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

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)D 3 ]; 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.—Patrick, R. P., Ames, B. N. Vitamin D hormone regulates serotonin synthesis. Part 1: relevance for autism. FASEB J . 28, 2398–2413 (2014). www.fasebj.org