Vitamin D hormone regulates serotonin synthesis. Part 1: relevance for autism.

Patrick RP, Ames BN. (2014) FASEB J. 28(6) 2398-413. doi: 10.1096/fj.13-246546. Epub 2014 Feb 20.

Web URL: View this and related abstracts via PubMed here. (And for free full text link, see FAB comment)

Abstract:

Serotonin and vitamin D have been proposed to play a role in autism; however, no causal mechanism has been established.

Here, we present evidence that vitamin D hormone (calcitriol) activates the transcription of the serotonin-synthesizing gene tryptophan hydroxylase 2 (TPH2) in the brain at a vitamin D response element (VDRE) and represses the transcription of TPH1 in tissues outside the blood-brain barrier at a distinct VDRE.

The proposed mechanism explains 4 major characteristics associated with autism: the low concentrations of serotonin in the brain and its elevated concentrations in tissues outside the blood-brain barrier; the low concentrations of the vitamin D hormone precursor 25-hydroxyvitamin D (25(OH)D3); the high male prevalence of autism; and the presence of maternal antibodies against fetal brain tissue.

Two peptide hormones, oxytocin and vasopressin, are also associated with autism and genes encoding the oxytocin-neurophysin I preproprotein, the oxytocin receptor, and the arginine vasopressin receptor contain VDREs for activation.

Supplementation with vitamin D and tryptophan is a practical and affordable solution to help prevent autism and possibly ameliorate some symptoms of the disorder.

KEYWORDS: autoimmunity, behavior, brain function, oxytocin, prenatal, vasopressin

FAB RESEARCH COMMENT:

This important new study identifies mechanisms by which Vitamin D deficiency may play a part in autism and other neurodevelopmental and psychiatric conditions.

The findings show how Vitamin D influences the production of serotonin (a key neurotransmitter implicated in autism and other conditions) in both the brain and the gut.

They also reveal that Vitamin D helps to regulate key hormones such as oxytocin and vasopressin (implicated in social bonding, among other things - and therefore potentially relevant in autism and related conditions involving impaired social and communication skills).

Both theory and association evidence already links low Vitamin D levels with Autistic Spectrum Disorders (and related conditions including ADHD and schizophrenia). Further research is still needed, however, to find out whether supplementation may reduce symptoms of these conditions.

Meanwhile, given the very high prevalence of Vitamin D deficiency in most developed countries, and its negative effects for physical health alone, this new research adds more weight to the many calls for this issue to be taken seriously by public health authorities, and for remedial action to be taken, especially among vulnerable groups.

This particularly includes women of childbearing age - as human as well as animal studies already show Vitamin D deficiency during pregnancy can negatively affect brain development, and animal studies clearly show some of these effects are irreversible.

Other well-documented risk factors for Vitamin D deficiency include darker skin, institutionalisation and age (with both young children and older adults at higher risk).

The free full text of this paper can be downloaded as a pdf (from academia.edu) here

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