Influence of birth weight on internalizing traits modulated by serotonergic genes.

Objective: Fetal growth predicts childhood behavioral problems associated with brain serotonergic systems. We hypothesized that allelic variations in genes involved in serotonergic function would moderate associations between birth weight (BW) and internalizing traits in childhood.

Methods: The Child Behavior Checklist was administered to 545 healthy Singaporean children at 8 to 12 years. BW, corrected for gestational age, and candidate single-nucleotide polymorphisms (SNPs) in the TPH2, HTR2A, and SCL6A4 genes were investigated.

Results: There was no significant main effect of BW on internalizing T scores (F = 1.08; P = .36). After multiple corrections, significant main effects on internalizing T scores were found for HTR2A rs2296972 (adjusted: F = 2.85; P = .019) and HTR2A rs6313 (adjusted: F = 5.91; P = .0002). Significant interactions were found between BW and SNPs for the TPH2 gene (rs2171363: P = .008; rs7305115: P = .007) and the HTR2A gene (rs2770304: P = .001; rs6313: P = .026) for internalizing T scores. The CC genotype of TPH2 rs2171363, GG genotype of TPH2 rs7305115, CC genotype of HTR2A rs2770304, and CC genotype of HTR2A rs6313 were associated with reduced internalizing scores for children born in the quartile above the midpoint. No significant main effects or interactions were found for SCL6A4 SNPs.

Conclusions: These findings suggest that sequence variations in genes involved in serotonergic functions modulate relationships between BW and internalizing traits and might be candidates for plasticity mechanisms that determine individual differences in responses to environmental influences over the course of development.