The role of tryptophan metabolic pathway in children with attention deficit hyperactivity disorder with and without comorbid oppositional defiant disorder and conduct disorder

Ebru Sağlam; Ayhan Bilgiç; Sedat Abuşoğlu; Ali Ünlü; Abdullah Sivrikaya

doi:10.1016/j.psychres.2021.113770

The role of tryptophan metabolic pathway in children with attention deficit hyperactivity disorder with and without comorbid oppositional defiant disorder and conduct disorder

Psychiatry Res. 2021 Apr:298:113770. doi: 10.1016/j.psychres.2021.113770. Epub 2021 Jan 28.

Authors

Ebru Sağlam¹, Ayhan Bilgiç², Sedat Abuşoğlu³, Ali Ünlü³, Abdullah Sivrikaya³

Affiliations

¹ Department of Child and Adolescent Psychiatry, Ankara Bilkent City Hospital, Ankara, Turkey. Electronic address: ebrusglm55@gmail.com.
² Department of Child and Adolescent Psychiatry, Meram School of Medicine, Necmettin Erbakan University, Konya, Turkey.
³ Department of Biochemistry, Selçuk University Faculty of Medicine, Konya, Turkey.

PMID: 33545424
DOI: 10.1016/j.psychres.2021.113770

Abstract

Accumulating data presented that tryptophan metabolic pathway (TMP) may play a role in attention-deficit/hyperactivity disorder (ADHD). However, no study have investigated potential role of TMP in disruptive behavior disorders coexisting with ADHD. This study compared serum levels of tryptophan, kynurenine, kynurenic acid, 3-hydroxykynurenine and 3-hydroxyantranilic acid in medication-free children with ADHD combined presentation (ADHD-C), with ADHD-C and oppositional defiant disorder (ODD), and with ADHD-C and conduct disorder (CD) versus healthy controls. The study also compared several ratios that are previously suggested to reflect the activities of the KP enzymes (kynurenine/tryptophan, kynurenic acid/kynurenine, 3-hydroxykynurenine/kynurenine) or neuroprotective activity (kynurenic acid/3-hydroxykynurenine) among groups. A total of 122 patients were enrolled: 46 children with ADHD-C alone, 43 children with ADHD-C+ODD, 33 children with ADHD-C+CD and 50 healthy controls. Targeted biochemical molecules were assessed by liquid chromatography-mass spectrometry/mass spectrometry. Compared to control group, serum kynurenine levels were significantly higher in the ADHD-C group, serum 3-hydroxykynurenine levels were significantly lower in the ADHD-C and ADHD-C+ODD groups, the serum kynurenic acid/kynurenine ratio was significantly higher in the ADHD-C, ADHD-C+ODD and ADHD-C+CD groups, and the serum 3-hydroxykynurenine/kynurenine ratio was significantly lower in the ADHD-C group. These findings suggest that TMP may play a role in the pathophysiology of ADHD-C.

Keywords: Attention-deficit/hyperactivity disorder; Conduct disorder; Kynurenine pathway; Oppositional defiant disorder; Tryptophan metabolic pathway.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Attention Deficit Disorder with Hyperactivity* / complications
Attention Deficit Disorder with Hyperactivity* / epidemiology
Attention Deficit and Disruptive Behavior Disorders / complications
Attention Deficit and Disruptive Behavior Disorders / epidemiology
Child
Comorbidity
Conduct Disorder* / epidemiology
Humans
Metabolic Networks and Pathways
Tryptophan

Substances

Tryptophan