NEONATAL VITAMIN D STATUS AND RISK OF SCHIZOPHRENIA: A POPULATION-BASED CASE-CONTROL STUDY

Context Clues from the epidemiology of schizophrenia suggest that low levels of developmental vitamin D may be associated with increased risk of schizophrenia. Objective To directly examine the association between neonatal vitamin D status and risk of schizophrenia. Design Individually matched case-control study drawn from a population-based cohort. Setting Danish national health registers and neonatal biobank. Participants A total of 424 individuals with schizophrenia and 424 controls matched for sex and date of birth. Main Outcome Measures The concentration of 25 hydroxyvitamin D 3 (25[OH]D3) was assessed from neonatal dried blood samples using a highly sensitive liquid chromatography tandem mass spectroscopy method. Relative risks were calculated for the matched pairs when examined for quintiles of 25(OH)D3. Results Compared with neonates in the fourth quintile (with 25[OH]D3 concentrations between 40.5 and 50.9 nmol/L), those in each of the lower 3 quintiles had a significantly increased risk of schizophrenia (2-fold elevated risk). Unexpectedly, those in the highest quintile also had a significantly increased risk of schizophrenia. Based on this analysis, the population-attributable fraction associated with neonatal vitamin D status was 44%. The relationship was not explained by a wide range of potential confounding or interacting variables. Conclusions Both low and high concentrations of neonatal vitamin D are associated with increased risk of schizophrenia, and it is feasible that this exposure could contribute to a sizeable proportion of cases in Denmark. In light of the substantial public health implications of this finding, there is an urgent need to further explore the effect of vitamin D status on brain development and later mental health.