Clinical correlates of diagnostic certainty in children and youths with Autistic Disorder.

BACKGROUND: Clinicians diagnosing autism rely on diagnostic criteria and instruments in combination with an implicit knowledge based on clinical expertise of the specific signs and presentations associated with the condition. This implicit knowledge influences how diagnostic criteria are interpreted, but it cannot be directly observed. Instead, insight into clinicians' understanding of autism can be gained by investigating their diagnostic certainty. Modest correlations between the certainty of an autism diagnosis and symptom load have been previously reported. Here, we investigated the associations of diagnostic certainty with specific items of the ADOS as well as other clinical features including head circumference. METHODS: Phenotypic data from the Simons Simplex Collection was used to investigate clinical correlates of diagnostic certainty in individuals diagnosed with Autistic Disorder (n = 1511, age 4 to 18 years). Participants were stratified by the ADOS module used to evaluate them. We investigated how diagnostic certainty was associated with total ADOS scores, age, and ADOS module. We calculated the odds-ratios of being diagnosed with the highest possible certainty given the presence or absence of different signs during the ADOS evaluation. Associations between diagnostic certainty and other cognitive and clinical variables were also assessed. RESULTS: In each ADOS module, some items showed a larger association with diagnostic certainty than others. Head circumference was significantly higher for individuals with the highest certainty rating across all three ADOS modules. In turn, head circumference was positively correlated with some of the ADOS items that were associated with diagnostic certainty, and was negatively correlated with verbal/nonverbal IQ ratio among those assessed with ADOS module 2. LIMITATIONS: The investigated cohort was heterogeneous, e.g. in terms of age, IQ, language level, and total ADOS score, which could impede the identification of associations that only exist in a subgroup of the population. The variability of the certainty ratings in the sample was low, limiting the power to identify potential associations with other variables. Additionally, the scoring of diagnostic certainty may vary between clinicians. CONCLUSION: Some ADOS items may better capture the signs that are most associated with clinicians' implicit knowledge of Autistic Disorder. If replicated in future studies, new diagnostic instruments with differentiated weighting of signs may be needed to better reflect this, possibly resulting in better specificity in standardized assessments.

Autistic preschoolers display reduced attention orientation for competition but intact facilitation from a parallel competitor: Eye-tracking and behavioral data.

LAY ABSTRACT: Recent research suggests that we might have underestimated the social motivation of autistic individuals. Autistic children might be engaged in a social situation, even if they seem not to be attending to people in a typical way. Our study investigated how young autistic children behave in a "parallel" situation, which we call "parallel competition," where people participate in friendly contests side-by-side but without direct interaction. First, we used eye-tracking technology to observe how much autistic children pay attention to two video scenarios: one depicting parallel competition, and the other where individuals play directly with each other. The results showed that autistic children looked less toward the parallel competition video than their typically developing peers. However, when autistic children took part in parallel competitions themselves, playing physical and cognitive games against a teacher, their performance improved relative to playing individually just as much as their typically developing peers. This suggests that even though autistic children pay attention to social events differently, they can still benefit from the presence of others. These findings suggest complementing traditional cooperative activities by incorporating parallel activities into educational programs for young autistic children. By doing so, we can create more inclusive learning environments for these children.

Debate: How far can we modify the expression of autism by modifying the environment?

Following Green (Child and Adolescent Mental Health, 2023, 28, 438) the emergence of a manifest autistic phenotype, during preschool years, represents a discontinuity from preclinical or subclinical states. We propose that this discontinuity suggests that autistic children experience superior interest for, and processing of non-social information, whereas children without autism favor social information processing. This is produced by perceptual over-functioning, still allowing self-taught non-social language learning in a substantial fraction of prototypical autistic children. A new set of rigorous intervention studies using Pediatric Autism Communication Therapy (PACT), based on the synchrony principle, brought autistic children below the ADOS diagnostic threshold (Whitehouse et al., JAMA Pediatrics, 2021, 175, e213298). We now know that adaptation of the child's social environment can produce changes in the manifestations of autism in the pre-school period and later. However, the limitation of these changes, combine with evidence of non-social learning of language suggests that clinicians should combine lateral tutorship (the parallel, unsynchronous exposure of information) with the synchrony (early dyadic communication and engagement) principle to create a new generation of strength-based interventions.

