The clinician perspective on sex differences in autism spectrum disorders

Research studies using existing samples of individuals with autism spectrum disorders have identified differences in symptoms between males and females. Differences are typically reported in school age and adolescence, with similarities in symptom presentation at earlier ages. However, existing studies on sex differences are significantly limited, making it challenging to discern if, how, and at what point in development females with autism spectrum disorder actually exhibit a different behavioral presentation than males. The purpose of this study was to gather impressions from a large group of clinicians to isolate specific areas for future study of sex differences. Clinicians were surveyed about their opinions and perceptions of symptom severity in females, as compared to males, at different points during development. They were also asked to provide open-ended responses about female symptom presentation. Consistent with previous literature, clinicians noted more sex-related differences in restricted and repetitive behaviors and fewer differences for social communication features. Differences were most commonly observed in school age and adolescence, suggesting this time period as a critical and particularly vulnerable window for females with autism spectrum disorder. The results are discussed in the context of other male/female differences across development so that more targeted investigations of autism spectrum disorder sex differences across development.

Keywords: adolescents; autism spectrum disorders; diagnosis; preschool children; qualitative research; repetitive behaviors and interests; school-age children; social cognition and social behavior.

Recent theoretical accounts have proposed excitation and inhibition (E/I) imbalance as a possible mechanistic, network-level hypothesis underlying neural and behavioral dysfunction across neurodevelopmental disorders, particularly autism spectrum disorder (ASD) and schizophrenia (SCZ). These two disorders share some overlap in their clinical presentation as well as convergence in their underlying genes and neurobiology. However, there are also clear points of dissociation in terms of phenotypes and putatively affected neural circuitry. We highlight emerging work from the clinical neuroscience literature examining neural correlates of E/I imbalance across children and adults with ASD and adults with both chronic and early-course SCZ. We discuss findings from diverse neuroimaging studies across distinct modalities, conducted with electroencephalography, magnetoencephalography, proton magnetic resonance spectroscopy, and functional magnetic resonance imaging, including effects observed both during task and at rest. Throughout this review, we discuss points of convergence and divergence in the ASD and SCZ literature, with a focus on disruptions in neural E/I balance. We also consider these findings in relation to predictions generated by theoretical neuroscience, particularly computational models predicting E/I imbalance across disorders. Finally, we discuss how human noninvasive neuroimaging can benefit from pharmacological challenge studies to reveal mechanisms in ASD and SCZ. Collectively, we attempt to shed light on shared and divergent neuroimaging effects across disorders with the goal of informing future research examining the mechanisms underlying the E/I imbalance hypothesis across neurodevelopmental disorders. We posit that such translational efforts are vital to facilitate development of neurobiologically informed treatment strategies across neuropsychiatric conditions.

Keywords: Autism; Computational modeling; E/I balance; Mechanism; Neuroimaging; Review; Schizophrenia.

Although evidence-based practices for autism spectrum disorders exist, they are often not effectively incorporated into school-based programs, indicating a need for enhanced training strategies for educators. This study examined the effects of immediate video feedback during coaching for teachers and paraprofessionals learning Classroom Pivotal Response Teaching (CPRT). Special education teachers, along with their classroom paraprofessionals, were randomly assigned to a coaching as usual (CAU) or a coaching with video enhancement (VE) condition. Both groups received both verbal and written feedback regarding strengths and weaknesses of their CPRT implementation. Additionally, the VE condition received video feedback during their coaching sessions. Overall, teachers demonstrated higher fidelity of implementation than paraprofessionals, t(44) = −2.73, p < .01, but no significant group differences were identified between VE and CAU conditions. Univariate analysis of variance models were conducted to examine the relationship between participant satisfaction regarding overall quality of the training and highest percentage of CPRT components passed, F(2, 37) = 3.93, p = .03. Results indicate use of the iPad may impact training outcomes and participant satisfaction with training procedures and add to the very limited literature on how technology may be used to enhance in-service training for teachers.Keywords group design, methodologies, professional development, tablets, iPad, technology

Pivotal response treatment (PRT) is an evidence-based behavioral intervention based on applied behavior analysis principles aimed to improve social communication skills in individuals with autism spectrum disorder (ASD). PRT adopts a more naturalistic approach and focuses on using a number of strategies to help increase children’s motivation during intervention. Since its conceptualization, PRT has received much empirical support for eliciting therapeutic gains in greater use of functional social communication skills in individuals with ASD. Building upon the empirical evidence supporting PRT, recent advancements have increasingly turned to using interdisciplinary research integrating neuroimaging techniques and behavioral measures to help identify objective biomarkers of treatment, which have two primary purposes. First, neuroimaging results can help characterize how PRT may elicit change, and facilitate partitioning of the heterogeneous profiles of neural mechanisms underlying similar profile of behavioral changes observed over PRT. Second, neuroimaging provides an objective means to both map and track how biomarkers may serve as reliable and sensitive predictors of responder profiles to PRT, assisting clinicians to identify who will most likely benefit from PRT. Together, a better understanding of both mechanisms of change and predictors of responder profile will help PRT to serve as a more precise and targeted intervention for individuals with ASD, thus moving towards the goal of precision medicine and improving quality of care. This review focuses on the recent emerging neuroimaging evidences supporting PRT, offering current perspectives on the importance of interdisciplinary research to help clinicians better understand how PRT works and predict who will respond to PRT.

