Peripheral Mitochondrial DNA Copy Number is Increased in Korean Attention-Deficit Hyperactivity Disorder Patients

Johanna Inhyang Kim; Soo-Young Lee; Mira Park; Si Yeon Kim; Jae-Won Kim; Soon Ae Kim; Bung-Nyun Kim

doi:10.3389/fpsyt.2019.00506

Peripheral Mitochondrial DNA Copy Number is Increased in Korean Attention-Deficit Hyperactivity Disorder Patients

Front Psychiatry. 2019 Jul 18:10:506. doi: 10.3389/fpsyt.2019.00506. eCollection 2019.

Authors

Johanna Inhyang Kim¹, Soo-Young Lee², Mira Park³, Si Yeon Kim³, Jae-Won Kim⁴, Soon Ae Kim², Bung-Nyun Kim⁴

Affiliations

¹ Department of Psychiatry, Hanyang University Medical Center, Seoul, South Korea.
² Department of Pharmacology, School of Medicine, Eulji University, Daejeon, South Korea.
³ Department of Preventive Medicine, School of Medicine, Eulji University, Daejeon, South Korea.
⁴ Division of Child and Adolescent Psychiatry, Department of Psychiatry, Seoul National University College of Medicine, Seoul, South Korea.

Abstract

The involvement of mitochondrial dysfunction in the pathophysiology of attention-deficit hyperactivity disorder (ADHD) has been suggested in several reports. Mitochondrial DNA (mtDNA) copy number as well as methylation of the D-loop region and peroxisome-proliferator-activated receptor γ co-activator-1α (PPARGC1A) are considered biomarkers for mitochondrial dysfunction. We compared the mtDNA copy number and methylation ratio of the D-loop region and PPARGC1A between ADHD patients and controls and also among ADHD subtypes. The present study included 70 subjects with ADHD and 70 age- and gender-matched healthy controls (HCs). We measured the relative mtDNA copy number in peripheral blood cells using quantitative polymerase chain reaction (qPCR), and the methylation ratio was measured using methylation-specific PCR (MSP) after bisulfite conversion. The relative mtDNA copy number was significantly higher in ADHD patients than in HCs (p = 0.028). The mtDNA methylation ratio of PPARGC1A was decreased in ADHD patients compared with HCs (p = 0.008). After adjusting for IQ level, only the mtDNA copy number differed between the ADHD and HCs (p = 0.01). There was a significant difference in the methylation ratio of PPARGC1A among ADHD subtypes. These results suggest the possible involvement of mitochondrial dysfunction in the pathophysiology of ADHD. Further large cohort studies investigating the correlation between clinical markers and biomarkers of mitochondrial dysfunction are warranted.

Keywords: attention-deficit hyperactivity disorder (ADHD); mitochondrial DNA (mtDNA); mitochondrial dysfunction; peroxisome-proliferator-activated receptor γ co-activator-1α,DNA methylation.