Molecular Psychiatry (2021)
Xiaoying Cui, John J. McGrath, Thomas H. J. Burne & Darryl W. Eyles
Overview Schizophrenia and Vitamin D contains the following summary
14 reasons to think that schizophrenia is associated with low vitamin D
1) 97% of patients with schizophrenia are vitamin D deficient
2) Schizophrenia varies with latitude (UVB) by 10X (controversy)
3) Schizophrenia is more common in those with dark skin (when away from the equator)
4) Schizophrenia is associated with low natal vitamin D
5) Schizophrenia has been increasing around the world when vitamin D has been decreasing (controversy)
6) Schizophrenia is associated with low birth rate, which is associated with low vitamin D
7) Schizophrenia is associated with Autism which is associated with low vitamin D
8) Schizophrenia Bulletin Editorial (Jan 2014) speculated that Vitamin D could be a major player
9) Schizophrenia 2X more likely if low vitamin D - meta-analysis
10) Schizophrenia increased 40 % for Spring births after Danes stopped vitamin D fortification
11) Schizophrenia is associated with season of birth
12) Schizophrenia is associated with poor Vitamin D Receptor genes
13) Schizophrenia risk is decreased if give Vitamin D after birth
14) Schizophrenia symptoms reduced when Vitamin D levels are restored
Healthy pregnancies need lots of vitamin D has the following
Problem | Vit. D Reduces | Evidence |
| 0. Chance of not conceiving | 3.4 times | Observe |
| 1. Miscarriage | 2.5 times | Observe |
| 2. Pre-eclampsia | 3.6 times | RCT |
| 3. Gestational Diabetes | 3 times | RCT |
| 4. Good 2nd trimester sleep quality | 3.5 times | Observe |
| 5. Premature birth | 2 times | RCT |
| 6. C-section - unplanned | 1.6 times | Observe |
| Stillbirth - OMEGA-3 | 4 times | RCT - Omega-3 |
| 7. Depression AFTER pregnancy | 1.4 times | RCT |
| 8. Small for Gestational Age | 1.6 times | meta-analysis |
| 9. Infant height, weight, head size within normal limits | RCT | |
| 10. Childhood Wheezing | 1.3 times | RCT |
| 11. Additional child is Autistic | 4 times | Intervention |
| 12.Young adult Multiple Sclerosis | 1.9 times | Observe |
| 13. Preeclampsia in young adult | 3.5 times | RCT |
| 14. Good motor skills @ age 3 | 1.4 times | Observe |
| 15. Childhood Mite allergy | 5 times | RCT |
| 16. Childhood Respiratory Tract visits | 2.5 times | RCT |
RCT = Randomized Controlled Trial
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Table of Contents
Many epidemiological studies have highlighted the link between vitamin D deficiency and schizophrenia. In particular, two prominent studies report an association between neonatal vitamin D deficiency and an increased risk of schizophrenia. In parallel, much has been learnt about the role of vitamin D in the developing central nervous system over the last two decades. Studies in rodent models of developmental vitamin D (DVD)-deficiency describe how brain development is altered leading to a range of neurobiological and behavioral phenotypes of interest to schizophrenia. While glutamate and gamma aminobutyric acid (GABA) systems have been little investigated in these models, alterations in developing dopamine systems are frequently reported. There have been far more studies reporting patients with schizophrenia have an increased risk of vitamin D deficiency compared to well controls. Here we have conducted a systematic review and meta-analysis that basically confirms this association and extends this to first-episode psychosis. However, patients with schizophrenia also have poorer general health, poorer diets, are frequently less active and also have an increased risk of other medical conditions, all factors which reduce circulating vitamin D levels. Therefore, we would urge caution in any causal interpretation of this association. We also summarize the inconsistent results from existing vitamin D supplementation trials in patients with schizophrenia. In respect to animal models of adult vitamin D deficiency, such exposures produce subtle neurochemical alterations and effects on cognition but do not appear to produce behavioral phenotypes of relevance to schizophrenia.
We conclude, the hypothesis that vitamin D deficiency during early life may increase the risk of schizophrenia remains plausible and warrants ongoing research.