| Autor: |
Claudio N. Soares, Roumen Milev, Faranak Farzan, Daniel J. Müller, Sidney H. Kennedy, Rudolf Uher, Jean-François Théroux, Francesco Leri, Laura M. Fiori, Raymond W. Lam, Qingqin Li, Chelsey Ju, Susan Rotzinger, Raoul Belzeaux, Sagar V. Parikh, Pierre Blier, Peter Giacobbe, Glenda MacQueen, Jane A. Foster, Gustavo Turecki, Benicio N. Frey, Zahia Aouabed, Gary Gang Chen |
| Rok vydání: |
2018 |
| Předmět: |
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| Zdroj: |
SSRN Electronic Journal. |
| ISSN: |
1556-5068 |
| DOI: |
10.2139/ssrn.3234907 |
| Popis: |
Background: Major depressive disorder (MDD) is primarily treated with antidepressants, yet many patients fail to respond to adequate trials. Understanding who is likely to respond to antidepressant treatment and/or what mediates this response is of considerable clinical importance. As part of the Canadian Biomarker Integration Network in Depression (CAN-BIND-1) initiative, we aimed to identify differential DNA methylation marks as epigenetic predictors of antidepressant response (ADR) in MDD patients. Methods: Healthy participants (n=112) and depressed participants (n=211) between 18-60 years of age were recruited across six Canadian clinical centers. Eligible depressed patients with MDD by DSM-IV-TR criteria and a Montgomery-Asberg Depression Rating Scale (MADRS) score of ≥24 were enrolled. Genome-wide DNA methylation analysis was conducted using the Infinium MethylationEPIC Beadchipb with DNA extracted from baseline peripheral blood samples prior to beginning an eight-week trial of escitalopram. Genome-wide mRNA expression analysis was conducted on the HumanHT-12 v4 Expression Beadchip in RNA extracted from leukocytes at baseline. Depressed patients were classified as non-responders (NRES) and responders (RES) according to changes in MADRS scores following eight weeks of treatment. Differentially methylated positions (DMPs) were identified in regions of differentially expressed genes and validated using a targeted sequencing approach. Replication was conducted with patients participating in a similar trial, the Douglas Biomarker Study. CAN-BIND-1 clinical trial was registered with the ClinicalTrials.gov identification #: NCT101655706. Findings: After depressed participants concluded the 8-week trial, 82 RES and 95 NRES were included in this study. Genome-wide differential DNA methylation revealed 2,572 DMPs (p |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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