Nutrition in early life interacts with genetic risk to influence preadult behaviour in the Raine Study

Early life nutrition is associated with child behaviour; however, the interplay with genetic vulnerability is understudied. We hypothesised that psychiatric genetic risk interacted with early nutrition to predict behavioural problems in childhood and adolescence.

The Raine Study participants with genetic information aged 2-17 were repeatedly evaluated with the child behaviour checklist total problems score (CBCL_TOT). Breastfeeding duration was recalled at age 1, 2 and 3 follow-up, and toddler diet derived by an age-1 24-h maternal recall (EAT1, scale 0-70, SD 10, higher scores proxying healthy diet). We derived polygenic scores (PGS) impacting general psychopathology: attention-deficit hyperactivity disorder (ADHD), depression, chronic multisite pain (CMSP), total behaviour problems and birthweight. In confounder-adjusted mixed-effects models of CBCL_TOT throughout follow-up we examined nutrition-by-PGS interactions.

In 1393 participants, a borderline signal suggests that 1 month longer breastfeeding reduces CBCL_TOT by -0.108 (95% CI [-0.184, -0.0289]) exclusively in individuals with a higher CMSP PGS (Interaction p = 0.03). In 1310 participants, a strong signal suggests that 1 EAT1 point increase results in a reduced CBCL_TOT by 0.121 points (95% CI [-0.171, -0.0704]) exclusively in individuals with a lower ADHD PGS (Interaction p = 0.0005). Post hoc analysis suggests that plant-based food consumption drives the favourable EAT1-CBCL_TOT association.

Nutrition in early life and psychiatric genetic risk may interact to determine lasting child behaviour. Contrary to our hypothesis, we find dietary benefits in individuals with lower ADHD PGS, necessitating replication. We also highlight the possibility of including genetics in early nutrition intervention trials for causal inference.