A prospective study to explore the relationship between MTHFR C677T genotype, physiological folate levels, and postpartum psychopathology in at-risk women.

Emily Morris,Angela Inglis,Colin Ross,Catriona Hippman,Rolan Batallones,Roger Dyer,Prescilla Carrion,Heather Andrighetti,Arianne Albert,Caitlin Slomp,William Honer,Jehannine Austin,Kyoung-Sae Na

doi:10.1371/journal.pone.0243936

Abstract

The etiology of postpartum psychopathologies are not well understood, but folate metabolism pathways are of potential interest. Demands for folate increase dramatically during pregnancy, low folate level has been associated with psychiatric disorders, and supplementation may improve symptomatology. The MTHFR C677T variant influences folate metabolism and has been implicated in depression during pregnancy. To conduct a prospective longitudinal study to explore the relationship between MTHFR C677T genotype, folate levels, and postpartum psychopathology in at-risk women. In the first three months postpartum, folate will moderate a relationship between MTHFR genotype and depression, with TT homozygous women having more symptoms than CC homozygous women. We recruited 365 pregnant women with a history of mood or psychotic disorder, and at 3 postpartum timepoints, administered the Edinburgh Postnatal Depression Scale (EPDS); Clinician-Administered Rating Scale for Mania (CARS-M) and the Positive and Negative Symptom Scale (PANSS) and drew blood for genotype/folate level analysis. We used robust linear regression to investigate interactions between genotype and folate level on the highest EPDS and CARS-M scores, and logistic regression to explore interactions with PANSS psychosis scores above/below cut-off. There was no significant interaction effect between MTHFR genotype and folate level on highest EPDS (p = 0.36), but there was a significant interaction between genotype, folate level and log(CARS-M) (p = 0.02); post-hoc analyses revealed differences in the effect of folate level between CC/CT, and TT genotypes, with folate level in CC and CT having an inverse relationship with symptoms of mania, while there was no relationship in participants with TT genotype. There was no significant interaction between MTHFR genotype and folate level on the likelihood of meeting positive symptom criteria for psychosis on the PANSS (p = 0.86). These data suggest that perhaps there is a relationship between MTHFR C677T, folate level and some symptoms of postpartum psychopathology.

Highlights

Postpartum psychiatric disorders are urgent health concerns that have important implications for mothers, infants, and their families
There was no significant interaction effect between Methyltetrahydrofolate reductase (MTHFR) genotype and folate level on highest Edinburgh Postnatal Depression Scale (EPDS) (p = 0.36), but there was a significant interaction between genotype, folate level and log(CARS-M) (p = 0.02); post-hoc analyses revealed differences in the effect of folate level between CC/CT, and TT genotypes, with folate level in CC and CT having an inverse relationship with symptoms of mania, while there was no relationship in participants with TT genotype
There was no significant interaction between MTHFR genotype and folate level on the likelihood of meeting positive symptom criteria for psychosis on the Positive and Negative Symptom Scale (PANSS) (p = 0.86)

Summary

Introduction

Postpartum psychiatric disorders are urgent health concerns that have important implications for mothers, infants, and their families. In the context of postpartum psychiatric disorders, the majority of investigations focus on either environmental contributors or the role of genetics [13,14,15,16,17,18] with few studies investigating gene and environment interactions (e.g. 5HTTLPR/ monoaminergic variations and stress [19, 20]).The need for studies of postpartum depression that integrate these elements has been recognized [21], and there are potential gene-environment interactions worthy of investigation in relation to postpartum psychopathology. The MTHFR C677T variant influences folate metabolism and has been implicated in depression during pregnancy

Methods

Results

Conclusion