4. Discussion
hyperactive/impulsive, neuroinflammation, ADHD
DISORDER
In this clinical trial on a sample of medication-naïve children and adolescents with ADHD, peripheral S100B levels were measured with two main objectives: (1) to establish comparisons with healthy children as controls; and (2) to observe gradual differences in serum S100B values in the ADHD group before (T0) and after (T3–T6) treatment with a triple therapy containing MPH, aMT and ω-3 PUFAs (EPA/DHA). Secondarily, we also reported the clinical effects obtained with this therapy based on the attention measures obtained in the MSVA and the reports from parents/guardians and teachers. At baseline (T0), we found significantly higher levels of S100B protein in the ADHD group compared to control participants. Focusing on the patients with ADHD, a significant increase in S100B values was observed when comparing the levels of this protein before treatment onset with those three and six months after starting therapy. However, S100B values at T3 and T6 were similar. The two components of attention, QA and SA scores, also showed a significant improvement after three and six months of therapy in relation to baseline values (T3 vs. T0 and T6 vs. T0), with no significant changes observed when comparing QA/SA scores between three and six months after treatment onset. When comparing S100B values between ADHD patients and controls, our results differed from the first studies presented by Oades et al. [The finding of significantly higher peripheral S100B concentrations in patients with ADHD in relation to non-related controls in our study is in line with the hypothesis of global neuroinflammation leading to the dopaminergic disruption observed in this disorder. A pro-inflammatory state in the brain would activate astrocytes, which would react by releasing S100B and activating the NF-kB-dependent inflammatory cascade through the interaction between S100B and RAGE [The most striking result was a paradoxically significant increase in S100B concentrations three months after starting therapy (T3) compared to baseline (T0) in the ADHD group, at the same time that a significant improvement in the attention scores (QA/SA) was also observed. In the study conducted by Fernández-López et al. [Our study contained several limitations: first, the design did not allow us to observe the relative effect on S100B due to MPH, whereas a clinical trial with different treatment arms would have provided information on the impact of each therapeutic component on this protein; second, we lacked evidence on the response triggered by this treatment in patients with a pure hyperactive/impulsive presentation, as the sample only included patients classified as predominantly inattentive or combined; third, the application of more flexible exclusion criteria with respect to the prior investigations conducted by Oades et al. [To date, this is the first trial reporting on gradual changes in peripheral S100B levels in children and adolescents with ADHD receiving a triple therapy containing MPH and the anti-inflammatory combination of aMT and EPA/DHA. The differences observed between patients with ADHD and controls provide evidence in line with the glial damage leading to dopaminergic disruption and consequent ADHD symptoms [