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

FASEB J. 2014 Jun;28(6):2398-413. doi: 10.1096/fj.13-246546. Epub 2014 Feb 20.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review
  • Twin Study

MeSH terms

  • African Continental Ancestry Group
  • Animals
  • Autistic Disorder / blood
  • Autistic Disorder / diet therapy
  • Autistic Disorder / epidemiology
  • Autistic Disorder / etiology*
  • Autoimmunity
  • Blood-Brain Barrier
  • Brain / drug effects
  • Brain / embryology
  • Brain / immunology
  • Brain Chemistry
  • Calcitriol
  • Digestive System Abnormalities / complications
  • Diseases in Twins
  • Estrogens / physiology
  • Female
  • Fetus / immunology
  • Humans
  • Incidence
  • Inflammation / chemically induced
  • Male
  • Maternal-Fetal Exchange / immunology
  • Models, Biological
  • Mothers
  • Oxytocin / blood
  • Oxytocin / therapeutic use
  • Pregnancy
  • Receptors, Calcitriol / metabolism
  • Serotonin / biosynthesis*
  • Serotonin / blood
  • Tryptophan Hydroxylase / biosynthesis
  • Tryptophan Hydroxylase / drug effects
  • Tryptophan Hydroxylase / genetics
  • Vitamin D / analogs & derivatives
  • Vitamin D / blood
  • Vitamin D / therapeutic use
  • Vitamin D Deficiency / epidemiology
  • Vitamin D Response Element / physiology

Substances

  • Estrogens
  • Receptors, Calcitriol
  • Vitamin D
  • Serotonin
  • Oxytocin
  • 25-hydroxyvitamin D
  • TPH1 protein, human
  • TPH2 protein, human
  • Tryptophan Hydroxylase
  • Calcitriol