Novel plasma metabolite markers of attention-deficit/hyperactivity disorder identified using high-performance chemical isotope labelling-based liquid chromatography-mass spectrometry

  • World J Biol Psychiatry. 2021 Feb;22(2):139-148. doi: 10.1080/15622975.2020.1762930.
Liang-Jen Wang  1 ,  Wen-Jiun Chou  1 ,  Ching-Shu Tsai  1 ,  Min-Jing Lee  1 ,  Sheng-Yu Lee  2  3 ,  Chia-Wei Hsu  4 ,  Pei-Chun Hsueh  5 ,  Chih-Ching Wu  6  7  8  9
Affiliations
  • 1. Department of Child and Adolescent Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
  • 2. Department of Psychiatry, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
  • 3. Department of Psychiatry, School of Medicine, and Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
  • 4. Agricultural Biotechnology Research Center, Academia Sinica, Taipei, Taiwan.
  • 5. Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
  • 6. Department of Medical Biotechnology and Laboratory Science, Chang Gung University, Taoyuan, Taiwan.
  • 7. Department of Otolaryngology-Head & Neck Surgery, Linkuo Chang Gung Memorial Hospital, Taoyuan, Taiwan.
  • 8. Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan.
  • 9. Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
PMID: 32351159 DOI: 10.1080/15622975.2020.1762930
Abstract

Objectives: Metabolites are the intermediate and final products of biological processes and ultimately reflect the responses of these processes to genetic regulation and environmental perturbations, including those involved in attention deficit/hyperactivity disorder (ADHD).

Methods: We identified a quantitative profile of plasma metabolites in 58 ADHD patients (mean age 9.0 years, 77.6% males) and 38 healthy control subjects (mean age 10.2 years, 55.3% males) using the high-performance chemical isotope labelling (CIL)-based liquid chromatography-mass spectrometry (LC-MS). Using a volcano plot and orthogonal projections to latent structure-discriminant analysis (OPLS-DA), we determined nine metabolites with differentially expressed levels in ADHD plasma samples.

Results: Compared to the control group, the plasma levels of guanosine, O-phosphoethanolamine, phenyl-leucine, hypoxanthine, 4-aminohippuric acid, 5-hydroxylysine, and L-cystine appeared increased in the ADHD patients, whilegentisic acid and tryptophyl-phenylalanine were down-regulated in the patients with ADHD. We found that the plasma levels of all nine metabolites were able to discriminate the ADHD group from the control group. Levels of O-phosphoethanolamine, 4-aminohippuric acid, 5-hydroxylysine, L-cystine, tryptophyl-phenylalanine, and gentisic acid were significantly correlated with clinical ADHD symptoms.

Conclusions: This study is the first to use the CIL-based LC-MS to profile ADHD plasma metabolites, and we identified nine novel metabolite biomarkers of ADHD.

Keywords
ADHD; LC-MS; biomarkers; chemical isotope labelling; metabolomics.
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