TY - JOUR
T1 - Validation study of microRNAs previously associated with antidepressant response in older adults treated for late-life depression with venlafaxine
AU - Marshe, Victoria S.
AU - Islam, Farhana
AU - Maciukiewicz, Malgorzata
AU - Fiori, Laura M.
AU - Yerko, Volodymyr
AU - Yang, Jennie
AU - Turecki, Gustavo
AU - Foster, Jane A.
AU - Kennedy, Sidney H.
AU - Blumberger, Daniel M.
AU - Karp, Jordan F.
AU - Kennedy, James L.
AU - Mulsant, Benoit H.
AU - Reynolds, Charles F.
AU - Lenze, Eric J.
AU - Müller, Daniel J.
N1 - Publisher Copyright:
© 2020
PY - 2020/6/8
Y1 - 2020/6/8
N2 - 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.
AB - 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.
KW - Late-life depression
KW - Pharmacogenetics
KW - Treatment response
KW - Venlafaxine
KW - miRNA
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U2 - 10.1016/j.pnpbp.2020.109867
DO - 10.1016/j.pnpbp.2020.109867
M3 - Article
C2 - 31954757
AN - SCOPUS:85078974805
SN - 0278-5846
VL - 100
JO - Progress in Neuro-Psychopharmacology and Biological Psychiatry
JF - Progress in Neuro-Psychopharmacology and Biological Psychiatry
M1 - 109867
ER -