Increased Glutamate Concentration in the Auditory Cortex of Persons With Autism and First-Degree Relatives: A 1H-MRS Study
Mark S. Brown, Debra Singel, Susan Hepburn, and Donald C. Rojas
We investigated the brain chemistry of the primary region of the brain involved in auditory processing in adults with autism spectrum disorder (ASD). Because of the highly heritable nature of ASD and the lack of prior brain chemistry data on unaffected first-degree relatives, we also enrolled parents of children with ASD (pASD), comparing both groups to a healthy adult control group. The technique used to quantify chemical signals was magnetic resonance spectroscopy (MRS), which we used to assess the concentration of auditory glutamate, the primary excitatory brain neurotransmitter, as well as other metabolites that assess neuronal integrity and metabolism. We found significantly higher levels of auditory glutamate in persons with ASD. In addition, increases in two other metabolites, n-acetyl-aspartate (NAA) and creatine (Cr), were observed in the ASD group. No differences were observed in the pASD group in any MRS measurement. We interpret the glutamate finding as suggestive of an increase in brain excitability, and the NAA and Cr findings as indicative of a change in brain energy metabolism in ASD. © 2012 INSAR/Wiley Periodicals, Inc.
Article citation: Autism Res 2013, 6: 1–10. DOI: 10.1002/aur.1260
Neonatal Brainstem Function and 4-Month Arousal-Modulated Attention Are Jointly Associated With Autism
Ira L. Cohen, Judith M. Gardner, Bernard Z. Karmel, Ha T. T. Phan, Phyllis Kittler, Tina Rovito Gomez, Maripaz G. Gonzalez, Elizabeth M. Lennon, Santosh Parab, and Anthony Barone
A stronger preference for high rates of stimulation when tested after feeding at 4 months of age has been reported in neonatal intensive care unit graduates who later were diagnosed with autism relative to those who were not. This visual preference is typical of newborns, is likely mediated by arousal systems in the brainstem, and should no longer be present by 4 months. The fact that it was so persistent in babies who later developed autism suggested they may have had atypical brainstem development or functioning. There exists a group of newborns who initially fail the auditory brainstem response (ABR; a measure of the integrity of their brainstem auditory pathways) screens but eventually recover by hospital discharge, suggesting that they have atypical brainstem development. We therefore examined the extent to which this problem with ABR functioning, along with 4-month-olds’ preference for high rates of stimulation, predicts the later occurrence of autism in toddlers and preschoolers. We found that preference for higher rates of stimulation at 4 months was highly associated with later measures of autism severity and with language development problems, but only in those who had initially abnormal ABRs. It was concluded that the joint occurrence of initially abnormal neonatal ABRs and preference for more stimulation at 4 months, both indices of early brainstem dysfunction, may be a marker for the development of autism. © 2012 INSAR/Wiley Periodicals, Inc.
Article citation: Autism Res 2013, 6: 11–22. DOI: 10.1002/aur.1259
Object-Directed Imitation in Children With High-Functioning Autism: Testing the Social Motivation Hypothesis
Mark Nielsen, Virginia Slaughter, and Cheryl Dissanayake
Past studies have found that children with autism have difficulties copying actions others do with their hands and bodies, but not actions directed at objects. One explanation is that object-directed actions have clear, functional outcomes that rely less on social or interpersonal motivation for their production than do bodily oriented actions. To investigate this, we compared the performance of a group of children with high-functioning autism (HFA) and a group of typically developing (TD) children on two distinct object-directed tasks that are considered highly social. For one task, an adult showed the children how to open a novel apparatus including the use of actions that were clearly unnecessary. For the other task, children were given a duplicate of an object an adult was playing with and could choose to copy her or do what they wanted with it. Our findings were surprising. Just like the TD children, on the first task the children with autism reproduced all of the actions shown to them by the adult when getting the apparatus open, and on the second task, they entered into extended bouts copying the adult. This work demonstrates that the capacity and propensity for overimitation and synchronic imitation are intact in children with HFA, and questions whether socially based imitation should be considered an autism-specific deficit. © 2012 INSAR/Wiley Periodicals, Inc.
Article citation: Autism Res 2013, 6: 23–32. DOI: 10.1002/aur.1261
Exploring the Relationship Between Anxiety and Insistence on Sameness in Autism Spectrum Disorders
Katherine Gotham, Somer L. Bishop, Vanessa Hus, Marisela Huerta, Sabata Lund, Andreas Buja, Abba Krieger, and Catherine Lord
Elevated anxiety symptoms are one of the most common forms of psychopathology to co-occur with autism spectrum disorders (ASDs). The purpose of this study was to explore the association between anxiety and ASD symptoms, particularly the degree to which the relationship is explained by insistence on sameness (IS) behaviors and/or cognitive ability. Within a large sample of children from a genetic consortium study of ASD, Child Behavior Checklist Anxiety Problems T-scores and Autism Diagnostic Interview-Revised “IS“ item raw totals were treated as measures of anxiety and IS, respectively; these variables were assessed for potential association with each other and with chronological age, verbal intelligence quotient (IQ), and a variety of ASD symptom and other behavioral variables. In children with ASD, anxiety and IS appear to be relatively independent of each other and of chronological age and IQ. Neither anxiety nor IS was significantly associated with other core autism features or ASD severity scores. Anxiety was associated with a number of general behavioral symptoms, including attention problems and aggression. In contrast, IS was not significantly associated with non-ASD-specific behavioral symptom domains. Describing research samples in terms of anxiety and IS variables may inform our understanding of the behavioral phenotype, biology, and genetics of the autism spectrum. © 2012 INSAR/Wiley Periodicals, Inc.
