Cortisol, Anxiety, and TNFα Mediate the Relationship Between BMI and Executive Functions

Overweight and obesity are associated with poorer executive functions (EF). The underlying mechanisms contributing to this relationship are not yet conclusive, but cortisol, anxiety, and inflammation are likely among the contributing factors. Our objective was to evaluate whether fibrinogen, tumour necrosis factor alpha (TNFα), cortisol, and anxiety significantly mediate the association between body mass index (BMI) z-score and EF (i.e., working memory, inhibition, cognitive flexibility, and a latent EF component) in both adolescents and adults. In this cross-sectional study, 268 participants aged 11-49 years with BMI values ranging from normal-weight to obesity were medically and neuropsychologically evaluated. Moderated multiple mediation analyses with mediators in parallel were conducted (X: BMI z-score; M: cortisol, anxiety, TNFα, and fibrinogen; Y: executive functions; Moderator: adolescent and adult groups). Our results suggested that TNFα mediated the association between BMI z-score and working memory only in adolescents (indirect effect = 0.09, 95% CI [0.03, 0.19]), whereas in adults, cortisol (indirect effect = -0.06, 95% CI [-0.13, -0.01]) and anxiety (indirect effect = 0.02, 95% CI [0.0001, 0.07]) mediated this association. Additionally, in adults, anxiety also mediated the relationship between BMI z-score and the latent EF component (indirect effect = 0.03, 95% CI [0.004, 0.08]). In the full sample, TNFα significantly mediated the relationship between BMI z-score and inhibition (indirect effect = -0.03, 95% CI [-0.06, -0.002]). In conclusion, our study suggests that inflammation, cortisol, and anxiety are biologically and psychologically plausible mechanisms through which BMI may influence cognitive performance. Large-scale longitudinal studies are needed to confirm these findings and to determine whether the observed associations are age-dependent.