Purpose of Review
We review the recent literature regarding the implications of gender on the diagnosis and treatment of autism spectrum disorder (ASD) in women and adolescent females. We also ...discuss important clinical observations in treating this population.
Recent Findings
Growing research supports gender specificity in ASD symptom presentation. Differing phenotypes, psychiatric co-morbidities, and level of “camouflaging” (behavioral coping strategies to conceal symptoms for use in social situations) are thought to further contribute to the discrepancy in prevalence rates and resulting misdiagnosis or delayed diagnosis in adolescent females and women.
Summary
Both nosological and cultural factors appear to be contributing to differences in the diagnosis of ASD in women. These differences in presentation have important implications for late diagnosis, treatment of ASD, and the quality of life for women with autism.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
What does an individual with autism spectrum disorder (ASD) perceive first: the forest or the trees? In spite of 30 years of research and influential theories like the weak central coherence (WCC) ...theory and the enhanced perceptual functioning (EPF) account, the interplay of local and global visual processing in ASD remains only partly understood. Research findings vary in indicating a local processing bias or a global processing deficit, and often contradict each other. We have applied a formal meta-analytic approach and combined 56 articles that tested about 1,000 ASD participants and used a wide range of stimuli and tasks to investigate local and global visual processing in ASD. Overall, results show no enhanced local visual processing nor a deficit in global visual processing. Detailed analysis reveals a difference in the temporal pattern of the local-global balance, that is, slow global processing in individuals with ASD. Whereas task-dependent interaction effects are obtained, gender, age, and IQ of either participant groups seem to have no direct influence on performance. Based on the overview of the literature, suggestions are made for future research.
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CEKLJ, FFLJ, NUK, ODKLJ, PEFLJ, UPUK
Somatosensory over-reactivity is common among patients with autism spectrum disorders (ASDs) and is hypothesized to contribute to core ASD behaviors. However, effective treatments for sensory ...over-reactivity and ASDs are lacking. We found distinct somatosensory neuron pathophysiological mechanisms underlie tactile abnormalities in different ASD mouse models and contribute to some ASD-related behaviors. Developmental loss of ASD-associated genes Shank3 or Mecp2 in peripheral mechanosensory neurons leads to region-specific brain abnormalities, revealing links between developmental somatosensory over-reactivity and the genesis of aberrant behaviors. Moreover, acute treatment with a peripherally restricted GABAA receptor agonist that acts directly on mechanosensory neurons reduced tactile over-reactivity in six distinct ASD models. Chronic treatment of Mecp2 and Shank3 mutant mice improved body condition, some brain abnormalities, anxiety-like behaviors, and some social impairments but not memory impairments, motor deficits, or overgrooming. Our findings reveal a potential therapeutic strategy targeting peripheral mechanosensory neurons to treat tactile over-reactivity and select ASD-related behaviors.