Article citation: Autism Res 2013, 6: 33–41. DOI: 10.1002/aur.1263
The Behavioral Phenotype in MECP2 Duplication Syndrome: A Comparison With Idiopathic Autism
Sarika U. Peters, Rachel J. Hundley, Amy K. Wilson, Zachary Warren, Alison Vehorn, Claudia M.B. Carvalho, James R. Lupski, and Melissa B. Ramocki
Clinical studies of single gene disorders with a high rate of autism have allowed for better assessment of gene function because of the significant effects of these mutations. An example of one of these single gene disorders is MECP2 duplication syndrome, which involves overexpression of the X-linked gene MECP2. Overexpression of MECP2 has been linked to nonsyndromic autism, and studies of MECP2 duplication syndrome have provided a model for understanding how overexpression of MECP2 specifically affects autism-related social behavior. To better characterize the importance of MECP2 overexpression to ASD-related behaviors, we compared the behaviors of boys with MECP2 duplication syndrome with nonverbal mental age-matched individuals with nonsyndromic autism. Within the MECP2 duplication group, we also examined how duplication size and gene content corresponded to clinical severity. We compared ten boys with MECP2 duplication syndrome (ages 3–10) with a matched group of nine nonverbal boys with nonsyndromic autism. Our results provide further support that core features of autism (e.g. social affect impairment, stereotyped behaviors) are shared among boys with MECP2 duplication syndrome and boys with autism alone. We found that hyposensitivity to pain and temperature was common in MECP2 duplication syndrome, while behaviors such as hyperactivity and aggression were uncommon. Within the MECP2 duplication group, breakpoint size did not predict differences in clinical severity. In sum, our results should provide a framework for investigating treatments that could have broader impact for individuals with autism and those with MECP2 duplications. © 2012 INSAR/Wiley Periodicals, Inc.
Article citation: Autism Res 2013, 6: 42–50. DOI: 10.1002/aur.1262
Macrocephaly as a Clinical Indicator of Genetic Subtypes in Autism
Steven Klein, Pantea Sharifi-Hannauer, and Julian A. Martinez-Agosto
An association between autism and large head size has been previously described. Historically, a subset of these cases have been correlated with mutations in the gene phosphatase and tensin homolog (PTEN). However, for the majority of cases, the etiology is not known. We have studied 33 patients with autism and large head size. Within this group, we confirm the association of PTEN mutations and extreme head size and identify mutations in 22% of cases, including three novel PTEN mutations. In addition, we define three novel phenotypic subgroups: (a) cases associated with somatic overgrowth, (b) those with disproportionate macrocephaly, and (c) those with relative macrocephaly. Members of these subgroups lack changes in the PTEN gene, and furthermore we report two novel copy number changes in these patients. © 2013 INSAR/Wiley Periodicals, Inc.
Article citation: Autism Res 2013, 6: 51–56. DOI: 10.1002/aur.1266
Use of Birth Certificates to Examine Maternal Occupational Exposures and Autism Spectrum Disorders in Offspring
Gayle C. Windham, Austin Sumner, Sherian X. Li, Meredith Anderson, Elizabeth Katz, Lisa A. Croen, and Judith K. Grether
There is current public interest in how chemicals and the environment may be related to autism, in part as a way to explain an apparent increase in its occurrence. Chemicals that affect the baby's development during pregnancy are of most concern. Using data already available, we looked at possible exposure of mothers and fathers to such chemicals at work. Parental occupation was obtained from birth certificates for a group of children with autism and a group without, all born in the San Francisco Bay Area in 1994. Possible chemical exposures were coded by experts without knowing which children were later diagnosed with autism. We found that around the time of birth, mothers of children who later developed autism were twice as likely to work in a job that involved chemicals as mothers of the comparison children without autism. Exposures that were more common among mothers of children with autism were engine exhaust and disinfectants. Fathers of children with autism were not more likely to work in exposed jobs. There have been a few other studies that support the possibility that exhaust or air pollution from cars may be related to autism. As one of the first studies to examine work exposures and autism, this study was done with records that had few details about the job or workplace, so definite conclusions cannot be reached from these results, but suggest further research on this topic is important. © 2013 INSAR/Wiley Periodicals, Inc.
Article citation: Autism Res 2013, 6: 57–63. DOI: 10.1002/aur.1275