Elsevier

Biological Psychiatry

Volume 69, Issue 6, 15 March 2011, Pages 520-525
Biological Psychiatry

Archival Report
Serotonin Transporter Polymorphism Moderates Effects of Prenatal Maternal Anxiety on Infant Negative Emotionality

https://doi.org/10.1016/j.biopsych.2010.10.006Get rights and content

Background

Consistent with the fetal programming hypothesis, effects of maternal prenatal anxiety have been found to predict various measures of infant temperament in the early postnatal period. In recent years, a polymorphism in the serotonin transporter gene (5-HTTLPR) emerged as a moderator of diverse environmental influences on different outcomes, with individuals carrying the short allele being generally more vulnerable to adversity.

Methods

We tested whether the association between self-reported maternal anxiety at 20 weeks gestation (Brief Symptom Inventory) and mother-rated infant negative emotionality at 6 months after birth (Infant Behavior Questionnaire-Revised) would be moderated by the 5-HTTLPR in a large Dutch cohort sample (n = 1513). We hypothesized that infants carrying the 5-HTTLPR short allele would be more susceptible and therefore more affected by both low and high prenatal maternal anxiety vis-à-vis negative emotionality than other genotypes.

Results

Findings of a significant gene × environment interaction (B = .65, p = .01) were supportive of a vulnerability model, with infants carrying the short allele being more negatively emotional when mothers reported anxiety during pregnancy, whereas there was no difference between genotypes on negative emotionality when maternal anxiety was low.

Conclusions

The association between maternal anxiety during pregnancy and negative emotionality in early infancy was significant in infants carrying one or more copies of the short allele but not in those homozygous for the long allele. The 5-HTTLPR short allele might increase vulnerability to adverse environmental influences as early as the fetal period.

Section snippets

Design

This research was embedded in the Generation R Study, a population-based cohort study investigating growth, development, and health from fetal life into young adulthood in Rotterdam, the Netherlands. The Generation R Study has previously been described in detail (22). Briefly, all pregnant women living in the study area with a delivery date between April 2002 and January 2006 were informed about the research project by community midwives and obstetricians. Inclusion criteria were: 1) residency

Results

The serotonin transporter polymorphism, 5-HTTLPR, was not associated with infant negative emotionality and, critically, maternal prenatal anxiety, according to bivariate correlations. The latter fact rules out the possibility of gene–environment correlation being misinterpreted as GXE interaction (17). See Table 2 for the bivariate correlations between variables.

For the hierarchical regression analysis, variables were entered in three steps to predict infant negative emotionality: Step 1

Discussion

The serotonin transporter polymorphism, 5-HTTLPR, moderated the effects of maternal anxiety during pregnancy on infant negative emotionality at 6 months after birth, as hypothesized. The hypothesized association between higher levels of maternal anxiety during pregnancy and higher levels of infant negative emotionality proved strongest for individuals with two short alleles, weakest for individuals with two long alleles, and intermediate for heterozygotes. To investigate whether the significant

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