Seeing the forest and the trees: Disentangling autism phenotypes in the age of DSM-5.

This paper, written in honor of Professor Ed Zigler, focuses on some of the themes in developmental disabilities research that were so central to his work. It has now been nearly 80 years since Leo Kanner first identified the prototypic form - early infantile autism - of what is now autism spectrum disorder. In this article we summarize the development of the concept and the important accumulation of knowledge over time that has now led us to the recognition of a broader autism phenotype just as, at the same time, the current official diagnostic system in the USA has narrowed the concept. We also address current controversies regarding autism as the diagnosis is impacted by age and developmental factors, gender, and cultural issues. In parallel to the work on intellectual deficiency and development pioneered by Zigler and his colleagues, we summarize some of the challenges for the years ahead.

Sex Differences on the ADOS-2.

The sex difference in the prevalence of autism spectrum disorder (ASD) may be magnified by sex differences on diagnostic measures. The current study compared autistic males and females on items on the gold-standard diagnostic measure, the Autism Diagnostic Observation Schedule, Second Edition (ADOS-2). In a sample of 8-to-17-year old autistic individuals from research (n = 229) and clinical settings (n = 238), females were less likely to show atypicalities on most items related to social-communication behaviors and on total and subscale scores. When controlling for overall intensity of symptomatology, no sex differences survived statistical corrections. Diagnostic criteria and/or gold-standard assessments may be less sensitive to female presentations of ASD and/or autistic females may exhibit fewer or less intense behaviors characteristic of ASD.

Autistic Characteristics in a Nationally Representative Clinical Sample of Adolescents Seeking Medical Gender-Affirming Treatment in Norway.

PURPOSE: Several studies have reported on the intersection of autism and gender incongruence (GI) in clinical populations. This study aims to investigate autistic characteristics and registered autism spectrum diagnoses (ASD) in a clinical cohort of 83 adolescents referred to the National Gender Team for Children and Adolescents in Norway during 2020. METHODS: Parents completed the Social Responsiveness Scale (SRS). Background information and registered psychiatric diagnoses were extracted from patient files. RESULTS: The results showed that 25% of the participants scored within the clinical range on the SRS: 27.4% of adolescents who were assigned female at birth (AFAB) and 19.0% of adolescents who were assigned male at birth (AMAB). AFAB had significantly higher scores on SRS Total Scale and the Social Motivation and Autistic Mannerisms subscales compared to the female norm group. AMAB had higher scores on the Social Motivation subscale and lower scores on the Social Awareness subscale, compared to the male norm population. Information from patient files revealed that 67.5% had one or more registered psychiatric diagnosis. 9.6% had received an ASD diagnosis, all AFAB. 18.1% had received an attention deficit hyperactivity disorder (ADHD) diagnosis. The most common psychiatric diagnoses were depression (25.3%) and anxiety disorders (18.1%). Further, 44.6% had a history of self-harm, and 15.7% had a history of a suicide attempt. CONCLUSION: The results showed an overrepresentation of ASD diagnoses and autistic characteristics measured by SRS for AFAB. There was an overrepresentation of psychiatric diagnoses for both the AFAB and the AMAB group in this study sample. Implications for treatment and future research are discussed.

Virtual and Augmented Reality in Social Skills Interventions for Individuals with Autism Spectrum Disorder: A Scoping Review.

In the last decade, there has been an increase in publications on technology-based interventions for autism spectrum disorder (ASD). Virtual reality based assessments and intervention tools are promising and have shown to be acceptable amongst individuals with ASD. This scoping review reports on 49 studies utilizing virtual reality and augmented reality technology in social skills interventions for individuals with ASD. The included studies mostly targeted children and adolescents, but few targeted very young children or adults. Our findings show that the mode number of participants with ASD is low, and that female participants are underrepresented. Our review suggests that there is need for studies that apply virtual and augmented realty with more rigorous designs involving established and evidenced-based intervention strategies.

What are we optimizing for in autism screening? Examination of algorithmic changes in the M-CHAT.