Keywords: ASD; PRT; biological motion; biomarkers; neuroimaging; precision medicine.

Sensory processing alterations are highly prevalent in autism spectrum disorder (ASD). Neurobiologically-based theories of ASD propose that abnormalities in the processing of temporal aspects of sensory input could underlie core symptoms of ASD. For example, rapid auditory temporal processing is critical for speech perception, and language difficulties are central to the social communication deficits defining the disorder. This study assessed visual and auditory temporal processing abilities and tested their relation to core ASD symptoms. 53 children (26 ASD, 27 TD) completed visual and auditory psychophysical gap detection tasks to measure gap detection thresholds (i.e., the minimum interval between sequential stimuli needed for individuals to perceive an interruption between the stimuli) in each domain. Children were also administered standardized language assessments such that the relation between individual differences in auditory gap detection thresholds and degree of language and communication difficulties among children with ASD could be assessed. Children with ASD had substantially higher auditory gap detection thresholds compared to children with TD, and auditory gap detection thresholds were correlated significantly with several measures of language processing in this population. No group differences were observed in the visual temporal processing. Results indicate a domain-specific impairment in rapid auditory temporal processing in ASD that is associated with greater difficulties in language processing. Findings provide qualified support for temporal processing theories of ASD and highlight the need for future research testing the nature, extent, and universality of auditory temporal processing deficits in this population. Autism Res 2017, 10: 1845-1856. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.

Keywords: ASD; audition; language; low level perception; temporal processing; vision.

Assessing anxiety in autism spectrum disorder (ASD) is inherently challenging due to overlapping (e.g., social avoidance) and ambiguous symptoms (e.g., fears of change). An ASD addendum to the Anxiety Disorders Interview Schedule-Child/Parent, Parent Version (ADIS/ASA) was developed to provide a systematic approach for differentiating traditional anxiety disorders from symptoms of ASD and more ambiguous, ASD-related anxiety symptoms. Interrater reliability and convergent and discriminant validity were examined in a sample of 69 youth with ASD (8-13 years, 75% male, IQ = 68-143) seeking treatment for anxiety. The parents of participants completed the ADIS/ASA and a battery of behavioral measures. A second rater independently observed and scored recordings of the original interviews. Findings suggest reliable measurement of comorbid (intraclass correlation = 0.85-0.98, κ = 0.67-0.91) as well as ambiguous anxiety-like symptoms (intraclass correlation = 0.87-95, κ = 0.77-0.90) in children with ASD. Convergent and discriminant validity were supported for the traditional anxiety symptoms on the ADIS/ASA, whereas convergent and discriminant validity were partially supported for the ambiguous anxiety-like symptoms. Results provide evidence for the reliability and validity of the ADIS/ASA as a measure of traditional anxiety categories in youth with ASD, with partial support for the validity of the ambiguous anxiety-like categories. Unlike other measures, the ADIS/ASA differentiates comorbid anxiety disorders from overlapping and ambiguous anxiety-like symptoms in ASD, allowing for more precise measurement and clinical conceptualization. Ambiguous anxiety-like symptoms appear phenomenologically distinct from comorbid anxiety disorders and may reflect either symptoms of ASD or a novel variant of anxiety in ASD.

Phelan-McDermid syndrome (PMS) is a single-locus cause of developmental delay, autism spectrum disorder, and minimal verbal abilities. There is an urgent need to identify objective outcome measures of expressive language for use in this and other minimally verbal populations. One potential tool is an automated language processor called Language ENvironment Analysis (LENA). LENA was used to obtain over 542 h of audio in 18 children with PMS. LENA performance was adequate in a subset of children with PMS, specifically younger children and those with fewer stereotypic vocalizations. One LENA-derived language measure, Vocalization Ratio, had improved accuracy in this sample and may represent a novel expressive language measure for use in severely affected populations.

Keywords: 22q13 deletion syndrome; Autism spectrum disorder; Automated vocal analysis; Language ENvironment Analysis; Minimally verbal; Phelan-McDermid syndrome.

