We report on an automatic technique for quantifying two types of repetitive speech: repetitions of what the child says him/herself (self-repeats) and of what is uttered by an interlocutor (echolalia). We apply this technique to a sample of 111 children between the ages of four and eight: 42 typically developing children (TD), 19 children with specific language impairment (SLI), 25 children with autism spectrum disorders (ASD) plus language impairment (ALI), and 25 children with ASD with normal, non-impaired language (ALN). The results indicate robust differences in echolalia between the TD and ASD groups as a whole (ALN + ALI), and between TD and ALN children. There were no significant differences between ALI and SLI children for echolalia or self-repetitions. The results confirm previous findings that children with ASD repeat the language of others more than other populations of children. On the other hand, self-repetition does not appear to be significantly more frequent in ASD, nor does it matter whether the child's echolalia occurred within one (immediate) or two turns (near-immediate) of the adult's original utterance. Furthermore, non-significant differences between ALN and SLI, between TD and SLI, and between ALI and TD are suggestive that echolalia may not be specific to ALN or to ASD in general. One important innovation of this work is an objective fully automatic technique for assessing the amount of repetition in a transcript of a child's utterances. Autism Res 2013, ●●: ●●–●●. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.

Methylenetetrahydrofolate reductase (MTHFR) is essential for DNA biosynthesis and the epigenetic process of DNA methylation, and its gene polymorphisms have been implicated as risk factors for birth defects, neurological disorders, and cancers. However, reports on the association of MTHFR polymorphisms with autism spectrum disorders (ASD) are inconclusive. Therefore, we investigated the relationship of the MTHFR polymorphisms (C677T and A1298C) and the risk of ASD by meta-analysis. Up to December 2012, eight case-control studies involving 1672 patients with ASD and 6760 controls were included for meta-analysis. The results showed that the C677T polymorphism was associated with significantly increased ASD risk in all the comparison models [T vs. C allele (frequency of allele): odds ratio (OR) = 1.42, 95% confidence interval (CI): 1.09–1.85; CT vs. CC (heterozygote): OR = 1.48, 95% CI: 1.09–2.00; TT vs. CC (homozygote): OR = 1.86, 95% CI: 1.08–3.20; CT+TT vs. CC (dominant model): OR = 1.56, 95% CI: 1.12–2.18; and TT vs. CC+CT (recessive model): OR = 1.51, 95% CI: 1.02–2.22], whereas the A1298C polymorphism was found to be significantly associated with reduced ASD risk but only in a recessive model (CC vs. AA+AC: OR = 0.73, 95% CI: 0.56–0.97). In addition, we stratified the patient population based on whether they were from a country with food fortification of folic acid or not. The meta-analysis showed that the C677T polymorphism was found to be associated with ASD only in children from countries without food fortification. Our study indicated that the MTHFR C677T polymorphism contributes to increased ASD risk, and periconceptional folic acid may reduce ASD risk in those with MTHFR 677C>T polymorphism. Autism Res 2013, ●●: ●●–●●. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.

We assessed whether autistic traits are related to the ability to identify flavour. In general, the colour of the food or drink facilitates identification of its flavour. In the current study, the colour of drinks either provided congruent, incongruent or ambiguous (colourless) information about the flavour. Participants identified the flavours of 12 drinks from a list and completed a measure of autistic traits, the Autism-Spectrum Quotient (AQ). In line with previous studies, flavour identification was impaired in incongruent conditions, while identification in congruent conditions was not improved when compared with that in ambiguous conditions. AQ scores were related to flavour identification in incongruent conditions, in that as the AQ score increased, accuracy of flavour identification decreased. There were no relationships found in the congruent or ambiguous conditions. This finding is in line with the idea that conflicting sensory information may be more disruptive for individuals on the autism spectrum. Autism Res 2013, ●●: ●●–●●. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.

