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.

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).

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.

Ethics of returning children's individual research findings: from principles to practice.

Little ethical recommendations on returning children's individual research findings are available for researchers in behavioral sciences, especially when compared to genetic research. Anecdotic evidence suggests that since parents are often interested in their child's individual research findings, researchers tend to offer this information as a form of compensation for research participation. Despite good intentions, these practices are not without potential harmful consequences for children. We were confronted with these difficulties and with the paucity of available guidance on this topic, being involved in a longitudinal, infant development study, i.e. tracking infants at risk for autism (TIARA). First, we review current ethical recommendations and discuss their limitations in the light of the TIARA study. Second, we will suggest to revise these recommendations, by identifying and applying the relevant bioethical principles and concepts at hand. Third, as an example of practical implementation, the adopted 'return of research findings'-policy for the TIARA-study is presented. The principles and concepts we engage with are the ancillary care responsibilities of the researcher, non-maleficence and beneficence, the right to an open future of the child, and the avoidance of therapeutic misconception. Ultimately, we present the concrete return of research findings policy implemented in the TIARA-study. Here, we suggest restricting the systematic return of children's individual research findings to cases where findings are considered clinically significant and actionable for the child. We discuss the broader implications for designing and conducting research in behavioral sciences with children.

Validation of the Language ENvironment Analysis (LENA) system for Dutch.

The validity of the Language ENvironment Analysis (LENA) System was evaluated for Dutch. 216 5-min samples (six samples per age per child) were selected from daylong recordings at 5, 10 and 14 months of age of native Dutch-speaking younger siblings of children with autism spectrum disorder (N = 6) and of typically developing children (N = 6). Two native Dutch-speaking coders counted the amount of adult words (AWC), child vocalisations (CVC) and conversational turns (CT). Consequently, correlations between LENA and human estimates were explored. Correlations were high for AWC at all ages (r = .73 to .81). Regarding CVC, estimates were moderately correlated at 5 months (r = .57) but the correlation decreased at 10 (r = .37) and 14 months (r = .14). Correlations for CT were low at all ages (r = .19 to .28). Lastly, correlations were not influenced by the risk status of the children.

Coping strategies of parents of children with autism spectrum disorder: a systematic review.

To deal with stress, parents of children with ASD use coping strategies that help to tackle the challenging situations of raising their child. This systematic review examines parental coping strategy's questionnaires, factors which influence these coping strategies, interactions between these strategies and perceived stress and their impact on parental quality of life. According to PRISMA guidelines, an electronic search was conducted on Medline, PsycInfo and Eric: 156 articles were identified and 11 studies were selected. Many types of self-reported questionnaires were used to assess parental coping strategies. Studies highlighted that parents of a child with ASD used more avoidance strategies and less social support-seeking strategies than those of typical children. Furthermore, problem-focused coping protects parental stress and quality of life, that on the contrary, emotion-focused coping is a risk factor for alteration. Our systematic review illustrates the need to adapt psychoeducational interventions for parents of children with ASD.

Language growth in very young siblings at risk for autism spectrum disorder.

BACKGROUND: Children with autism spectrum disorder (ASD) show substantial variability in their language development. Language problems are highly prevalent in these children. In addition, the quality of early language abilities contributes to the overall development of these children and is highly predictive of their adult outcome. Yet, little is known about language development in children at risk of ASD during the first years of life. AIMS: To compare early receptive language (RL) and expressive language (EL) development in children at risk of ASD and determine predictors of language development. METHODS & PROCEDURES: Developmental trajectories of RL and EL were investigated from 10 to 36 months of age in younger siblings of typically developing children (LR-sibs, N = 30) and in younger siblings of children with ASD (HR-sibs, N = 31) using the Mullen Scales of Early Learning. Furthermore, both child and demographic characteristics were examined as possible predictors of language development. OUTCOMES & RESULTS: Both groups showed similar growth curves for RL and EL and the majority of the children showed average (within ±1.5 SD of the mean) or above-average language abilities. Nevertheless, the mean growth of EL was lower and the variation in growth of both RL and EL was higher in HR-sibs than in LR-sibs. Furthermore, early child characteristics were predictive of language development in both groups. Yet, some child characteristics seemed to be of more importance in HR-sibs than in LR-sibs. Consequently, lower non-verbal abilities at 10 months in both groups and a higher degree of ASD characteristics at 14 months in HR-sibs may be indicative of difficulties in language development. CONCLUSIONS & IMPLICATIONS: HR-sibs show more variation in their language development than LR-sibs during the first 3 years of life. The majority of HR-sibs, however, did not present with below-average language abilities. Yet, early characteristics of ASD may be a red flag for difficulties in the language development of HR-sibs.

