Validation study of microRNAs previously associated with antidepressant response in older adults treated for late-life depression with venlafaxine

Victoria S. Marshe, Farhana Islam, Malgorzata Maciukiewicz, Laura M. Fiori, Volodymyr Yerko, Jennie Yang, Gustavo Turecki, Jane A. Foster, Sidney H. Kennedy, Daniel M. Blumberger, Jordan F. Karp, James L. Kennedy, Benoit H. Mulsant, Charles F. Reynolds, Eric J. Lenze, Daniel J. Müller

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Background: MicroRNAs (miRNAs) are small 22 nucleotides long, non-coding RNAs that are potential biomarkers for antidepressant treatment response. We aimed to replicate previous associations of miRNAs with antidepressant treatment response in a sample of older adults diagnosed with late-life depression. Methods: Our sample included 184 older adults diagnosed with moderately severe depression that received open-label venlafaxine (up to 300 mg/day) for approximately 12 weeks. We quantified miRNA expression levels at baseline and week 12 for miRNAs miR-1202, miR-135a-5p, miR-16-5p, miR-146a-5p, miR-146b-5p, miR-425-3p, and miR-24-3p to explore their association with remission status, response trajectories, and time-to-remission. Results: At T0 and T12, there were no differences in miRNA expression levels between remitters and non-remitters. However, remitters showed a trend toward higher baseline miR-135a-5p (Median = 11.3 [9.9, 15.7], p = .083). Prior to correction, baseline miR-135a-5p expression levels showed an association with remission status (OR = 1.8 [1.0, 3.3], p = .037). Individuals with higher baseline miR-135a-5p showed better response trajectories (F = 4.5, FDR-corrected p = 4.4 × 10−4), particularly at weeks 10 and 12 (p <. 05). In addition, individuals with higher miR-135a-5p expression reached remission faster than those with lower expression (HR = 0.6 [0.4, 0.9], FDR-corrected p = .055). Limitations: Although the sample size was relatively modest, our findings are consistent with the literature suggesting that higher miR-135a-5p levels may be associated with better antidepressant treatment response. Conclusions: However, the miRNA signature of antidepressant response in older adults may be different as compared to younger adults.

Original languageEnglish (US)
Article number109867
JournalProgress in Neuro-Psychopharmacology and Biological Psychiatry
Volume100
DOIs
StatePublished - Jun 8 2020
Externally publishedYes

Keywords

  • Late-life depression
  • miRNA
  • Pharmacogenetics
  • Treatment response
  • Venlafaxine

ASJC Scopus subject areas

  • Pharmacology
  • Biological Psychiatry

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