title: Prenatal exposure to maternal depressed mood and the MTHFR C677T variant affect SLC6A4 methylation in infants at birth.
abstract: BACKGROUND
  Prenatal and early postnatal exposure to maternal depression may "program" childhood behavior via epigenetic processes such as DNA methylation. Methylenetetrahydro-folate reductase (MTHFR) is an important enzyme in the generation of methyl groups for DNA methylation. The common MTHFR C677T variant is associated with depression in men and non-pregnant women, and with global changes in DNA methylation. This study investigated the effect of maternal MTHFR C677T genotype on antenatal maternal mood, and their impact on the gene-specific methylation in pregnant women and their newborn infants. The methylation status of SLC6A4, which encodes the transmembrane serotonin transporter, and BDNF, which encodes brain derived neurotrophic factor, were assessed because of their potential role in behaviour.
  
  
  RESULTS
  Depressed mood was assessed by the Edinburgh Postnatal Depression Scale (EPDS) and the Hamilton Rating Scale for Depression (HAM-D) in women (n = 82, all taking folate) during the 2(nd) and 3(rd) trimesters of pregnancy. The methylation status of SLC6A4 and BDNF were assessed in 3rd trimester maternal peripheral leukocytes and in umbilical cord leukocytes collected from their infants at birth. Women with the MTHFR 677TT genotype had greater 2(nd) trimester depressed mood (p<0.05). Increased 2(nd) trimester maternal depressed mood (EPDS scores) was associated with decreased maternal and infant SLC6A4 promoter methylation (p<0.05), but had no effect on BDNF promoter methylation.
  
  
  CONCLUSIONS
  These findings show that the MTHFR C677T variant is associated with greater depressed mood during pregnancy. We further showed that prenatal exposure to maternal depressed mood affects gene-specific DNA methylation patterns. These findings support the concept that alterations in epigenetic processes may contribute to developmental programming of behaviour by maternal depression.
authors.affiliation: Department of Pediatrics, Child & Family Research Institute, University of British Columbia, Vancouver, Canada. angela.devlin@ubc.ca
authors.forename: Angela M
authors.initials: AM
authors.lastname: Devlin
authors.forename: Ursula
authors.initials: U
authors.lastname: Brain
authors.forename: Jehannine
authors.initials: J
authors.lastname: Austin
authors.forename: Tim F
authors.initials: TF
authors.lastname: Oberlander
mesh_terms: D000328:Adult; D001483:Base Sequence; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics; D019175:DNA Methylation; D003863:Depression; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D018811:Maternal Exposure; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D009035:Mothers; D036801:Parturition; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D011401:Promoter Regions, Genetic / Q000235:genetics; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D042965:Methylenetetrahydrofolate Reductase (NADPH2)
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