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Licensed Unlicensed Requires Authentication Published by De Gruyter February 24, 2022

CYP450 2D6 and 2C19 genotypes in ADHD: not related with treatment resistance but with over-representation of 2C19 ultra-metabolizers

  • Meryem Ozlem Kutuk ORCID logo , Ali Evren Tufan , Zehra Topal , Ufuk Acikbas , Gulen Guler , Bahriye Karakas , Huveyda Basaga , Fethiye Kilicaslan , Ebru Altintas , Yeliz Aka and Ozgur Kutuk EMAIL logo



Cytochrome P450 (CYP450) is a major enzyme system involved in drug metabolism as well as regulation of brain function. Although individual variability in CYP enzymes have been studied in terms of personality traits and treatment effects, no study up to now evaluated CYP polymorphisms in children with attention deficit/hyperactivity disorder (ADHD). We aimed to define the genetic profiles of CYP2D6 and CYP2C19 relevant alleles in children with ADHD according to treatment status and compare the frequencies according to past results.


Three hundred and seventeen patients with ADHD-Combined Presentation were enrolled; symptom severity was evaluated by parents and clinicians while adverse effects of previous treatments were evaluated with parent and child reports. Reverse blotting on strip assays was used for genotyping and descriptive and bivariate analyses were conducted. A p-value was set at 0.05 (two-tailed).


Children were divided into treatment-naïve (n=194, 61.2%) and treatment-resistant (n=123, 38.8%) groups. Within the whole sample PM, EM and UM status according to 2D6 were 3.8% (n=12), 94.3% (n=299) and 21.9% (n=6); respectively. PM, IM, EM and UM status according to 2C19 were 2.5% (n=8), 19.8% (n=63), 48.6% (n=154) and 29.0% (n=92), respectively. No relationship with treatment resistance, comorbidity or gender could be found. Importantly, CYP2C19 UMs were significantly more frequent in ADHD patients compared to previous studies in the general population.


CYPs may be a rewarding avenue of research to elucidate the etiology and treatment of patients with ADHD.

Corresponding author: Ozgur Kutuk, Baskent University School of Medicine, Adana Dr. Turgut Noyan Research and Medical Center, 01250, Yuregir, Adana, Turkey, E-mail:

  1. Research funding: Baskent University Research Fund. Donald J. Cohen Fellowship Program (DJCFP) for International Scholars in Child and Adolescent Mental Health.

  2. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  3. Competing interests: Authors state no conflict of interest.

  4. Informed consent: Informed consent was obtained from all individuals included in this study.

  5. Ethical approval: This study was approved by Baskent University Institutional Review Board and Ethics Committee (Project no: KA18/159, Date: 06/06/2018).


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Supplementary Material

The online version of this article offers supplementary material (

Received: 2021-07-18
Accepted: 2022-01-03
Published Online: 2022-02-24

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