Indole Tryptophan Metabolism and Cytokine S100B in Children with Attention-Deficit/Hyperactivity Disorder: Daily Fluctuations, Responses to Methylphenidate, and Interrelationship with Depressive Symptomatology.

Abstract

Background: Indole tryptophan metabolites (ITMs), mainly produced at the gastrointestinal level, participate in bidirectional gut-brain communication and have been implicated in neuropsychiatric pathologies, including attention-deficit/hyperactivity disorder (ADHD). Method: A total of 179 children, 5-14 years of age, including a healthy control group (CG, n = 49), and 107 patients with ADHD participated in the study. The ADHD group was further subdivided into predominantly attention deficit (PAD) and predominantly hyperactive impulsive (PHI) subgroups. Blood samples were drawn at 20:00 and 09:00 hours, and urine was collected between blood draws, at baseline and after 4.63 ± 2.3 months of methylphenidate treatment in the ADHD group. Levels and daily fluctuations of ITM were measured by tandem mass spectrometer, and S100B (as a glial inflammatory marker) by enzyme-linked immunosorbent assay. Factorial analysis of variance (Stata 12.0) was performed with groups/subgroups, time (baseline/after treatment), hour of day (morning/evening), and presence of depressive symptoms (DS; no/yes) as factors. Results: Tryptamine and indoleacetic acid (IAA) showed no differences between the CG and ADHD groups. Tryptamine exhibited higher evening values (p