Gene-exercise interaction on brain health in children with overweight/obesity: The ActiveBrains randomized controlled trial

We investigated the interaction between a genetic score and an exercise intervention on brain health in children with overweight/obesity. One hundred one children with overweight/obesity (10.0 ± 1.5 years, 59% girls) were randomized into a 20-week combined exercise intervention or a control group. Several cognitive and academic outcomes were measured with validated tests. Hippocampal volume was quantified using magnetic resonance imaging. Six brain health-related polymorphisms (rs6265 [ BDNF], rs2253206 [ CREB1], rs2289656 [ NTRK2], rs4680 [ COMT], rs429358, and rs7412 [ APOE]) were genotyped. Cognitive flexibility and academic skills improved significantly more in the exercise than in the control group only in the children with a "favorable" genetic profile (mean z score, 0.41-0.67 [95% CI 0.11 to 1.18], yet not in those with "less favorable" genetic profile. An individual response analysis showed that children responded to exercise in cognitive flexibility only in the "genetically favorable" group (i.e. 62% of them had a meaningful [≥0.2 Cohen d] increase in the exercise group compared with only 25% in the control group). This finding was consistent in per-protocol and intention-to-treat analyses (P=0.01 and P=0.03, respectively). The results were not significant or not consistent for the rest of outcomes studied. Our findings suggest that having a more favorable genetic profile makes children with overweight-obesity more responsive to exercise, particularly for cognitive flexibility.