Lay Abstracts

Male Gender Bias in Autism and Pediatric Autoimmunity

Kevin G. Becker

LAY ABSTRACT

Males have a higher incidence of autism than females by approximately 4:1. Similarly, males have a higher incidence of some pediatric autoimmune diseases as compared with females. The basis for these disparities is largely unknown. In recent years, there is growing evidence that immune and autoimmune dysregulation may be involved in autism. It is suggested here that the hormonal and immune processes that may contribute to a male preponderance in some pediatric autoimmune disorders may play a role in the male preponderance in autism. Published 2012 INSAR/Wiley Periodicals, Inc. This publication is a U.S. Government work and, as such, is in the public domain in the United States of America.

Article Citation: Autism Res 2012, 5: 77–83. DOI: 10.1002/aur.1227

Disordered Porphyrin Metabolism: A Potential Biological Marker for Autism Risk Assessment

Nicholas J. Heyer, Diana Echeverria, and James S. Woods

LAY ABSTRACT

Autism is a serious neurological disorder that is difficult to diagnose early when effective treatment can be provided. To address this concern, scientists are looking for unusual clinical features called “biomarkers”, that are specifically found only in autistic children with common symptoms. Such biomarkers could be used by doctors to distinguish those children from others and to design a personalized approach to their treatment. In this study, we examined one such biomarker that appears to be present in approximately one third of children with autism. This biomarker is based on metabolic products called porphyrins, which are found in everybody's urine. We found that the levels of several of these porphyrins are much higher in urine of some children with autism compared with neurotypical children of the same age. Additionally, when children with autism were randomly compared with neurotypical children or children with other developmental disorders, these porphyrin biomarkers correctly identified more than thirty percent of autistic children without incorrectly identifying a single nonautistic child. These findings suggest that porphyrin biomarkers are strong predictors of autism and that they may be useful as part of a symptom profile for identifying a particular subset of autistic children. © 2012 INSAR/Wiley Periodicals, Inc.

Article citation: Autism Res 2012, 5: 84–92. DOI: 10.1002/aur.236

Allelic Variation Within the Putative Autism Spectrum Disorder Risk Gene Homeobox A1 and Cerebellar Maturation in Typically Developing Children and Adolescents

Armin Raznahan, Yohan Lee, Catherine Vaituzis, Lan Tran, Susan Mackie, Henning Tiemeier, Liv Calsen, Francois Lalonde, Dede Greenstein, and Jay Giedd

LAY ABSTRACT

Autism is known to be highly heritable, and has been associated with abnormalities in the development of several brain structures, including the cerebellum. Previous research has hinted that a gene controlling the development of posterior brain regions such as the cerebellum, may influence risk for autism. This gene is called homeobox domain A1 (HOXA1), and the variant within HOXA1 that has been most studied in relation to autism (A218G) falls within a gene region that is important for HOXA1 protein functioning. Although we know that autism appear to influence the dynamics of brain development, and that cerebellar anatomy continues to change over the lifespan—we do not know if A218G genotype influences cerebellar development over time. We studied this issue in typically developing controls who had a total of 296 repeat structural brain scans taken between ages of 5 and 23 years. The volume of multiple cerebellar components was measures by hand in each scan, and we related developmental changes in these volumes to A218G genotype. We found that, in a part of the cerebellum implicated in autism, A218G genotype modified the rate of cerebellar growth. This suggests for the first time that the putative ASD risk gene HOXA1 has the capacity to modify the longitudinal development of cerebellar systems implicated in ASD neurobiology. © 2012 INSAR/Wiley Periodicals, Inc.

Article citation: Autism Res 2012, 5: 93–100. DOI: 10.1002/aur.238

Gastrointestinal Dysfunction in Autism: Parental Report, Clinical Evaluation, and Associated Factors

Phillip Gorrindo, Kent C. Williams, Evon B. Lee, Lynn S. Walker, Susan G. McGrew, and Pat Levitt

LAY ABSTRACT

Gastrointestinal dysfunction (GID) in children with autism spectrum disorder (ASD) is not well understood. Differences in factors associated with GID, such as eating habits, have been reported between ASD and non-ASD populations, but relationships between these factors and GID have not been examined. There is also the possibility that what we do know about GID in ASD is influenced by parents’ perceptions of GID in their children. Although parents know their children best, they are not necessarily experts in determining GID. This study examined how well parents and pediatric gastrointestinal clinicians agree on GID in children, and how factors thought to relate to GID in ASD, actually do relate to GID. One hundred twenty-one children were studied, in three groups: co-occurring ASD and GID, ASD without GID, and GID without ASD. Clinical evaluations by pediatric gastroenterologists validated parental reports of GID in ASD, with constipation the leading type of GID in ASD. Presence of GID in ASD was not associated with differences in diet or medications, but was associated with language and social impairments. These findings suggest that healthcare providers of children with ASD should be vigilant for GID, particularly in children who lack the ability to communicate verbally. © 2012 INSAR/Wiley Periodicals, Inc.