Building a theoretical framework for autism spectrum disorders screening instruments in Europe.

BACKGROUND: This study addresses the need for a theoretical base to develop more effective early autism spectrum disorders (ASD) detection tools. The structure that underlies early ASD detection is explored by evaluating the opinions of experts on ASD screening tools currently used in Europe. METHOD: A process of face and content validity was performed. First, the best constructs were selected from the relevant tests: Checklist for Early Signs of Developmental Disorders (CESDD), Checklist for Autism in Toddlers (CHAT), Early Screening of Autistic Traits Questionnaire (ESAT), Modified Checklist for Autism in Toddlers (M-CHAT), Social Communication Questionnaire (SCQ) and Communication and Symbolic Behaviour Scales Developmental Profile (CSBS-DP). The diagnostic content validity model by Fehring (1986, 1994) was adapted to make the selection. Afterwards, the items, taken from these tests, were selected to fit into each construct, using the same methodology. RESULTS: Twelve of the 18 constructs were selected by the experts and 11 items were chosen from a total of 130, reduced to eight after eliminating tautologies. CONCLUSIONS: Mapping these constructs and items on to the DSM-5 diagnostic criteria for ASD indicated good face and content validity. Results of this research will contribute to efforts to improve early ASD screening instruments and identify the key behaviours that experts in ASD see as the most relevant for early detection.

New insights into the phenotype of FARS2 deficiency.

Mutations in FARS2 are known to cause dysfunction of mitochondrial translation due to deficient aminoacylation of the mitochondrial phenylalanine tRNA. Here, we report three novel mutations in FARS2 found in two patients in a compound heterozygous state. The missense mutation c.1082C>T (p.Pro361Leu) was detected in both patients. The mutations c.461C>T (p.Ala154Val) and c.521_523delTGG (p.Val174del) were each detected in one patient. We report abnormal in vitro aminoacylation assays as a functional validation of the molecular genetic findings. Based on the phenotypic data of previously reported subjects and the two subjects reported here, we conclude that FARS2 deficiency can be associated with two phenotypes: (i) an epileptic phenotype, and (ii) a spastic paraplegia phenotype.

A Novel Way to Measure and Predict Development: A Heuristic Approach to Facilitate the Early Detection of Neurodevelopmental Disorders.

PURPOSE OF REVIEW: Substantial research exists focusing on the various aspects and domains of early human development. However, there is a clear blind spot in early postnatal development when dealing with neurodevelopmental disorders, especially those that manifest themselves clinically only in late infancy or even in childhood. RECENT FINDINGS: This early developmental period may represent an important timeframe to study these disorders but has historically received far less research attention. We believe that only a comprehensive interdisciplinary approach will enable us to detect and delineate specific parameters for specific neurodevelopmental disorders at a very early age to improve early detection/diagnosis, enable prospective studies and eventually facilitate randomised trials of early intervention. In this article, we propose a dynamic framework for characterising neurofunctional biomarkers associated with specific disorders in the development of infants and children. We have named this automated detection 'Fingerprint Model', suggesting one possible approach to accurately and early identify neurodevelopmental disorders.

Altered intrinsic organisation of brain networks implicated in attentional processes in adult attention-deficit/hyperactivity disorder: a resting-state study of attention, default mode and salience network connectivity.

Deficits in task-related attentional engagement in attention-deficit/hyperactivity disorder (ADHD) have been hypothesised to be due to altered interrelationships between attention, default mode and salience networks. We examined the intrinsic connectivity during rest within and between these networks. Six-minute resting-state scans were obtained. Using a network-based approach, connectivity within and between the dorsal and ventral attention, the default mode and the salience networks was compared between the ADHD and control group. The ADHD group displayed hyperconnectivity between the two attention networks and within the default mode and ventral attention network. The salience network was hypoconnected to the dorsal attention network. There were trends towards hyperconnectivity within the dorsal attention network and between the salience and ventral attention network in ADHD. Connectivity within and between other networks was unrelated to ADHD. Our findings highlight the altered connectivity within and between attention networks, and between them and the salience network in ADHD. One hypothesis to be tested in future studies is that individuals with ADHD are affected by an imbalance between ventral and dorsal attention systems with the former playing a dominant role during task engagement, making individuals with ADHD highly susceptible to distraction by salient task-irrelevant stimuli.

