DNA Methylation of Fluoxetine Response in Child and Adolescence: Preliminary Results
Albert Martínez-Pinteño, Natàlia Rodríguez, Ana Blázquez, María Teresa Plana, Eva Varela, Patricia Gassó, Amàlia Lafuente, Luisa Lázaro, Sergi Mas
Abstract
Purpose: The search for predictors of antidepressant response is gaining increasing attention, with epigenetic markers attracting a great deal of interest. We performed a genome-wide study assessing baseline differences in DNA methylation between Responders and Non-Responders. Patients and Methods: Twenty-two children and adolescents, receiving fluoxetine treatment for the first time, were classified as Responders or Non-Responders according to CGI-I score after 8 weeks of fluoxetine treatment. Genome-wide DNA methylation was profiled using the Illumina Infinium MethylationEPIC BeadChip Kit and analyzed using the Chip Analysis Methylation Pipeline (ChAMP). Results: We identified 21 CpG sites significantly (FDR< 0.05) associated with fluoxetine response that showed meaningful differences (Δβ> ± 0.2) in methylation level between Responders and Non-Responders. Two genes, RHOJ ( Ras Homolog Family Member J ) and OR2L13 (Olfactory Receptor family 2 subfamily L member 13) , presented more than one significant CpG sites. Conclusion: Our findings provide new insights into the molecular mechanisms underlying the complex phenotype of antidepressant response, indicating that methylation at specific genes could be a promising biomarker that needs further replication in large cohorts. Keywords: epigenomics, epigenetics, DNA methylation, pharmacogenetics, antidepressants