Factors associated with receptive and expressive language in autistic children and siblings: A systematic review.

Background & aims: Language abilities of autistic children and children at elevated likelihood for autism (EL-siblings) are highly heterogeneous, and many of them develop language deficits. It is as of yet unclear why language abilities of autistic children and EL-siblings vary, although an interaction of multiple influential factors is likely at play. In this review, we describe research articles that identify one or multiple of such factors associated with the receptive or expressive language abilities of autistic children and EL-siblings since the introduction of the DSM-5. Our aim was to identify and summarize factors that are linked to language development in autistic children and siblings in the recent literature to ultimately gain insight into the heterogeneity of language abilities in these children. Methods: The search strategy of this review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The following databases were consulted: Embase, MEDLINE, Web of Science Core Collection, and Scopus. Inclusion criteria for studies were the presence of a sample of autistic children no older than 7 years old who were diagnosed with autism spectrum disorder per the criteria of the DSM-5. Intervention studies and studies without an explicitly reported language measure were excluded. Risk of bias assessment was completed using the Newcastle-Ottawa Scales. Ultimately, 55 articles were included in this review. Main contribution: Fifty-six factors were identified to be related to receptive or expressive language abilities of autistic children and EL-siblings. They were grouped into three main categories: biological factors; psychosocial and environmental factors; and age-related and developmental factors, each with different subcategories. Although many of the identified variables were only examined in one article, some well-researched associated factors were reported across multiple studies and were present in both autistic children and EL-siblings, in particular joint attention, nonverbal cognitive abilities and frontal EEG power. Better insight in these factors associated with language abilities in autistic children and siblings at elevated likelihood can inform future intervention strategies to reduce language deficits and its corresponding negative consequences in these children. Conclusions: Our results confirm that multiple different factors likely underlie language deficits in autism. Important aspects that should be considered are, among others, social factors such as joint attention, child characteristics such as nonverbal cognition, and neurocognitive factors.

Neural correlates of response to joint attention in 2-to-5-year-olds in relation to ASD and social-communicative abilities: An fNIRS and behavioral study.

Autism spectrum disorder (ASD) is associated with life-long challenges with social cognition, and one of its earliest and most common manifestations is atypical joint attention, which is a pivotal skill in social-cognitive and linguistic development. Early interventions for ASD children often focus on training initiation of joint attention (IJA) and response to joint attention bids (RJA), which are important for social communication and cognition. Here, we used functional near-infrared spectroscopy and behavioral measures to test typically developing (TD, n = 17) and ASD children (n = 18), to address the relationship between the neural correlates of RJA and social-communicative behavior. Group-level differences were present for RJA-specific activation over right temporal sites, where TD children showed higher levels of activation during RJA than ASD children, whereas the two groups did not differ in the control condition. Correlations between neural activation and behavioral traits suggest that, in ASD children, neural activation during RJA is related to the frequency of RJA behavior when the former is measured over left temporal sites, and to social affect symptoms when considered for right temporal sites. Possible implications of the evidenced correlations are discussed.

Social responsiveness in children with developmental coordination disorder.

BACKGROUND: Developmental coordination disorder (DCD) is a neurodevelopmental disorder characterized by deficits in performing motor tasks. Research suggests social skills are also altered. OBJECTIVE: To investigate (1) whether the presence of DCD affects social responsiveness, (2) whether the co-occurrence of autism spectrum disorder (ASD) affects social responsiveness in children with DCD, and (3) whether there is an association between motor performance and social responsiveness in children with DCD. METHODS: Based on parental reports, children aged 5 to 15.5 years were assigned to one of three groups: DCD only (noASD, n = 67), DCD and suspected ASD (sASD, n = 13), and DCD and confirmed ASD (cASD, n = 22). Parental answers to the Social Responsiveness Scale (SRS-2) and the DCD-Questionnaire (DCD-Q) were compared to norm values using one sample t-tests, and between groups using ANOVA and MANOVA. Pearson correlation coefficients explored the relationship between the SRS-2 and DCD-Q in the total group and per group. RESULTS: Compared to norm values, difficulties in all areas of social responsiveness were reported in children with DCD, regardless of group (p<0.001). Compared to the noASD group, more unfavorable SRS-2 total T-scores and poorer DCD-Q scores were observed in sASD and cASD groups. Only in the total group, motor performance showed significant weak to moderate associations with the SRS-2 total T-score and all subscales except for 'social motivation' (r=-0.306 to -0.405; p ≤ 0.02). CONCLUSION: Social responsiveness difficulties are more common in children with DCD and are more severe in the ASD groups. Motor performance and social responsiveness are weak to moderately associated. CLINICAL TRIAL REGISTRATION NUMBER: NCT05092893 (https://clinicaltrials.gov/study/NCT05092893).

