Knockout of NMDA Receptors in Parvalbumin Interneurons Recreates Autism-like Phenotypes
John A. Saunders, Valerie M. Tatard-Leitman, Jimmy Suh, Eddie N. Billingslea, Timothy P. Roberts, and Steven J. Siegel
Autism is a disabling disease that results in social and cognitive problems. However, there are not many treatments for autism, in part because there are no methods for determining which pharmaceutical agents will be helpful and therefore worthwhile to develop. This paper examines brain signals and behavioral changes in autism present in our mouse models. If these models are shown to be similar to the disease autism with respect to specific outcome measures, then they may be useful to develop treatments to alleviate a subset of symptoms. © 2013 INSAR/Wiley Periodicals, Inc.
Article citation: Autism Res 2013, 6: 69–77. DOI: 10.1002/aur.1264
Longitudinal Heschl's Gyrus Growth During Childhood and Adolescence in Typical Development and Autism
Molly D. Prigge, Erin D. Bigler, P. Thomas Fletcher, Brandon A. Zielinski, Caitlin Ravichandran, Jeffrey Anderson, Alyson Froehlich, Tracy Abildskov, Evangelia Papadopolous, Kathryn Maasberg, Jared A. Nielsen, Andrew L. Alexander, Nicholas Lange, and Janet Lainhart
Heightened auditory sensitivity and atypical processing of sounds by the brain are common in autism. Functional studies that measure brain activity suggest abnormal neural response to sounds, yet the development underlying atypical sound processing in autism is unknown. We examined the growth of the first cortical area of the brain to process sound, the primary auditory cortex, also known as Heschl's gyrus. The volume of Heschl's gyrus gray and white matter was measured using structural magnetic resonance imaging in 40 children and adolescents with autism and 17 typically developing participants. Up to three time points of volumetric brain data, collected on average every 2.5 years, were examined from individuals 3–12 years of age at their first scan. Our study is the first to examine volumetric changes during childhood and adolescence in Heschl's gyrus longitudinally, or in the same individuals over time. Consistent with previous studies using only one time point of data, no differences between the participant groups were found in Heschl's gyrus gray matter volume. However, reduced longitudinal growth of Heschl's gyrus gray matter volume was found in the right hemisphere in autism. Reduced longitudinal white matter growth in the left hemisphere was found in the right-handed autism participants. Atypical growth of Heschl's gyrus white matter volume was found bilaterally in the autism individuals with a history of delayed onset of spoken language. Heightened reported sensitivity to sounds, obtained from the Sensory Profile, was associated with reduced gray matter volume growth in the right hemisphere. Our longitudinal analyses revealed dynamic gray and white matter changes in Heschl's gyrus throughout childhood and adolescence in both typical development and autism. © 2013 INSAR/Wiley Periodicals, Inc.
Article citation: Autism Res 2013, 6: 78–90. DOI: 10.1002/aur.1265
Oxytocin and Vasopressin in Children and Adolescents With Autism Spectrum Disorders: Sex Differences and Associations With Symptoms
Meghan Miller, Karen L. Bales, Sandra L. Taylor, Jong Yoon, Caroline M. Hostetler, Cameron S. Carter, and Marjorie Solomon
Oxytocin (OT) and arginine vasopressin (AVP) are neuropeptides that are involved in affiliative and social behavior. Previous studies have shown that boys with autism spectrum disorders (ASD) have lower levels of OT than boys without ASD, and treatment studies have found that intranasal infusions of OT increase social behaviors in mostly males with ASD. With this study, we provide basic and novel information on the involvement of OT and AVP in ASD, with an investigation of blood plasma levels of these neuropeptides in 75 preadolescent and adolescent girls and boys ages 8–18: 40 with high-functioning ASD and 35 typically developing children. We related OT and AVP levels to social, language, repetitive behavior, and internalizing symptom measures in these individuals. Girls had higher levels of OT while boys had higher levels of AVP. There were no differences in OT or AVP levels between the ASD and typically developing groups. Higher OT values were associated with greater anxiety in all girls and with less impaired social language in all boys and girls. Higher levels of AVP were associated with greater restricted and repetitive behaviors in girls with ASD, whereas lower levels of AVP were associated with lower levels of these behaviors in boys with ASD. Results challenge the prevailing view that OT levels are lower in individuals with ASD, and suggest that there are distinct mechanisms of action for OT and AVP underlying anxiety and repetitive behavior symptoms for boys versus girls. © 2013 INSAR/Wiley Periodicals, Inc.
