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

Abstract

We investigated the interaction between a genetic score and an exercise intervention on brain health in children with over-weight/obesity. One hundred one children with overweight/obesity (10.0 ± 1.5 yr, 59% girls) were randomized into a 20-wkcombined 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 [meanz-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 Cohend) 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 (P¼0.01 andP¼0.03, 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.