We speculate that prenatal vitamin D supplements in women at risk of hypovitaminosis D could reduce the risk of schizophrenia in their offspring. Because of the long lag between the exposure and the outcome, undertaking randomized clinical trials to test this hypothesis will be a challenge. However, prenatal supplementation trials are currently underway that focus on a range of neonatal and child health outcomes.50
These studies could provide the schizophrenia research community with the opportunity to follow-up the long-term mental health of these offspring. If these studies failed to establish an association between prenatal hypovitaminosis D and an increased risk of schizophrenia, the hypothesis could be rejected.
To date, our research has focused on prenatal hypovitaminosis D. However, it is feasible that hypovitaminosis D during childhood and puberty could also influence brain development. The risk of schizophrenia is increased in both (a
) second-generation dark-skinned migrants (who would be exposed to low vitamin D prenatally and postnatally) and (b
) first-generation migrants (who would only be exposed postnatally).22
There is some indirect evidence to support a link between postnatal hypovitaminosis D and risk of schizophrenia. A birth cohort study51
found a link between the absence of vitamin D supplementation during the first year of life and an increased risk of schizophrenia in men. If the critical window extends into childhood, one would predict that those with rickets (a bone disorder associated with chronic hypovitaminosis D and poor calcium intake during childhood) would have an increased risk of schizophrenia.
With respect to hypovitaminosis D during adulthood, there is currently a lack of convincing evidence to link this exposure with short-term cognitive or behavioral impairment.52
However, there is strong evidence from in vitro studies showing that vitamin D has neuroprotective properties.53–57
Thus, it is feasible that chronic hypovitaminosis D could leave individuals more vulnerable to subsequent neurobiological insults. For example, migrant groups exposed to both “social defeat”58
and hypovitaminosis D may be less able to buffer neurotoxicity related to stress-related mechanisms.59
Inspired by recent studies suggesting a protective effect for fish oil supplements,60
we speculate that the risk of developing psychosis in vulnerable individuals may be amplified in those with low vitamin D and that recovery from first episode psychosis may be enhanced by optimal vitamin D concentrations. These research questions are tractable and could be addressed with pragmatic randomized controlled trials. Because vitamin D is safe, cheap, acceptable to the general public, and could help a range of physical health outcomes, there is a public health case to undertake these exploratory trials promptly.61
Based on lessons learned from cancer epidemiology, we must remain mindful that some promising nutritional candidates identified from observational epidemiology are subsequently found to be ineffective when assessed in randomized controlled trials.62
Currently, we lack sufficient evidence to make public health recommendations about the use of vitamin D for the prevention of schizophrenia. We lack crucial information about the critical window during which time hypovitaminosis D impacts on brain function, and we do not understand the mechanisms underpinning the apparent nonlinear relationship between neonatal vitamin D and risk of schizophrenia.