title: Vitamin D hormone regulates serotonin synthesis. Part 1: relevance for autism.
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.
authors.affiliation: Nutrition and Metabolism Center, Children's Hospital Oakland Research Institute, Oakland, California, USA rpatrick@chori.org bames@chori.org.
authors.forename: Rhonda P
authors.initials: RP
authors.lastname: Patrick
authors.affiliation: Nutrition and Metabolism Center, Children's Hospital Oakland Research Institute, Oakland, California, USA rpatrick@chori.org bames@chori.org.
authors.forename: Bruce N
authors.initials: BN
authors.lastname: Ames
mesh_terms: D000818:Animals; D001321:Autistic Disorder / Q000097:blood / Q000178:diet therapy / Q000453:epidemiology / Q000209:etiology*; D015551:Autoimmunity; D044383:Black People; D001812:Blood-Brain Barrier; D001921:Brain / Q000187:drug effects / Q000196:embryology / Q000276:immunology; D001923:Brain Chemistry; D002117:Calcitriol; D004065:Digestive System Abnormalities / Q000150:complications; D004200:Diseases in Twins; D004967:Estrogens / Q000502:physiology; D005260:Female; D005333:Fetus / Q000276:immunology; D006801:Humans; D015994:Incidence; D007249:Inflammation / Q000139:chemically induced; D008297:Male; D008431:Maternal-Fetal Exchange / Q000276:immunology; D008954:Models, Biological; D009035:Mothers; D010121:Oxytocin / Q000097:blood / Q000627:therapeutic use; D011247:Pregnancy; D018167:Receptors, Calcitriol / Q000378:metabolism; D012701:Serotonin / Q000096:biosynthesis* / Q000097:blood; D014365:Tryptophan Hydroxylase / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics; D014807:Vitamin D / Q000031:analogs & derivatives / Q000097:blood / Q000627:therapeutic use; D014808:Vitamin D Deficiency / Q000453:epidemiology; D030181:Vitamin D Response Element / Q000502:physiology
chemical_list: D004967:Estrogens; D018167:Receptors, Calcitriol; D014807:Vitamin D; D012701:Serotonin; D010121:Oxytocin; C104450:25-hydroxyvitamin D; C497467:TPH1 protein, human; C494784:TPH2 protein, human; D014365:Tryptophan Hydroxylase; D002117:Calcitriol
keywords: autoimmunity; behavior; brain function; oxytocin; prenatal; vasopressin