
antidepressant
major depressive disorder
miRNA
side effects
Journal
The international journal of neuropsychopharmacology
ISSN: 1469-5111
Titre abrégé: Int J Neuropsychopharmacol
Pays: England
ID NLM: 9815893
Informations de publication
Date de publication:
01 02 2020
01 02 2020
Historique:
received:
09
09
2019
accepted:
06
12
2019
pubmed:
11
12
2019
medline:
26
11
2020
entrez:
11
12
2019
Statut:
ppublish
Résumé
Antidepressant drugs are effective therapies for major depressive disorder; 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 effects. The aim of this study was to assess microRNA (miRNA) changes associated with side effects during escitalopram treatment and their downstream effects on target gene expression. A total 160 patients with major depressive disorder 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 miRNA whose expression changed, we used target prediction algorithms to identify putative messenger RNA (mRNA) targets and assessed their expression. Nausea was experienced by 42.5% of patients. We identified 45 miRNAs whose expression changed on 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 microRNAs (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 = .01)]. We identified an overexpression of miR185-5p during escitalopram treatment of major depressive disorder, which was negatively associated with intensity of nausea, and identified a potential mRNA target that may mediate this effect.
Identifiants
pubmed: 31819986
pii: 5670827
doi: 10.1093/ijnp/pyz066
pmc: PMC7093997
doi:
Substances chimiques
MicroRNAs
0
Serotonin Uptake Inhibitors
0
Citalopram
0DHU5B8D6V
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
88-95Subventions
Organisme : CIHR
ID : FDN148374
Pays : Canada
Organisme : CIHR
ID : EGM141899
Pays : Canada
Organisme : CIHR
ID : ENP161427
Pays : Canada
Informations de copyright
© The Author(s) 2019. Published by Oxford University Press on behalf of CINP.
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