Genetic variants in the tryptophan hydroxylase 2 gene (TPH2) and depression during and after pregnancy

A number of studies indicate that altered serotonergic transmission may be a risk factor for depression in the peripartum period. The aim of this study was to investigate whether genetic polymorphisms in the TPH2 gene, the gene product of which is the rate-limiting enzyme in the biosynthesis of serotonin in the central nervous system, are associated with depressive symptoms in pregnancy and the postpartum period.

In a cohort of 361 Caucasians, the severity of depression was assessed prospectively during pregnancy (third trimester) and the postpartum period (2-3 days and 6-8 months) using the Edinburgh Postnatal Depression Scale (EPDS). Tagging single nucleotide polymorphisms (SNPs) in TPH2 and SNPs that are known to be of functional relevance were genotyped. For each haplotype block or SNP, a multifactorial linear mixed model was performed to analyse the EPDS values over time.

The haplotype block in the promoter region of TPH2 showed significant associations with depression values during pregnancy and 6-8 months afterwards. Additionally, a haplotype block in intron 8 had an influence on depression values during pregnancy, but not after birth. There was a significant interaction between time and haplotypes and the severity of depression. The effect of TPH2 haplotypes on EPDS values was strongest during pregnancy and 6 months after birth, with a low depression rating in the first few days after delivery for all women.

In this cohort, TPH2 haplotypes known to be of functional relevance were found to be associated with different EPDS values during and after pregnancy. These haplotypes were associated with depressive symptoms both before and after delivery and were thus not specific for postpartum-onset depression. This underlines the relevance of these functional polymorphisms for depression in general and the importance of longitudinal assessments in research on postpartum depression.