Development, psychometric evaluation, and factor analysis of an instrument measuring quality of life in autistic preschoolers.

INTRODUCTION: Early interventions for autistic children should target their quality of life (QoL) but require adapted measures. The association of a child's temperament and parental characteristics with the QoL of autistic children remains unknown. METHODS: We constructed an autism module based on a thematic analysis, a Delphi survey with experts, and a pre-test with parents to be completed alongside the proxy version of the PedsQL 4.0. We explored compliance, responsiveness, internal consistency, convergent validity, and factor structure with 157 parents of autistic preschool children. We examined the association between child and parental characteristics with the QoL of autistic children using correlation analysis, principal component analysis, hierarchical ascending classification, and linear regression. Sociodemographic information was collected via multiple choice questions, autism severity via Autism Diagnostic Observation Schedule (ADOS) scores, and parental acceptance and child's temperament via the Acceptance and Action Questionnaire and the Emotionality, Activity, and Sociability. RESULTS: An autism module comprised of 27 items emerged. Psychometric evaluation resulted in a 24-item autism module with good internal consistency and significant convergent validity. ADOS total score was not significantly related to QoL, contrary to children's sleep issues, children's emotionality, and parental acceptance. CONCLUSIONS: The autism module is a reliable QoL proxy measure for autistic preschool children. Results suggest parental interventions targeting children's QoL.

A longitudinal study on language acquisition in monozygotic twins concordant for autism and hyperlexia.

BACKGROUND: Hyperlexia, a strong orientation towards written materials, along with a discrepancy between the precocious acquisition of decoding skills and weaker comprehension abilities, characterizes up to 20% of autistic children. Sometimes perceived as an obstacle to oral language acquisition, hyperlexia may alternatively be the first step in a non-social pathway of language acquisition in autism. METHOD: We describe two monozygotic twin brothers, both autistic and hyperlexic, from the ages of 4 to 8 years old. Following an in-depth diagnostic assessment, we investigated cross-sectionally and longitudinally their verbal and non-verbal cognitive abilities, language, reading and writing skills, interests, and strengths. RESULTS: The twins' features, including their high non-verbal level of intelligence, their special interests, and their skills in various domains, were highly similar. Their language consisted exclusively of letters and numbers until their fourth year. After that, their vocabulary broadened until they developed full sentences, and their perception-related interests expanded and merged over time to serve the development of other skills. CONCLUSION: Our results show that hyperlexic skills can be harnessed to favor oral language development. Given the strong concordance between the twins' cognitive and behavioral phenotypes, we discuss the environmental and genetic influence that could explain their abilities.

Language acquisition can be truly atypical in autism: Beyond joint attention.

Language profiles in autism are variable and atypical, with frequent speech onset delays, but also, in some cases, unusually steep growth of structural language skills. Joint attention is often seen as a major predictor of language in autism, even though low joint attention is a core characteristic of autism, independent of language levels. In this systematic review of 71 studies, we ask whether, in autism, joint attention predicts advanced or only early language skills, and whether it may be independent of language outcomes. We consider only conservative estimates, and flag studies that include heterogenous samples or no control for non-verbal cognition. Our review suggests that joint attention plays a pivotal role for the emergence of language, but is also consistent with the idea that some autistic children may acquire language independently of joint attention skills. We propose that language in autism should not necessarily be modelled as a quantitative or chronological deviation from typical language development, and outline directions to bring autistic individuals' atypicality within the focus of scientific inquiry.

Prototypical autism: New diagnostic criteria and asymmetrical bifurcation model.