Article citation: Autism Res 2012, 5: 101–108. DOI: 10.1002/aur.237

Comprehension of Wh-Questions Precedes Their Production in Typical Development and Autism Spectrum Disorders

Anthony Goodwin, Deborah Fein, and Letitia R. Naigles

LAY ABSTRACT

Children with autism produce few wh-questions, compared to their typically developing peers. It is unclear if this is because of social-pragmatic difficulties, or if they have not yet learned the grammar for asking wh-questions. If children do not know how to use grammatical rules to produce questions, they might simply repeat sentences that they have heard without completely understanding them first. We visited the homes of 15 children with autism and 18 typically developing children with similar language abilities, across a three-year period. At each visit, children watched a video that depicted an apple hitting a flower and keys hitting a book. The children were then shown the items side-by-side on the screen and the audio asked “what hit the flower?” and “what did the keys hit?” We filmed the children's eye movements and analyzed how long they looked at the named item, compared to when they heard “where is the flower/keys?” At each visit, we also filmed a 30-minute mother-child play session and analyzed the types of questions that the children asked. Children with autism showed comprehension of wh-questions at a later age than typically developing children, but at a similar level of overall language development. Neither group produced wh-questions before they had demonstrated that they understood the underlying grammatical rules. Therefore, children with autism seem to process wh-questions in the same way as their typically developing peers, just at a later age. This paper discusses the implications of our findings for the language development of children with autism. © 2012 INSAR/Wiley Periodicals, Inc.

Article citation: Autism Res 2012, 5: 109–123. DOI: 10.1002/aur.1220

Motor Learning Relies on Integrated Sensory Inputs in ADHD, but Over-Selectively on Proprioception in Autism Spectrum Conditions

Jun Izawa, Sarah E. Pekny, Mollie K. Marko, Courtney C. Haswell, Reza Shadmehr, and Stewart H. Mostofsky

LAY ABSTRACT

Children with autism spectrum disorder (ASD) show deficits in development of motor skills, in addition to core deficits in social skill development. In a previous study (Haswell et al.), we found that children with autism show a key difference in how they learn motor actions, with a bias for relying on joint position rather than visual feedback; further, this pattern of motor learning predicted impaired motor, imitation, and social abilities. We were interested in finding out whether this altered motor learning pattern was specific to autism. To do so, we examined children with attention deficit hyperactivity disorder (ADHD), who also show deficits in motor control. Children learned a novel movement, and we measured rates of motor learning, generalization patterns of motor learning, and variability of motor speed during learning. We found children with ASD show a slower rate of learning and, consistent with previous findings, an altered pattern of generalization that was predictive of impaired motor, imitation, and social impairment. In contrast, children with ADHD showed a normal rate of learning and a normal pattern of generalization; instead, they (and they alone) showed excessive variability in movement speed. The findings suggest that there is a specific pattern of altered motor learning associated with autism. © 2012 INSAR/Wiley Periodicals, Inc.

Article Citation: Autism Res 2012, 5: 124–136. DOI: 10.1002/aur.1222

Cluster Analysis of Autistic Patients Based on Principal Pathogenetic Components

Roberto Sacco, Carlo Lenti, Monica Saccani, Paolo Curatolo, Barbara Manzi, Carmela Bravaccio, and Antonio M. Persico

LAY ABSTRACT

Autism spectrum disorder (ASD) is notoriously a heterogeneous disease. In this study, Sacco and colleagues begin dividing patients into “clusters,” subgroups likely sharing at least some basic underlying mechanisms. To this aim, the authors employ four “principal components” that they have recently identified, namely (I) “sensory dysfunction and abnormalities in the sleep–wake rhythm;” (II) “immune system abnormalities” also including maternal complications during pregnancy and/or repeated spontaneous abortions; (III) “cognitive/motor developmental delay;” and (III) “repetitive behavior.” Using hierarchical and k-means clustering, the same 245 autistic patients assessed in the principal component analysis can be divided into four clusters: (a) 43 (17.6%) have prominent immune abnormalities accompanied by some sleep problems and sensory issues; (b) 44 (18.0%) display sleep–wake cycle disruption and sensory symptoms, with little or no immune dysfunction; (c) stereotypies predominate in 75 (31.0%); and (d) 83 (33.9%) show a mixture of all four components, with greater disruptive behaviors and mental retardation. Component II, “immune system abnormalities,” is best at separating out patients, followed by component IV, “stereotypic behaviors.” These patient clusters, if replicated, will deserve further investigation to verify whether these subgroups of ASD patients differ in genetic and immune abnormalities, symptom course, and response to therapies. © 2012 INSAR/Wiley Periodicals, Inc.

Article Citation: Autism Res 2012, 5: 137–147. DOI: 10.1002/aur.1226