Early developmental pathways to childhood symptoms of attention-deficit hyperactivity disorder (ADHD), anxiety, and autism spectrum disorder (ASD)

Background Children with autism spectrum disorder (ASD) often have co-occurring symptoms of attention-deficit/hyperactivity disorder (ADHD) and/or anxiety. It is unclear whether these disorders arise from shared or distinct developmental pathways. We explored this question by testing the specificity of early-life (infant and toddler) predictors of mid-childhood ADHD and anxiety symptoms compared to ASD symptoms. Methods Infants (n = 104) at high and low familial risk for ASD took part in research assessments at 7, 14, 24, and 38 months and 7 years of age. Symptoms of ASD, ADHD, and anxiety were measured by parent report at age 7. Activity levels and inhibitory control, also measured by parent report, in infancy and toddlerhood were used as early-life predictors of ADHD symptoms. Fearfulness and shyness measured in infancy and toddlerhood were used as early-life predictors of anxiety symptoms. Correlations and path analysis models tested associations between early-life predictors and mid-childhood ADHD and anxiety symptoms compared to mid-childhood ASD symptoms, and the influence of controlling for ASD symptoms on those associations. Results Increased activity levels and poor inhibitory control were correlated with ADHD symptoms and not ASD or anxiety; these associations were unchanged in path models controlling for risk-group and ASD symptoms. Increased fearfulness and shyness were correlated with anxiety symptoms, but also ASD symptoms. When controlling for risk-group in path analysis, the association between shyness and anxiety became non-significant, and when further controlling for ASD symptoms the association between fearfulness and anxiety became marginal. Conclusions The specificity of early-life predictors to ADHD symptoms suggests early developmental pathways to ADHD might be distinct from ASD. The overlap in early-life predictors of anxiety and ASD suggests that these disorders are difficult to differentiate early in life, which could reflect the presence of common developmental pathways or convergence in early behavioural manifestations of these disorders. Keywords ASD, ADHD, anxiety, comorbidity, early developmental pathwaysWe are very grateful for the important contributions BASIS families have made towards this study. The research was supported by the BASIS funding consortium led by Autistica (www.basisnetwork.org), Autism Speaks, a UK Medical Research Council Programme Grant (G0701484) to M.H. Johnson, and the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Trust and King’s College London. R. Bedford is supported by a Sir Henry Wellcome Postdoctoral Fellowship. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. The authors have no conflicts of interests

Modelling trajectories of social and non-social development in infants at high risk for autism spectrum disorder

In this thesis, multivariate statistical modelling approaches are applied to longitudinal data\ud to examine how social and non-social abilities in infancy relate to later developmental and\ud clinical outcomes in infants at high- and low-risk for autism spectrum disorder (ASD). ASD\ud is a heritable developmental disorder, rarely diagnosed before 2 years, and characterised by\ud impairments in social interaction, communication and restricted and repetitive behaviours\ud (DSM-IV-TR, American Psychiatric Association, 2000). The application of multivariate\ud techniques to experimental, clinical and questionnaire data from 54 high-risk infants (who\ud have an older sibling with ASD) and 50 low-risk controls, seen at 7, 13, 24 and 36 months,\ud enables the simultaneous modelling of multiple factors in relation to ASD outcome.\ud In Chapter 3, eye-tracking of gaze following behaviour demonstrated that infants who later\ud develop ASD symptoms can correctly follow another person's eye-gaze, but by 13 months\ud they show reduced looking to the gazed-at object compared to typically developing infants.\ud Looking time is an index of referential understanding and was also related to children's\ud subsequent receptive vocabulary. Chapter 4 reported that both high- and low-risk 24-montholds\ud can apply mutual exclusivity (the principle that each object has one name) to make a\ud word-object mapping. However, high-risk toddlers did not use social feedback to learn the\ud word, and this difficulty was related to their lower receptive vocabularies. Further, 13 month\ud looking time (from the gaze following task) predicted later learning from reinforcing\ud feedback, suggesting a degree of continuity in children's social understanding across\ud development. Finally, Chapter 5 found that social (gaze following) and non-social\ud (disengagement) attention independently predict ASD, and while disengagement predicts\ud looking time early in development, the measures become de-correlated over time. The\ud findings suggest that in order to understand the variable developmental trajectories leading to\ud ASD, multiple risk markers over time should be analysed

What you see is what you get: contextual modulation of face scanning in typical and atypical development

Infants’ visual scanning of social scenes is influenced by both exogenously and endogenously driven shifts of attention. We manipulate these factors by contrasting individual infants’ distribution of visual attention to the eyes relative to the mouth when viewing complex dynamic scenes with multiple communicative signals (e.g. peek-a-boo), relative to the same infant viewing simpler scenes where only single features move (moving eyes, mouth and hands). We explore the relationship between context-dependent scanning patterns and later social and communication outcomes in two groups of infants, with and without familial risk for autism. Our findings suggest that in complex scenes requiring more endogenous control of attention, increased scanning of the mouth region relative to the eyes at 7 months is associated with superior expressive language (EL) at 36 months. This relationship holds even after controlling for outcome group. In contrast, in simple scenes where only the mouth is moving, those infants, irrespective of their group membership, who direct their attention to the repetitive moving feature, i.e. the mouth, have poorer EL at 36 months. Taken together, our findings suggest that scanning of complex social scenes does not begin as strikingly different in those infants later diagnosed with autism