Predictors of autism spectrum disorder diagnosis in a spanish sample of preterm children with very low birthweight: A cross-sectional study.

Background and Aims: Autism spectrum disorder (ASD) is a neurodevelopmental disorder with a higher likelihood of being diagnosed in preterm populations. Likewise, low birthweight has also been connected with an increased likelihood of ASD. The objectives were to study the frequency and define the relationship between ASD, gestational age, birthweight, and growth percentiles for preterm children. Methods: A sample of preterm children with very low birthweight was selected from the Spanish population at 7-10 years old. Families were contacted from the hospital, and they were offered an appointment to conduct a neuropsychological assessment. The children who showed signs of ASD were referred to the diagnostic unit for differential diagnosis. Results: A total of 57 children completed full assessments, with 4 confirmed ASD diagnoses. The estimated prevalence was 7.02%. There were statistically significant weak correlations between ASD and gestational age (τb = -0.23), and birthweight (τb = -0.25), suggesting there is a higher likelihood of developing ASD for those born smaller or earlier in their gestation. Conclusion: These results could improve ASD detection and outcomes for this vulnerable population while also supporting and enhancing previous findings.

Investigating the development of the autonomic nervous system in infancy through pupillometry.

We aim to investigate early developmental trajectories of the autonomic nervous system (ANS) as indexed by the pupillary light reflex (PLR) in infants with (i.e. preterm birth, feeding difficulties, or siblings of children with autism spectrum disorder) and without (controls) increased likelihood for atypical ANS development. We used eye-tracking to capture the PLR in 216 infants in a longitudinal follow-up study spanning 5 to 24 months of age, and linear mixed models to investigate effects of age and group on three PLR parameters: baseline pupil diameter, latency to constriction and relative constriction amplitude. An increase with age was found in baseline pupil diameter (F(3,273.21) = 13.15, p < 0.001, [Formula: see text] = 0.13), latency to constriction (F(3,326.41) = 3.84, p = 0.010, [Formula: see text] = 0.03) and relative constriction amplitude(F(3,282.53) = 3.70, p = 0.012, [Formula: see text] = 0.04). Group differences were found for baseline pupil diameter (F(3,235.91) = 9.40, p < 0.001, [Formula: see text] = 0.11), with larger diameter in preterms and siblings than in controls, and for latency to constriction (F(3,237.10) = 3.48, p = 0.017, [Formula: see text] = 0.04), with preterms having a longer latency than controls. The results align with previous evidence, with development over time that could be explained by ANS maturation. To better understand the cause of the group differences, further research in a larger sample is necessary, combining pupillometry with other measures to further validate its value.

Verbal behavior development theory and relational frame theory: Reflecting on similarities and differences.

Relational frame theory and verbal behavior development theory are two behavior-analytic perspectives on human language and cognition. Despite sharing reliance on Skinner's analysis of verbal behavior, relational frame theory and verbal behavior development theory have largely been developed independently, with initial applications in clinical psychology and education/development, respectively. The overarching goal of the current paper is to provide an overview of both theories and explore points of contact that have been highlighted by conceptual developments in both fields. Verbal behavior development theory research has identified how behavioral developmental cusps make it possible for children to learn language incidentally. Recent developments in relational frame theory have outlined the dynamic variables involved across the levels and dimensions of arbitrarily applicable relational responding, and we argue for the concept of mutually entailed orienting as an act of human cooperation that drives arbitrarily applicable relational responding. Together these theories address early language development and children's incidental learning of names. We present broad similarities between the two approaches in the types of functional analyses they generate and discuss areas for future research.

