Perinatal folate-related exposures and risk of psychotic symptoms in the ALSPAC birth cohort☆
Received 25 August 2009; received in revised form 26 February 2010; accepted 7 March 2010. published online 26 April 2010.
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 18weeks 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.
aThe MRC Centre for Causal Analyses in Translational Epidemiology, University of Bristol, Oakfield House, Oakfield Grove, Bristol, BS8 2BN, UK
bDepartment of Social Medicine, University of Bristol, Canynge Hall, 39 Whatley Rd, Bristol BS8 2PS, UK
cDepartment of Community Based Medicine, Cotham House, University of Bristol, Cotham Hill, Bristol, BS6 6JL, UK
dDepartment of Psychological Medicine, School of Medicine, Cardiff University, Heath Park, Cardiff CF14 4XN, UK
Corresponding author. The MRC Centre for Causal Analyses in Translational Epidemiology, University of Bristol, Oakfield House, Oakfield Grove, Bristol, BS8 2BN, UK. Tel.: +44 117 33 10101; fax: +44 117 33 10123.
☆ Re-prints should be sent to the corresponding author. This research was funded by the Department of Social Medicine, University of Bristol.
ABSTRACT