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•Distinct pathophysiologies cause peripheral sensory neuron dysfunction in ASD models•Peripheral somatosensory neuron dysfunction alters brain development and behavior•A peripherally restricted GABAAR agonist, isoguvacine, reduces tactile sensitivity•Chronic isoguvacine treatment improves a subset of ASD-related phenotypes in mice
Treatment with a peripherally restricted GABAA receptor agonist in multiple distinct autism spectrum disorder mouse models reveals a potential therapeutic strategy for select ASD-related behaviors.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Parent training (PT) has emerged as a promising treatment for disruptive behavior in children with autism spectrum disorder (ASD). This review summarizes the essential elements of PT for disruptive ...behavior in children with ASD and evaluates the available evidence for PT using both descriptive and meta-analytic procedures. We searched Medline, PsycINFO, and PubMed databases (1980–2016) in peer-reviewed journals for randomized controlled trials (RCTs) of PT for disruptive behavior in children with ASD. The systematic search of 2023 publications yielded eight RCTs involving a total of 653 participants. We calculated effect sizes using either raw post-treatment means and standard deviations for each treatment group (PT and control) or group mean differences with associated 95% confidence intervals (CIs). Differences in post-treatment means were converted to a standardized difference in means (SMD) for each primary outcome. Results support the efficacy of PT for disruptive behavior in children with ASD, with a SMD of −0.59 95% CI (−0.88, −0.30);
p
< 0.001. Across these eight studies, there was significant heterogeneity in the effect of PT on disruptive behavior. This variability is likely due to differences in sample size, number of treatment sessions, study duration, and control condition employed. Current findings provide solid support for the efficacy of PT for disruptive behavior in children with ASD. Future studies should focus on effectiveness trials to promote wider implementation of PT in clinical settings.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Gene Ontology analyses of autism spectrum disorders (ASD) risk genes have repeatedly highlighted synaptic function and transcriptional regulation as key points of convergence. However, these analyses ...rely on incomplete knowledge of gene function across brain development. Here we leverage Xenopus tropicalis to study in vivo ten genes with the strongest statistical evidence for association with ASD. All genes are expressed in developing telencephalon at time points mapping to human mid-prenatal development, and mutations lead to an increase in the ratio of neural progenitor cells to maturing neurons, supporting previous in silico systems biological findings implicating cortical neurons in ASD vulnerability, but expanding the range of convergent functions to include neurogenesis. Systematic chemical screening identifies that estrogen, via Sonic hedgehog signaling, rescues this convergent phenotype in Xenopus and human models of brain development, suggesting a resilience factor that may mitigate a range of ASD genetic risks.
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•In vivo analysis of autism genes reveals a convergent vulnerability in neurogenesis•Systems biological analysis implicates the inner cortical plate and subventricular zone•Estrogen can mitigate the effects of disparate autism gene mutations•Estrogen inhibits Sonic hedgehog signaling
Using parallel in vivo analyses and systems biological approaches, Willsey et al. implicate cortical neurogenesis as a point of convergent vulnerability in autism spectrum disorders. They identify estrogen as a resilience factor for multiple, disparate autism genes and reveal a conserved role for estrogen in repressing Sonic hedgehog signaling.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background
Autism spectrum disorder (ASD) is a behaviourally diagnosed condition. It is defined by impairments in social communication or the presence of restricted or repetitive behaviours, or both. ...Diagnosis is made according to existing classification systems. In recent years, especially following publication of the Diagnostic and Statistical Manual of Mental Disorders ‐ Fifth Edition (DSM‐5; APA 2013), children are given the diagnosis of ASD, rather than subclassifications of the spectrum such as autistic disorder, Asperger syndrome, or pervasive developmental disorder ‐ not otherwise specified. Tests to diagnose ASD have been developed using parent or carer interview, child observation, or a combination of both.
Objectives
Primary objectives
1. To identify which diagnostic tools, including updated versions, most accurately diagnose ASD in preschool children when compared with multi‐disciplinary team clinical judgement.
2. To identify how the best of the interview tools compare with CARS, then how CARS compares with ADOS.
a. Which ASD diagnostic tool ‐ among ADOS, ADI‐R, CARS, DISCO, GARS, and 3di ‐ has the best diagnostic test accuracy?
b. Is the diagnostic test accuracy of any one test sufficient for that test to be suitable as a sole assessment tool for preschool children?
c. Is there any combination of tests that, if offered in sequence, would provide suitable diagnostic test accuracy and enhance test efficiency?
d. If data are available, does the combination of an interview tool with a structured observation test have better diagnostic test accuracy (i.e. fewer false‐positives and fewer false‐negatives) than either test alone?
As only one interview tool was identified, we modified the first three aims to a single aim (Differences between protocol and review): This Review evaluated diagnostic tests in terms of sensitivity and specificity. Specificity is the most important factor for diagnosis; however, both sensitivity and specificity are of interest in this Review because there is an inherent trade‐off between these two factors.
