According to new research from Northeastern University pharmacy professor
Richard Deth and colleagues from the University of Nebraska, Tufts, and
Johns Hopkins University, there is an apparent link between exposure to
certain neurodevelopmental toxins and an increased possibility of developing
neurological disorders including autism and attention-deficit hyperactivity
disorder. The research – the first to offer an explanation for possible
causes of two increasingly common childhood neurological disorders – will be
published in the April 2004 issue of the journal Molecular Psychiatry, and
earlier as advance online publication.

Though some speculation exists regarding this link, Deth and his colleagues
found that exposure to toxins, such as ethanol and heavy metals (including
lead, aluminum and the ethylmercury-containing preservative thimerosal)
potently interrupt growth factor signaling, causing adverse effects on
methylation reactions (i.e. the transfer of carbon atoms). Methylation, in
turn, plays a significant role in regulating normal DNA function and gene
expression, and is critical to proper neurological development in infants
and children. Scientists and practitioners have identified an increase in
diagnoses of autism and ADHD in particular, though the reasons why are
largely unknown.

In their work, the scientists found that insulin-like growth factor-1
(IGF-1) and the neurotransmitter dopamine both stimulated folate-dependent
methylation pathways in neuronal cells. At the same time they noted that
compounds like thimerosal, ethanol and metals (like lead and mercury)
effectively inhibited these same biochemical pathways at concentrations that
are typically found following vaccination or other sources of exposure. By
better understanding what happens when infants and children are exposed to
these materials, the work of Deth and his colleagues helps to explain how
environmental contact with metals and administration of certain vaccines may
lead to serious disorders that manifest themselves during childhood,
including autism and ADHD.

"Scientists certainly acknowledge that exposure to neurotoxins like ethanol
and heavy metals can cause developmental disorders, but until now, the
precise mechanisms underlying their toxicity have not been known." said
Deth. "The recent increase in the incidence of autism led us to speculate
that environmental exposures, including vaccine additives might contribute
to the triggering of this disorder."

Thimerosal, which was largely phased out in the U.S. and in Europe starting
in 2000,was often used for its preservative abilities in multi-dose units of
vaccines for diseases like hepatitis, whooping cough, tetanus and diptheria.
Today, most vaccines carry only trace amounts of it, according to the CDC.
But in larger, multi-dose vials of these vaccines, often shipped to and used
in third world countries, thimerosal is still very common. Multi-dose flu
vaccines still contain thimerosal.

Additionally, the scientists recently obtained more insight into the
mechanism by which thimerosal interferes with folate-dependent methylation.
It acts by inhibiting the biosynthesis of the active form of vitamin B12
(methylcobalamin), which is of particular interest because doctors treating
autistic kids are having good success with the administration of
methycobalamin.

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Citation source: Molecular Psychiatry 2004 Volume 9, advance online
publication doi:10.1038/sj.mp.4001476

For further information on this work, please contact Ms. Christine Phelan,
Northeastern University, Pharmaceutical Sciences, 716 Columbus Avenue 5th
Floor, Boston, Massachusetts 02120, USA; phone: 617-373-5455; FAX:
617-373-5383; e-mail: cp@ur.neu.edu

Molecular Psychiatry is published by the Nature Publishing Group.
http://www.nature.com/mp

Editor: Julio Licinio, M.D.; phone: +1 310 825-7113; FAX: +1 310 206-6715;
e-mail: licinio@ucla.edu

For a copy of this article please contact Aimee Midei, e-mail:
molecularpsychiatry@mednet.ucla.edu.

MOLECULAR PSYCHIATRY IS THE SOURCE OF THIS MATERIAL.