Neonatal vitamin D status and risk of schizophrenia: a population-based case-control study.
BACKGROUND
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.


METHODS
Individually matched case-control study drawn from a population-based cohort.


METHODS
Danish national health registers and neonatal biobank.


METHODS
A total of 424 individuals with schizophrenia and 424 controls matched for sex and date of birth.


METHODS
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.
McGrath
John J
JJ
Queensland Centre for Mental Health Research, The Park Centre for Mental Health, Wacol, Australia.
Eyles
Darryl W
DW
Pedersen
Carsten B
CB
Anderson
Cameron
C
Ko
Pauline
P
Burne
Thomas H
TH
Norgaard-Pedersen
Bent
B
Hougaard
David M
DM
Mortensen
Preben B
PB
D000328:Adult; D002112:Calcifediol / Q000097:blood; D016022:Case-Control Studies; D002851:Chromatography, High Pressure Liquid; D015331:Cohort Studies; D003718:Denmark / Q000453:epidemiology; D054242:Emigrants and Immigrants / Q000706:statistics & numerical data; D005260:Female; D006801:Humans; D007231:Infant, Newborn / Q000097:blood*; D008297:Male; D044382:Population Groups / Q000706:statistics & numerical data; D012042:Registries / Q000706:statistics & numerical data; D012111:Residence Characteristics; D012307:Risk Factors; D012559:Schizophrenia / Q000453:epidemiology*; D012621:Seasons; D053719:Tandem Mass Spectrometry; D014807:Vitamin D / Q000097:blood*
D014807:Vitamin D; D002112:Calcifediol