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

Prog Neuropsychopharmacol Biol Psychiatry. 2020 Jun 8;100:109867. doi: 10.1016/j.pnpbp.2020.109867. Epub 2020 Jan 16.


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.

Keywords: Late-life depression; Pharmacogenetics; Treatment response; Venlafaxine; miRNA.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Aged
  • Antidepressive Agents / therapeutic use*
  • Antidepressive Agents, Second-Generation / therapeutic use
  • Biomarkers / metabolism
  • Cohort Studies
  • Depression / drug therapy*
  • Depression / genetics
  • Depression / metabolism*
  • Female
  • Humans
  • Male
  • MicroRNAs / biosynthesis*
  • MicroRNAs / genetics
  • Middle Aged
  • Treatment Outcome
  • Venlafaxine Hydrochloride / therapeutic use*


  • Antidepressive Agents
  • Antidepressive Agents, Second-Generation
  • Biomarkers
  • MIRN135 microRNA, human
  • MicroRNAs
  • Venlafaxine Hydrochloride