Background: Phelan-McDermid syndrome (PMS) occurs as a result of a chromosomal abnormality, most frequently
deletion, in the long arm of chromosome 22, involving the SHANK3 gene. Our goal was to prospectively assess the
neurological phenotype in this syndrome.
METHODS: Twenty-nine participants were recruited from ongoing studies in PMS at the Seaver Autism Center. They
had a structured, uniform neurological examination performed by a pediatric neurologist (Y.F.). Abnormal findings
were graded as mild, moderate or severe. In addition, reports of seizures, magnetic resonance imaging (MRI) and
electroencephalograms (EEG) were reviewed. We calculated the frequency and severity of neurological
abnormalities, as well as correlations between items on the neurological examination and items on the Mullen Scales
of Early Learning and on the Vineland Adaptive Behavioral Scales (VABS).
RESULTS: Hypotonia, abnormal gait, fine motor coordination deficits, and expressive and receptive language delays
were present in all participants. Attention deficits were present in 96% (severe in 62%), and abnormal visual tracking
was present in 86%. A history of seizures was obtained in 44.8% of participants but 46.1% of these were febrile only.
Of the 13 EEG reports available for review – 69.2% were abnormal- with epileptic features present in 53.8%.
Abnormalities were present in 62.5% of MRI reports. Correlations were found between neurological abnormalities
and scores on the Mullen and Vineland Scales.
CONCLUSIONS: Neurological abnormalities are very common in PMS and are correlated with measures of cognitive
and adaptive functioning. The neurological examination may be used for clinical diagnosis, identification of PMS
phenotypes, and, in the future, for evaluation of therapy.

Previous work has demonstrated that social attention is related to early language abilities. We explored whether we can facilitate word learning among children with autism by directing attention to areas of the scene that have been demonstrated as relevant for successful word learning. We tracked eye movements to faces and objects while children watched videos of a woman teaching them new words. Test trials measured participants’ recognition of these novel word-object pairings. Results indicate that for children with autism and typically developing children, pointing to the speaker’s mouth while labeling a novel object impaired performance, likely because it distracted participants from the target object. In contrast, for children with autism, holding the object close to the speaker’s mouth improved performance.

Keywords: Attention to faces; Autism; Eye-tracking; Joint attention; Word-learning.

Up to 40% of children with Autism Spectrum Disorder (ASD) exhibit co-occurring anxiety symptoms. Despite recent success in mitigating anxiety symptoms in school-aged children with ASD (mean age >9 years) using adapted versions of Cognitive Behavioural Therapy, little is known about potential treatment outcomes for younger children. To address the gap in the literature, this open-label study evaluated change in anxiety following a 16-week open-label trial of Pivotal Response Treatment (PRT) in children with ASD aged 4-8 years. PRT is a behavioural treatment based on the principles of Applied Behaviour Analysis and has a primary aim of increasing social communication skills in children with ASD through natural reinforcements. To minimise conflation of anxiety and other co-occurring symptoms such as disruptive behaviour and attention-deficit hyperactivity disorder, we measured anxiety using the autism anxiety subscale of the Child and Adolescent Symptom Inventory (CASI) devised by Sukhodolsky et al. (2008). We observed significant anxiety reduction over 16-weeks of PRT. Furthermore, anxiety reduction was independent of changes in autism symptom severity. This study shows promising results for PRT as an intervention for reducing anxiety in young children with ASD.

Keywords: Autism Spectrum Disorder (ASD); Pivotal Response Treatment (PRT); anxiety.

Few evidence-based practices, defined as the use of empirically supported research and clinical expertise for children with autism, have been successfully implemented and sustained in schools. This study examined the perspectives of school personnel ( n = 39) on implementing a social engagement intervention for children with autism. Semi-structured interviews, informed by the Domitrovich et al. (2008) framework, were conducted. Participants were asked about (1) school factors that affect the general implementation of evidence-based practices, (2) their specific experiences implementing the social engagement intervention, and (3) barriers to and facilitators of implementing the social engagement intervention. Data were analyzed using an integrated approach. General (e.g. implementation process, leadership, support, and staff) and intervention-specific (e.g. staff, barriers, and facilitators) implementation themes were identified. These findings suggest that a variety of factors should be considered when implementing evidence-based practices in schools and that implementing social engagement interventions for children with autism may require additional specific support for implementation.

Keywords: autism; implementation; schools; social engagement intervention.

Background: We examined racial/ethnic disparities in school-based behavioral health service use for children with psychiatric disorders.

Methods: Medicaid claims data were used to compare the behavioral healthcare service use of 23,601 children aged 5-17 years by psychiatric disorder (autism, attention deficit hyperactivity disorder [ADHD], conduct/oppositional defiant disorder, and “other”) and by race/ethnicity (African-American, Hispanic, white, and other). Logistic and generalized linear regression analyses were used.

Results: Differences in service use by racial/ethnic group were identified within and across diagnostic groups, both for in-school service use and out-of-school service use. For all disorders, Hispanic children had significantly lower use of in-school services than white children. Among children with ADHD, African-American children were less likely to receive in-school services than white children; however, there were no differences in adjusted annual mean Medicaid expenditures for in-school services by race/ethnicity or psychiatric disorders. Statistically significant differences by race/ethnicity were found for out-of-school service use for children with ADHD and other psychiatric disorders. There were significant differences by race/ethnicity in out-of-school service use for each diagnostic group.

Conclusions: Differences in the use of school-based behavioral health services by racial and ethnic groups suggest the need for culturally appropriate outreach and tailoring of services to improve service utilization.

Keywords: Medicaid; behavioral health; health disparity; mental health; school-based health services.