Re: Biomarkers of Environmental Toxicity and Susceptibility in Autism Reply

Institute of Chronic Illnesses, Inc., Silver Spring, Maryland, USA.
Journal of the neurological sciences (Impact Factor: 2.26). 10/2008; 280(1-2):101-8. DOI: 10.1016/j.jns.2008.08.021
Source: PubMed

ABSTRACT Autism spectrum disorders (ASDs) may result from a combination of genetic/biochemical susceptibilities in the form of a reduced ability to excrete mercury and/or increased environmental exposure at key developmental times. Urinary porphyrins and transsulfuration metabolites in participants diagnosed with an ASD were examined. A prospective, blinded study was undertaken to evaluate a cohort of 28 participants with an ASD diagnosis for Childhood Autism Rating Scale (CARS) scores, urinary porphyrins, and transsulfuration metabolites. Testing was conducted using Vitamin Diagnostics, Inc. (CLIA-approved) and Laboratoire Philippe Auguste (ISO-approved). Participants with severe ASDs had significantly increased mercury intoxication-associated urinary porphyrins (pentacarboxyporphyrin, precoproporphyrin, and coproporphyrin) in comparison to participants with mild ASDs, whereas other urinary porphyrins were similar in both groups. Significantly decreased plasma levels of reduced glutathione (GSH), cysteine, and sulfate were observed among study participants relative to controls. In contrast, study participants had significantly increased plasma oxidized glutathione (GSSG) relative to controls. Mercury intoxication-associated urinary porphyrins were significantly correlated with increasing CARS scores and GSSG levels, whereas other urinary porphyrins did not show these relationships. The urinary porphyrin and CARS score correlations observed among study participants suggest that mercury intoxication is significantly associated with autistic symptoms. The transsulfuration abnormalities observed among study participants indicate that mercury intoxication was associated with increased oxidative stress and decreased detoxification capacity.

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Available from: Mark R Geier, Aug 30, 2015
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    • "Links to oxidative stress have been identified in studies showing a decrease in the reduced form of glutathione (GSH) and the total amount of glutathione in both the brain (Chauhan et al., 2012; Rose et al., 2012a) and peripheral blood (Geier and Geier, 2006; James et al., 2006; Geier et al., 2009a, b; James et al., 2009; Al-Yafee et al., 2011) of ASD patients. However, the oxidized form of glutathione (GSSG) has been reported to be increased (James et al., 2004, 2006, 2009; Geier et al., 2009a; Adams et al., 2011; Chauhan et al., 2012; Rose et al., 2012a). Moreover, Rose et al. showed that oxidative damage has an impact on the inflammatory response in the brain of autism patients, with an increase of 3-chlorotyrosine (3-CT) and a decrease in aconitase activity (Rose et al., 2012a). "
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    ABSTRACT: Autism spectrum disorders (ASD) are a heterogeneous group of disorders which have complex behavioural phenotypes. Although ASD is a highly heritable neuropsychiatric disorder, genetic research alone has not provided a profound understanding of the underlying causes. Recent developments using biochemical tools such as transcriptomics, proteomics and cellular models, will pave the way to gain new insights into the underlying pathological pathways. This review addresses the state-of-the-art in the search for molecular biomarkers for ASD. In particular, the most important findings in the biochemical field are highlighted and the need for establishing streamlined interaction between behavioural studies, genetics and proteomics is stressed. Eventually, these approaches will lead to suitable translational ASD models and, therefore, a better disease understanding which may facilitate novel drug discovery efforts in this challenging field.
    The International Journal of Neuropsychopharmacology 11/2013; 17(04):1-23. DOI:10.1017/S146114571300117X · 5.26 Impact Factor
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    • "Methylation capacity is also decreased in autism.[10] Moreover, the transsulfuration abnormality is associated with autism symptoms.[11] Besides, improvement of the transmethylation/transsulfuration pathways is associated with the reduction of autism symptoms.[12] "
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    ABSTRACT: There are a limited number of Food and Drug Administration (FDA)-approved medications for the treatment of autism. Meanwhile, oxidative stress and neuroinflammation are supposed to play a causative role in autism. N-acetylcysteine may provide cystine, a precursor for glutathione (GSH), which is an important antioxidant factor in the brain. We here report a child with autism, whose symptoms were markedly decreased after taking oral N-acetylcysteine 800 mg/day, in three divided doses. His social interaction was significantly increased. The score of social impairment on a visual analog scale decreased from 10 to 6 in the two-month trial. The aggressive behaviors decreased from 10 to 3. This case suggests that N-acetylcysteine may decrease some symptoms of autism.
    Journal of research in medical sciences 10/2012; 17(10):985-7. · 0.61 Impact Factor
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    • "Humans have been exposed to methyl Hg mainly through eating seafoods and to inorganic Hg through inhalation of fuel combustion (Pacyna et al., 2006; Knobeloch et al., 2007). Although both organic and inorganic Hg are well-known neurotoxicants, whether Hg can induce or enhance ASD-like behavior remains to be definitely proven or disproven (DeStefano, 2007; Geier et al., 2009; Hertz-Picciotto et al., 2010; Price et al., 2010). Previously, we have shown that developmental exposure of A.SW (H-2 s ) mice to Hg chloride (HgCl 2 ), but not methyl-Hg, resulted in elevated serum IgG, IgG anti-brain Ab levels, and brain IgG deposition (Zhang et al., 2011). "
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    ABSTRACT: The effects of mercury (Hg) on social behavior and the mechanisms involved remain unknown. This study shows that Hg chloride (HgCl(2)) exposure during fetal development does not impair social behavior of a mouse strain susceptible to environment-induced autistic-like behavior based on the parental phenotype. On the contrary, Hg exposure elevated the sociability of females. Since B6 mice are behaviorally normal and BTBR mice display low levels of sociability, the F(1) offspring (B6BF(1)) of female B6 mice and male BTBR mice were used to investigate their social behavior and the effects of Hg. Developmental Hg-treatment increased the serum IgG levels of the post-natal day (pnd) 21 offspring, but not pnd70 offspring or the B6 dams. After Hg treatment, there were negligible levels of serum IgG anti-brain antibodies (Ab) in the pnd21 and pnd70 offspring as well as their dams. However, Hg did elevate IgG deposition in multiple assayed brain regions of the pnd21 offspring, but the higher levels were no longer present at pnd70. Cytokine levels were not changed in pnd21 or pnd70 brain by Hg exposure, suggesting neuroinflammation was not induced. Social behavior was assayed at pnd70. Surprisingly, Hg-treatment significantly enhanced sociability of female B6BF(1) offspring, but not that of the male offspring. Our data indicates that developmental exposure to HgCl(2) did not impair social behavior of B6BF(1) offspring, but it enhanced the sociability of females, which was significantly lower in adult B6BF(1) females than B6BF(1) males in the absence of any Hg exposure.
    Journal of Immunotoxicology 06/2012; 9(4). DOI:10.3109/1547691X.2012.682663 · 1.91 Impact Factor
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