DNA Methylation of Fluoxetine Response in Child and Adolescence: Preliminary Results

Albert Martinez-Pinteño; Natalia Rodriguez; Ana Blázquez; Maria Teresa Plana; Eva Varela; Patricia Gassó; Amalia Lafuente; Luisa Lazaro; Sergi Mas

doi:10.2147/PGPM.S289480

DNA Methylation of Fluoxetine Response in Child and Adolescence: Preliminary Results

Pharmgenomics Pers Med. 2021 Apr 19:14:459-467. doi: 10.2147/PGPM.S289480. eCollection 2021.

Authors

Albert Martinez-Pinteño^#¹, Natalia Rodriguez^#¹, Ana Blázquez², Maria Teresa Plana², Eva Varela², Patricia Gassó^{1

3}, Amalia Lafuente^{1

3

4}, Luisa Lazaro^{2

3

4

5}, Sergi Mas^{1

3

4}

Affiliations

¹ Department of Basic Clinal Practice, Pharmacology Unit, University of Barcelona, Barcelona, Spain.
² Department of Child and Adolescent Psychiatry and Psychology, Institute of Neurosciences, Hospital Clinic de Barcelona, Barcelona, Spain.
³ Clinical and Experimental Neuroscience Area, The August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain.
⁴ G04 Group, Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Carlos III Health Institute, Madrid, Spain.
⁵ Department of Medicine, University of Barcelona, Barcelona, Spain.

^# Contributed equally.

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: DNA methylation; antidepressants; epigenetics; epigenomics; pharmacogenetics.

Grants and funding

This work was supported by the Alicia Koplowitz Foundation; Ministerio de Economía y Competitividad-Instituto de Salud Carlos III-Fondo Europeo de Desarrollo Regional (FEDER)-Unión Europea (PI16/01086). Support was also given by the CERCA Programme/the Government of Catalonia, Secretaria d’Universitats i Recerca del Departament d’Economia i Coneixement to the “Child Psychiatry and Psychology Group” (2017SGR881) and to the “Clinical Pharmacology and Pharmacogenetics Group” (2017SGR1562). Funding sources had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.