Sex differences in the association between infant markers and later autistic traits

BACKGROUND: Although it is well established that the prevalence of autism spectrum disorder (ASD) is higher in males than females, there is relatively little understanding of the underlying mechanisms and their developmental time course. Sex-specific protective or risk factors have often been invoked to explain these differences, but such factors are yet to be identified. METHODS: We take a developmental approach, using a prospective sample of 104 infants at high and low familial risk for ASD, to characterise sex differences in infant markers known to predict emerging autism symptoms. We examine three markers previously shown to be associated with later autistic social-communication symptoms: the Autism Observation Scale for Infants (AOSI) total score, attention disengagement speed and gaze following behaviour. Our aim was to test whether sex differences were already present in these markers at 1 year of age, which would suggest sex-specific mechanisms of risk or protection. RESULTS: While no sex differences were found in any of the three markers investigated, we found sex differences in their relationship to 3-year autism traits; all three markers significantly predicted later autism traits only in the boys. CONCLUSIONS: Previously identified ‘early autism markers’ were associated with later autism symptoms only in boys. This suggests that there may be additional moderating risk or protective factors which remain to be identified. Our findings have important implications for prospective studies in terms of directly testing for the moderating effect of sex on emerging autistic traits

Toddlers’ fine motor milestone achievement is associated with early touchscreen scrolling

Touchscreen technologies provide an intuitive and attractive source of sensory/cognitive stimulation for young children. Despite fears that usage may have a negative impact on toddlers’ cognitive development, empirical evidence is lacking. The current study presents results from the UK Toddler Attentional Behaviours and LEarning with Touchscreens (TABLET) project, examining the association between toddlers’ touchscreen use and the attainment of developmental milestones. Data were gathered in an online survey of 715 parents of 6- to 36-month-olds to address two research questions: (1) How does touchscreen use change from 6 to 36 months? (2) In toddlers (19–36 months, i.e., above the median age, n = 366), how does retrospectively reported age of first touchscreen usage relate to gross motor (i.e., walking), fine motor (i.e., stacking blocks), and language (i.e., producing two-word utterances) milestones? In our sample, the proportion of children using touchscreens, as well as the average daily usage time, increased with age (youngest quartile, 6–11 months: 51.22% users, 8.53 min per day; oldest quartile, 26–36 months: 92.05% users, average use of 43.95 min per day). In toddlers, aged 19–36 months, age of first touchscreen use was significantly associated with fine motor (stacking blocks), p = 0.03, after controlling for covariates age, sex, mother’s education (a proxy for socioeconomic status) as well as age of early fine motor milestone achievement (pincer grip). This effect was only present for active scrolling of the touchscreen p = 0.04, not for video watching. No significant relationships were found between touchscreen use and either gross motor or language milestones. Touchscreen use increases rapidly over the first 3 years of life. In the current study, we find no evidence to support a negative association between the age of first touchscreen usage and developmental milestones. Indeed, earlier touchscreen use, specifically scrolling of the screen, was associated with earlier fine motor achievement. Future longitudinal studies are required to elucidate the temporal order and mechanisms of this association, and to examine the impact of touchscreen use on other, more fine-grained, measures of behavioral, cognitive, and neural development

Neurocognitive and observational markers: prediction of autism spectrum disorder from infancy to mid-childhood

Background Prospective studies of infants at high familial risk for autism spectrum disorder (ASD) have identified a number of putative early markers that are associated with ASD outcome at 3 years of age. However, some diagnostic changes occur between toddlerhood and mid-childhood, which raises the question of whether infant markers remain associated with diagnosis into mid-childhood. Methods First, we tested whether infant neurocognitive markers (7-month neural response to eye gaze shifts and 14-month visual disengagement latencies) as well as an observational marker of emerging ASD behaviours (the Autism Observation Scale for Infants; AOSI) predicted ASD outcome in high-risk (HR) 7-year-olds with and without an ASD diagnosis (HR-ASD and HR-No ASD) and low risk (LR) controls. Second, we tested whether the neurocognitive markers offer predictive power over and above the AOSI. Results Both neurocognitive markers distinguished children with an ASD diagnosis at 7 years of age from those in the HR-No ASD and LR groups. Exploratory analysis suggested that neurocognitive markers may further differentiate stable versus lost/late diagnosis across the 3 to 7 year period, which will need to be tested in larger samples. At both 7 and 14 months, combining the neurocognitive marker with the AOSI offered a significantly improved model fit over the AOSI alone. Conclusions Infant neurocognitive markers relate to ASD in mid-childhood, improving predictive power over and above an early observational marker. The findings have implications for understanding the neurodevelopmental mechanisms that lead from risk to disorder and for identification of potential targets of pre-emptive intervention

Investigating the Mechanisms Driving Referent Selection and Retention in Toddlers at Typical and Elevated Likelihood for Autism Spectrum Disorder.