The current "autism spectrum" DSM 5 diagnostic criteria and autism standardized diagnostic instruments promote considerable heterogeneity or clinical indecision and may be detrimental to the advancement of fundamental research on autism mechanisms. To increase clinical specificity and reorient research towards core autistic presentations, we propose new diagnostic criteria for prototypical autism during the age of 2- to 5-years. We include autism within other non-dominant, familiarly aggregated phenomena sharing asymmetrical developmental bifurcations, such as twin pregnancy, left handedness, and breech presentation/delivery. Following this model, nature, trajectory, and positive/negative signs structure of autism would result from the polarized problem of whether or not language and information is processed in a socially biased manner. Prototypical autism would follow a canonical developmental trajectory by which a gradual decline in social bias in the processing of incoming information, overtly beginning at the end of the first year, bifurcates into a prototypical autistic presentation in the second half of the second year of life. This bifurcation event is followed by a plateau, in which these atypicalities show maximal stringency and distinctiveness, and then ultimately, in most cases, by partial normalization. During the plateau period, the orientation towards, and processing of, information is considerably modified, with an absence of bias for social information, contrasting with a high level of interest in complex, unbiased information, independently of its social or non-social nature. Integrating autism into asymmetrical developmental bifurcations would explain the absence of deleterious neurological and genetic markers and the presence of familial transmission in canonical autistic presentations.

Genesis, modelling and methodological remedies to autism heterogeneity.

Diagnostic criteria used in autism research have undergone a shift towards the inclusion of a larger population, paralleled by increasing, but variable, estimates of autism prevalence across clinical settings and continents. A categorical diagnosis of autism spectrum disorder is now consistent with large variations in language, intelligence, comorbidity, and severity, leading to a heterogeneous sample of individuals, increasingly distant from the initial prototypical descriptions. We review the history of autism diagnosis and subtyping, and the evidence of heterogeneity in autism at the cognitive, neurological, and genetic levels. We describe two strategies to address the problem of heterogeneity: clustering, and truncated-compartmentalized enrollment strategy based on prototype recognition. The advances made using clustering methods have been modest. We present an alternative, new strategy for dissecting autism heterogeneity, emphasizing incorporation of prototypical samples in research cohorts, comparison of subgroups defined by specific ranges of values for the clinical specifiers, and retesting the generality of neurobiological results considered to be acquired from the entire autism spectrum on prototypical cohorts defined by narrow specifiers values.

Psychometric validation of the French version of the PedsQLTM4.0 generic health-related quality of life questionnaire for 2-4-year-old children.

The Pediatric Quality of Life Inventory version 4.0 (PedsQLTM4.0) is an internationally recognized, generic, health-related quality of life (HRQoL) questionnaire, but its proxy 2-4-year-old version has not been validated in France. This study proposes a psychometric validation of this tool for French children aged 2 to 4 years and 11 months. A total of 220 parents of typically developing children participated. Acceptability was explored. Internal consistency was tested using Cronbach's alpha. Factor structure was tested using an exploratory structural equation modeling (ESEM). Risk of bias was assessed regarding gender and age effect on HRQoL using Student's t test. Except for school functioning, compliance was good (< 2.9%). No floor effects were observed, but ceiling effects were found for all scores. The total score had good internal consistency (Cronbach's α = .82). The Cronbach's α of each subscale was between .53 and .71. Factor analysis rejected the original 4-factor structure and revealed an alternative 2-factor structure. The total score and emotional scale score did not appear to be sensitive to gender or child age.  Conclusions: The PedsQLTM4.0 generic HRQoL questionnaire presents good psychometric properties, regarding acceptability and reliability. For use among French children aged 2 to 4 years and 11 months, we recommend retaining the total score and the emotional scale score.

A convergent structure-function substrate of cognitive imbalances in autism.

BACKGROUND: Autism spectrum disorder (ASD) is a common neurodevelopmental diagnosis showing substantial phenotypic heterogeneity. A leading example can be found in verbal and nonverbal cognitive skills, which vary from elevated to impaired compared with neurotypical individuals. Moreover, deficits in verbal profiles often coexist with normal or superior performance in the nonverbal domain. METHODS: To study brain substrates underlying cognitive imbalance in ASD, we capitalized categorical and dimensional IQ profiling as well as multimodal neuroimaging. RESULTS: IQ analyses revealed a marked verbal to nonverbal IQ imbalance in ASD across 2 datasets (Dataset-1: 155 ASD, 151 controls; Dataset-2: 270 ASD, 490 controls). Neuroimaging analysis in Dataset-1 revealed a structure-function substrate of cognitive imbalance, characterized by atypical cortical thickening and altered functional integration of language networks alongside sensory and higher cognitive areas. CONCLUSION: Although verbal and nonverbal intelligence have been considered as specifiers unrelated to autism diagnosis, our results indicate that intelligence disparities are accentuated in ASD and reflected by a consistent structure-function substrate affecting multiple brain networks. Our findings motivate the incorporation of cognitive imbalances in future autism research, which may help to parse the phenotypic heterogeneity and inform intervention-oriented subtyping in ASD.

