%0 Journal Article
%T Alterations in Sensitivity to Estrogen, Dihydrotestosterone, and Xenogens in B-Lymphocytes from Children with Autism Spectrum Disorder and Their Unaffected Twins/Siblings
%A Martyn A. Sharpe
%A Taylor L. Gist
%A David S. Baskin
%J Journal of Toxicology
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/159810
%X It has been postulated that androgen overexposure in a susceptible person leads to excessive brain masculinization and the autism spectrum disorder (ASD) phenotype. In this study, the responses to estradiol (E2), dihydrotestosterone (DHT), and dichlorodiphenyldichloroethylene (DDE) on B-lymphocytes from ASD subjects and controls are compared. B cells were obtained from 11 ASD subjects, their unaffected fraternal twins, and nontwin siblings. Controls were obtained from a different cell bank. Lactate dehydrogenase (LDH) and sodium 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) reduction levels were measured after incubation with different concentrations of E2, DHT, and DDE. XTT/LDH ratio, representative of mitochondria number per cell, was calculated. E2, DHT, and DDE all cause ¡°U¡±-shaped growth curves, as measured by LDH levels. ASD B cells show less growth depression compared to siblings and controls ( ). They also have reduced XTT/LDH ratios ( ) when compared to external controls, whereas siblings had values of XTT/LDH between ASD and external controls. B-lymphocytes from people with ASD exhibit a differential response to E2, DHT, and hormone disruptors in regard to cell growth and mitochondrial upregulation when compared to non-ASD siblings and external controls. Specifically, ASD B-lymphocytes show significantly less growth depression and less mitochondrial upregulation when exposed to these effectors. A mitochondrial deficit in ASD individuals is implied. 1. Introduction Autism spectrum disorder (ASD) is a developmental disorder characterized by abnormal communication, social impairment, and stereotyped restricted interests and behavior. There has been a 10-fold increase in the incidence of ASD over the last two decades, with ASD now affecting 1 in 88 US children [1, 2]. ASD has a 5£¿:£¿1 male to female gender bias and is usually diagnosed before 4 years of age. Other male biased conditions [3] including dyslexia [4], specific language impairment, ADHD, and oppositional defiant disorder (ODD) have also increased during the last few decades [3, 4]. The cost of supporting people with ASD in Great Britain, including the cost of lost productivity, is 2.7b/year for children and 25b/year for adults [5]. Medical expenditures on individuals with ASD in the US are 4.1¨C6.2 greater than for those without, with average annual healthcare expenditures of approximately $6000/child reported and precipitously rising [6, 7]. Phenotypic analyses of male biased cognitive disorders suggest that genetic influences increase susceptibility to
%U http://www.hindawi.com/journals/jt/2013/159810/