Young people with an autism spectrum disorder (ASD) are more likely to have heightened levels of anxiety compared with their typically developing (non-ASD) peers. The reasons for this are poorly understood, and there has been little research investigating the cognitive correlates of anxiety in individuals with ASD. Typically developing youth with anxiety disorders have frequently been found to show an attentional bias toward threatening information. In this study, we examined whether such a bias was also found in young people with ASD and anxiety symptoms. The protocol utilized two versions of the dot-probe paradigm, the first with emotional faces and the second with emotional words. Participants comprised 38 boys with an ASD and 41 typically developing controls aged 10–16 years of age. Those with an ASD displayed higher levels of parent- and child-rated anxiety (both P < 0.001) and depression (P < 0.001) compared with controls. However, there were no significant group differences in attentional bias scores and no significant relationship between anxiety and attentional bias in either the face or word tasks, for either group. Our findings suggest that, for young people with ASD, unlike non-ASD individuals with an anxiety disorder, high levels of anxiety may not be associated with attentional bias to threat. This may indicate that anxiety in ASD has different cognitive correlates from anxiety in the typically developing population. Further conclusions, study limitations, and future directions are discussed. Autism Res 2013, ●●: ●●–●●. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.

We tested the hypothesis that the direction of gaze of target faces may play a role in reported face recognition deficits in those with an autism spectrum disorder (ASD). In previous studies, typically developing children and adults better remembered faces in which the eyes were gazing directly at them compared with faces in which the eyes were averted. In the current study, high-functioning children and adolescents with an ASD and age- and IQ-matched typically developing controls were shown a series of pictures of faces in a study phase. These pictures were of individuals whose gaze was either directed straight ahead or whose gaze was averted to one side. We tested the memory for these study faces in a recognition task in which the faces were shown with their eyes closed. The typically developing group better remembered the direct-gaze faces, whereas the ASD participants did not show this effect. These results imply that there may be an important link between gaze direction and face recognition abilities in ASD. Autism Res 2013, ●●: ●●–●●. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.

Autism spectrum disorders (ASDs) are associated with a marked disturbance of neural functional connectivity, which may arise from disrupted organization of white matter. The aim of this study was to use constrained spherical deconvolution (CSD)-based tractography to isolate and characterize major intrahemispheric white matter tracts that are important in visuospatial processing. CSD-based tractography avoids a number of critical confounds that are associated with diffusion tensor tractography, and to our knowledge, this is the first time that this advanced diffusion tractography method has been used in autism research. Twenty-five participants with ASD and aged 25, intelligence quotient-matched controls completed a high angular resolution diffusion imaging scan. The inferior fronto-occipital fasciculus (IFOF) and arcuate fasciculus were isolated using CSD-based tractography. Quantitative diffusion measures of white matter microstructural organization were compared between groups and associated with visuospatial processing performance. Significant alteration of white matter organization was present in the right IFOF in individuals with ASD. In addition, poorer visuospatial processing was associated in individuals with ASD with disrupted white matter in the right IFOF. Using a novel, advanced tractography method to isolate major intrahemispheric white matter tracts in autism, this research has demonstrated that there are significant alterations in the microstructural organization of white matter in the right IFOF in ASD. This alteration was associated with poorer visuospatial processing performance in the ASD group. This study provides an insight into structural brain abnormalities that may influence atypical visuospatial processing in autism. Autism Res 2013, ●●: ●●–●●. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.

Comparison of brain function between children and adults with autism provides an understanding of the effects of the disorder and associated maturational differences on language processing. Functional imaging (functional magnetic resonance imaging) was used to examine brain activation and cortical synchronization during the processing of literal and ironic texts in 15 children with autism, 14 children with typical development, 13 adults with autism, and 12 adult controls. Both the children and adults with autism had lower functional connectivity (synchronization of brain activity among activated areas) than their age and ability comparison group in the left hemisphere language network during irony processing, and neither autism group had an increase in functional connectivity in response to increased task demands. Activation differences for the literal and irony conditions occurred in key language-processing regions (left middle temporal, left pars triangularis, left pars opercularis, left medial frontal, and right middle temporal). The children and adults with autism differed from each other in the use of some brain regions during the irony task, with the adults with autism having activation levels similar to those of the control groups. Overall, the children and adults with autism differed from the adult and child controls in (a) the degree of network coordination, (b) the distribution of the workload among member nodes, and (3) the dynamic recruitment of regions in response to text content. Moreover, the differences between the two autism age groups may be indicative of positive changes in the neural function related to language processing associated with maturation and/or educational experience. Autism Res 2013, ●●: ●●–●●. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.