Using developmental regression to reorganize the clinical importance of autistic atypicalities.

Early regression (ER) is often reported in autistic children with a prototypical phenotype and has been proposed as a possible pathognomonic sign present in most autistic children. Despite the uncertainties attached to its definition and report, using ER to anchor the autism phenotype could help identify the signs that best contribute to an autism diagnosis. We extracted retrospective data from 1547 autistic children between the ages of 6 and 18 years from the Simons Simplex collection. Logistic regression identified the atypicalities associated with a history of ER. Stepwise variable selection using logistic regression analysis followed by a bootstrap procedure of 1000 iterations identified the cluster of atypicalities best associated with ER. Linear and logistic regressions measured the association between combinations of atypicalities within the identified cluster and adaptative behaviors, diagnostic areas of severity, and other categories. Seven atypicalities significantly increased the likelihood of having experienced ER (OR = 1.73-2.13). Four ("hand leading-ever", "pronominal reversal-ever", "never shakes head at age 4-5" and "stereotypic use of objects or interest in parts of objects-ever"), when grouped together, best characterized the phenotype of verbal autistic children with ER. This clustering of signs was associated with certain persistent language difficulties, higher summary scores on a diagnostic scale for autism, and greater odds of receiving an "autistic disorder" diagnosis instead of another pervasive developmental disorder (PDD) diagnosis. These results raise questions about using language as a clinical specifier, defining cross-sectional signs independent of their relationship with an early developmental trajectory, and relying on polythetic criteria or equivalent weighted autistic atypicalities.

Representativeness of autistic samples in studies recruiting through social media.

Survey-based research with recruitment through online channels is a convenient way to obtain large samples and has recently been increasingly used in autism research. However, sampling from online channels may be associated with a high risk of sampling bias causing findings not to be generalizable to the autism population. Here we examined autism studies that have sampled on social media for markers of sampling bias. Most samples showed one or more indicators of sampling bias, in the form of reversed sex ratio, higher employment rates, higher education level, lower fraction of individuals with intellectual disability, and later age of diagnosis than would be expected when comparing with for example population study results from published research. Findings from many of the included studies are therefore difficult to generalize to the broader autism population. Suggestions for how research strategies may be adapted to address some of the problems are discussed. LAY SUMMARY: Online surveys offer a convenient way to recruit large numbers of participants for autism research. However, the resulting samples may not fully reflect the autism population. Here we investigated the samples of 36 autism studies that recruited participants online and found that the demographic composition tended to deviate from what has been reported about the autism population in previous research. The results may thus not be generalizable to autism in general.

Positive, negative, neutral-or unknown? The perceived valence of emotions expressed by young autistic children in a novel context suited to autism.

LAY ABSTRACT: Autistic people are believed to have emotions that are too negative and not positive enough, starting early in life. Their facial expressions are also persistently judged to be unusual, as reflected in criteria used to identify autism. But it is possible that common autistic facial expressions are poorly understood by observers, as suggested by a range of findings from research. Another issue is that autistic emotions have always been assessed in contexts suited to non-autistics. In our study, the facial expressions of young autistic and typical children were rated as positive, negative, neutral, or "unknown"-a category we created for emotions that observers notice but do not understand. These emotions were assessed using a context suited to autistic children, including objects of potential interest to them. We found that in this context, autistic and typical children did not differ in positive, negative, or neutral facial emotions. They did differ in unknown emotions, which were found only in autistic children. We also found that repetitive behaviors in autistic children co-occurred with positive, neutral, and unknown emotions, but not with negative emotions. In a context which suits their characteristics, autistic children do not show emotions that are too negative or not positive enough. They do show emotions perceived as unknown, which means we need to improve our understanding of their full emotional repertoire.

Positive and differential diagnosis of autism in verbal women of typical intelligence: A Delphi study.

