Is S100B Involved in Attention-Deficit/Hyperactivity Disorder (ADHD)? Comparisons with Controls and Changes Following a Triple Therapy Containing Methylphenidate, Melatonin and ω-3 PUFAs

Abstract

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.

Peripheral S100B Protein Levels in Five Major Psychiatric Disorders: A Systematic Review

“…In BD, studies are conducted in manic [62,[93][94][95][96] or depressive episodes [77,97,98], as well as in euthymia [71,[99][100][101][102], also with inconsistent results; however, a recent meta-analysis confirmed increased S100B levels in bipolar disorder [120]. In ASD, elevation [103][104][105][106], no differences [107][108][109][110] in S100B levels were reported, and parallel results were found in ADHD studies (no differences [113][114][115] or higher [116,117] S100B levels in patient groups), though in ADHD, three out of five publications were performed on the same group, analyzing different clinical aspects [113][114][115].…”

“…Three measures: baseline, after three (T3), and six (T6) months of therapy were performed. A significant increase in S100B levels between baseline and T3 and sustained elevated S100B at T6 was observed, along with an improvement in attention scores [ 117 ].…”

Maternal pre-pregnancy and prenatal penicillin, neonatal inflammation and growth factors are associated to ADHD in the offspring

“…Analyses of the biomarkers were made on extractions from the dried blood spot samples using a Meso-Scale Discovery based in-house developed multiplex assay targeting 3 biomarkers for inflammation (Interleukin-18 (IL-18), Monocyte Chemotactic Protein (MCP-1), C-Reactive Protein (CRP)), 1 anti-inflammatory marker (soluble Tumor Necrosis Factor Receptor-1 (sTNF RI)), all as an indication for infection in the pregnancy. The other biomarkers have all been associated with ADHD or ASD in other studies, and may indicate problems with the neuronal development: 1 biomarker for stress (Heat Shock Protein-70 (HSP70)) ( Özaslan et al, 2022 ), 2 growth factors (Vascular Endothelial Growth Factor A (VEGF-A) ( Yurteri et al, 2019 ), Epidermal Growth Factor (EGF) ( Tonhajzerova et al, 2021 )), 3 neurotrophic biomarkers important for brain development and/or damage (Brain-Derived Neurotrophic Factor (BDNF) ( Gumus et al, 2022 ), Neurotrophin-3 (NT-3) ( Tostes et al, 2012 ), and S100 calcium binding protein B (S100B) ( Ouadih-Moran et al, 2023 )), as described previously ( Kiilerich et al, 2021 ).…”

Efficacy and safety of a daytime anxiolytic containing technologically processed antibodies to the S100 protein. Overview of clinical studies

“…Что касается СДВГ, накапливаются данные, которые подтверждают роль в его патогенезе нейровоспаления, повреждения глии с нарушениями ее функций и последующих изменений дофаминергической нейротрансмиссии; при этом немногочисленные исследования белка S100B при СДВГ как маркера глиальной дисфункции показали противоречивые результаты, хотя и опубликованы данные о повышении его периферических уровней [47].…”