Best Practice & Research Clinical Endocrinology & Metabolism
11Vitamin D and the brain
Introduction
Research in the last 10 years has yielded a large amount of knowledge regarding vitamin D and its previously unknown role in brain development and function. For example, the distribution of the vitamin D receptor (VDR) and the enzyme associated with the synthesis of the active form of the hormone 1α-hydroxylase (CYP27B1) has been mapped in human brain.1 Moreover, vitamin D may also be an important modulator of brain development. Indeed developmental vitamin D (DVD) deficiency has been proposed as a risk factor for several psychiatric disorders of developmental origin, such as schizophrenia and autism2, *3 and the biological plausibility of these hypotheses has been supported by several studies using animal models.4, *5, 6, 7 Finally, several animal and clinical studies indicate that vitamin D may be somewhat ‘neuroprotective’ for conditions such as epilepsy, multiple sclerosis, Parkinson’s disease and chronic stress.
Section snippets
Vitamin D and the vitamin D receptor in the brain
The major metabolites of vitamin D include 25OHD3, 1,25OH2D3 and 24,25OH2D3, and these are present in human cerebrospinal fluid (CSF).8 In a similar fashion to other neurosteroids, vitamin D metabolites have been found to cross the blood brain barrier.9 Blood brain barrier permeability may not be necessary, however, because the P450 enzymes involved with the conversion of 25OHD3 to 1,25OH2D3 and 1,25OH2D3 to 24,25OH2D3 (CYP27B1 and CYP24A1, respectively) are present in the brain. CYP27B1 has
Developmental vitamin D deficiency as a risk factor for neuropsychiatric disorders
Based on several epidemiological findings, it has been hypothesized that low prenatal vitamin D may be a risk-modifying factor for schizophrenia.3 The most consistent finding in schizophrenia epidemiology is the season of birth effect – those born in Winter/Spring are more likely to develop the disorder than those born in Summer/Autumn.23, 24, 25, 26 This is more pronounced as distance from the equator increases.27 Secondly, increased rates of schizophrenia are found in those born in urban
Excitotoxicity and epilepsy
There is some evidence that vitamin D has a protective effect on neurons in vivo. For example, systemic administration of vitamin D (in the form of calcitriol) has been shown to increase levels of antioxidants, such as glutathione in the brain.78, 79 Furthermore, 1,25OH2D3 blocked the neuronal uptake of reactive oxygen species such as hydrogen peroxide and protected against excitotoxicity from glutamate.80 This may be mediated, at least in part, by the effects of vitamin D on calcium channels.
Future directions and conclusions
The rapid accumulation of experimental evidence over the past 10 years indicating vitamin D could play a role in brain development and function is compelling.112 Models of DVD deficiency in rodents may provide important discoveries in aiding our understanding of the neurobiology of psychiatric diseases. Considering the epidemiological evidence linking vitamin D with a variety of adverse neurological, psychiatric and cognitive outcomes, 113, 114 further well-designed observational studies, and,
Conflict of interest statement
The authors have no conflicts of interest to declare.
Role of funding source
None applicable.
Acknowledgements
This work was supported by the Australian National Health and Medical Research Council, and Queensland Health.
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Cited by (206)
Molecular insights into the pathogenic impact of vitamin D deficiency in neurological disorders
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2023, Life SciencesCitation Excerpt :On the other hand, some studies suggested other treatment methods, such as using antioxidants and vitamins for hypothyroidism-induced memory disorder [29,51]. Due to the presence of VD metabolites and their receptors in the various areas of the brain, especially the hippocampus, it is suggested VD plays a pivotal role in maintaining normal brain function and nervous system development [52]. In the present study, six weeks of treatment with VD caused a substantial decrease in the number of TUNEL+ cells in the hippocampus, suggesting the neuronal protection impact of VD in hypothyroidism.
Therapeutic and mechanistic intervention of vitamin D in neuropsychiatric disorders
2022, Psychiatry ResearchDecreased vitamin D levels in obsessive-compulsive disorder patients
2023, CNS SpectrumsDoes vitamin D protect or treat Parkinson’s disease? A narrative review
2024, Naunyn-Schmiedeberg's Archives of Pharmacology
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Most important references indicated with asterisk.