September 26, 2019
Metabolic "signatures" in baby teeth can distinguish attention deficit hyperactivity disorder (ADHD) from autism spectrum disorder (ASD) as well as cases in which both neurodevelopmental disorders are present, preliminary research suggests.
Such signatures involve alterations in metabolism of certain essential elements and toxic metals, suggesting metabolic regulation of nutrients and toxins play a role in these neurodevelopmental disorders.
"It's important to stress that this is not a diagnostic tool, but because we are picking up this dysregulation in metabolism during the prenatal period, there are potential implications for an early detection tool — with a lot more research," coauthor Christine Austin, PhD, of the Icahn School of Medicine at Mount Sinai in New York, told Medscape Medical News.
The study was published online September 25 in Translational Psychiatry.
Prenatal Exposure to Toxins
The researchers analyzed baby teeth to derive temporal profiles of prenatal and early-life exposure to 10 metals. The cohort of 74 children from the Roots of Autism and ADHD Twin Study in Sweden (RATSS) included 41 neurotypical children (controls), 13 children with ADHD, 8 with ASD, and 12 with ADHD and ASD.
The researchers found that each condition had a unique metabolic signature that shows a combination of dysregulation in metabolic pathways involving essential and toxic elements.
In ADHD, there was evidence of decreased cycle stability, duration, and complexity in cobalt, copper, lead, zinc, and vanadium exposure profiles.
Prior studies have shown that increased levels of lead are correlated with the severity of ADHD symptoms, and a handful of studies describe possible roles for zinc in ADHD, investigators note.
Several enzymes believed to have an essential role in the neurophysiology of ADHD are dependent on copper. Zinc or copper dysregulation may also increase susceptibility to oxidative damage of tissues or oxidative stress of the brain by damaging antioxidant defenses, a possible pathophysiology of ADHD.
"Interestingly, we were not only able to identify distinct elemental signatures for those with either ADHD or ASD, but also in combined behavioral presentations. This finding at the molecular level is in broad agreement with clinical features of these conditions where significant overlap is observed in symptomatology," the investigators write.
Gateway to Further Studies
"Environmental epidemiologists typically study exposure to essential and toxic elements by examining how much of a given element a child was exposed to, but our work indicates that the way a child metabolizes environmental exposures is essential to healthy neurodevelopment," study coauthor Paul Curtin, PhD, of the Icahn School of Medicine at Mount Sinai in New York, said in news release.
Austin cautioned that the study was small and the results are preliminary. "The next step is probably to expand the study to more populations and see if these trends hold," she told Medscape Medical News.
Ruth Milanaik, DO, director of neonatal developmental follow-up programs, Cohen Children's Medical Center, New Hyde Park, New York, also urged caution in interpreting the findings.
The findings in this study are "interesting in theory" and are a "gateway to more studies, but they are far from being clinically relevant at the moment, or conclusive," she told Medscape Medical News.
Milanaik noted that the precise cause of ADHD or autism remain unclear. "There is a genetic component and there is an 'other,' which could be environmental," she said, "and we should always be in search of the 'other.'"
The study was funded by the Swedish Research Council, Vinnova, Formas, FORTE, the Swedish Brain foundation (Hjärnfonden), Stockholm Brain Institute, Autism and Asperger Association Stockholm, Queen Silvia's Jubilee Fund, Solstickan Foundation, PRIMA Child and Adult Psychiatry, the Pediatric Research Foundation at Astrid Lindgren Children's Hospital, the Swedish Foundation for Strategic Research, Jerring Foundation, the Swedish Order of Freemasons, Kempe-Carlgrenska Foundation, Sunnderdahls Handikappsfond, The Jeansson Foundation, and EU-AIMS (European Autism Intervention). The study authors and Milanaik have disclosed no relevant financial relationships.