by Hakon Heimer
Low levels of vitamin D are not an independent risk factor for late-life depression, according to a study in the March issue of Acta Psychiatrica Scandinavica. In an editorial accompanying the study, John McGrath of Aarhus University in Denmark and the University of Queensland in Australia writes, "[W]e must be slaves to the data, and be prepared to reject vitamin D-related hypotheses."
Vitamin D has emerged as a suspect in a number of neuropsychiatric disorders, both in terms of prenatal and adult deficiencies. McGrath and his colleagues in Australia have focused on a hypothesized link between prenatal vitamin D and schizophrenia from a number of angles. The hypothesis stems in part from epidemiologic studies reporting more cases of schizophrenia at higher, less sunny latitudes and in people born in winter and spring.
The new study by Henning Tiemeier and colleagues at University Medical Center Rotterdam in the Netherlands (Jovanova et al., 2017) took advantage of the famous Rotterdam prospective study of aging, wherein subjects have a battery of measurements, including vitamin D levels and depressive symptoms, at baseline and at regular follow-ups.
While the study showed that vitamin D deficiency is associated with depressive symptoms, the deficiency does not precede depression. Instead, it seems to be a function of lifestyle, e.g., staying indoors more.
"With respect to the hypothesis that vitamin D deficiency is a causal risk factor for depression, the current evidence does not support this hypothesis," McGrath writes. However, he notes that randomized, controlled trials, several of which are underway, will provide stronger evidence.
In a short email interview with SRF, John McGrath isn't ready to concede the case that prenatal vitamin D levels could create risk for later mental illness. He continues work to explore developmental links between vitamin D and psychotic disorders or autism.
Q&A With John McGrath
Q: Do these findings in depression influence how you see the prospects for more research into the relationship between vitamin D and psychosis?
A: We have shown in animal models that developmental vitamin D deficiency produces a different phenotype from adult vitamin D deficiency. With respect to psychosis, we are still focused on gestational vitamin D. We are working on new studies in Denmark. We recently published a study based on the Generation R birth cohort that found an association between gestation and cord blood vitamin D concentration, and higher autism-related scores. (Vinkhuyzen et al., 2016)
Q: Will the current randomized trials underway address mental illness links, and do you know when they will be completed?
A: I think some of the studies may include mental health outcomes (e.g., self-report measures), but none have specified mental disorders as a primary outcome. Currently, there is not enough evidence to suggest that adult vitamin D deficiency is a cause of adult-onset mental disorders. My hunch is that vitamin D deficiency may contribute to worse outcomes in those with neuropsychiatric disorders―but this is a "two hit" model. Of course, many people with mental disorders have low vitamin D, and thus they need to have supplements in order to help their bone health and reduce risk of falls (good evidence to support these outcomes). But, we do not expect that the use of vitamin D supplements will "cure" their antecedent mental disorders.
Q: Negative results such as the Jovanova study and last year’s report on fish oil for psychosis-risk patients could make the field less interested in research on fundamental or, as you say, “promiscuous,” molecules (e.g., also folate). Is that justified, and what sort of research do you think we should support on such molecules?
A: The Jovanova study was an observational study, while the recent fish oil study was a Randomized Controlled Trial. It is disappointing that the new RCT does not replicate the findings of the original fish oil study. We would expect nutrition-related augmentation studies to have a small effect size; thus, we do need large studies to detect these weak effects. With respect to prenatal vitamin D and folate, it is not practical or ethical to do RCTs of prenatal interventions and follow up for 20 to 30 years. So if we wish to build an evidence base to justify their use, we will need to look for more proximal outcomes (e.g., autism spectrum disorders) or surrogates―early-onset outcomes. Unfortunately, we currently lack these in schizophrenia research. It will be a challenge for the field.