Play in Relation to Autism Traits in Young Children at Elevated Likelihood for Autism Spectrum Disorder.

Play of younger siblings of children with autism spectrum disorder (ASD) (siblings; n = 44), very preterm children (preterms; n = 44), and children at typical likelihood for ASD (n = 36) was observed at 24 months. Children with ASD and atypical development engaged less in spontaneous (pre-)symbolic play than typically developing children. Total duration of spontaneous and elicited (pre-)symbolic play was associated with later ASD traits in siblings. However, no association between most play variables and ASD traits was found in preterms. This suggests possible different ASD-trajectories between siblings and preterms. Thus, spontaneous (pre-)symbolic play may be indicative of developmental challenges across several populations, and results highlight the need to move beyond studying only siblings in order to broaden our understanding of ASD.

Emerging Verbal Functions in Early Infancy: Lessons from Observational and Computational Approaches on Typical Development and Neurodevelopmental Disorders.

Objectives: Research on typically developing (TD) children and those with neurodevelopmental disorders and genetic syndromes was targeted. Specifically, studies on autism spectrum disorder, Down syndrome, Rett syndrome, fragile X syndrome, cerebral palsy, Angelman syndrome, tuberous sclerosis complex, Williams-Beuren syndrome, Cri-du-chat syndrome, Prader-Willi syndrome, and West syndrome were searched. The objectives are to review observational and computational studies on the emergence of (pre-)babbling vocalisations and outline findings on acoustic characteristics of early verbal functions. Methods: A comprehensive review of the literature was performed including observational and computational studies focusing on spontaneous infant vocalisations at the pre-babbling age of TD children, individuals with genetic or neurodevelopmental disorders. Results: While there is substantial knowledge about early vocal development in TD infants, the pre-babbling phase in infants with neurodevelopmental and genetic syndromes is scarcely scrutinised. Related approaches, paradigms, and definitions vary substantially and insights into the onset and characteristics of early verbal functions in most above-mentioned disorders are missing. Most studies focused on acoustic low-level descriptors (e.g. fundamental frequency) which bore limited clinical relevance. This calls for computational approaches to analyse features of infant typical and atypical verbal development. Conclusions: Pre-babbling vocalisations as precursor for future speech-language functions may reveal valuable signs for identifying infants at risk for atypical development. Observational studies should be complemented by computational approaches to enable in-depth understanding of the developing speech-language functions. By disentangling features of typical and atypical early verbal development, computational approaches may support clinical screening and evaluation.

Atypical brain network development of infants at elevated likelihood for autism spectrum disorder during the first year of life.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by behavioral features that appear early in life. Although studies have shown that atypical brain functional and structural connectivity are associated with these behavioral traits, the occurrence and initial alterations of brain networks have not been fully investigated. The current study aimed to map early brain network efficiency and information transferring in infants at elevated likelihood (EL) compared to infants at typical likelihood (TL) for ASD in the first year of life. This study used a resting-state functional near-infrared spectroscopy (fNIRS) approach to obtain the length and strength of functional connections in the frontal and temporal areas in 45 5-month-old and 38 10-month-old infants. Modular organization and small-world properties were detected in both EL and TL infants at 5 and 10 months. In 5-month-old EL infants, local and nodal efficiency were significantly greater than age-matched TL infants, indicating overgrown local connections. Furthermore, we used a support vector machine (SVM) model to classify infants with or without EL based on the obtained global properties of the network, achieving an accuracy of 77.6%. These results suggest that infants with EL for ASD exhibit inefficiencies in the organization of brain networks during the first year of life.

Urine lactate concentration as a non-invasive screener for metabolic abnormalities: Findings in children with autism spectrum disorder and regression.

