Inflammatory biomarkers and brain health indicators in children with overweight and obesity: The ActiveBrains project.

ABSTRACT

INTRODUCTION: Chronic inflammation plays an important role on the pathogenesis of several cardiovascular and metabolic diseases, as well as on brain function and behaviour. The aim of the present study was to examine the associations between inflammatory biomarkers and a wide range of brain health indicators (i.e., academic performance, executive function, behavioural and emotional functioning, and brain volume) in children with overweight/obesity. METHODS: A total of 107 children (10.0 ±â€¯1.1 years, 41% girls) from the ActiveBrains project were included in the analysis. Five inflammatory biomarkers were analysed in plasma white blood cell (WBC) count, interleukin-6 (IL-6), interleukin-1ß, tumor necrosis factor-α (TNF-α), and C-reactive protein (CRP). Academic performance was assessed by Woodcock-Muñoz Tests of Achievement. Executive function was assessed through the Design Fluency Test for cognitive flexibility, the Stroop test for cognitive inhibition, and the Delayed Non-Match-to-Sample task for working memory. Behavioural and emotional functioning was evaluated through the Behavior Assessment System for Children (BASC) questionnaire. Total and regional brain volume was assessed by magnetic resonance imaging. RESULTS: IL-6 was inversely associated with adaptive skills (ß = -0.228; p = 0.030), while TNF-α was related to mathematics (ß = -0.198; p = 0.034). In addition, CRP was positively associated with externalizing (ß = 0.246; p = 0.046) and internalizing problems (ß = 0.234; p = 0.039), as well as the behavioural symptoms index (ß = 0.236; p = 0.047). However, these significant associations disappeared after multiple comparisons correction. Inflammatory biomarkers were not associated with executive function and total brain volumes. Regarding regional brain analyses, WBC was positively associated with gray matter volume in the left middle temporal gyrus (ß = 0.387; p < 0.001, k = 44), and CRP was positively associated with gray matter volume in the right superior temporal gyrus (ß = 0.439; p < 0.001, k = 29). Additionally, when adjusting by total brain volume, CRP was positively associated with gray matter volume in the right supplementary motor cortex (ß = 0.453; p < 0.001, k = 51). Moreover, both, IL-6 (ß = 0.366; p < 0.001, k = 81) and TNF-α (ß = 0.368; p < 0.001, k = 62) were positively associated with white matter volume around the right inferior frontal gyrus pars opercularis, while CRP was inversely associated with white matter volume around the left superior frontal gyrus (ß = -0.482; p < 0.001, k = 82). After adjusting by total brain volume, CRP was also inversely associated with white matter volume in 3 additional clusters (ß ranging from -0.473 to -0.404; p < 0.001, k = 87). CONCLUSIONS: Inflammation was slightly associated with brain health (i.e., academic performance, behavioural and emotional functioning and regional brain volume) in children with overweight or obesity. Further larger longitudinal and interventional studies are warranted to elucidate the short-term and long-term effect of systemic low-grade inflammation on children's brain health.