{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T09:57:28Z","timestamp":1770458248434,"version":"3.49.0"},"reference-count":60,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2020,12,14]],"date-time":"2020-12-14T00:00:00Z","timestamp":1607904000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["mop 8270"],"award-info":[{"award-number":["mop 8270"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>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 <jats:italic>MTHFR C677T<\/jats:italic> variant influences folate metabolism and has been implicated in depression during pregnancy.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Objective<\/jats:title>\n<jats:p>To conduct a prospective longitudinal study to explore the relationship between <jats:italic>MTHFR C677T<\/jats:italic> genotype, folate levels, and postpartum psychopathology in at-risk women.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Hypothesis<\/jats:title>\n<jats:p>In the first three months postpartum, folate will moderate a relationship between <jats:italic>MTHFR<\/jats:italic> genotype and depression, with <jats:italic>TT<\/jats:italic> homozygous women having more symptoms than <jats:italic>CC<\/jats:italic> homozygous women.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Methods<\/jats:title>\n<jats:p>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.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec005\">\n<jats:title>Results<\/jats:title>\n<jats:p>There was no significant interaction effect between <jats:italic>MTHFR<\/jats:italic> 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 <jats:italic>CC\/CT<\/jats:italic>, and <jats:italic>TT<\/jats:italic> genotypes, with folate level in <jats:italic>CC<\/jats:italic> and <jats:italic>CT<\/jats:italic> having an inverse relationship with symptoms of mania, while there was no relationship in participants with <jats:italic>TT<\/jats:italic> genotype. There was no significant interaction between <jats:italic>MTHFR<\/jats:italic> genotype and folate level on the likelihood of meeting positive symptom criteria for psychosis on the PANSS (p = 0.86).<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec006\">\n<jats:title>Discussion<\/jats:title>\n<jats:p>These data suggest that perhaps there is a relationship between <jats:italic>MTHFR C677T<\/jats:italic>, folate level and some symptoms of postpartum psychopathology.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0243936","type":"journal-article","created":{"date-parts":[[2020,12,14]],"date-time":"2020-12-14T18:40:24Z","timestamp":1607971224000},"page":"e0243936","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":11,"title":["A prospective study to explore the relationship between MTHFR C677T genotype, physiological folate levels, and postpartum psychopathology in at-risk 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