There is increasing evidence that diseases caused by dysfunctional mitochondria (MD) are associated with autism spectrum disorder (ASD). A comprehensive meta-analysis showed that developmental regression was reported in half of the children with ASD and mitochondrial dysfunction which is much higher than in the general population of ASD. The aim of the present exploratory study was to determine lactate concentrations in urine of children with ASD, as a non-invasive large-scale screening method for metabolic abnormalities including mitochondrial dysfunction and its possible association with regression. First, clinical characteristics of MD were examined in 99 children (3-11 years) with ASD. Second, clinical characteristics of MD, severity of ASD and reported regression were compared between children with the 20% lowest lactate concentrations and those with the 20% highest lactate concentrations in urine. Third, clinical characteristics of MD and lactate concentration in urine were compared in children with (n = 37) and without (n = 62) reported regression. An association of urine lactate concentrations with mitochondrial dysfunction and regression could not be demonstrated in our large ASD cohort. However, since ASD children were reported by their parents to show a broad range of phenotypic characteristics of MD (e.g., gastro-intestinal and respiratory impairments), and lactate concentrations in urine are not always increased in individuals with MD, the presence of milder mitochondrial dysfunction cannot be excluded. Development of alternative biomarkers and their implementation in prospective studies following developmental trajectories of infants at elevated likelihood for ASD will be needed in the future to further unravel the association of ASD with mitochondrial dysfunction and eventually improve early detection.

Social referencing training in children with autism spectrum disorder: A randomized controlled study.

Children with autism spectrum disorder (ASD) have been shown to exhibit fewer instances of social referencing compared to their typically developing peers. The current study evaluated the effectiveness of multiple-exemplar training, prompting, and social reinforcement to teach social referencing. We used a single-blind randomized control trial with a multiple-baseline design nested within the experimental group to evaluate treatment effects. Twenty-five children with ASD participated. Participants in the treatment group showed significantly higher social referencing scores. However, there were no statistically significant differences between the groups in the posttraining initiating and responding to joint attention scores. The clinical implications of our findings are discussed.

The impact of COVID-19 measures on parent-reported restricted and repetitive behaviours in pre-school children with autism.

Background: COVID-19 restrictive measures have had a considerable impact on daily life routines, which may be especially challenging for families of children with autism. In pre-schoolers with autism, it is likely that the disruption of routines mainly impacts the presence of restrictive and repetitive behaviours (RRBs). Furthermore, influence of comorbid conditions, secondary behavioural difficulties and home environment characteristics on RRBs was explored. Method: A cross-sectional online survey design was used to collect parent-report data on 254 children with autism (2.5-6 years) during lockdown in the early months of the pandemic. RRBs were assessed using the Repetitive Behaviour Scale-Revised (RBS-R). Results: Parents reported a significant increase in stereotypic, self-injurious, compulsive and ritualistic behaviour, and restricted interests after implementation of COVID-19 restrictions. The presence of a co-occurring condition, such as language impairments or intellectual disability, was associated with more self-injurious and stereotypic behaviour. However, there was no effect of home environment on RRBs. Further, most children showed increases in internalising and/or externalising behaviour. Increased inattentive behaviour was associated with more ritualistic and stereotypic behaviour, and restricted interests. Decreases in hyperactivity were related to more restricted interests. Importantly, in a subset of children, parents reported less behavioural difficulties during the lockdown. Conclusions: Findings highlight the importance of flexible implementation and continuity of care for pre-schoolers with autism and support for parents. Further follow-up of children with autism and RRBs, and co-occurring behavioural difficulties is needed and could enhance our understanding of the long-term effects associated with sudden restrictive measures to daily routines.

Developmental changes in the brain response to speech during the first year of life: A near-infrared spectroscopy study of dutch-learning infants.

Language acquisition in the first year of life plays an important role in human development. Although recent research has increased our knowledge of early language development, the origins and developmental trajectories of language processing during infancy are still being debated. One important issue is whether the infant brain has already developed adult-like functional cortical specialization and lateralization for speech and language processing. Although a relatively large number of previous studies have investigated the cortical specialization for speech processing in newborns by comparing responses to normal speech with responses to time-reversed speech as a control, the subsequent development of this differential response is less well understood. In the current study, our primary goal was, therefore, to expand our knowledge of functional specialization for speech during the first year of life. By using functional near-infrared spectroscopy (fNIRS), we examined the hemodynamic responses in the temporal cortex to forward-going speech in the native language, Dutch, and backward Dutch in seventy-eight infants aged 5 and 10 months. We observed that five-month-old infants show bilateral activation to both forward and backward speech without obvious hemispheric lateralization for language, while ten-month-old infants show greater left-lateralized inverted responses (e.g., reduction in oxyhaemoglobin and increase in deoxyhaemoglobin) to forward speech than to backward speech. Overall, our findings indicate that the neural correlates of language processing undergo developmental changes in the first year of life.

