Autism Spectrum Disorders Are Associated with an Elevated Autoantibody Response to Tissue Transglutaminase-2

Allen Rosenspire, Wonsuk Yoo, Sheri Menard, and Anthony R. Torres


Recently scientists have suggested that in some autistic children, autism may be related to autoimmune disease. That is, in some instances of autism, it may be that the child's own immune system could be attacking the nervous system. We have looked for evidence of this by examining antibodies in the blood of autistic children and their parents. We have found that a significant fraction of these individuals make antibodies at a higher level than normal to a self protein named transglutaminase 2 (TG2). We have also found that the production of these antibodies at high levels is strongly associated with certain genes located in what is known as the HLA region of the geneome that is important in many immune reactions. TG2 is an enzyme that has many functions, but of particular interest to us is its involvement in the central nervous system, where it is necessary for the formation of healthy synapses (connection sites) between neurons. As other researchers have reported that disruption of these synapses is in some cases associated with autism, it is possible that auto-antibodies to TG2 interfere with synapses in the central nervous system, and by doing so promote autism. © 2011 INSAR/Wiley Periodicals, Inc.

Article Citation:Autism Res2011, 4: 242–249. DOI: 10.1002/aur.194

MAOA, DBH, and SLC6A4 Variants in CHARGE: A Case-Control Study of Autism Spectrum Disorders

Flora Tassone, Lihong Qi, Wenting Zhang, Robin L. Hansen, Isaac N. Pessah, and Irva Hertz-Picciotto


We have studied three polymorphisms, the serotonin transporter promoter region polymorphism (5-HTTLPR), the dopamine hydroxylase (DBH) and the Monoamine Oxidase A (MAOA) in families participating in the CHARGE (Childhood Autism Risks from Genetics and the Environment) Study. Our goals were to determine whether allelic variations in candidate genes were associated with higher risk of autism. Autism diagnoses, established using both the ADI and ADOS, was confirmed in 190 families with a child who had ASD, 129 of which had a child with autism. In addition, 169 families with a typically developing child were eligible for genotyping. Our findings indicate that in the CHARGE cohort there is no association between the serotonin transporter and the dopamine hydroxylase loci and autism spectrum disorder. However, a potential role of allelic variation of the MAOA loci in Autism Spectrum Disorders was observed. © 2011 INSAR/Wiley Periodicals, Inc.

Article Citation:Autism Res2011, 4: 250–261. DOI: 10.1002/aur.196

Glyoxalase I Polymorphism rs2736654 Causing the Ala111Glu Substitution Modulates the Enzyme Activity—Implications in Autism

Madhabi Barua, Edmund C. Jenkins, Wenqiang Chen, Salomon Kuizon, Raju K. Pullarkat, and Mohammed A. Junaid


Autism is a complex developmental disability characterized by abnormalities in spoken language, socialization and repetitive behaviors. In recent years, an increase in the number of autism cases worldwide has been reported. Researchers have found evidence that autism is caused by multiple genetic factors, and a number of potential risk genes have been identified. Earlier we have found an increased frequency in subject with autism of a form of the enzyme glyoxalase I (Glo1) that has glutamic acid at position 111. By using lymphoblastoid and neuronal cells in culture, we now present evidence that this form of Glo1 is reduced in function, and consequently accumulates a toxic metabolite called methylglyoxal (MG). MG can form conjugates with cellular proteins, thereby compromising their function. We propose that an increase in conjugated proteins causes over-expression of receptors that bind these altered proteins, which in turn can initiate cascades of potentially harmful events. These studies suggest that in a subset of individuals with autism, the occurrence of the Glo1 polymorphism may precipitate changes in cellular structure and function that support risk for autism. © 2011 INSAR/Wiley Periodicals, Inc.

Article Citation:Autism Res2011, 4: 262–270. DOI: 10.1002/aur.197

Bridging Autism, Science and Society: Moving Toward an Ethically Informed Approach to Autism Research

Elizabeth Pellicano and Marc Stears


New discoveries in genetics and neuroscience are transforming our understanding of autism, including its causes and its consequences, and have excited much attention, even prompting media speculation about a long-term “cure”. Yet this research opens up a whole host of social and ethical issues that have been hitherto largely unexplored by scientists themselves. In this paper, we draw upon the findings of a major international gathering of researchers, ethicists, and activists, to present the first major analysis of these social and ethical issues. We outline the scientific developments that have provoked the most discomfort, analyze the response to these developments, and trace the current state of the ethical debate. Having done so, we contend that these ethical questions are unlikely to be resolved as they depend on entrenched disagreements as to the nature and desirability of autistic difference. We conclude by suggesting some ways forward so that we can begin to build a bridge between scientists and the broader autism community. © 2011 INSAR/Wiley Periodicals, Inc.