Article citation: Autism Res 2013, 6: 91–102. DOI: 10.1002/aur.1270
Stability and Validity of an Automated Measure of Vocal Development From Day-Long Samples in Children With and Without Autism Spectrum Disorder
Paul J. Yoder, D. Kimbrough Oller, Jeffrey A. Richards, Sharmistha Gray, and Jill Gilkerson
Measuring the degree to which young children's vocalizations, many of which are non-words, have acoustic characteristics similar to speech may eventually help us match expectations and treatment methods to individual needs and abilities. To accomplish this goal, we need vocal measures that have scientific utility. The current study indicates that a single all-day recording and subsequent computer-analysis of its acoustic characteristics produces a measure of vocal development that is highly related to expressive language in children with ASD and in children who are typically developing. These findings provide the needed basis for future use of this measure for clinical and scientific purposes. © 2013 INSAR/Wiley Periodicals, Inc.
Article citation: Autism Res 2013, 6: 103–107. DOI: 10.1002/aur.1271
Endogenous Spatial Attention: Evidence for Intact Functioning in Adults With Autism
Michael A. Grubb, Marlene Behrmann, Ryan Egan, Nancy J. Minshew, Marisa Carrasco, and David J. Heeger
Attention allows us to selectively process the vast amount of information with which we are confronted. Focusing on a certain location of the visual scene (visual spatial attention) enables the prioritization of some aspects of information while ignoring others. Rapid manipulation of the attention field (i.e. the location and spread of visual spatial attention) is a critical aspect of human cognition, and previous research on spatial attention in individuals with autism spectrum disorders (ASD) has produced inconsistent results. In a series of three experiments, we evaluated claims in the literature that individuals with ASD exhibit a deficit in voluntarily controlling the deployment and size of the spatial attention field. We measured how well participants perform a visual discrimination task (accuracy) and how quickly they do so (reaction time), with and without spatial uncertainty (i.e. the lack of predictability concerning the spatial position of the upcoming stimulus). We found that high-functioning adults with autism exhibited slower reactions times overall with spatial uncertainty, but the effects of attention on performance accuracies and reaction times were indistinguishable between individuals with autism and typically developing individuals, in all three experiments. These results provide evidence of intact voluntary spatial attention in high-functioning adults with ASD, suggesting that atypical spatial attention cannot be a latent characteristic of autism in general. © 2013 INSAR/Wiley Periodicals, Inc.
Article citation: Autism Res 2013, 6: 108–118. DOI: 10.1002/aur.1269
Proton Magnetic Resonance Spectroscopy as a Probe into the Pathophysiology of Autism Spectrum Disorders (ASD): A Review
Joshua M. Baruth, Christopher A. Wall, Marc C. Patterson, and John D. Port
Proton magnetic resonance spectroscopy (1H-MRS) is a safe, noninvasive way of measuring biochemical and metabolite levels in individuals with autism spectrum disorders (ASD). Findings to date suggest ASD is associated with widespread reduction of metabolites important for neuron function (e.g. N-acetylaspartate, creatine plus phosphocreatine); however, variable findings, and even substantial increases, are not uncommon, depending on the study and brain region. Widespread reduction of these metabolites likely reflects impaired neuronal function related to abnormal neurodevelopmental processes in ASD. Future studies should attempt to control for variability in subject age and functioning level, which would assist in evaluating the relationship between 1H-MRS metabolic levels and abnormal neurodevelopmental processes. Furthermore, more 1H-MRS studies that span long periods of time in both control and ASD subjects are needed, to attempt to standardize metabolite levels across different developmental periods. This will provide a standardized way of measuring metabolic differences as well as treatment responses. With the improvement of 1H-MRS scanning technology, 1H-MRS will continue to be an important tool in ASD research. © 2013 INSAR/Wiley Periodicals, Inc.
Article citation: Autism Res 2013, 6: 119–133. DOI: 10.1002/aur.1273
The Broad Autism Phenotype Questionnaire: Prevalence and Diagnostic Classification
Noah J. Sasson, Kristen S. L. Lam, Debra Childress, Morgan Parlier, Julie L. Daniels, and Joseph Piven
The Broad Autism Phenotype (BAP) refers to the presence of mild autism characteristics frequently found in relatives of individuals with autism. The current study administered the Broad Autism Phenotype Questionnaire (BAPQ), a measure designed to quantify independent features of the BAP, to a sample of 1,692 parents of a child with autism (PCAs) and comparison parents (CPs). After providing statistical confirmation that the BAPQ is a reliable instrument, we report new cutoff scores designed to help others use the BAPQ to diagnostically identify the BAP. The prevalence rate of BAP features in our sample ranged between 14–23% for PCAs and between 5–9% for CPs. Additionally, PCAs were more likely than CPs to have multiple BAP features. These findings provide further evidence that the BAP confers a genetic liability for autism, and indicate that the BAPQ is an efficient and reliable measure for quantifying dissociable BAP characteristics in family members of an individual with autism. © 2013 INSAR/Wiley Periodicals, Inc.
Article citation: Autism Res 2013, 6: 134–143. DOI: 10.1002/aur.1272