A large-scale Danish study published in Lancet Psychiatry offers robust evidence linking neonatal vitamin D deficiency to an increased risk of neurodevelopmental disorders—namely, schizophrenia, attention-deficit/hyperactivity disorder (ADHD), and autism spectrum disorder (ASD).
Researchers examined individual-level biomarker data from a Danish neonatal biobank, then combined that with genome-wide association study (GWAS) summary statistics and polygenic scores for 25(OH)D and DBP. Consistently, lower 25(OH)D levels were associated with higher risk of schizophrenia, ADHD, and ASD. Notably, schizophrenia showed the strongest and most consistent associations across all analytic models—including measured biomarkers, genetic predictors, and Mendelian randomization (MR) analyses.
The researchers were particularly attentive to the risk of genetic confounding and reverse causation. They applied reverse MR techniques to test whether genetic liability for psychiatric disorders might influence 25(OH)D levels, a possibility raised in prior work. While reverse causation was detected in major depressive disorder, bipolar disorder, and schizophrenia (suggesting genetic variants associated with these disorders could influence maternal behavior and, thus, neonatal vitamin D status), such an effect was not seen for DBP. This finding supports the view that DBP may have a more direct protective role, especially in relation to ADHD.
Public health implications are significant. The authors estimate that shifting all neonates into the top three quintiles of 25(OH)D concentration (>21.5 nmol/L) could prevent 15% of schizophrenia, 9% of ADHD, and 5% of ASD cases. These estimates emphasize the potential value of vitamin D supplementation during pregnancy and early infancy. However, translating these findings into clinical practice is not straightforward. A recent randomized controlled trial (RCT) in Denmark comparing high vs. standard doses of prenatal vitamin D found no significant reduction in ASD or ADHD risk, highlighting possible limitations in timing, dosage, or trial design.
Mechanistically, the link between vitamin D and neurodevelopment is well-supported. The vitamin D receptor is expressed in brain regions rich in dopaminergic neurons, such as the substantia nigra, and animal models have shown that deficiency during critical windows of brain development alters the structure and function of dopaminergic pathways—key systems implicated in disorders like schizophrenia and ADHD.
In conclusion, this study presents convergent, multi-method evidence supporting the role of early-life vitamin D status in shaping long-term psychiatric outcomes. While causality cannot be definitively established, the alignment of observational, genetic, and mechanistic data makes a compelling case for the preventative potential of vitamin D optimization in early development.
Sources: Lancet Psychiatry