LAY ABSTRACT: The diagnostic criteria for autism are relatively vague and can lead to both under- and over-diagnosis if applied as a checklist. The highest level of agreement that a person is autistic occurs when experienced clinicians are able to make use of their clinical judgment. However, it is not always clear what this judgment consists of. Given that particular issues exist when assessing for autism in adult women, we wanted to explore how expert clinicians address difficult diagnostic situations in this population. We interviewed 20 experienced psychologists and psychiatrists from seven countries and discussed how they conducted autism assessments in adult women. We then came up with a list of 35 statements that described participant views. Our participants completed an online survey where they rated their agreement with these statements and provided feedback on how the statements were worded and organized. We obtained a final list of 37 suggested clinical guidelines. Participants agreed that diagnostic tools and questionnaires had to be coupled with judgment and expertise. Participants felt that trauma and Borderline Personality Disorder could be difficult to differentiate from autism, and agreed on some ways to address this issue. Participants agreed that self-identification to the autism spectrum was frequent, and that it was important to provide alternative support when they did not ultimately diagnose autism.

Searching for What Really Matters: A Thematic Analysis of Quality of Life among Preschool Children on the Autism Spectrum.

Quality of life (QoL) is an essential measure when assessing health interventions. Most early interventions for preschool children on the spectrum evaluate the effects on autism symptoms. However, researchers increasingly believe that good interventions should also improve the QoL of these children. Domains of QoL among preschool children on the autism spectrum have not previously been researched. We interviewed adults on the spectrum to explore early childhood experiences that made their lives satisfying. Our data revealed four major themes: interests, environmental regularity, sensory differences and social interactions. This study provides the first insights on aspects of life important to pre-schoolers on the spectrum. Findings will contribute to developing items for a measure of QoL among this population.

Clinical Situations in Which the Diagnosis of Autism is Debatable: An Analysis and Recommendations.

The "autism spectrum disorder" (ASD) construct and its current diagnostic criteria have led to the inclusion of increasingly heterogeneous and decreasingly atypical individuals under its definition. This broad category, based on the polymorphic clinical expression of common genetic variants underpinning the risk of autism, is likely beneficial for certain individuals. However, determining the boundaries between ASD and typical individuals, as well as those with other neurodevelopmental conditions, remains an issue of which the importance is growing with the increase in ASD prevalence. We identified four clinical contexts associated with a questionable, poorly justified, or unhelpful ASD diagnosis: (1) those in which diagnostic instruments raise uncertainties, (2) in the context of a subclinical presentation, (3) when early autistic signs tend to fade away during development, and (4) when comorbidities are prominent. We argue that in certain cases, a diagnosis of ASD may not be the most suitable, timely, or helpful medical act and provide recommendations for clinical practice when facing such situations.

Childhood diagnoses in individuals identified as autistics in adulthood.

BACKGROUND: Autism is a developmental condition, where symptoms are expected to occur in childhood, but a significant number of individuals are diagnosed with autism for the first time in adulthood. Here, we examine diagnoses given in childhood among individuals that are diagnosed with autism in adulthood, to investigate whether the late autism diagnosis might be explained by misdiagnosis in childhood or diagnostic overshadowing. METHODS: Through the Danish National Patient Registry, we identified individuals diagnosed with autism in adulthood (N = 2199), as well as a control sample with no records of an autism diagnosis (N = 460,798) and calculated how many had received different psychiatric or neurological diagnoses in childhood. RESULTS: We found that most childhood diagnoses were overrepresented in those with an adult autism diagnosis, and attention-deficit hyperactivity disorder, affective disorders, anxiety, and stress disorders were the most prevalent childhood conditions in this group. However, 69% of males and 61% of females with adult autism diagnoses were not found to have received any of the investigated diagnoses before 18 years of age, and most childhood diagnoses were given after the age of 12. LIMITATIONS: Milder to moderate cases of psychiatric conditions that have been solely treated by family physicians or school psychologists may not be fully included in our dataset. The study is based on data from the Danish health care system, and further research is needed to assess whether the findings can be generalized to other countries. CONCLUSION: A majority of those with an adult autism diagnosis had no records of having received any of the investigated diagnoses in childhood. In these cases, the late autism diagnosis is therefore unlikely to be explained by either misdiagnosis or overshadowing. This result is at odds with the prevailing notion that autistic symptoms tend to diminish with age. Therefore, further research is warranted to examine how and if early signs of autism may have manifested among these individuals, and how similar they are to autistic people diagnosed earlier in their development.