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Query: UMLS:C0004352 (autism)
 32,579 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The serotonin metabolism was extensively studied in 22 couples of autistic children and age- and sex-matched controls. Histamine, calcium, and uric acid were also measured in urine and whole blood or plasma. Autistics and controls did not differ in histamine, and only minor changes were noticed in calcium content. According to previous reports, serotonin levels were often, but not always, elevated in the blood of autistic children. Based on data including urinary serotonin and 5-hydroxyindoleacetic acid, platelet serotonin uptake and efflux, platelet monoamine oxidase and glutathione peroxidase activities, and uric acid and plasma tryptophan, the origin(s) of such hyperserotonemia in autism appear(s) to be of metabolic origin, i.e., a decreased catabolism and/or an increased biosynthesis of serotonin.
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PMID:Serotonin metabolism and other biochemical parameters in infantile autism. A controlled study of 22 autistic children. 246 21

Autism is a behaviorally defined disorder of unknown etiology that is thought to be influenced by genetic and environmental factors. High levels of homocysteine and oxidative stress are generally associated with neuropsychiatric disorders. The purpose of this study was to compare the level of homocysteine and other biomarkers in children with autism to corresponding values in age-matched healthy children. We measured total homocysteine (tHcy), vitamin B(12), paraoxonase and arylesterase activities of human paraoxonase 1 (PON1) in plasma and glutathione peroxidase (GPx) activity in erythrocytes from 21 children: 12 with autism (age: 8.29 +/- 2.76 years) and 9 controls (age: 8.33 +/- 1.82 years). We found statistically significant differences in tHcy levels and in arylesterase activity of PON1 in children with autism compared to the control group: 9.83 +/- 2.75 vs. 7.51 +/- 0.93 micromol/L (P < or =0.01) and 72.57 +/- 11.73 vs. 81.83 +/- 7.39 kU/L (P < or =0.005). In the autistic group there was a strong negative correlation between tHcy and GPx activity and the vitamin B(12) level was low or suboptimal. In conclusion, our study shows that in children with autism there are higher levels of tHcy, which is negatively correlated with GPx activity, low PON1 arylesterase activity and suboptimal levels of vitamin B(12).
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PMID:High levels of homocysteine and low serum paraoxonase 1 arylesterase activity in children with autism. 1629 37

Autism is a severe developmental disorder with poorly understood etiology. Oxidative stress in autism has been studied at the membrane level and also by measuring products of lipid peroxidation, detoxifying agents (such as glutathione), and antioxidants involved in the defense system against reactive oxygen species (ROS). Lipid peroxidation markers are elevated in autism, indicating that oxidative stress is increased in this disease. Levels of major antioxidant serum proteins, namely transferrin (iron-binding protein) and ceruloplasmin (copper-binding protein), are decreased in children with autism. There is a positive correlation between reduced levels of these proteins and loss of previously acquired language skills in children with autism. The alterations in ceruloplasmin and transferrin levels may lead to abnormal iron and copper metabolism in autism. The membrane phospholipids, the prime target of ROS, are also altered in autism. The levels of phosphatidylethanolamine (PE) are decreased, and phosphatidylserine (PS) levels are increased in the erythrocyte membrane of children with autism as compared to their unaffected siblings. Several studies have suggested alterations in the activities of antioxidant enzymes such as superoxide dismutase, glutathione peroxidase, and catalase in autism. Additionally, altered glutathione levels and homocysteine/methionine metabolism, increased inflammation, excitotoxicity, as well as mitochondrial and immune dysfunction have been suggested in autism. Furthermore, environmental and genetic factors may increase vulnerability to oxidative stress in autism. Taken together, these studies suggest increased oxidative stress in autism that may contribute to the development of this disease. A mechanism linking oxidative stress with membrane lipid abnormalities, inflammation, aberrant immune response, impaired energy metabolism and excitotoxicity, leading to clinical symptoms and pathogenesis of autism is proposed.
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PMID:Oxidative stress in autism. 1676 63