Secondary objectives
1. To determine whether any diagnostic test has greater diagnostic test accuracy for age‐specific subgroups within the preschool age range.
Search methods
In July 2016, we searched CENTRAL, MEDLINE, Embase, PsycINFO, 10 other databases, and the reference lists of all included publications.
Selection criteria
Publications had to:
1. report diagnostic test accuracy for any of the following six included diagnostic tools: Autism Diagnostic Interview ‐ Revised (ADI‐R), Gilliam Autism Rating Scale (GARS), Diagnostic Interview for Social and Communication Disorder (DISCO), Developmental, Dimensional, and Diagnostic Interview (3di), Autism Diagnostic Observation Schedule ‐ Generic (ADOS), and Childhood Autism Rating Scale (CARS);
2. include children of preschool age (under six years of age) suspected of having an ASD; and
3. have a multi‐disciplinary assessment, or similar, as the reference standard.
Eligible studies included cohort, cross‐sectional, randomised test accuracy, and case‐control studies. The target condition was ASD.
Data collection and analysis
Two review authors independently assessed all studies for inclusion and extracted data using standardised forms. A third review author settled disagreements. We assessed methodological quality using the QUADAS‐2 instrument (Quality Assessment of Studies of Diagnostic Accuracy ‐ Revised). We conducted separate univariate random‐effects logistical regressions for sensitivity and specificity for CARS and ADI‐R. We conducted meta‐analyses of pairs of sensitivity and specificity using bivariate random‐effects methods for ADOS.
Main results
In this Review, we included 21 sets of analyses reporting different tools or cohorts of children from 13 publications, many with high risk of bias or potential conflicts of interest or a combination of both. Overall, the prevalence of ASD for children in the included analyses was 74%.
For versions and modules of ADOS, there were 12 analyses with 1625 children. Sensitivity of ADOS ranged from 0.76 to 0.98, and specificity ranged from 0.20 to 1.00. The summary sensitivity was 0.94 (95% confidence interval (CI) 0.89 to 0.97), and the summary specificity was 0.80 (95% CI 0.68 to 0.88).
For CARS, there were four analyses with 641 children. Sensitivity of CARS ranged from 0.66 to 0.89, and specificity ranged from 0.21 to 1.00. The summary sensitivity for CARS was 0.80 (95% CI 0.61 to 0.91), and the summary specificity was 0.88 (95% CI 0.64 to 0.96).
For ADI‐R, there were five analyses with 634 children. Sensitivity for ADI‐R ranged from 0.19 to 0.75, and specificity ranged from 0.63 to 1.00. The summary sensitivity for the ADI‐R was 0.52 (95% CI 0.32 to 0.71), and the summary specificity was 0.84 (95% CI 0.61 to 0.95).
Studies that compared tests were few and too small to allow clear conclusions.
In two studies that included analyses for both ADI‐R and ADOS, tests scored similarly for sensitivity, but ADOS scored higher for specificity. In two studies that included analyses for ADI‐R, ADOS, and CARS, ADOS had the highest sensitivity and CARS the highest specificity.
In one study that explored individual and additive sensitivity and specificity of ADOS and ADI‐R, combining the two tests did not increase the sensitivity nor the specificity of ADOS used alone.
Performance for all tests was lower when we excluded studies at high risk of bias.
Authors' conclusions
We observed substantial variation in sensitivity and specificity of all tests, which was likely attributable to methodological differences and variations in the clinical characteristics of populations recruited.
When we compared summary statistics for ADOS, CARS, and ADI‐R, we found that ADOS was most sensitive. All tools performed similarly for specificity. In lower prevalence populations, the risk of falsely identifying children who do not have ASD would be higher.
Now available are new versions of tools that require diagnostic test accuracy assessment, ideally in clinically relevant situations, with methods at low risk of bias and in children of varying abilities.
