Prenatal Effects of Selective Serotonin Reuptake Inhibitor Antidepressants, Serotonin Transporter Promoter Genotype (SLC6A4), and Maternal Mood on Child Behavior at 3 Years of Age

Objectives: To investigate whether prenatal selective serotonin reuptake inhibitor (SSRI) antidepressant exposure affects behavior in 3-year-olds of antenatally anxious or depressed mothers and whether risk was moderated by the serotonin transporter promoter (SLC6A4) genotype. Design: Prospective longitudinal cohort design. Setting: Vancouver. Participants: Mothers and their 3-year-old children (n = 33 SSRI exposed and n = 42 nonexposed). Main Exposures: Prenatal exposure to SSRI antidepressants and prenatal and postnatal maternal mood disturbances. Main Outcome Measures: Parent report of child behavior (ChildBehavior Checklist, ages 1.5-5 years) and the child SLC6A4 genotype. The covariates used were maternal mood during the third trimester, 3 months post partum, and at the 3-year follow-up study and the child's 5-minute Apgar score. Results: Prenatal exposure to both maternal depressed mood and SSRI antidepressants were associated with increased internalizing behaviors during early childhood, whereas current maternal mood increased risk for externalizing behaviors. Increased child anxiety and depression symptoms were predicted by higher third-trimester maternal anxiety only in children with 2 short S alleles. In contrast, increased aggression and externalizing behaviors were predicted by third-trimester maternal anxiety only in children with 2 copies of the L allele. Conclusions: Exposure to prenatal SSRIs and maternal mood had distinct effects on child behavior at 3 years of age, reflected in an increased level of internalizing behaviors. The impact of antenatal maternal anxiety on child mood was moderated by the child SLC6A4 genotype. Despite SSRI treatment for prenatal maternal mood disturbances, childhood behavior at 3 years of age remained at risk.