It has been suggested that atypical amygdala function contributes to the social impairments characteristic of autism spectrum disorders (ASDs). Previous research has demonstrated that adolescents and adults with ASD generate normal response during a fear-potentiated startle paradigm, suggesting this aspect of amygdala function is intact and may not account for the social dysfunction associated with the condition. The amygdala also plays a crucial role in the expression of anxiety and may contribute to high rates of reported anxiety in individuals with ASD. The present study partially replicates prior work by examining the fear-potentiated startle response in adolescents with ASD, and extends this to investigate the relationship between startle response and anxiety. Eyeblink magnitude and latency (electromyographic activity; EMG) were collected from 20 adolescents with ASD and 19 typically developing (TD) age-matched adolescents during a fear-potentiated startle paradigm. Parent-report and self-report of anxiety and additional psychiatric symptoms were collected. Parental reports indicated higher rates of associated psychopathology in adolescents with ASD compared with TD adolescents. Consistent with previous results, both groups showed normal potentiated startle response, and no group differences in EMG were found. Symptoms of anxiety and level of social impairment were unrelated to startle response. These findings held for all levels of anxiety, suggesting that within the context of the fear-potentiated startle paradigm, amygdala response is not associated with degree of atypical social or emotional functioning in ASD. Autism Res 2013, ●●: ●●–●●. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.

Serotonin, a neurotransmitter found throughout the brain and body, has long been of interest in autism. Repeated findings of elevated platelet serotonin levels in approximately one third of children with autism has led some to believe that dysfunctional serotonin signaling may be a causal mechanism for the disorder. Because serotonin is critical to fetal brain development, concerns have arisen regarding prenatal exposure to substances that manipulate serotonin levels, such as selective serotonin reuptake inhibitors (SSRIs). This review examines evidence regarding the serotonin system and autism spectrum disorders (ASD), as well as what the literature has reported thus far on developmental effects of prenatal exposure to SSRIs. Possible mechanisms by which SSRIs could affect the fetus during pregnancy and clinical implications are also discussed. Though the majority of studies conducted in infants and children suggest prenatal exposure to SSRIs does not affect neurodevelopment, interpretation must be tempered given small sample sizes. The only published study that focused on prenatal SSRI exposure and ASD found an increased risk with exposure to SSRIs, especially during the first trimester. Obstacles that will be faced in future research are isolating medication effects from maternal depression and, given the infrequent occurrence of exposure and outcome, obtaining an adequate sample size. Whether serotonin is an etiologic factor in ASD, and what it points to as a marker for subgrouping, remains unclear. Understanding how the development of ASD might be affected by prenatal factors that influence serotonin levels, such as SSRIs, could identify modifiable targets for prevention. Autism Res 2013, ●●: ●●–●●. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.

This follow-up study investigated the predictive power of early cognitive atypicalities. Specifically, it examined whether early individual differences in specific cognitive skills, including theory of mind, executive function, and central coherence, could uniquely account for variation in autistic children's behaviors—social communication, repetitive behaviors, and interests and insistence on sameness—at follow-up. Thirty-seven cognitively able children with an autism spectrum condition were assessed on tests tapping verbal and nonverbal ability, theory of mind (false-belief prediction), executive function (planning ability, cognitive flexibility, and inhibitory control), and central coherence (local processing) at intake and their behavioral functioning (social communication, repetitive behaviors and interests, insistence on sameness) 3 years later. Individual differences in early executive but not theory of mind skills predicted variation in children's social communication. Individual differences in children's early executive function also predicted the degree of repetitive behaviors and interests at follow-up. There were no predictive relationships between early central coherence and children's insistence on sameness. These findings challenge the notion that distinct cognitive atypicalities map on to specific behavioral features of autism. Instead, early variation in executive function plays a key role in helping to shape autistic children's emerging behaviors, including their social communication and repetitive behaviors and interests. Autism Res 2013, ●●: ●●–●●. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.

