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

  title={Vitamin D hormone regulates serotonin synthesis. Part 1: relevance for autism},
  author={Rhonda P. Patrick and Bruce N. Ames},
  journal={The FASEB Journal},
  pages={2398 - 2413}
Serotonin and vitamin D have been proposed to play a role in autism; however, no causal mechanism has been established. [] Key Result 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…

1,25‐Dihydroxyvitamin D regulates expression of the tryptophan hydroxylase 2 and leptin genes: implication for behavioral influences of vitamin D

  • I. KanekoM. Sabir P. Jurutka
  • Biology
    FASEB journal : official publication of the Federation of American Societies for Experimental Biology
  • 2015
The results imply that vitamin D affects brain serotonin concentrations, which may be relevant to psychiatric disorders, such as autism, and may control leptin levels and affect eating behavior.

Vitamin D and autism, what’s new?

  • J. Cannell
  • Medicine
    Reviews in Endocrine and Metabolic Disorders
  • 2017
Pediatricians and family practitioners should evaluate the current evidence on autism and vitamin D and act accordingly, and seek to prevent autism by supplementing pregnant and lactating women and infants and young children with high dose vitamin D, checking 25(OH)D levels every 3 months.

Vitamin D and the omega‐3 fatty acids control serotonin synthesis and action, part 2: relevance for ADHD, bipolar disorder, schizophrenia, and impulsive behavior

  • Rhonda P. PatrickB. Ames
  • Psychology, Biology
    FASEB journal : official publication of the Federation of American Societies for Experimental Biology
  • 2015
A model whereby insufficient levels of vitamin D, EPA, or DHA, in combination with genetic factors and at key periods during development, would lead to dysfunctional serotonin activation and function is proposed and suggests that optimizing vitamin D and marine omega‐3 fatty acid intake may help prevent and modulate the severity of brain dysfunction.

Defining vitamin D receptor expression in the brain using a novel VDRCre mouse

A new mouse tool is generated that allows us to visualize VDR‐expressing cells and to characterize their functions and it is demonstrated that the cre activity in the VDRCre mouse brain (as reported by a cre‐dependent tdTomato expression) is highly overlapping with endogenous VDR mRNAs.

The Effect of Vitamin D3 Supplementation on Serum BDNF, Dopamine and Serotonin in Children with Attention-Deficit/Hyperactivity Disorder.

Vitamin D3 supplementation in children with ADHD can increase serum dopamine levels, but further studies are needed to determine the effects of vitamin D on neurotrophic factors and serotonin.

Serum concentration of 25-hydroxyvitamin D in autism spectrum disorder: a systematic review and meta-analysis

Levels of serum 25(OH) D in participants with ASD were significantly lower than controls, suggesting that lower vitamin D level might be a risk factor for ASD.

Vitamin D: Brain and Behavior

What is learned over these past 20 years regarding the genomic and nongenomic actions of vitamin D in shaping brain development, neurophysiology, and behavior in animal models is focused on.

Developmental vitamin D deficiency and autism: Putative pathogenic mechanisms

Vitamin D Deficiency and Autism Spectrum Disorder.

Further Randomized Controlled Trials studies carried out during pregnancy and early infancy are necessary for better understanding the possible contribution of vitamin D deficiency in the etiopathogenesis of autism and the potential efficacy of the hormone supplementation on the improvement of ASD core symptoms.



Possible association between autism and variants in the brain‐expressed tryptophan hydroxylase gene (TPH2)

  • H. CoonD. Dunn W. McMahon
  • Biology
    American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics
  • 2005
It is concluded that TPH2 may play a modest role in autism susceptibility, perhaps relating specifically to repetitive behaviors, pending replication of this result.

Autism and vitamin D.

A unique central tryptophan hydroxylase isoform.

Developmental changes in brain serotonin synthesis capacity in autistic and nonautistic children

The data suggest that humans undergo a period of high brain serotonin synthesis capacity during childhood, and that this developmental process is disrupted in autistic children.

Autism and serotonin transporter gene polymorphisms: A systematic review and meta‐analysis

  • Christine HuangS. Santangelo
  • Biology
    American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics
  • 2008
The meta‐analysis failed to find a significant overall association between either of the 5‐HTT polymorphisms examined and autism, and there was significant heterogeneity by ethnicity.

Late Developmental Stage-Specific Role of Tryptophan Hydroxylase 1 in Brain Serotonin Levels

It is found that TPH1 is expressed preferentially during the late developmental stage in the mouse brain, and showed higher affinity to tryptophan and stronger enzyme activity than TPH2 in a condition reflecting that of the developing brainstem.

Genetics of childhood disorders: XLV. Autism, part 4: serotonin in autism.

  • G. Anderson
  • Biology, Psychology
    Journal of the American Academy of Child and Adolescent Psychiatry
  • 2002
Providing a more empirical basis are studies showing therapeutic benefit of serotonergic agents in autism, reports of 5-HT–related neuroendocrine abnormalities, the well-characterized platelet hyperserotonemia, and recently reported associations between autism and 5HT-related genes.

Ontogeny of brain and blood serotonin levels in 5‐HT1A receptor knockout mice: potential relevance to the neurobiology of autism

The most consistent neurochemical finding in autism has been elevated group mean levels of blood platelet 5‐hydroxytryptamine (5‐HT, serotonin), and the possible causes of these dynamic shifts were explored by examining correlations between central and peripheral levels of 5‐ HT, 5‐HIAA and tryptophan.

Selective use of multiple vitamin D response elements underlies the 1 α,25-dihydroxyvitamin D3-mediated negative regulation of the human CYP27B1 gene

This study reveals the existence of two new VDR-binding regions in the distal promoter, 2.6 and 3.2 kb upstream from the TSS, that bind vitamin D receptor–retinoid X receptor complexes that reflect tissues that are permissive and non-permissive to the phenomenon of 1α,25(OH)2D3-mediated down-regulation of this gene.