Determinants of satisfaction with the detection process of autism in Europe: Results from the ASDEU study.

LAY ABSTRACT: Professional guidance and support in response to first concerns appears to be an important predictor of the level of satisfaction with the detection process of autism in young children. In this study, we analyzed the views of 1342 family members, including 1278 parents, who completed an online survey form collecting information about their experience and satisfaction with the early detection of autism in their child. Specifically, we were interested in how specific experiences with the detection process relate to the satisfaction with it and whether we could identify important predictors of satisfaction. The detection process is an emotionally charged period for parents, often described as painful, chaotic, and lengthy. A better understanding of their experiences is important to take appropriate action to improve the detection process. In our sample, the level of satisfaction with the detection process varied greatly from one respondent to another. Among the different experiences we considered, whether or not respondents received professional guidance and support in response to first concerns explained most of this variation. We also found that difficulty finding information about detection services, lack of professional guidance and support in response to first concerns, having to find a diagnostic service on one's own, and longer delays between confirmation of concerns and first appointment with a specialist were experiences associated with a greater likelihood of being unsatisfied. The findings of this study highlight the importance of the parent-professional relationship in the detection process and have important practical implications for health administrations to improve the detection process.

Polygenic association between attention-deficit/hyperactivity disorder liability and cognitive impairments.

BACKGROUND: A recent genome-wide association study (GWAS) identified 12 independent loci significantly associated with attention-deficit/hyperactivity disorder (ADHD). Polygenic risk scores (PRS), derived from the GWAS, can be used to assess genetic overlap between ADHD and other traits. Using ADHD samples from several international sites, we derived PRS for ADHD from the recent GWAS to test whether genetic variants that contribute to ADHD also influence two cognitive functions that show strong association with ADHD: attention regulation and response inhibition, captured by reaction time variability (RTV) and commission errors (CE). METHODS: The discovery GWAS included 19 099 ADHD cases and 34 194 control participants. The combined target sample included 845 people with ADHD (age: 8-40 years). RTV and CE were available from reaction time and response inhibition tasks. ADHD PRS were calculated from the GWAS using a leave-one-study-out approach. Regression analyses were run to investigate whether ADHD PRS were associated with CE and RTV. Results across sites were combined via random effect meta-analyses. RESULTS: When combining the studies in meta-analyses, results were significant for RTV (R2 = 0.011, ß = 0.088, p = 0.02) but not for CE (R2 = 0.011, ß = 0.013, p = 0.732). No significant association was found between ADHD PRS and RTV or CE in any sample individually (p > 0.10). CONCLUSIONS: We detected a significant association between PRS for ADHD and RTV (but not CE) in individuals with ADHD, suggesting that common genetic risk variants for ADHD influence attention regulation.

Perceptions of parents of the impact of autism spectrum disorder on their quality of life and correlates: comparison between mothers and fathers.

PURPOSE: To compare mothers and fathers perceptions of the impact of autism spectrum disorder on their Quality of Life (QoL), we used the Parental-Developmental Disorders-Quality of Life scale (Par-DD-QoL). METHOD: The perception of QoL of mothers and fathers was compared for 130 pairs of parents of children with ASD and the associated variables were investigated. RESULTS: Mothers perceived a significantly greater impact of ASD on their QoL than fathers. Parents perceived a higher impact of ASD on global QoL when their child's adaptive skills were low and when the level of aberrant behaviors was high. More precisely, the perception of QoL by the mothers was negatively associated with their child's internalized disorders, whereas the perception of QoL by the fathers was negatively associated with their child's externalized disorders. Neither the mothers' nor the fathers' perception of the impact on QoL was associated with their children's age or the severity of their autistic symptoms. Some parental factors, such as being members of a family association, having benefited from training in ASD and having experienced a disruption in professional activity were associated with a greater impact on their QoL. CONCLUSION: Our finding that the perceived impact of ASD on QoL differed between mothers and fathers argues for individualized psychosocial support. Moreover, the strong correlation between the child's clinical characteristics and the perception by parents of a higher impact of ASD on QoL should be seen as red flag concerning the needs of the parents in terms of social and educational support. TRIAL REGISTRATION NUMBER: NCT02625116 (October 2015).