Extremely Preterm Born Children at Very High Risk for Developing Autism Spectrum Disorder.

This study aimed to provide a more comprehensive picture of the prevalence of autism spectrum disorder (ASD) in a geographic cohort of extremely preterm born adolescents by using established diagnostic instruments in addition to screening instruments. 53 participants passed a screening procedure with two screening instruments and a diagnostic evaluation with a semi-structured assessment and a parent interview. 28 % of the adolescents had a community based clinical diagnosis of ASD. When research diagnoses were also taken into account, this rate increased to 40 %. Intellectual disability, language impairment and behavioural difficulties are characteristic for these children with ASD. This study is to our knowledge the first to use ASD-specific diagnostic instruments to confirm ASD diagnoses in extremely preterm born children in early adolescence. The study expands findings of previous research and raises the need for follow-up into late childhood and early adolescence.

Impulsivity in cocaine-dependent individuals with and without attention-deficit/hyperactivity disorder.

BACKGROUND: Cocaine-dependent individuals (CDI) display increased impulsivity. However, despite its multifactorial nature most studies in CDI have treated impulsivity monolithically. Moreover, the impact of attention-deficit/hyperactivity disorder (ADHD) has often not been taken into account. This study investigates whether CDI with ADHD (CDI+ADHD) differ from CDI without an ADHD diagnosis and healthy controls (HC) on several impulsivity measures. METHODS: Thirty-four CDI, 25 CDI+ADHD and 28 HC participated in this study. Trait impulsivity was assessed with the motor, attentional and non-planning subscales of the Barratt Impulsiveness Scale (BIS-11). Neurocognitive dimensions of impulsivity were examined with the stop signal task (SST), delay discounting task (DDT) and information sampling task (IST). RESULTS: Relative to HC, both CDI and CDI+ADHD scored higher on all BIS-11 subscales, required more time to inhibit their responses (SST) and sampled less information before making a decision (IST). Greater discounting of delayed rewards (DDT) was only found among CDI+ADHD. Compared to CDI without ADHD, CDI+ADHD scored higher on the BIS-11 non-planning and total scale and showed higher discounting rates. CONCLUSION: CDI score higher on several indices of impulsivity relative to HC, regardless of whether they have concomitant ADHD or not. CDI+ADHD are specifically characterized by a lack of future orientation compared to CDI without ADHD. © 2015 S. Karger AG, Basel.

Anticipatory processes in brain state switching - evidence from a novel cued-switching task implicating default mode and salience networks.

The default mode network (DMN) is the core brain system supporting internally oriented cognition. The ability to attenuate the DMN when switching to externally oriented processing is a prerequisite for effective performance and adaptive self-regulation. Right anterior insula (rAI), a core hub of the salience network (SN), has been proposed to control the switching from DMN to task-relevant brain networks. Little is currently known about the extent of anticipatory processes subserved by DMN and SN during switching. We investigated anticipatory DMN and SN modulation using a novel cued-switching task of between-state (rest-to-task/task-to-rest) and within-state (task-to-task) transitions. Twenty healthy adults performed the task implemented in an event-related functional magnetic resonance imaging (fMRI) design. Increases in activity were observed in the DMN regions in response to cues signalling upcoming rest. DMN attenuation was observed for rest-to-task switch cues. Obversely, DMN was up-regulated by task-to-rest cues. The strongest rAI response was observed to rest-to-task switch cues. Task-to-task switch cues elicited smaller rAI activation, whereas no significant rAI activation occurred for task-to-rest switches. Our data provide the first evidence that DMN modulation occurs rapidly and can be elicited by short duration cues signalling rest- and task-related state switches. The role of rAI appears to be limited to certain switch types - those implicating transition from a resting state and to tasks involving active cognitive engagement.

Neonatal and neurodevelopmental outcome of children aged 3-10 years born following assisted oocyte activation.