Chromosomal copy number variants (CNV) are the most common genetic lesion found in autism. Many autism-associated CNVs are duplications of chromosome 15q. Although most cases of interstitial (int) dup(15) that present clinically are de novo and maternally derived or inherited, both pathogenic and unaffected paternal duplications of 15q have been identified. We performed a phenotype/genotype analysis of individuals with interstitial 15q duplications to broaden our understanding of the 15q syndrome and investigate the contribution of 15q duplication to increased autism risk. All subjects were recruited solely on the basis of interstitial duplication 15q11.2-q13 status. Comparative array genome hybridization was used to determine the duplication size and boundaries while the methylation status of the maternally methylated small nuclear ribonucleoprotein polypeptide N gene was used to determine the parent of origin of the duplication. We determined the duplication size and parental origin for 14 int dup(15) subjects: 10 maternal and 4 paternal cases. The majority of int dup(15) cases recruited were maternal in origin, most likely due to our finding that maternal duplication was coincident with autism spectrum disorder. The size of the duplication did not correlate with the severity of the phenotype as established by Autism Diagnostic Observation Scale calibrated severity score. We identified phenotypes not comprehensively described before in this cohort including mild facial dysmorphism, sleep problems and an unusual electroencephalogram variant. Our results are consistent with the hypothesis that the maternally expressed ubiquitin protein ligase E3A gene is primarily responsible for the autism phenotype in int dup(15) since all maternal cases tested presented on the autism spectrum. Autism Res 2013, ●●: ●●–●●. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.

Abundant evidence indicates that both genetic and environmental factors contribute to the etiology of autism spectrum disorders (ASDs). However, limited knowledge is available concerning these contributing factors. An epidemiology study reported a link between increased incidence of autism and living closely to major highways, suggesting a possible role for pollutants from highway traffic. We investigated whether maternal exposure to diesel exhaust particles (DEP) negatively affects fetal development leading to autism-like phenotype in mice. Female mice and their offspring were exposed to DEP during pregnancy and nursing. Adult male offspring were then tested for behaviors reflecting the typical symptoms of ASD patients. Compared to control mice, DEP-exposed offspring exhibited higher locomotor activity, elevated levels of self-grooming in the presence of an unfamiliar mouse, and increased rearing behaviors, which may be relevant to the restricted and repetitive behaviors seen in ASD patients. However, the DEP-exposed mice did not exhibit deficits in social interactions or social communication which are the key features of ASD. These results suggest that early life exposure to DEP could have an impact on mouse development leading to observable changes in animal behaviors. Further studies are needed to reveal other environmental insults and genetic factors that would lead to animal models expressing key phenotypes of the autism spectrum disorders. Autism Res 2013, ●●: ●●–●●. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.

The present study explores behavioral and sleep outcomes in preschool-age siblings of children with autism spectrum disorders (ASD). This study focuses on behavior problems that are common in children with ASD, such as emotional reactivity, anxiety, inattention, aggression, and sleep problems. Infant siblings were recruited from families with at least one older child with ASD (high-risk group, n = 104) or families with no history of ASD (low-risk group, n = 76). As part of a longitudinal prospective study, children completed the Mullen Scales of Early Learning and the Autism Diagnostic Observation Schedule, and parents completed the Child Behavior Checklist (CBCL) and the Social Communication Questionnaire at 36 months of age. This study focuses on developmental concerns outside of ASD; therefore, only siblings who did not develop an ASD were included in analyses. Negative binomial regression analyses revealed that children in the high-risk group were more likely to have elevated behavior problems on the CBCL Anxious/Depressed and Aggression subscales. To explore sleep problems as a correlate of these behavior problems, a second series of models was specified. For both groups of children, sleep problems were associated with elevated behavior problems in each of the areas assessed (reactivity, anxiety, somatic complaints, withdrawal, attention, and aggression). These findings support close monitoring of children with a family history of ASD for both behavioral and sleep issues. Autism Res 2013, ●●: ●●–●●. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.