Nonsimultaneous stimulus presentations and their role in listener naming.

Previous studies on naming have presented the object and its name simultaneously during both training and testing, and thus the training component may establish a transformation of function directly between the object and the name. Successful tests for listener naming may thus not require the emergence of a novel (entailed) transformation of function. The current study aimed to control for this possibility by presenting the object and the name sequentially and nonsimultaneously. Eight typically developing toddlers participated in the current study. During name training, objects and names were presented nonsimultaneously, and all participants failed to emit listener-naming responses during the first test session. Subsequently, 4 participants received multiple exemplar training, which led to improvements in listener naming for all 4; and speaker naming for only 1 participant. As a control condition, the remaining 4 participants were tested repeatedly, without multiple exemplar training, and did not show any consistent improvements in their listener or speaker performances. Multiple exemplar training thus appeared to be effective in establishing generalized listener responses, which involved generating entailed transformation of functions. The strategy of using nonsimultaneous stimulus presentations could allow for greater precision in identifying the behavioral processes involved in listener-naming.

Standardized motor assessments before the age of five predicting school-aged motor outcome including DCD: A systematic review.

AIM: Developmental Coordination Disorder (DCD) is a common neurodevelopmental disorder usually diagnosed at primary-school-age. This systematic review aimed to summarize available standardized motor assessments before five years of age predicting DCD, complex Minor Neurological Disorder (cMND) and motor delay assessed by a standardized motor test. METHODS: A systematic search was performed in MEDLINE, CINAHL, WoS, Scopus, CENTRAL and ERIC. A hand search was executed. Only data of non-Cerebral Palsy children was included. RESULTS: At or before two years, the BSID, motor subtests of GMDS, NOMAS, and NSMDA might be valuable in detecting school-aged motor delay, while starting at three years, the PDMS, motor subtests of GMDS, NSDMA, M-ABC-2, and CAMPB show promising results. General movements Assessment is associated with cMND, but does not seem sensitive enough to detect DCD. Predictive values are superior in high-risk groups and improve as children age. However, no assessment instrument reached 80% sensitivity and specificity. CONCLUSION: Standardized motor assessments before five years seem valuable in detecting early motor problems. More longitudinal research commencing in infancy, including multiple assessments over time and the implementation of clear diagnostic criteria is imperative.

Early non-social behavioural indicators of autism spectrum disorder (ASD) in siblings at elevated likelihood for ASD: a systematic review.

We aimed at identifying early non-social behavioural indicators that predict later ASD. Likewise, we were interested in the moment in which non-social signs discriminate between children at elevated likelihood for ASD with a later diagnosis of ASD, and children at elevated likelihood for ASD with a typical developmental outcome. In addition, we intended to explore the developmental evolution of children's symptomatology over time. A systematic literature search was conducted for longitudinal studies on early non-social behavioural indicators among siblings at elevated likelihood for ASD. The following databases were searched: PUBMED, Web of Science, PsycINFO, CINAHL and EMBASE. The study identification process was conducted by two reviewers independently. Compared to siblings at elevated likelihood for ASD with a typical developmental outcome, siblings at elevated likelihood for ASD with later ASD show impairments in attention disengagement, in gross and fine motor development and characteristic restricted and repetitive interests and behaviours, starting at 12 months of age. Moreover, early attention disengagement exerts a predictive role towards a later ASD diagnosis, given that from 12 months siblings at elevated likelihood for ASD who will receive an independent ASD diagnosis towards 24-36 months present marked difficulties in disengaging in comparison with siblings at elevated likelihood for ASD that will not satisfy the criteria for an ASD diagnosis. The findings call for a more comprehensive vision on early indicators of ASD. Further research is needed to extend results to other behavioural domains.