Assisted oocyte activation (AOA) using a calcium ionophore has been used for more than a decade following intracytoplasmic sperm injection (ICSI) fertilization failure. However, since AOA does not mimic precisely the physiological fertilization process, concerns exist about its use in human assisted reproduction. This study assessed the neonatal and neurodevelopmental outcome of children aged ≥ 3 years who had been born following AOA in our centre. Twenty-one children participated in the study (81% response rate; mean age 63.6 ± 21.07 months). Neonatal data were collected via questionnaires. Neurodevelopmental outcome was tested using the Reynell Developmental Language Scales or Clinical Evaluation of Language Fundamentals, Wechsler Preschool and Primary Scale of Intelligence or Wechsler Intelligence Scale for Children, and the Movement Assessment Battery for Children III. Behaviour was scored by the Social Communication Questionnaire, the Child Behaviour Checklist and the Teachers Report Form. For all tests and questionnaires, the mean outcomes lay within the expected ranges. These are first data on the developmental outcome of AOA children. The high response rate and the robustness of the tests support the data, which are reassuring although still considered preliminary. Therefore, AOA should still be performed only in selected couples.

Social-communicative abilities as treatment goals for preschool children with autism spectrum disorder: the importance of imitation, joint attention, and play.

Autism spectrum disorder (ASD) is a pervasive developmental disorder with a lifelong impact on multiple domains of functioning. Often, a diagnosis is possible by 3 years of age. Given the benefits of early intervention, it is advisable to start treatment as soon as possible after the diagnosis has been made. Among other factors, early intervention should focus on social-communicative abilities such as imitation, joint attention, and play. In this review, the typical developmental course and functions of these social-communicative abilities are described, and the problems young children with ASD experience in this domain. In addition, different approaches to promoting these abilities are explained. The authors recommend the inclusion of imitation, joint attention, and play as treatment goals in community settings for children with ASD.

Screening for autism spectrum disorders: state of the art in Europe.

A large number of studies have reported on the validity of autism spectrum disorder (ASD) screening procedures. An overall understanding of these studies' findings cannot be based solely on the level of internal validity of each, since screening instruments might perform differently according to certain factors in different settings. Europe has led the field with the development of the first screening tool and first prospective screening study of autism. This paper seeks to provide an overview of ASD screening studies and ongoing programmes across Europe, and identify variables that have influenced the outcomes of such studies. Results show that, to date, over 70,000 children have been screened in Europe using 18 different screening procedures. Differences among findings across studies have enabled us to identify ten factors that may influence screening results. Although it is impossible to draw firm conclusions as to which screening procedure is most effective, this analysis might facilitate the choice of a screening method that best fits a specific scenario, and this, in turn, may eventually improve early ASD detection procedures.

Language development of children born following intracytoplasmic sperm injection (ICSI) combined with assisted oocyte activation (AOA).

BACKGROUND: The effect of assisted reproduction technology (ART) on language development is still unclear. Moreover, different techniques are introduced at rapid pace and are not always accompanied by extensive follow-up programmes. AIMS: To investigate the language development of 3-10-year-old children born following ART using intracytoplasmic sperm injection (ICSI) combined with assisted oocyte activation (AOA), which is a highly specialized technique applied in cases with a history of fertilization failure following conventional ICSI. Secondly, a comparison is made between the language development of singletons and twins. METHODS & PROCEDURES: Twenty children, six boys and 14 girls, born following ICSI combined with AOA and older than 3 years were included in the study. The mean age of the children was 5;4 years (range = 3;1-10;4 years; SD = 1;8 years). Expressive and receptive language development were assessed using the Clinical Evaluation of Language Fundamentals (CELF-IV-NL) for children older than 5 years and the Reynell Developmental Language Scales (RTOS) for children younger than or equal to 5 years. OUTCOMES & RESULTS: The mean total score for language ability (in percentiles) was 56.8 (SD = 33.6), which corresponds to normal language skills. Significantly higher scores were found for AOA singletons compared with twins. For the general language, none of the children scored within the clinical zone for language disability corresponding with a percentile lower than 5. CONCLUSION & IMPLICATIONS: This study presents the first data concerning language outcome in 3-10-year-old children born following AOA. General language scores of the AOA children in this study are located within the normal ranges. The language development of singletons was significantly better compared with twins. Although the results are reassuring for language development, in future long-term follow-up studies in this population are necessary.

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.