The present study objectives were to examine the performance of the new M-CHAT-R algorithm to the original M-CHAT algorithm. The main purpose was to examine if the algorithmic changes increase identification of children later diagnosed with ASD, and to examine if there is a trade-off when changing algorithms. We included 54,463 screened cases from the Norwegian Mother and Child Cohort Study. Children were screened using the 23 items of the M-CHAT at 18 months. Further, the performance of the M-CHAT-R algorithm was compared to the M-CHAT algorithm on the 23-items. In total, 337 individuals were later diagnosed with ASD. Using M-CHAT-R algorithm decreased the number of correctly identified ASD children by 12 compared to M-CHAT, with no children with ASD screening negative on the M-CHAT criteria subsequently screening positive utilizing the M-CHAT-R algorithm. A nonparametric McNemar's test determined a statistically significant difference in identifying ASD utilizing the M-CHAT-R algorithm. The present study examined the application of 20-item MCHAT-R scoring criterion to the 23-item MCHAT. We found that this resulted in decreased sensitivity and increased specificity for identifying children with ASD, which is a trade-off that needs further investigation in terms of cost-effectiveness. However, further research is needed to optimize screening for ASD in the early developmental period to increase identification of false negatives.

Editorial S.I: Early Identification in Autism Spectrum Disorders: The Present and Future, and Advances in Early Identification.

Early identification of autism spectrum disorder (ASD) is considered by most scholars and clinicians to be a feasible and useful step for improving the wellbeing of individuals on the autism spectrum and their families. Arguments supporting early detection efforts include the benefit of earlier access to services providing autism-specific evidence-based interventions (Vivanti et al., Journal of Autism and Developmental Disorders, 46(7), 2441-2449, 2016; Zwaigenbaum et al., Pediatrics, 136(Suppl), S10-S40, 2015), and its potential to mitigate or even prevent the challenges associated with ASD symptoms, reduce care costs, and improve the quality of life and productivity of individuals with ASD (Constantino et al., Pediatrics, 146(3), e20193629, 2020; Jacobson et al., Behavioral Interventions, 13(4), 201-226, 1998; Jacobson and Mulick, Journal of Autism and Developmental Disorders, 30(6), 585-593, 2000). Nevertheless, controversies and challenges in this field exist.

Virtual reality and naturalistic developmental behavioral interventions for children with autism spectrum disorder.

BACKGROUND: Naturalistic Developmental Behavioral Interventions (NDBI) have been evaluated as the most promising interventions for children with autism spectrum disorder. In recent years, a growing body of literature suggests that technological advancements such as Virtual Reality (VR) are promising intervention tools. However, to the best of our knowledge no studies have combined evidence-based practice with such tools. AIM: This article aims to review the current literature combining NDBI and VR, and provide suggestions on merging NDBI-approaches with VR. METHODS: This article is divided into two parts, where we first conduct a review mapping the research applying NDBI-approaches in VR. In the second part we argue how to apply the common features of NDBI into VR-technology. RESULTS: Our findings show that no VR-studies explicitly rely on NDBI-approaches, but some utilize elements in their interventions that are considered to be common features to NDBI. CONCLUSIONS AND IMPLICATIONS: As the results show, to date, no VR-based studies have utilized NDBI in their intervention. We therefore, in the second part of this article, suggests ways to merge VR and NDBI and introduce the term Virtual Naturalistic Developmental Behavioral Interventions (VNDBI). VNDBI is an innovative way of implementing NDBI which will contribute in making interventions more accessible in central as well as remote locations, while reducing unwanted variation between service sites. VNDBI will advance the possibilities of individually tailoring and widen the area of interventions. In addition, VNDBI can provide the field with new knowledge on effective components enhancing the accuracy in the intervention packages and thus move forward the research field and clinical practice.

Functional Outcomes of Children Identified Early in the Developmental Period as at Risk for ASD Utilizing the The Norwegian Mother, Father and Child Cohort Study (MoBa).

Early identification of autism spectrum disorder (ASD) is regarded as crucial for swift access to early intervention and, subsequently, better outcomes later in life. However, current instruments miss large proportions of children who later go on to be diagnosed with ASD, raising a question of what these instruments measure. The present study utilized data from the Norwegian Mother, Father, and Child Cohort Study and the Autism Birth Cohort study to explore the subsequent developmental and diagnostic characteristics of children raising developmental concern on the six-critical discriminative item criterion of the M-CHAT (DFA6) at 18 months of age (N = 834). The DFA6 identified 28.8% of children diagnosed with ASD (N = 163), but 4.4% with language disorder (N = 188) and 81.3% with intellectual disability (N = 32) without ASD. Scoring in the «at-risk¼ range was associated with lower IQ, impaired functional language, and greater severity of autism symptoms whether children had ASD or not.

Short Report: Social Perception of High School Students with ASD in Norway.