Purpose of Review
Neuropsychological assessment involves the comprehensive evaluation of intellectual, attentional, executive, social-cognitive, language, and motor functioning. Such assessments are ...used to characterize areas of strength and weakness, inform differential diagnosis, guide treatment planning, and evaluate change over time. Individuals with autism spectrum disorder (ASD) present with varied clinical presentations, which can make the design of testing batteries and subsequent interpretation of results challenging. Here we provide an overview of neuropsychological domains as they relate to the evaluation of individuals with ASD.
Recent Findings
Individuals with ASD demonstrate unique patterns of neuropsychological functioning across various domains. Recent findings related to intellectual, adaptive, executive, attentional, social, language, motor, and autism-specific functioning are reviewed.
Summary
Clarifying the relationship between ASD symptoms and neuropsychological functioning is critical for differential diagnosis and for optimal treatment planning. Tools and methods for developing appropriate neuropsychological testing protocols for individuals with ASD are discussed.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
There have been numerous attempts to explain the enigma of autism, but existing neurocognitive theories often provide merely a refined description of 1 cluster of symptoms. Here we argue that ...deficits in executive functioning, theory of mind, and central coherence can all be understood as the consequence of a core deficit in the flexibility with which people with autism spectrum disorder can process violations to their expectations. More formally we argue that the human mind processes information by making and testing predictions and that the errors resulting from violations to these predictions are given a uniform, inflexibly high weight in autism spectrum disorder. The complex, fluctuating nature of regularities in the world and the stochastic and noisy biological system through which people experience it require that, in the real world, people not only learn from their errors but also need to (meta-)learn to sometimes ignore errors. Especially when situations (e.g., social) or stimuli (e.g., faces) become too complex or dynamic, people need to tolerate a certain degree of error in order to develop a more abstract level of representation. Starting from an inability to flexibly process prediction errors, a number of seemingly core deficits become logically secondary symptoms. Moreover, an insistence on sameness or the acting out of stereotyped and repetitive behaviors can be understood as attempts to provide a reassuring sense of predictive success in a world otherwise filled with error.
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CEKLJ, FFLJ, NUK, ODKLJ, PEFLJ, UPUK
Purpose of Review
This synthesis of treatment research related to anxiety and depression in adolescents and adults with autism spectrum disorder (ASD) focuses on the scientific support for various ...forms of psychosocial interventions, useful adaptations to standard interventions, and engagement of candidate therapeutic mechanisms.
Recent Findings
There is considerable evidence for the efficacy of cognitive-behavioral therapy (CBT) to treat co-occurring problems with anxiety, but there has been relatively little research on treatment of co-occurring depression. Multiple mechanisms of treatment effect have been proposed, but there has been little demonstration of target engagement via experimental therapeutics.
Summary
Comorbidity between ASD and anxiety and/or mood problems is common. Although there is evidence for the use of CBT for anxiety, little work has addressed how to effectively treat depression. There is emerging support for alternative treatment approaches, such as mindfulness-based interventions. We encourage rigorous, collaborative approaches to identify and manipulate putative mechanisms of change.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Clinical trials of pharmacological candidates targeting the core features of autism have largely failed. This is despite evidence linking differences in multiple neurochemical systems to brain ...function in autism. While this has in part been explained by the heterogeneity of the autistic population, the field has largely relied upon association studies to link brain chemistry to function. The only way to directly establish that a neurotransmitter or neuromodulator is involved in a candidate brain function is to change it and observe a shift in that function. This experimental approach dominates preclinical neuroscience, but not human studies. There is little direct experimental evidence describing how neurochemical systems modulate information processing in the living human brain. Thus, our understanding of how neurochemical differences contribute to neurodiversity is limited, impeding our ability to translate findings from animal studies into humans. Here, we introduce our 'shiftability' paradigm, an approach to bridge the translational gap in autism research. We provide an overview of the guiding principles and methodologies we use to directly test the hypothesis that neurochemical systems function differently in autistic and non-autistic individuals.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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