Mechanism of nitrogen metabolism-related parameters and enzyme activities in the pathophysiology of autism

<p>Abstract</p> <p>Background</p> <p>There is evidence that impaired metabolism play an important role in the etiology of many neuropsychiatric disorders. Although this has not been investigated to date, several recent studies proposed that nitrogen metabolism-related parameters may have a pathophysiological role in autism.</p> <p>Methods</p> <p>The study enrolled 20 Saudi boys with autism aged 4 to 12 years and 20 healthy controls matched for age and gender. Levels of creatine, urea, ammonia, gamma-aminobutyric acid (GABA), glutamate:glutamine (Glu:Gln) ratio, and enzymatic activities of glutamate dehydrogenase, 5'-nucleotidase, and adenosine deaminase (ADA) were determined in plasma samples from both groups.</p> <p>Results</p> <p>We found a significant elevation of creatine, 5'-nucleotidase, GABA, and glutamic acid and a significant decrease in the enzymatic activity of ADA and glutamine level in patients with autism compared with healthy controls. The most significant variation between the two groups was found in the Glu:Gln ratio.</p> <p>Conclusion</p> <p>A raised Glu:Gln ratio together with positive correlations in creatine, GABA, and 5'-nucleotidase levels could contribute to the pathophysiology of autism, and might be useful diagnostic markers. The mechanism through which these parameters might be related to autism is discussed in detail.</p

Mean serum-level of common organic pollutants is predictive of behavioral severity in children with autism spectrum disorders

Autism spectrum disorders (ASD), and their pathogenesis, are growing public health concerns. This study evaluated common organic pollutant serum-concentrations in children, as it related to behavioral severity determined by rating scales and the Autism Diagnostic Observation Schedule (ADOS). Thirty children, ages 2–9, with ASD and thirty controls matched by age, sex, and socioeconomic status were evaluated using direct blood serum sampling and ADOS. Pooling concentrations of all studied pollutants into a single variable yielded cohort-specific neurobehavioral relationships. Pooled serum-concentration correlated significantly with increasing behavioral severity on the ADOS in the ASD cohort (p = 0.011, r = 0.54), but not controls (p = 0.60, r = 0.11). Logistic regression significantly correlated mean pollutant serum-concentration with the probability of diagnosis of behaviorally severe autism, defined as ADOS >14, across all participants (odds ratio = 3.43 [95% confidence: 1.14–10.4], p = 0.0287). No specific analyte correlated with ADOS in either cohort. The ASD cohort displayed greater quantitative variance of analyte concentrations than controls (p = 0.006), suggesting a wide range of detoxification functioning in the ASD cohort. This study supports the hypothesis that environmental exposure to organic pollutants may play a significant role in the behavioral presentation of autism