Polymorphic variations in the serotonin transporter gene (5-HTT) moderate the depressogenic effects of tryptophan depletion. After childbirth there is a sharp reduction in brain tryptophan availability, thus polymorphic variations in 5-HTT may play a similar role in the post-partum period.

To study the role of 5-HTT polymorphic variations in mood changes after delivery.

One thousand, eight hundred and four depression-free Spanish women were studied post-partum. We evaluated depressive symptoms at 2–3 days, 8 weeks and 32 weeks post-partum. We used diagnostic interview to confirm major depression for all probable cases. Based on two polymorphisms of 5-HTT (5-HTTLPR and STin2 VNTR), three genotype combinations were created to reflect different levels of 5-HTT expression.

One hundred and seventy-three women (12.7%) experienced major depression during the 32-week post-partum period. Depressive symptoms were associated with the high-expression 5-HTT genotypes in a dose–response fashion at 8 weeks post-partum, but not at 32 weeks.

High-expression 5-HTT genotypes may render women more vulnerable to depressive symptoms after childbirth.