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A view of response and resistance to atomoxetine treatment in children with ADHD: effects of CYP2C19 polymorphisms and BDNF levels

  • Pharmacogenetics
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Objective

Although several genes have previously been studied about the treatment of Attention Deficit Hyperactivity Disorder (ADHD), the number of studies investigating the effects of genes on atomoxetine (ATX) treatment is very limited. In this study, we aimed to investigate the effect of CYP2C19 polymorphisms, which have a role in ATX biotransformation, on the treatment response and also to assess whether there is a relationship between BDNF and treatment response in children and adolescents with ADHD.

Methods

One hundred children with ADHD and 100 healthy controls (HCs) were included in this study. The treatment response was assessed 2 months after the start of the ATX treatment. DNA samples from peripheral venous blood were replicated using PCR and analyzed using the ILLUMINA next-generation sequencing method. The resulting fastqs were analyzed using Basespace’s Variant Interpreter Program. Plasma BDNF levels were evaluated with ELISA kits.

Results

Treatment response was found to be lower in both heterozygous and homozygous carriers of the c.681G > A (CYP2C19*2) polymorphism. When the BDNF level was compared, it was found to be significantly higher in the ADHD group compared to HCs. Also, BDNF has a stronger predictive value for assessing resistance to ATX treatment.

Conclusions

To our knowledge, this is the first study to assess the effects of CYP2C19 polymorphisms and BDNF levels together on ATX treatment in children. Further studies with an extensive population are needed to better understand the effects of CYP2C19 polymorphisms on treatment and side effects, as well as the effects of BDNF levels.

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Funding

This study was supported by the Scientific Research Center of Erciyes University (Grant number TOA-2018–7800). The Scientific Research Center of Erciyes University had no role in study design; in the collection, analysis, and interpretation of data; and in the writing of the report.

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Authors and Affiliations

  1. Department of Child and Adolescent Psychiatry, Erciyes University School of Medicine, Kayseri, 38039, Turkey

    Esra Demirci

  2. Genome and Stem Cell Center (GENKOK)/Erciyes University Faculty of Medicine Department of Medical Biology, Erciyes University, Kayseri, Turkey

    Elif Funda Sener, Muge Gulcihan Onal & Fatma Dal

  3. Department of Child and Adolescent Psychiatry, Kayseri City Hospital, Kayseri, Turkey

    Melike Kevser Gul

Authors
  1. Esra Demirci
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  2. Elif Funda Sener
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  3. Melike Kevser Gul
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  4. Muge Gulcihan Onal
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  5. Fatma Dal
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Contributions

Designed the study: ED and EFS. Performed the experiments or case: ED and MKG. Analyses of gene variants: FD, EFS, and MGO. Analyzed the data: ED, MKG, EFS, and MGO. Wrote the paper: ED and EFS. All authors have read and approved the final manuscript.

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Correspondence to Esra Demirci.

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The authors declare no competing interests.

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This study was conducted between 2017 and 2019. Preliminary data of the study has been presented as a verbal presentation in May 2021 at the 30th National Child and Adolescent Psychiatry Congress in Turkey and is not currently under consideration for publication in another journal.

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Demirci, E., Sener, E.F., Gul, M.K. et al. A view of response and resistance to atomoxetine treatment in children with ADHD: effects of CYP2C19 polymorphisms and BDNF levels. Eur J Clin Pharmacol 78, 1095–1104 (2022). https://doi.org/10.1007/s00228-022-03321-2

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  • DOI: https://doi.org/10.1007/s00228-022-03321-2

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