Vitamin D is a neuro-steroid that is active in brain development, having effects on cellular proliferation, differentiation, calcium signalling, neurotransmission, neuroprotection and synaptic plasticity.¹ Vitamin D affects numerous neurotransmitters and neurotrophic factors relevant for mental disorders, and an increasing amount of evidence points to gestational vitamin D deficiency as a causative factor in the development of schizophrenia and autism.^2-4

Indications from the epidemiology of schizophrenia, such as the increased risk in those born in winter/spring, have led to the hypothesis that prenatal vitamin D deficiency may increase the risk of later schizophrenia.⁴ A case-control study (n = 848) demonstrated that the risk of schizophrenia was significantly associated with vitamin D levels (p=0.01), with neonates with vitamin D deficiency (<40.5 nmol/L) having a 2-fold elevated risk of being diagnosed with schizophrenia in later life.⁵ A more recent study also confirmed that neonatal vitamin D deficiency (<20.4 nmol/L) was associated with a significantly increased risk of schizophrenia compared to those in the reference category (p=0.004).⁴ As the developing foetus is totally reliant on maternal vitamin D stores, and neonatal vitamin D concentrations are strongly correlated with maternal sera concentrations at birth6, these findings support the hypothesis that maternal vitamin D deficiency is a risk factor for schizophrenia in the offspring.  

The association between gestational vitamin D deficiency and a continuous measure of autism-related traits at 6 years (Social Responsiveness Scale; SRS) was determined in a large population-based cohort of mothers and their children (n = 4229). Vitamin D was assessed from maternal mid-gestation sera and from neonatal sera (collected from cord blood). Compared with the Vitamin D sufficient group (>50 nmol/L), those who were vitamin D deficient (<25 nmol/L) had significantly higher (more abnormal) SRS scores (mid-gestation n = 2866, p<0.001; cord blood n = 1712, p=0.01).⁷

In terms of prevention, a small study showed vitamin D supplementation during pregnancy (5000 IU/day) and during infancy and early childhood (1000 IU/day) significantly reduced the expected incidence of autism, in mothers who already had one autistic child from 20% to 5%.2  The use of at least 2000 IU of vitamin D during the first year of life was associated with a reduced risk of schizophrenia in males compared to those on lower doses.⁸

It is generally recognised that both genetic and non-genetic risk factors can be shared across different psychiatric phenotypes, and as such, it is feasible that optimising prenatal vitamin D status with targeted supplementation may not only lower the risk of neurodevelopmental disorders such as autism and schizophrenia, but also impact on a broader range of mental health outcomes.⁴

Addressing or preventing a vitamin D deficiency before conception is an optimal strategy to counteract the effects of inadequate vitamin D status, particularly during preconception, pregnancy and breastfeeding.   

A vitamin D supplement (as cholecalciferol, vitamin D3) should be commenced at least 8-12 weeks prior to conception at a dose necessary to address the degree of deficiency (see below).^9,10

• Vitamin D sufficiency >75 nmol/L – 800-1,000 IU/day
• Suboptimal vitamin D levels 50-75 nmol/L – 1,000-2,000 IU/day
• Vitamin D insufficiency 25-50 nmol/L – 2,000-3,000 IU/day
• Vitamin D deficiency 15-25 nmol/L – 3,000-5,000 IU/day for up to 12 weeks, then retest
• Severe vitamin D deficiency <15 nmol/L, 50,000 IU/week (or 7,000 IU/day) for up to 12 weeks, then retest

There is no evidence that pregnancy or lactation increase the susceptibility for adverse effects of vitamin D intake,¹¹ and the recommended target range for non-pregnant adults of 80-250 nmol/L also appears to be a safe range during pregnancy.¹²  A maintenance dose of vitamin D of 1000-2000 IU/day is recommended until the cessation of lactation, and ongoing for those at risk of deficiency.¹³

References      

                                    

1. Ali, A., X. Cui, and D. Eyles, Developmental vitamin D deficiency and autism: Putative pathogenic mechanisms. J Steroid Biochem Mol Biol, 2018. 175: p. 108-118.
2. Cannell, J.J., Vitamin D and autism, what's new? Rev Endocr Metab Disord, 2017. 18(2): p. 183-193.
3. Humble, M.B., Vitamin D, light and mental health. J Photochem Photobiol B, 2010. 101(2): p. 142-9.
4. Eyles, D.W., et al., The association between neonatal vitamin D status and risk of schizophrenia. Sci Rep, 2018. 8(1): p. 17692.
5. McGrath, J.J., et al., Neonatal vitamin D status and risk of schizophrenia: a population-based case-control study. Arch Gen Psychiatry, 2010. 67(9): p. 889-94.
6. Eyles, D.W., et al., The utility of neonatal dried blood spots for the assessment of neonatal vitamin D status. Paediatr Perinat Epidemiol, 2010. 24(3): p. 303-8.
7. Vinkhuyzen, A.A.E., et al., Gestational vitamin D deficiency and autism-related traits: the Generation R Study. Mol Psychiatry, 2018. 23(2): p. 240-246.
8. McGrath, J., et al., Vitamin D supplementation during the first year of life and risk of schizophrenia: a Finnish birth cohort study. Schizophr Res, 2004. 67(2-3): p. 237-45.
9. Kennel, K.A., M.T. Drake, and D.L. Hurley, Vitamin D Deficiency in Adults: When to Test and How to Treat. Mayo Clinic Proceedings, 2010. 85(8): p. 752-758.
10. Joshi, D., J.R. Center, and J.A. Eisman, Vitamin D Deficiency in Adults. Australian Prescriber, 2010(33): p. 103-106.
11. European Food Safety Authority (EFSA), Scientific Opinion on the Tolerable Upper Intake Level of Vitamin D. EFSA Journal, 2012. 10(7): p. 2813.
12. Mulligan, M.L., et al., Implications of vitamin D deficiency in pregnancy and lactation. Am J Obstet Gynecol, 2010. 202(5): p. 429.e1-429.e4299.
13. Kaushal, M. and N. Magon, Vitamin D in pregnancy: A metabolic outlook. Indian J Endocrinol Metab, 2013. 17(1): p. 76-82.