The Vitamin D Connection
Six years ago, Professor John McGrath and his colleagues at the University of Queensland in Australia, pointed out that vitamin D, "the neglected neurosteroid," was crucial for proper brain development. In the same paper, they reported that activated vitamin D increases nerve growth factor in the brain and the vitamin D receptor appears in a wide variety of brain tissue quite early in the development of the baby. These two facts alone led them to conclude that vitamin D deficiency "should be examined in more detail as a candidate risk factor for neurodevelopmental...disorders." McGrath J, Feron F, Eyles D, Mackay-Sim A. Vitamin D: the neglected neurosteroid? Trends Neurosci. 2001 Oct;24(10):570–2.
In 2006, Dr. Alan Kalueff and his colleagues went further, suggesting vitamin D offers "neuroprotection, possible interplay with several brain neurotransmitter system and hormones, as well as regulation of behaviors." In 2007, Dr. Kalueff, now at the National Institutes of Mental Health, reviewed the nootropic (brain-enhancing) properties of vitamin D in even more detail and concluded that the scientific data stress the importance of the mother having enough vitamin D while she is pregnant and the child having enough vitamin D after birth for "normal brain functioning." There is no doubt vitamin D affects the brain, and does so profoundly. Kalueff AV, et al. The vitamin D neuroendocrine system as a target for novel neurotropic drugs. CNS Neurol Disord Drug Targets. 2006 Jun;5(3):363–71. Kalueff AV, Tuohimaa P. Neurosteroid hormone vitamin D and its utility in clinical nutrition. Curr Opin Clin Nutr Metab Care. 2007 Jan;10(1):12–9.
Given what we know about neurosteroids, in our search for the genetics of autism it is reasonable to search for a gene which:
- is environmentally responsive.
- codes for a systemic steroid that is also a potent neurosteroid.
- profoundly affects brain development
- has had its levels decrease over the same time that autism has increased.
- is affected differently by estrogen and testosterone.
- has levels that are much lower in blacks than in whites.
- explains all the bizarre epidemiology of autism.
A tall order indeed.
An inborn error of metabolism that causes a rare form of rickets, pseudo-vitamin D deficiency rickets, involves the defective manufacture of activated vitamin D. While no one has assessed afflicted children for signs of autism, these children clearly display autistic markers such as hypotonia (flabby muscles), decreased activity, developmental motor delay, listlessness, and failure to thrive.
Much more interesting is the fact that children with Williams Syndrome (rare congenital disorder due to a missing piece of chromosome seven) often have greatly elevated activated vitamin D levels for several months in early life. They usually present in later life with remarkable sociability, overfriendliness, empathy, and willingness to initiate social interaction—strikingly the opposite personality of autistic children. Knudtzon J, Aksnes L, Akslen LA, Aarskog D. Elevated 1,25-dihydroxyvitamin D and normocalcaemia in presumed familial Williams syndrome. Clin Genet. 1987 Dec;32(6):369–74. Mervis CB, Klein-Tasman BP. Williams syndrome: cognition, personality, and adaptive behavior. Ment Retard Dev Disabil Res Rev. 2000;6(2):148–58.
So, abnormally-low activated vitamin D levels produce infants with symptoms of autism while abnormally-high levels produce children with personalities the exact opposite of autism.
Variations in the DNA sequence of vitamin D receptor are common and called vitamin D receptor (VDR) polymorphisms (many-shaped receptors). No one has studied them in autism, but a highly significant association exists between one VDR polymorphism and larger head size. Larger head sizes are common in autism, especially in childhood. Handoko HY, et al. Polymorphisms in the vitamin D receptor and their associations with risk of schizophrenia and selected anthropometric measures. Am J Hum Biol. 2006 May–Jun;18(3):415–7. Lainhart JE, et al. Head circumference and height in autism: a study by the Collaborative Program of Excellence in Autism. Am J Med Genet A. 2006 Nov 1;140(21):2257–74.» page: autism index 1 2 3 4 5 6 7 8 9 10 11