Diagnosis of an autism spectrum disorder (ASD) requires a qualitative assessment of social aptitude: one person judging whether another person interacts in a “typical” way. We hypothesized that mice could be used to make a similar judgment if they prefer “typical” over “atypical” social interactions with mouse models relevant to ASD. We used wild-type C57BL/6 (B6) mice as “judges” and evaluated their preference for a chamber containing a “typical” (B6 or 129S6) or an “atypical” mouse. For our atypical mouse stimuli, we chose two inbred strains with well-documented social phenotypes (BTBR and BALB/c), as well a mutant line with abnormal social behavior and seizures (Gabrb3 +/−). Overall, we observed a stimulus by time interaction (P < 0.0001), with B6 mice preferring the typical mouse chamber during the last 10 min of the 30-min test. For two of the individual stimulus pairings, we observed a similar chamber by time interaction (BALB/c vs. 129S6, P = 0.0007; Gabrb3 +/− vs. 129S6, P = 0.033). For the third stimulus pairing, we found a trend for preference of the typical mouse across time (BTBR vs. B6, P = 0.051). We repeated the experiments using 129S6 mice as judges and found a significant overall interaction (P = 0.034), but only one stimulus pairing reached significance on its own (BALB/c vs. 129S6, P = 0.0021). These data suggest that a characteristic pattern of exploration in B6 mice can distinguish some socially atypical animals from controls. Autism Res 2013, ●●: ●●–●●. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.

It is widely accepted that we use contextual information to guide our gaze when searching for an object. People with autism spectrum disorder (ASD) also utilise contextual information in this way; yet, their visual search in tasks of this kind is much slower compared with people without ASD. The aim of the current study was to explore the reason for this by measuring eye movements. Eye movement analyses revealed that the slowing of visual search was not caused by making a greater number of fixations. Instead, participants in the ASD group were slower to launch their first saccade, and the duration of their fixations was longer. These results indicate that slowed search in ASD in contextual learning tasks is not due to differences in the spatial allocation of attention but due to temporal delays in the initial-reflexive orienting of attention and subsequent-focused attention. These results have broader implications for understanding the unusual attention profile of individuals with ASD and how their attention may be shaped by learning. Autism Res 2013, ●●: ●●–●●. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.

The aim of this study was to examine whether the relationship between maternal psychological well-being and behavior problems in children with an autism spectrum disorder (ASD) is bidirectional. Data were available at 9 months, 3 years, and 5 years old for 132 children with ASD, identified from a population-representative sample of UK children. Three-wave cross-lagged models examined reciprocal effects between child behavior and maternal well-being (psychological distress, physical health functioning, and life satisfaction). Results indicated that the relationships between maternal well-being and child problem behaviors were not bidirectional. Specifically, findings suggested that while early behavior problems are not a risk factor for later maternal well-being, maternal psychological distress, physical health limitations, and lower life satisfaction are risk factors for later child behavior problems. Autism Res 2013, ●●: ●●–●●. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.

Emerging evidence for differences between individuals with autism spectrum disorder (ASD) and neurotypical (NT) individuals in somatic processing and brain response to touch suggests somatosensory cortex as a promising substrate for elucidating differences in functional brain connectivity between individuals with and without autism. Signals from adjacent digits project to neighboring locations or representations in somatosensory cortex. When a digit is stimulated, i.e. touched, its representation in cortex is directly activated; local intracortical connections indirectly activate nonprimary cortical representations corresponding to adjacent digits. The response of the nonprimary cortical representations is thus a proxy for connection strength. Local overconnectivity in autism implies that the nonprimary/primary response ratios of the ASD group will be higher than those of the NT group. D1 and D2 of the dominant hand of the participant were individually stimulated while we recorded neural responses using magnetoencephalography. The cortical representations of D1 and D2 (somatosensory-evoked fields) were computed from the ensemble-averaged data using (a) dipole model fits and (b) singular value decomposition. Individual adjacent/primary response ratios were measured, and group response ratio data were fitted with straight lines. Local overconnectivity in autism implies steeper ASD vs. NT group slopes. Our findings did not support local overconnectivity. Slopes were found to be significantly shallower for the ASD group than the NT group. Our findings support the idea of local underconnectivity in the somatosensory cortex of the brains of individuals with ASD. Autism Res 2013, ●●: ●●–●●. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.