An increasing number of students with autism spectrum disorder (ASD) enroll in inclusive schools and classrooms. The aim of this study was to research how students with ASD experience the social aspect of inclusive high schools. Five adolescences with Asperger syndrome were interviewed, and the results show that high school was perceived as an important platform for social training, and an equally important place to find new friends and acquaintances. A majority of the participants had experienced loneliness and bullying in junior high school. However, they experienced high school as a new start, with a more open and inclusive environment. Nevertheless, several of the participants expressed that they used quite a lot of energy on social settings, such as interpreting social situations and on being amongst a larger group of students. In order to support this group of adolescents in their schooling, it is important to look at their strength and resources, and not only focus on the challenges and difficulties.

Detecting Autism Spectrum Disorder in Children With ADHD and Social Disability.

Objective: The social disability associated with ADHD often makes diagnostic and treatment decision making challenging. This protocol investigates the test performance of the Autism Mental Status Exam (AMSE) in detecting autism spectrum disorder (ASD) in a sample of 45 children with ADHD and ASD symptomatology. The AMSE is a brief ASD diagnostic assessment administered in the context of a clinical exam. Method: All participants received a developmental evaluation, including the AMSE, followed by independent gold standard diagnostic assessments including the Autism Diagnostic Observation Schedule (ADOS) and the Autism Diagnostic Interview-Revised (ADI-R). Results: Receiver operating characteristics (ROC) curve analysis indicated strong sensitivity and specificity in this population. Optimal cutoff scores are provided. Conclusion: The AMSE holds promise as a brief ASD assessment tool for children with ADHD and ASD symptomatology and as a guide for treatment and referral decisions at the point of care.

A Review Update on Gender Dysphoria and ASD and Response to Corrections.

Here we address the earlier published review by Øien et al. (J Autism Dev Disord, https://doi.org/10.1007/s10803-018-3686-7 , 2018) and the subsequent comments by Zucker and VanderLaan (J Autism Dev Disord, https://doi.org/10.1007/s10803-018-3748-x , 2018). The current commentary is a response to the corrections put forth by the latter authors where aspects related to diagnostic criteria of Gender Dysphoria and corrections to the existence of a control group were noted. Additionally, to highlight that research on Gender Dysphoria and ASD is becoming a very fast and growing field we also present an update of the original review which show a 13% increase of empirical studies published only in the past few months.

Gender Dysphoria, Sexuality and Autism Spectrum Disorders: A Systematic Map Review.

In this systematic map review, we aimed (1) at identifying studies including the co-occurrence of autism spectrum disorders (ASD) and gender dysphoria (GD) between 1946 and 2018, and (2) to present the papers included in this systematic map review to provide authors in the field of GD, sexuality and ASD with an important database of studies focusing on this very complex topic. The field is of emerging interest, as observed by the large increase of studies over the past decades, especially since 2015. However, future challenges are to be addressed in future studies.

Pros and Cons of Character Portrayals of Autism on TV and Film.

Portrayals of characters with autism spectrum disorder (ASD) and/or with autistic traits on film and in TV-series are increasing. Such portrayals may contribute in increasing awareness of the condition but can also increase stereotypes. Thus, these character portrayals are subject to heated debate within the ASD-community, but also in the general public at large. Following our recent published study on character portrayals of ASD on film and TV we here address some central issues related advantages and disadvantage of such portrayals.

The Scientific Study of Parents and Caregivers of Children with ASD: A Flourishing Field but Still Work to be Done.

There is a long history of research on parents and caregivers of individuals within autism. Parents and other primary caregivers typically play the most important part in the lives of persons with ASD although the need for support as the child becomes of age varies widely. This special issue includes 30 articles on central areas related to parenting and caregiving for people with ASD. Some of the key themes include intervention and training, mental health issues related to parent and family stress, measurement and assessment, and parent-child transactional processes. Other articles in this issue consider different but equally important topics such as sibling as potential future caregivers and parent support of preschool peer relationships.

Enhancing the understanding of clinically meaningful results: A clinical research perspective.

Published research often address aspects related to "statistical significance" but fail to address the clinical and practical importance and meaning of results. Our main objectives in this article are to investigate the merit of common measures of Effect Size in statistical research and to highlight the importance of the simple Relative Risk ratio. In this article we present data where we consider two widely utilized effect size measures (Cohen's d and Pearson's r) in relations to relative risk. We conclude that probability analyses of risk surpass the most commonly used statistical approach used in clinical trials today and should thus be the preferred compared to the misuse and misunderstanding of reporting for instance p-values alone.

