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: 2.47). 10/2008; 280(1-2):101-8. DOI: 10.1016/j.jns.2008.08.021
Source: PubMed


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, Oct 04, 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 · 4.01 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. · 0.65 Impact Factor
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    • "Evidence suggests that children with autism spectrum disorder (ASD) have a greater susceptibility to heavy-metal intoxication than typically developing children (Holmes et al. 2003, Kern and Jones 2006, Rose et al. 2008, Nataf et al. 2008, James et al. 2009, Geier et al. 2009a, Majewska et al. 2010, Youn et al. 2010, Kern et al. 2011a). For example, children with ASD have been found to have low plasma glutathione (GSH) and sulfate (SO 4 ) levels (Waring and Klovrza 2000, James et al. 2004, 2006, 2009, Geier and Geier 2006, Geier et al. 2009c, Pasca et al. 2009, Adams et al. 2011), both of which are critically important for detoxification (Gutman 2002, Kern et al. 2004). "
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    ABSTRACT: The purpose of this review is to examine the parallels between the effects mercury intoxication on the brain and the brain pathology found in autism spectrum disorder (ASD). This review finds evidence of many parallels between the two, including: (1) microtubule degeneration, specifically large, long-range axon degeneration with subsequent abortive axonal sprouting (short, thin axons); (2) dentritic overgrowth; (3) neuroinflammation; (4) microglial/astrocytic activation; (5) brain immune response activation; (6) elevated glial fibrillary acidic protein; (7) oxidative stress and lipid peroxidation; (8) decreased reduced glutathione levels and elevated oxidized glutathione; (9) mitochondrial dysfunction; (10) disruption in calcium homeostasis and signaling; (11) inhibition of glutamic acid decarboxylase (GAD) activity; (12) disruption of GABAergic and glutamatergic homeostasis; (13) inhibition of IGF-1 and methionine synthase activity; (14) impairment in methylation; (15) vascular endothelial cell dysfunction and pathological changes of the blood vessels; (16) decreased cerebral/cerebellar blood flow; (17) increased amyloid precursor protein; (18) loss of granule and Purkinje neurons in the cerebellum; (19) increased pro-inflammatory cytokine levels in the brain (TNF-α, IFN-γ, IL-1β, IL-8); and (20) aberrant nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB). This review also discusses the ability of mercury to potentiate and work synergistically with other toxins and pathogens in a way that may contribute to the brain pathology in ASD. The evidence suggests that mercury may be either causal or contributory in the brain pathology in ASD, possibly working synergistically with other toxic compounds or pathogens to produce the brain pathology observed in those diagnosed with an ASD.
    Acta neurobiologiae experimentalis 07/2012; 72(2):113-53. · 1.29 Impact Factor
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