Autism is a disabling neurodevelopmental disorder characterized by social deficits, language impairment, and repetitive behaviors with few effective treatments. New evidence suggests that autism has reliable electrophysiological endophenotypes and that these measures may be caused by n-methyl-d-aspartic acid receptor (NMDAR) disruption on parvalbumin (PV)-containing interneurons. These findings could be used to create new translational biomarkers. Recent developments have allowed for cell-type selective knockout of NMDARs in order to examine the perturbations caused by disrupting specific circuits. This study examines several electrophysiological and behavioral measures disrupted in autism using a PV-selective reduction in NMDA R1 subunit. Mouse electroencephalograph (EEG) was recorded in response to auditory stimuli. Event-related potential (ERP) component amplitude and latency analysis, social testing, and premating ultrasonic vocalizations (USVs) recordings were performed. Correlations were examined between the ERP latency and behavioral measures. The N1 ERP latency was delayed, sociability was reduced, and mating USVs were impaired in PV-selective NMDA Receptor 1 Knockout (NR1 KO) as compared with wild-type mice. There was a significant correlation between N1 latency and sociability but not between N1 latency and premating USV power or T-maze performance. The increases in N1 latency, impaired sociability, and reduced vocalizations in PV-selective NR1 KO mice mimic similar changes found in autism. Electrophysiological changes correlate to reduced sociability, indicating that the local circuit mechanisms controlling N1 latency may be utilized in social function. Therefore, we propose that behavioral and electrophysiological alterations in PV-selective NR1 KO mice may serve as a useful model for therapeutic development in autism. Autism Res 2013, 6: 69–77. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.

Heightened auditory sensitivity and atypical auditory processing are common in autism. Functional studies suggest abnormal neural response and hemispheric activation to auditory stimuli, yet the neurodevelopment underlying atypical auditory function in autism is unknown. In this study, we model longitudinal volumetric growth of Heschl's gyrus gray matter and white matter during childhood and adolescence in 40 individuals with autism and 17 typically developing participants. Up to three time points of magnetic resonance imaging data, collected on average every 2.5 years, were examined from individuals 3–12 years of age at the time of their first scan. Consistent with previous cross-sectional studies, no group differences were found in Heschl's gyrus gray matter volume or asymmetry. However, reduced longitudinal gray matter volumetric growth was found in the right Heschl's gyrus in autism. Reduced longitudinal white matter growth in the left hemisphere was found in the right-handed autism participants. Atypical Heschl's gyrus white matter volumetric growth was found bilaterally in the autism individuals with a history of delayed onset of spoken language. Heightened auditory sensitivity, obtained from the Sensory Profile, was associated with reduced volumetric gray matter 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. Autism Res 2013, 6: 78–90. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.

There has been intensified interest in the neuropeptides oxytocin (OT) and arginine vasopressin (AVP) in autism spectrum disorders (ASD) given their role in affiliative and social behavior in animals, positive results of treatment studies using OT, and findings that genetic polymorphisms in the AVP–OT pathway are present in individuals with ASD. Nearly all such studies in humans have focused only on males. With this preliminary study, we provide basic and novel information on the involvement of OT and AVP in autism, 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 (19 girls, 21 boys) and 35 typically developing children (16 girls, 19 boys). We related neuropeptide levels to social, language, repetitive behavior, and internalizing symptom measures in these individuals. There were significant gender effects: Girls showed higher levels of OT, while boys had significantly higher levels of AVP. There were no significant effects of diagnosis on OT or AVP. Higher OT values were associated with greater anxiety in all girls, and with better pragmatic language in all boys and girls. AVP levels were positively associated with restricted and repetitive behaviors in girls with ASD but negatively (nonsignificantly) associated with these behaviors in boys with ASD. Our results challenge the prevailing view that plasma OT levels are lower in individuals with ASD, and suggest that there are distinct and sexually dimorphic mechanisms of action for OT and AVP underlying anxiety and repetitive behaviors. Autism Res 2013, 6: 91–102. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.