It was suggested that children's referent selection may not lay memory traces sufficiently strong to lead to retention of new word-object mappings. If this was the case we expect incorrect selections to be easily rectified through feedback. Previous work suggested this to be the case in toddlers at typical likelihood (TL) but not in those at elevated likelihood (EL) for autism spectrum disorder (ASD) (Bedford et al., ). Yet group differences in lexical knowledge may have confounded these findings. Here, TL (N = 29) and EL toddlers (N = 75) chose one of two unfamiliar objects as a referent for a new word. Both groups retained the word-referent mapping above chance when their choices were immediately reinforced but were at chance after corrective feedback. The same pattern of results was obtained when children observed another experimenter make the initial referent choice. Thus, children's referent choices lay memory traces that compete with subsequent correction; these strong word-object associations are not a result of children actively choosing potential referents for new words

Do pre-schoolers with high touchscreen use show executive function differences?

The recent increase in children's use of digital media, both TV and touchscreen devices (e.g., tablets and smartphones), has been associated with developmental differences in Executive Functions (EF). It has been hypothesised that early exposure to attention-commanding and contingent stimulation provided by touchscreens may increase reliance on bottom-up perceptual processes and limit the opportunity for practice of voluntary (i.e., top-down) attention leading to differences in EF. This study tests the concurrent and longitudinal associations between touchscreen use (high use, HU ≥ 15 min/day; low use, LU < 15 min/day), and two components of EF (working-memory/cognitive-flexibility, and impulse/self-control), building explicitly on recent developmental models that point to a bidimensional structure of EF during toddlerhood and pre-school years. A longitudinal sample of 46 3.5-year-olds (23 girls) was tested on a battery of lab-based measures and matched at 12 months on a range of background variables including temperament. Touchscreen HU showed significantly reduced performance in lab-based Working Memory/Cognitive Flexibility, although this became non-significant when controlling for background TV. Impulse/Self-control was not significantly associated with touchscreen use but was negatively associated with non-child-directed television. Our results provide partial support for the hypothesis that using touchscreen devices might reduce capacity for top-down behaviour control, and indicate that broader media environment may be implicated in early executive function development. However, it may also be the case that individuals who are predisposed towards exogenous stimulation are more drawn to screen use. Future studies are needed to replicate findings, demonstrate causality, and investigate bidirectionality

Infant regulatory function acts as a protective factor for later traits of autism spectrum disorder and attention deficit/hyperactivity disorder but not callous unemotional traits.

BACKGROUND: Reduced executive functions (EF) are commonly associated with developmental conditions (e.g., autism spectrum disorder, ASD; attention deficit/hyperactivity disorder, ADHD), although EF seems to be typical in children with callous unemotional (CU) traits. Regulatory function (RF) is a proposed infant precursor that maps on onto factors driving later EF. Here, we first test whether RF is specifically and negatively associated with ASD and ADHD traits, but not CU traits. Second, we test whether RF can act as a protective factor, by moderating the association between infant markers and subsequent ASD and ADHD traits. METHODS: Participants were 79 infants at high (N = 42) and low (N = 37) familial risk for ASD. Data come from the 14-month infant visit (Autism Observational Scale for Infants; AOSI; activity level and RF from the Infant Behavior Questionnaire; IBQ) and the 7-year visit (ASD traits: Social Responsiveness Scale, SRS; ADHD traits: Conners 3, CU traits: Inventory of Callous Unemotional Traits). RESULTS: Infant RF was negatively associated with later traits of ASD (B = - 0.5, p = 0.01) and ADHD inattention (B = - 0.24, p = 0.02) but not hyperactivity (B = - 0.25, p = 0.10) or CU traits (B = 0.02, p = 0.86). RF moderated the association between infant AOSI score and ASD traits, with a significant effect in those with low RF (B = 0.10, p = 0.006), not high RF (B = 0.01, p = 0.78). Similarly, for ADHD, infant activity level was associated with later ADHD inattention in those with low (B = 0.17, p = 0.04) but not high RF (B = 0.07, p = 0.48). For ADHD hyperactivity symptoms, activity level was predictive at both high and low levels of RF. CONCLUSIONS: Strong RF may allow children to compensate for other atypicalities, thus attenuating the association between infant markers and later disorder traits. Whilst infant RF was associated with both ASD and ADHD inattention traits, there was no association with ADHD hyperactivity or CU traits. This suggests that any protective effect may not be universal and emphasises the need for a better understanding of the underlying moderating mechanisms