Sex-Differences in Children Referred for Assessment: An Exploratory Analysis of the Autism Mental Status Exam (AMSE).

The autism mental status exam is an eight-item observational assessment that structures the way we observe and document signs and symptoms of ASD. Investigations of test performance indicate strong sensitivity and specificity using gold-standard assessment as reference standard. This study aims to explore potential sex differences in AMSE test performance and observations of 123 children referred for autism assessment. Results indicates more language deficits in females with ASD than in males with ASD and less sensory symptoms in females compared to males with ASD. The AMSE performance is similar in identifying ASD and non-ASD in females compared to males. Less disruptive behaviors in females, might cause a need for a bigger hit to other areas of development to raise concern.

Clinical Features of Children With Autism Who Passed 18-Month Screening.

OBJECTIVES: We compared sex-stratified developmental and temperamental profiles at 18 months in children screening negative for autism spectrum disorder (ASD) on the Modified Checklist for Autism in Toddlers (M-CHAT) but later receiving diagnoses of ASD (false-negative group) versus those without later ASD diagnoses (true-negative group). METHODS: We included 68 197 screen-negative cases from the Norwegian Mother and Child Cohort Study (49.1% girls). Children were screened by using the 6 critical items of the M-CHAT at 18 months. Groups were compared on domains of the Ages and Stages Questionnaire and the Emotionality Activity Sociability Temperament Survey. RESULTS: Despite passing M-CHAT screening at 18 months, children in the false-negative group exhibited delays in social, communication, and motor skills compared with the true-negative group. Differences were more pronounced in girls. However, with regard to shyness, boys in the false-negative group were rated as more shy than their true-negative counterparts, but girls in the false-negative group were rated as less shy than their counterparts in the true-negative group. CONCLUSIONS: This is the first study to reveal that children who pass M-CHAT screening at 18 months and are later diagnosed with ASD exhibit delays in core social and communication areas as well as fine motor skills at 18 months. Differences appeared to be more pronounced in girls. With these findings, we underscore the need to enhance the understanding of early markers of ASD in boys and girls, as well as factors affecting parental report on early delays and abnormalities, to improve the sensitivity of screening instruments.

Sex differences in fear of pain: item-level analysis of the Fear of Pain Questionnaire III.

OBJECTIVES: This study aimed to investigate sex differences in fear of pain (FOP) measured by the Fear of Pain Questionnaire III (FPQ-III) in a nonclinical sample. The FPQ-III is a self-report inventory measuring FOP, with 30 items, divided into three subscales: Severe, Minor and Medical Pain. METHODS: A total of 185 subjects participated (49.7% females) in this study. Sex differences on overall FOP, the subscales, and at item level were examined. One-way analysis of variance tested the association between sex and FOP, measured by overall FOP and the subscales. Ordinal regression analysis enabled item-level analysis of the FPQ-III and was conducted to explore further specificity of FOP in males compared to females. RESULTS: Overall FOP and fear of Severe Pain was significantly higher in females than in males, as measured by the FPQ-Total and the FPQ-Severe. Moreover, females were more likely to report higher FOP than males on 16 items (p<0.05). Further inspection revealed that females scored significantly higher than males on all items on the Severe Pain subscale. When controlling for multiple comparisons six items reached significance (p<0.001). Five of these items belonged to the subscale Severe Pain. When controlling for overall FOP one item, also from the Severe Pain subscale, reached significance (p<0.001). CONCLUSION: There are sex differences in severe FOP, with higher FOP in females compared to males. Potential explanations are sex differences in the 1) psychosocial mechanisms of fear and anxiety, and 2) emotional reactions to and interpretation of FPQ-III Severe Pain items.

Parent-Endorsed Sex Differences in Toddlers with and Without ASD: Utilizing the M-CHAT.

Sex differences in typical development can provide context for understanding ASD. Baron-Cohen (Trends Cogn Sci 6(6):248-254, 2002) suggested ASD could be considered an extreme expression of normal male, compared to female, phenotypic profiles. In this paper, sex-specific M-CHAT scores from N = 53,728 18-month-old toddlers, including n = 185 (32 females) with ASD, were examined. Results suggest a nuanced view of the "extreme male brain theory of autism". At an item level, almost every male versus female disadvantage in the broader population was consistent with M-CHAT vulnerabilities in ASD. However, controlling for total M-CHAT failures, this male disadvantage was more equivocal and many classically ASD-associated features were found more common in non-ASD. Within ASD, females showed relative strengths in joint attention, but impairments in imitation.