No Moderating Effect of 5-HTTLPR on Associations Between Antenatal Anxiety and Infant Behavior

Elizabeth C Braithwaite,Paul G Ramchandani,Thomas G O'Connor,Marinus H Van Ijzendoorn,Marian J Bakermans-Kranenburg,Vivette Glover,Elena Netsi,Jonathan Evans,Michael J Meaney,Susannah E Murphy

doi:10.1016/j.jaac.2013.02.010

Abstract

ObjectiveMaternal antenatal anxiety is associated with an increased risk of behavioral disturbances in offspring. Recent work has suggested that the effect of maternal antenatal anxiety on infant temperament at 6 months is moderated by the serotonin transporter polymorphism 5-HTTLPR, with carriers of the short allele more susceptible to the adverse behavioral outcomes of maternal antenatal anxiety. These findings, however, are yet to be replicated and extended beyond infancy. The aim of the current study was to assess this same potential moderator (5-HTTLPR) in a large population-based cohort study, and to determine whether or not the effects persist into childhood and early adolescence.MethodData from the Avon Longitudinal Study of Children and Parents (ALSPAC) cohort (N = 3,946) were used to assess whether the 5-HTTLPR genotype moderated the association between self-reported maternal antenatal anxiety (Crown Crisp Index) in pregnancy, and child temperament at 6 months (Infant Temperament Questionnaire), and also later behavioral and emotional problems on the Strengths and Difficulties Questionnaire from age 4 to 13 years.ResultsWe found no evidence to suggest that the 5-HTTLPR polymorphism moderated the effects of maternal antenatal anxiety on infant temperament at 6 months or infant behavioral and emotional problems from childhood through to adolescence.ConclusionOur results, based on a large prospective community sample that assessed children from infancy to early adolescence, provide a thorough test of, but no evidence for, a genetic moderation of the effects of maternal antenatal anxiety by 5-HTTLPR.

Highlights

There is a growing awareness that environmental exposure to stress can shape developmental trajectories as early as the fetal period
There is considerable debate about the validity of these findings, given two negative meta-analyses of the gene-by-environment (GÂE) interactions,[13,14] one positive meta-analysis, and two relevant papers that suggest that the initial finding may be a false-positive result.[15,16]. We extend this line of research in the current study by testing the hypothesis that 5-HTTLPR moderates the effect of maternal antenatal anxiety on infant temperament and behavioral and emotional problems
Increased aggression and externalizing behaviors were predicted by high third-trimester anxiety only in children with 2 copies of the l allele. These findings suggest that 5-HTTLPR does moderate behavioral outcomes of maternal antenatal anxiety; these results must be interpreted with caution, given the small sample size

Summary

Introduction

There is a growing awareness that environmental exposure to stress can shape developmental trajectories as early as the fetal period. This has been described in terms of the fetal programming hypothesis[1,2] that stipulates that the phenotype of a fetus may be altered during the antenatal period in accordance with maternal cues. Maternal anxiety during pregnancy is associated with an increased risk of behavioral and emotional disturbances in offspring.[3,4,5] A prominent challenge in this field is to disentangle the extent to which intergenerational transmission of mood disturbances are attributable to genetic or

Methods

Results

Conclusion