Article Citation:Autism Res2011, 4: 271–282. DOI: 10.1002/aur.201

Perceptual Grouping Abilities in Individuals with Autism Spectrum Disorder; Exploring Patterns of Ability in Relation to Grouping Type and Levels of Development

Emily K. Farran and Mark J. Brosnan


The profile of visuo-spatial cognitive abilities in Autism Spectrum Disorder (ASD) has provoked much discussion. Specifically, researchers have been interested in the characteristics of perceptual processing in ASD. In this study we investigated perceptual grouping, a type of perceptual processing in which parts of an image are automatically grouped together based on their shared properties. For example, when presented with a matrix of circles, arranged into alternating rows of black circles and white circles, one typically perceives the matrix as rows of same coloured circles rather than as individual circles. This is known as grouping by luminance similarity. Similar effects are observed for rows of squares versus circles (grouping by shape similarity), or for elements that are spaced closer together horizontally than they are vertically (grouping by proximity). Perceptual grouping is important in everyday life as it makes us more efficient processors; it directs our attention to relevant aspects of the visual array and helps us to recognise objects. In this study, nineteen males with ASD and nineteen typically developing males of the same level of non-verbal ability, took part in five different perceptual grouping tasks. The tasks measured the ability to perceptually group by proximity, alignment, luminance similarity, shape similarity and orientation similarity. The ASD group showed typical performance for grouping by proximity and by alignment, but a general impairment for grouping by shape similarity. In addition, the groups showed different patterns of processing for grouping by orientation similarity and luminance similarity. Group differences were also observed developmentally; for the ASD group, with the exception of grouping by shape similarity, perceptual grouping performance was poorer for individuals with lower non-verbal ability scores than for those with higher non-verbal ability scores. In contrast, for the typically developing control group perceptual grouping performance was not related to non-verbal ability scores. © 2011 INSAR/Wiley Periodicals, Inc.

Article Citation:Autism Res2011, 4: 283–292. DOI: 10.1002/aur.202

No Evidence for IL1RAPL1 Involvement in Selected High-Risk Autism Pedigrees from the AGRE Data Set

Kristina Allen-Brady, Guiqing Cai, Dale Cannon, Reid Robison, William M. McMahon, Hilary Coon, and Joseph D. Buxbaum


Finding genes that contribute to Autism Spectrum Disorder (ASD) has been very challenging and new strategies are needed to aid in the process. We previously tried a strategy of identifying pedigrees that likely show dominant inheritance of ASD to see if this subset could help find autism genes. We identified 86 such pedigrees in the Autism Resource Exchange (AGRE) and identified a region on chromosome X that showed evidence of an ASD gene. In this follow-up study, we report our efforts to sequence a strong candidate gene in the chromosome X region for ASD, namely IL1RAPL1. We sequenced 14 male cases from 14 families (one case per family). We observed no deleterious mutations or deletions in the IL1RAPL1 gene. It is possible that there are other factors that influence the IL1RAPL1 gene and were not screened as part of this study or other genes in the region may be responsible. Additional work is needed to explore these other possibilities. © 2011 INSAR/Wiley Periodicals, Inc.

Article Citation:Autism Res2011, 4: 293–296. DOI: 10.1002/aur.195

The Development of Perceptual Expertise in Autism Spectrum Conditions

Cara Damiano, Owen Churches, Howard Ring, and Simon Baron-Cohen


Adults with autism spectrum conditions (ASC) may use a different strategy to process faces compared to typical adults, who are ‘face experts’ as a result of their vast social experience. It is not clear if this different face processing strategy is exclusive to faces, or if it would be observed with any complex object with which one has extensive experience. To address this question, the current study examined the extent to which individuals with ASC could become experts with unfamiliar, non-face objects. All participants completed a two-week online training program with objects called Greebles. Participants were tested throughout the training, to measure their level of expertise with Greebles. Before and after training, participants completed a task with upright and inverted Greebles and faces to examine how the strategies used with each category of objects changed as a result of training. It was found that, in both a group of participants with ASC and a typical comparison group, experience led to development of an expert level of ability and the development of a novel processing strategy associated with expertise. These findings have implications for the development of more effective face processing interventions for individuals with ASC. © 2011 INSAR/Wiley Periodicals, Inc.

Article Citation:Autism Res2011, 4: 297–301. DOI: 10.1002/aur.205