Influence of birth weight on internalizing traits modulated by serotonergic genes
Birit F P Broekman1, Yiong Huak Chan, Liang Goh
1Department of Psychological Medicine, National University Hospital, National University of Singapore, Singapore. pcmle@nus.edu.sg
Insights
Fetal growth influences childhood behavior, with gene variations impacting this link. Specific gene variants in serotonin pathways modify the relationship between birth weight and internalizing behaviors in children.
Area of Science:
- Neuroscience
- Behavioral Genetics
- Developmental Psychology
Background:
- Fetal growth is linked to childhood behavioral outcomes.
- Serotonergic systems in the brain play a role in these behaviors.
- Genetic variations may influence individual responses to early life conditions.
Purpose of the Study:
- To investigate if genetic variations in serotonergic genes moderate the association between birth weight and childhood internalizing traits.
- To explore the role of specific gene polymorphisms in modulating developmental pathways.
Main Methods:
- Utilized the Child Behavior Checklist in 545 Singaporean children (8-12 years).
- Analyzed birth weight (corrected for gestational age) and single-nucleotide polymorphisms (SNPs) in TPH2, HTR2A, and SCL6A4 genes.
- Employed statistical analyses to identify main effects and gene-environment interactions.
Main Results:
- No significant main effect of birth weight on internalizing scores.
- Significant main effects for HTR2A SNPs (rs2296972, rs6313) on internalizing scores.
- Significant interactions between birth weight and SNPs in TPH2 (rs2171363, rs7305115) and HTR2A (rs2770304, rs6313) genes.
- Specific genotypes (e.g., TPH2 rs2171363 CC) were associated with reduced internalizing scores in higher birth weight quartiles.
Conclusions:
- Sequence variations in serotonergic genes modulate the relationship between birth weight and internalizing traits.
- These genetic variations may represent mechanisms of developmental plasticity.
- Individual differences in behavioral responses to environmental influences are influenced by gene-environment interactions.
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.
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