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

doi:10.1016/j.pnpbp.2020.109867

. 2020 Jun 8:100:109867.

doi: 10.1016/j.pnpbp.2020.109867. Epub 2020 Jan 16.

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

Victoria S Marshe¹, Farhana Islam², Malgorzata Maciukiewicz³, Laura M Fiori⁴, Volodymyr Yerko⁴, Jennie Yang⁴, Gustavo Turecki⁴, Jane A Foster⁵, Sidney H Kennedy⁶, Daniel M Blumberger⁷, Jordan F Karp⁸, James L Kennedy⁷, Benoit H Mulsant⁷, Charles F Reynolds 3rd⁹, Eric J Lenze¹⁰, Daniel J Müller¹¹

Affiliations

¹ Institute of Medical Science, University of Toronto, Toronto, ON, Canada; Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada.
² Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada; Department of Pharmacology & Toxicology, University of Toronto, Toronto, ON, Canada.
³ Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada; Center of Experimental Rheumatology, Department of Rheumatology, University Hospital Zurich, Switzerland.
⁴ McGill Group for Suicide Studies, Douglas Mental Health University Institute, McGill University, Verdun, Quebec, Canada.
⁵ Department of Psychiatry, University Health Network, Toronto, ON, Canada; Department of Psychiatry and Behavioral Neurosciences, McMaster University, Hamilton, ON, Canada.
⁶ Institute of Medical Science, University of Toronto, Toronto, ON, Canada; Department of Psychiatry, University Health Network, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada; Keenan Research Centre, St. Michael's Hospital, Toronto, ON, Canada.
⁷ Institute of Medical Science, University of Toronto, Toronto, ON, Canada; Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
⁸ Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA; VA Pittsburgh Health System, Geriatric Research Education and Clinical Center, Pittsburgh, PA, USA.
⁹ Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.
¹⁰ Healthy Mind Lab, Department of Psychiatry, Washington University, St. Louis, MO, USA.
¹¹ Institute of Medical Science, University of Toronto, Toronto, ON, Canada; Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada; Department of Pharmacology & Toxicology, University of Toronto, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada. Electronic address: daniel.mueller@camh.ca.

PMID: 31954757
DOI: 10.1016/j.pnpbp.2020.109867

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

Victoria S Marshe et al. Prog Neuropsychopharmacol Biol Psychiatry. 2020.

. 2020 Jun 8:100:109867.

doi: 10.1016/j.pnpbp.2020.109867. Epub 2020 Jan 16.

Authors

Affiliations

¹ Institute of Medical Science, University of Toronto, Toronto, ON, Canada; Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada.
² Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada; Department of Pharmacology & Toxicology, University of Toronto, Toronto, ON, Canada.
³ Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada; Center of Experimental Rheumatology, Department of Rheumatology, University Hospital Zurich, Switzerland.
⁴ McGill Group for Suicide Studies, Douglas Mental Health University Institute, McGill University, Verdun, Quebec, Canada.
⁵ Department of Psychiatry, University Health Network, Toronto, ON, Canada; Department of Psychiatry and Behavioral Neurosciences, McMaster University, Hamilton, ON, Canada.
⁶ Institute of Medical Science, University of Toronto, Toronto, ON, Canada; Department of Psychiatry, University Health Network, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada; Keenan Research Centre, St. Michael's Hospital, Toronto, ON, Canada.
⁷ Institute of Medical Science, University of Toronto, Toronto, ON, Canada; Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
⁸ Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA; VA Pittsburgh Health System, Geriatric Research Education and Clinical Center, Pittsburgh, PA, USA.
⁹ Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.
¹⁰ Healthy Mind Lab, Department of Psychiatry, Washington University, St. Louis, MO, USA.
¹¹ Institute of Medical Science, University of Toronto, Toronto, ON, Canada; Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada; Department of Pharmacology & Toxicology, University of Toronto, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada. Electronic address: daniel.mueller@camh.ca.

PMID: 31954757
DOI: 10.1016/j.pnpbp.2020.109867

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.

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

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

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

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