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Therapeutic response to Paroxetine in major depressive disorders predicted by DNA methylation

Type: dissertation
Study design: Observational Study
Abstract: Background: Antidepressants have variable therapeutic effects, depending on genetic and environmental factors.Approximately 30% of major depressive disorder (MDD) patients do not respond significantly to antidepressants such as Paroxetine, a selective serotonin reuptake inhibitor (SSRI).However, the biological mechanisms behind this phenomenon are mostly unknown.Here we examined the role of patients' epigenetic background in SSRI effectiveness.Methods: Genomewide DNA methylation analysis of the peripheral blood of Japanese MDD patients was performed by using the Infinium HumanMethylation450 BeadChip.Results: We compared the results of the 10 patients who best responded to Paroxetine (BR) with the 10 worst responders (WR), and found 623 CpG sites with a >10% difference in DNA methylation level.Among them, 218 sites were nominally significant between BR and WR (p < 0.05), and 2 sites (cg00594917 and cg07260927) were significantly different after False Discovery Rate (FDR) correction (q < 0.05).The methylation difference was greatest at cg00594917, located in the first exon of the PPFIA4 gene, which codes for Liprin-α (p=0.00012).Hierarchical cluster analysis of 23 CpG sites in the PPFIA4 gene distinguished BR and WR except for 1 WR patient.The cg07260927 site was located in the 5'UTR of the Heparin sulfate-glucosamine 3-sulfotransferase 1 (HS3ST1) gene (p=0.00013).Hierarchical cluster analysis of 28 CpG sites in HS3ST1 distinguished BR and WR except for 1 WR and 2 BR patients.Conclusion: Our results suggest that patients' DNA methylation profile at specific genes such as PPFIA4 and HS3ST1 is associated with individual variations in therapeutic responses to
Language: English
Field: Medicine
Open Access status: green
OpenAlex ID: W7146081764
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