title: Perinatal folate-related exposures and risk of psychotic symptoms in the ALSPAC birth cohort.
abstract: BACKGROUND
  It is unclear to what extent non-clinical psychotic experiences during childhood and adolescence share underlying aetiological mechanisms with schizophrenia. One candidate mechanism for schizophrenia involves the epigenetic status of the developing fetus, which depends on the internal folate-status of mother and child. Our study examines the relationships between multiple determinants of perinatal folate-status and development of psychotic experiences in adolescence.
  
  
  METHODS
  Study participants were up to 5344 mother-child pairs from the Avon Longitudinal Study of Parents and their Children, UK, with information on maternal and/or child MTHFR C677T genotype, maternal folate intake (supplementation at 18/32- weeks gestation; dietary intake at 32- weeks gestation) and psychosis-like symptoms (PLIKS) for children assessed at age 12.
  
  
  RESULTS
  Nominal evidence was observed that maternal folate supplementation at 18 weeks increased the odds of PLIKS in children (odds ratio(OR)=1.34; 95%-CI:[1.00;1.76]) and, consistent with this, that children of MTHFR C667T TT homozygous mothers had decreased odds of PLIKS (OR=0.72; 95%CI:[0.50;1.02]; recessive model) with strongest effects in boys (OR=0.44, 95%-CI:[0.22;0.79]; sex-specific p=0.029). None of the reported effects remained significant when corrected for multiple testing.
  
  
  CONCLUSIONS
  Overall, this study found no support that maternal/child MTHFR C677T genotype and maternal folate intake during pregnancy contribute to common aetiological pathways that are shared between schizophrenia and non-clinical psychotic symptoms in adolescents, assuming that decreased folate-status increases schizophrenia risk.
authors.affiliation: The MRC Centre for Causal Analyses in Translational Epidemiology, University of Bristol, Oakfield House, Oakfield Grove, Bristol, BS8 2BN, UK. b.glaser@bristol.ac.uk
authors.forename: B
authors.initials: B
authors.lastname: Glaser
authors.forename: A E
authors.initials: AE
authors.lastname: Ades
authors.forename: S
authors.initials: S
authors.lastname: Lewis
authors.forename: P
authors.initials: P
authors.lastname: Emmet
authors.forename: G
authors.initials: G
authors.lastname: Lewis
authors.forename: G Davey
authors.initials: GD
authors.lastname: Smith
authors.forename: S
authors.initials: S
authors.lastname: Zammit
mesh_terms: D002648:Child; D018672:Community Health Planning; D005260:Female; D005492:Folic Acid / Q000378:metabolism*; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D033261:Maternal-Fetal Relations; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D009034:Mother-Child Relations; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011618:Psychotic Disorders / Q000209:etiology* / Q000235:genetics* / Q000378:metabolism; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D005492:Folic Acid; D042965:Methylenetetrahydrofolate Reductase (NADPH2)