Clinical observations suggest that certain gut and dietary factors may transiently worsen symptoms in autism spectrum disorders (ASD), epilepsy and some inheritable metabolic disorders. Propionic acid (PPA) is a short chain fatty acid and an important intermediate of cellular metabolism. PPA is also a by-product of a subpopulation of human gut enterobacteria and is a common food preservative. We examined the behavioural, electrophysiological, neuropathological, and biochemical effects of treatment with PPA and related compounds in adult rats. Intraventricular infusions of PPA produced reversible repetitive dystonic behaviours, hyperactivity, turning behaviour, retropulsion, caudate spiking, and the progressive development of limbic kindled seizures, suggesting that this compound has central effects. Biochemical analyses of brain homogenates from PPA treated rats showed an increase in oxidative stress markers (e.g., lipid peroxidation and protein carbonylation) and glutathione S-transferase activity coupled with a decrease in glutathione and glutathione peroxidase activity. Neurohistological examinations of hippocampus and adjacent white matter (external capsule) of PPA treated rats revealed increased reactive astrogliosis (GFAP immunoreactivity) and activated microglia (CD68 immunoreactivity) suggestive of a neuroinflammatory process. This was coupled with a lack of cytotoxicity (cell counts, cleaved caspase 3' immunoreactivity), and an increase in phosphorylated CREB immunoreactivity. We propose that some types of autism may be partial forms of genetically inherited or acquired disorders involving altered PPA metabolism. Thus, intraventricular administration of PPA in rats may provide a means to model some aspects of human ASD in rats.
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PMID:Neurobiological effects of intraventricular propionic acid in rats: possible role of short chain fatty acids on the pathogenesis and characteristics of autism spectrum disorders. 1695 May 24

Genetic factors can contribute to autistic disorder (AD). Abnormal genes of oxidative stress pathways and increased oxidative stress have been reported in autism spectrum disorders. Polymorphisms of genes involved in glutathione metabolism, e.g. GSTP1 and GSTM1 are reportedly associated with autistic disorder. We investigated a GCG repeat polymorphism of a human glutathione peroxidase (GPX1) polyalanine repeat (ALA5, ALA6 and ALA7) in 103 trios of AD (probands and parents) using the transmission disequilibrium test. Significant transmission disequilibrium (p=0.044) was found in the overall transmission of the three alleles. The ALA6 allele was under transmitted (p=0.017). These results suggest that possessing this ALA6 allele may be protective for AD. Future study of interaction of the GPX1 GCG repeat and other gene polymorphisms such as the MnSOD ALA16 or the GPX1 Pro198Leu polymorphism in this cohort of AD families may shed light in whether the combination of the ALA6 allele with another polymorphism of antioxidant allele contributes to the increased oxidative stress in autism.
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PMID:Genetic variant of glutathione peroxidase 1 in autism. 1919 3

Oxidative stress during development may predispose humans to neurodegenerative disorders in old age. Moreover, numerous ailments of brain disproportionately affect one of the genders. We therefore hypothesized that, activities of enzymes regenerating and utilizing glutathione (GSH) show sexual dimorphism and developmental differences in rat brain. To test this hypothesis, we collected cortex tissue from male and female Sprague-Dawley rats at post-natal day (PN) 5, PN 10, PN 20, PN 30, and PN 60. We measured tissue levels of NADP-linked isocitrate dehydrogenase (NADP-ICDH), glucose-6-phosphate dehydrogenase (G6PDH), and, glutathione reductase (GR) by UV spectrophotometry and determined glutathione peroxidase (GPx) expression therein by western blotting. Our results showed that sexual maturation had an impact on activities of enzymes that regenerate and utilize GSH and rat female cortex had more anti-oxidant capacity. Moreover, age-related decline in the activities of these key enzymes were observed. Reduced glutathione and NADPH protects the brain from oxidative stress. Thus, our results may have implications for neurodegenerative disorders like Parkinson's disease and developmental disorders of brain like autism in which oxidative stress plays a key role.
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PMID:Reduced glutathione regenerating enzymes undergo developmental decline and sexual dimorphism in the rat cerebral cortex. 1945 May 67

Autism is a neurodevelopmental disorder of childhood with poorly understood etiology and pathology. This pilot study aims to evaluate the levels of antioxidant enzymes, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and levels of malondialdehyde (MDA), a marker of lipid peroxidation, in Egyptian autistic children. Autism is a neurodevelopmental disorder of childhood with poorly understood etiology and pathology. The present study included 20 children with autism diagnosed by DSM-IV-TR criteria and Childhood Autism Rating Scale. Controls included 25 age-matched healthy children. Cases were referred to Outpatient Clinic of Children with Special Needs Department, National Research Center, Cairo, Egypt. We compared levels of SOD, GSH-Px, and MDA in children with autism and controls. In children less than 6 years of age, levels of SOD, and GSH-Px were significantly lower in autistic children compared with their controls, while MDA was significantly higher among patients than controls. In children older than 6 years, there was no significant difference in any of these values between cases and controls. We concluded that children with autism are more vulnerable to oxidative stress in the form of increased lipid peroxidation and deficient antioxidant defense mechanism especially at younger children. We highlight that autistic children might benefit from antioxidants supplementation coupled with polyunsaturated fatty acids. Moreover, early assessment of antioxidant status would have better prognosis as it may decrease the oxidative stress before inducing more irreversible brain damage.
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PMID:Evaluation of oxidative stress in autism: defective antioxidant enzymes and increased lipid peroxidation. 2084 86