Individual difference measures of vocal development may eventually aid our understanding of the variability in spoken language acquisition in children with autism spectrum disorder (ASD). Large samples of child vocalizations may be needed to maximize the stability of vocal development estimates. Day-long vocal samples can now be automatically analyzed based on acoustic characteristics of speech likeness identified in theoretically driven and empirically cross-validated quantitative models of typical vocal development. This report indicates that a single day-long recording can produce a stable estimate for a measure of vocal development that is highly related to expressive spoken language in a group of young children with ASD and in a group that is typically developing. Autism Res 2013, 6: 103–107. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.

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 psychophysical 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 the spatial distribution of performance accuracies and reaction times to quantify the sizes and locations of the attention field, 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 reaction 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 endogenous spatial attention function in high-functioning adults with ASD, suggesting that atypical endogenous attention cannot be a latent characteristic of autism in general. Autism Res 2013, 6: 108–118. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.

Proton magnetic resonance spectroscopy (¹H-MRS) is a safe, noninvasive way of quantifying in vivo biochemical and metabolite concentration levels in individuals with Autism Spectrum Disorders (ASD). Findings to date suggest ASD is associated with widespread reduction in N-acetylaspartate (NAA), creatine plus phosphocreatine (Cr), choline-containing compounds (Cho), myo-inositol (mI), and glutamate plus glutamine plus gamma-Aminobutyric Acid (Glx); however, variable findings, and even substantial increases, are not uncommon depending on the study and/or region-of-interest. Widespread reduction of NAA, Cr, Cho, mI, and Glx in ASD likely reflects impaired neuronal function and/or metabolism related to abnormal neurodevelopmental processes. Future studies should attempt to relate ¹H-MRS findings to histological findings and control for variability in subject age and functioning level; this would assist in evaluating the relationship between ¹H-MRS metabolic levels and neuronal and glial cell densities, as well as neurodevelopmental process associated with ASD. Furthermore, more longitudinal ¹H-MRS studies are needed in both control and ASD subjects to attempt to standardize metabolite levels across different developmental periods in well-defined endophenotypes. This will provide for a standard rubric for which metabolic aberrations (as well as treatment responses) can be measured. With higher magnetic field strengths and spectral-editing techniques capable of quantifying less-concentrated metabolites, ¹H-MRS will continue to be an important tool in ASD research. Autism Res 2013, 6: 119–133. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.

The Broad Autism Phenotype Questionnaire (BAPQ) was administered to a large community-based sample of biological parents of children with autism (PCAs) and comparison parents (CPs) (n = 1,692). Exploratory factor analysis and internal consistency parameters confirmed a robust three-factor structure of the BAPQ, corresponding to the proposed aloof, pragmatic language and rigidity subscales. Based upon the distribution of Broad Autism Phenotype (BAP) features in the general population, new normative cutoff values for BAPQ subscales were established that provide increased specificity relative to those previously reported, and thus enhance the utility of the BAPQ for diagnostically classifying the BAP. These cutoffs were also used to estimate prevalence of the BAP and its three components, with rates ranging between 14–23% for PCAs and between 5–9% for CPs. Analysis of patterns of BAP characteristics within family members revealed that BAP features were more likely to co-occur in PCAs relative to CPs. Collectively, these findings extend the utility of the BAPQ and provide additional evidence that it is an efficient and reliable tool for disaggregating the heterogeneity of autism through the identification of meaningful subgroups of parents. Autism Res 2013, 6: 134–143. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.