1. Introduction
inflammation, Attention-deficit, hyperactivity, hyperactivity disorder, impulsivity, ADHD, neurodevelopmental disorder
DISORDER, INFLAMMATION, PATHOPHYSIOLOGY, DISEASES, CORTEX
This work is part of the doctoral thesis of this author.Background: Increasing evidence supports a neuroinflammatory basis in ADHD damaging glial function and thereby altering dopaminergic (DA) neurotransmission. Previous studies focusing on the S100B protein as a marker of glial function have shown contradictory results. We conducted a clinical trial to investigate differences in S100B levels between ADHD patients and controls, as well as observe gradual changes in S100B concentrations after a triple therapy (TT) containing methylphenidate (MPH), melatonin (aMT) and omega-3 fatty acids (ω-3 PUFAs). Methods: 62 medication-naïve children with ADHD (ADHD-G) and 65 healthy controls (C-G) were recruited. Serum S100B was measured at baseline (T0) in ADHD-G/C-G, and three (T3) and six months (T6) after starting TT in the ADHD-G, together with attention scores. Results: A significant increase in S100B was observed in the ADHD-G vs. C-G. In the ADHD-G, significantly higher S100B values were observed for comparisons between T0–T3 and between T0–T6, accompanied by a significant improvement in attention scores for the same timepoint comparisons. No significant differences were found for S100B between T3–T6. Conclusion: Our results agree with the hypothesis of glial damage in ADHD. Further studies on the link between DA and S100B are required to explain the transient increase in S100B following TT. Attention-deficit and/or hyperactivity disorder (ADHD) is a common neurodevelopmental disorder in children and adolescents, characterized by the impairing presence of inattention, hyperactivity, and impulsivity [The pathophysiology of ADHD is not completely understood. Core symptoms have been linked to disruptions in the maturation of the cerebellum, caudate and prefrontal cortex (PFC). These areas create a network involved in the regulation of executive functions (attention, working memory, behavioral inhibition, and planning) [The mechanisms leading to the catecholaminergic disruption observed in this disorder are multifactorial [The cytokine-related neurotrophin S100B, mainly secreted by astrocytes and oligodendrocytes, is a well-known biomarker of glial function [Variations in S100B levels have been associated with neuropsychiatric diseases for which a redox imbalance and inflammatory basis are proposed [Nowadays, increasing evidence supports a neuroinflammatory origin of ADHD, as an association was found with single-nucleotide polymorphisms (SNPs) in genes involved in angiogenesis and inflammation [Psychostimulants, and particularly the different formulations of methylphenidate (MPH), continue to be the first-line pharmacological treatment for ADHD. MPH blocks the presynaptic DA and NE transporters that respectively reuptake these neurotransmitters, thus facilitating catecholaminergic neurotransmission [Based on the interaction with DA/NE neurotransmitters and the pro-inflammatory actions of S100B, we support that this protein may act as a mediator in the neuroinflammatory mechanisms leading to the catecholaminergic disruption preceding ADHD symptoms. Accordingly, we hypothesized that: (1) S100B concentrations in pediatric patients with ADHD should differ from controls; and (2) variations in S100B levels should accompany the clinical response of ADHD patients with a triple therapy consisting of MPH, aMT and ω-3 PUFAs. In this dual three-month-phase clinical trial on children and adolescents with ADHD, we aimed at (1) evaluating differences in serum S100B levels between ADHD patients and healthy controls; and (2) assessing gradual changes in both serum S100B concentrations and clinical symptoms (as per attention scores) after initiating treatment with a combination of MPH, aMT and ω-3 PUFAs.