Neonatal Vitamin D Status Linked to Schizophrenia Risk

Schizophrenia is a poorly understood group of brain disorders characterized by impairments in cognition, perception and affect, with a lifetime prevalence of 0.7%. People with schizophrenia may seem like they have lost touch with reality.

As with other heterogeneous disorders, the expectation is that schizophrenia is associated with many different causal factors involving both common and rare genetic variants, as well as a range of environmental exposures. With respect to environmental risk factors for schizophrenia, much attention has focused on modifiable prenatal and early life exposures.


A team of scientists from Australia and Denmark working with the University of Queensland (St. Lucia, Australia) analyzed vitamin D (25OHD) concentration in dried blood samples taken from Danish newborns between 1981 and 2000 who went on to develop schizophrenia as young adults. Most of these cases developed schizophrenia between September 2005 and December 2008. Controls, drawn from the same birth cohort, were individually matched on sex and date of birth, and were alive and free of schizophrenia at the time of onset of the matched case. The dried blood spots (DBS) were stored at -20 ⁰C.

DBS (samples and calibrants) were hydrated and processed and analyzed on a liquid chromatography–tandem mass spectrometry (LC-MS/MS) system consisted of a Nexera X2 UHPLC, comprising a SIL-30AC autosampler (50 µL loop), two LC-30AD binary pumps, DGU-20A5 degasser, and CTO-30A oven, and interfaced to a 5500 QTRAP mass spectrometer with Atmospheric Pressure Chemical Ionisation (APCI) TurboIonSpray ion source. DNA was extracted from the neonatal dried blood spots and genotyped.

The scientists reported that based on the combined sample, both the lowest and second lowest 25OHD quintiles were associated with an increased risk of schizophrenia compared to the reference fourth quintile. None of the other comparisons were statistically significant. This confirmed that neonatal vitamin D deficiency was associated with a significantly increased risk of schizophrenia. Those with 25OHD below 20.4 nmol/L, which is consistent with standard definitions of vitamin D deficiency, had a 44% increased risk of schizophrenia compared to those in the reference category.

John McGrath, MD, PhD, a professor of psychiatry and lead author of the study said, “We hypothesized that low vitamin D levels in pregnant women due to a lack of sun exposure during winter months might underlie this risk, and investigated the association between vitamin D deficiency and risk of schizophrenia. As the developing fetus is totally reliant on the mother's vitamin D stores, our findings suggest that ensuring pregnant women have adequate levels of vitamin D may result in the prevention of some schizophrenia cases, in a manner comparable to the role folate supplementation has played in the prevention of spina bifida.” The study was published on December 6, 2018, in the journal Scientific Reports.

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