Table 1.
Summary of Evidence Related to the Vitamin D Hypothesis of Schizophrenia
| Analytic Epidemiology | |
| Finnish birth cohort | Absence of vitamin D supplement in first year of life associated with increased risk of schizophrenia in males.51 |
| US banked maternal sera | 25-Hydroxyvitamin D3 (25OHD) was detectable in 30-y-old banked maternal sera. Low vitamin D associated with winter birth and maternal African American ethnicity. Inconclusive results with respect to schizophrenia.45 |
| Danish case-control study | Low vitamin D associated with season of birth and migrant status. Low 25OHD associated with an increased risk of schizophrenia but nonlinear relationship.48 |
| Biological plausibility and assay development | |
| Human postmortem study | Vitamin D receptor (VDR) and key enzyme (CYP27B1) widely distributed in normal adult brain. High expression of VDR in subtantia nigra.28 |
| Rat studies | VDR first expressed in embryo at day 15 in proliferative zones.3 |
| Assay technique | 25OHD measured in 20- to 30-y-old neonatal dried blood spots (DBS). Concentrations in DBS correlated with neonatal cord blood.46,47 |
| Developmental vitamin D rodent models | |
| Brain structure | Enlarged lateral ventricles in neonates and in adult offspring repleted at weaning.31,33 |
| Genomics and proteomics | Altered expression of genes and proteins involved in mitochondrial, cytoskeletal, and synaptic plasticity (whole brain, adult offspring).34,35 Altered expression of calcium-binding proteins (nucleus accumbens, adult offspring).36 |
| Behavior | Hyperlocomotion in novel settings.38,39 |
| Hyperlocomotion phenotype associated with late (but not early) gestational hypovitaminosis D.39 | |
| Increased exploratory behavior in mouse.4 | |
| Sensitivity to MK-801 and amphetamine.38,40 | |
| Increased sensitivity to dopaminergic antagonist (haloperidol).38 | |
| Altered latent inhibition.42 | |
| Altered prepulse inhibition in offspring with chronic adult exposure.5 | |
| Cellular neuroscience | Altered dopamine transporter expression and dopaminergic neurotransmission.40 |
| Altered catechol-O-methyl transferase and dopamine metabolites.41 | |
| Altered neurogenesis in cell culture and altered sensitivity to 1,25-dihydroxyvitamin D3.29 | |
| Increased neuronal proliferation and reduced differentiation and apoptosis.31,32 | |