Serotonin transporter polymorphism moderates effects of prenatal maternal anxiety on infant negative emotionality

Michael Pluess*, Fleur P. Velders, Jay Belsky, Marinus H. Van IJzendoorn, Marian J. Bakermans-Kranenburg, Vincent W.V. Jaddoe, Albert Hofman, Pascal P. Arp, Frank C. Verhulst, Henning Tiemeier

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review


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 X 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.

Original languageEnglish
Pages (from-to)520-525
Number of pages6
JournalBiological Psychiatry
Issue number6
Publication statusPublished - 15 Mar 2011
Externally publishedYes


  • 5-HTTLPR
  • differential susceptibility
  • gene X environment (GXE) interaction
  • infant temperament
  • prenatal programming
  • serotonin transporter


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