The vitamin D hormone regulates serotonin synthesis. Part 1: Importance for autism

Summary:

It has been suggested that serotonin and vitamin D play a role in autism; however, a causal mechanism has not yet been established. Here it is shown that the 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 suppresses the transcription of TPH1 in tissues outside the blood-brain barrier at another VDRE. The proposed mechanism explains four important features associated with autism: the low concentrations of serotonin in the brain and its increased 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 the genes encoding the oxytocin-neurophysin I preprotein, 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 prevent autism and possibly alleviate some symptoms of the disorder.-Patrick, R. P., Ames, B. N. Vitamin D hormone regulates serotonin synthesis.

Part 1: Importance for autism. FASEB J. 28, 2398-2413 (2014). www.fasebj.org

Discussion

We propose an underlying mechanism that reveals how vitamin D hormone critically influences serotonin synthesis in the brain through TPH2, which contains a VDRE that coincides with activation. This mechanism explains how low vitamin D hormone levels lead to abnormal serotonin synthesis and thus to abnormal brain development. It has already been established that the bioavailability of tryptophan in the brain is correlated with the concentration of serotonin in the brain (25, 31). The vitamin D hormone level can also be linked to the serotonin concentration in the brain. Low vitamin D hormone levels during fetal and neonatal development could lead to poor TPH2 expression and subsequently to lower serotonin concentrations in the developing brain. The important role of TPH2-mediated serotonin production in shaping brain structure and neuronal wiring during early neurodevelopment is well established (174). This mechanism suggests that an adequate vitamin D hormone level during pregnancy and the intake of tryptophan and vitamin D via food in early childhood can have a decisive influence on the serotonin level in the brain and thus on the structure and neuronal circuitry of the brain.