The role of tryptophan metabolic pathway in children with attention deficit hyperactivity disorder with and without comorbid oppositional defiant disorder and conduct disorder. (April 2021)

• Record Type: Journal Article
• Authors: Sağlam, Ebru; Bilgiç, Ayhan; Abuşoğlu, Sedat; Ünlü, Ali; Sivrikaya, Abdullah
• Is Part Of: Psychiatry research. Volume 298(2021)
• Publication Date: 2021-04
• Subjects: Attention-deficit/hyperactivity disorder -- Oppositional defiant disorder -- Conduct disorder -- Tryptophan metabolic pathway -- Kynurenine pathway; TRP tryptophan -- TMP tryptophan metabolic pathway -- KP kynurenine pathway -- 5-HT 5-hydroxytryptamine or serotonin -- IDO Indoleamine 2, 3-dioxygenase -- TDO TRP 2, 3-dioxygenase -- KYN kynurenine -- 3-HK 3-Hydroxykynurenine -- KMO kynurenine mono-oxygenase -- 3-HAA 3-hydroxyanthranilic acid -- QUIN quinolinic acid -- KAT kynurenine aminotransferase -- KYNA kynurenic acid -- AA anthranilic acid; Psychiatry -- Periodicals; Psychiatry -- periodicals; Psychiatrie -- Périodiques; 616.89
• DOI: 10.1016/j.psychres.2021.113770
• Languages: English
• ISSNs: 0165-1781

Abstract

Highlights: KYN levels were higher in ADHD-C group. 3-HK levels were lower in ADHD-C and ADHD-C+ODD groups. Kynurenic acid/KYN ratio was lower in all patient groups. Hydroxykynurenine/KYN ratio was lower in ADHD-C group. KYN pathway metabolite levels did not differ among three patient groups. 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.