Sonic hedgehog signaling and brain-derived neurotrophic factor play a neuro-protective role against oxidative stress in autism. Sonic hedgehog also increases Bcl-2 expression and the activities of superoxide dismutase and glutathione peroxidase. The level or activity of Bcl-2, brain-derived neurotrophic factor, and the activities of superoxide dismutase and glutathione peroxidase are decreased in autism. Sonic hedgehog also decreases the production of malondialdehyde that its level is high in autism. Therefore, it is supposed that sonic hedgehog may be associated with oxidative stress in autism through other pathways too.
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PMID:Malondialdehyde, Bcl-2, superoxide dismutase and glutathione peroxidase may mediate the association of sonic hedgehog protein and oxidative stress in autism. 2214 57

Recent evidence suggests that children with autism have impaired detoxification capacity and may suffer from chronic oxidative stress. To our knowledge, there has been no study focusing on oxidative metabolism specifically in Asperger syndrome (a milder form of autism) or comparing this metabolism with other psychiatric disorders. In this study, total antioxidant status (TAOS), non-enzymatic (glutathione and homocysteine) and enzymatic (catalase, superoxide dismutase, and glutathione peroxidase) antioxidants, and lipid peroxidation were measured in plasma or erythrocyte lysates in a group of adolescent patients with Asperger syndrome, a group of adolescents with a first episode of psychosis, and a group of healthy controls at baseline and at 8-12 weeks. TAOS was also analyzed at 1 year. TAOS was reduced in Asperger individuals compared with healthy controls and psychosis patients, after covarying by age and antipsychotic treatment. This reduced antioxidant capacity did not depend on any of the individual antioxidant variables measured. Psychosis patients had increased homocysteine levels in plasma and decreased copper and ceruloplasmin at baseline. In conclusion, Asperger patients seem to have chronic low detoxifying capacity. No impaired detoxifying capacity was found in the first-episode psychosis group in the first year of illness.
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PMID:Plasma antioxidant capacity is reduced in Asperger syndrome. 2222 20

Autism spectrum disorders (ASDs) are rarely diagnosed in children younger than 2 years, because diagnosis is based entirely on behavioral tests. Oxidative damage may play a central role in this pathogenesis, together with the interconnected transmethylation cycle and transsulfuration pathway. In an attempt to clarify and quantify the relationship between oxidative stress-related blood biomarkers and ASDs, a systematic literature review was carried out. For each identified study, mean biomarker levels were compared in cases and controls providing a point estimate, the mean ratio, for each biomarker. After meta-analysis, the ASD patients showed decreased blood levels of reduced glutathione (27%), glutathione peroxidase (18%), methionine (13%), and cysteine (14%) and increased concentrations of oxidized glutathione (45%) relative to controls, whereas superoxide dismutase, homocysteine, and cystathionine showed no association with ASDs. For the C677T allele in the methylene tetrahydrofolate reductase gene (MTHFR), homozygous mutant subjects (TT) showed a meta-OR of 2.26 (95% CI 1.30-3.91) of being affected by ASD with respect to the homozygous nonmutant (CC). Case-control studies on blood levels of vitamins suggest a lack of association (folic acid and vitamin B12) or rare association (vitamins A, B6, C, D, E). Sparse results were available for other biomarkers (ceruloplasmin, catalase, cysteinylglycine, thiobarbituric acid-reactive substances, nitric oxide) and for polymorphisms in other genes. Existing evidence is heterogeneous and many studies are limited by small sample size and effects. In conclusion, existing evidence suggests a role for glutathione metabolism, the transmethylation cycle, and the transsulfuration pathway, although these findings should be interpreted with caution, and larger, more standardized studies are warranted.
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PMID:Oxidative stress-related biomarkers in autism: systematic review and meta-analyses. 2254 47


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