The national priority to advance early detection and intervention for children with autism spectrum disorder (ASD) has not reduced the late age of ASD diagnosis in the US over several consecutive Centers for Disease Control and Prevention (CDC) surveillance cohorts, with traditionally under-served populations accessing diagnosis later still. In this review, we explore a potential perceptual barrier to this enterprise which views ASD in terms that are contradicted by current science, and which may have its origins in the current definition of the condition and in its historical associations. To address this perceptual barrier, we propose a re-definition of ASD in early brain development terms, with a view to revisit the world of opportunities afforded by current science to optimize children's outcomes despite the risks that they are born with. This view is presented here to counter outdated notions that potentially devastating disability is determined the moment a child is born, and that these burdens are inevitable, with opportunities for improvement being constrained to only alleviation of symptoms or limited improvements in adaptive skills. The impetus for this piece is the concern that such views of complex neurodevelopmental conditions, such as ASD, can become self-fulfilling science and policy, in ways that are diametrically opposed to what we currently know, and are learning every day, of how genetic risk becomes, or not, instantiated as lifetime disabilities.

Impairment in reciprocal social behavior (RSB), an essential component of early social competence, clinically defines autism spectrum disorder (ASD). However, the behavioral and genetic architecture of RSB in toddlerhood, when ASD first emerges, has not been fully characterized. We analyzed data from a quantitative video-referenced rating of RSB (vrRSB) in two toddler samples: a community-based volunteer research registry (n = 1,563) and an ethnically diverse, longitudinal twin sample ascertained from two state birth registries (n = 714). Variation in RSB was continuously distributed, temporally stable, significantly associated with ASD risk at age 18 months, and only modestly explained by sociodemographic and medical factors (r2 = 9.4%). Five latent RSB factors were identified and corresponded to aspects of social communication or restricted repetitive behaviors, the two core ASD symptom domains. Quantitative genetic analyses indicated substantial heritability for all factors at age 24 months (h2 ≥ .61). Genetic influences strongly overlapped across all factors, with a social motivation factor showing evidence of newly-emerging genetic influences between the ages of 18 and 24 months. RSB constitutes a heritable, trait-like competency whose factorial and genetic structure is generalized across diverse populations, demonstrating its role as an early, enduring dimension of inherited variation in human social behavior. Substantially overlapping RSB domains, measurable when core ASD features arise and consolidate, may serve as markers of specific pathways to autism and anchors to inform determinants of autism's heterogeneity.

Understanding differences in social-emotional behavior can help identify atypical development. This study examined the differences in social-emotional development in children at increased risk of an autism spectrum disorder (ASD) diagnosis (infant siblings of children diagnosed with the disorder). Parents completed the Brief Infant-Toddler Social-Emotional Assessment (BITSEA) to determine its ability to flag children with later-diagnosed ASD in a high-risk (HR) sibling population. Parents of HR (n = 311) and low-risk (LR; no family history of ASD; n = 127) children completed the BITSEA when their children were 18 months old and all children underwent a diagnostic assessment for ASD at age 3 years. All six subscales of the BITSEA (Problems, Competence, ASD Problems, ASD Competence, Total ASD Score, and Red Flags) distinguished between those in the HR group who were diagnosed with ASD (n = 84) compared to non-ASD-diagnosed children (both HR-N and LR). One subscale (BITSEA Competence) differentiated between the HR children not diagnosed with ASD and the LR group. The results suggest that tracking early social-emotional development may have implications for all HR children, as they are at increased risk of ASD but also other developmental or mental health conditions.

Infant siblings of children with autism spectrum disorder (ASD) exhibit greater heterogeneity in behavioral presentation and outcomes relative to infants at low familial risk (LR), yet there is limited understanding of the diverse developmental profiles that characterize these infants. We applied a hierarchical agglomerative cluster analysis approach to parse developmental heterogeneity in 420 toddlers with heightened (HR) and low (LR) familial risk for ASD using measures of four dimensions of development: language, social, play, and restricted and repetitive behaviors (RRB). Results revealed a two-cluster solution. Comparisons of clusters revealed significantly lower language, social, and play performance, and higher levels of restricted and repetitive behaviors in Cluster 1 relative to Cluster 2. In Cluster 1, 25% of children were later diagnosed with ASD compared to 8% in Cluster 2. Comparisons within Cluster 1 between subgroups of toddlers having ASD+ versus ASD− 36-month outcomes revealed significantly lower functioning in the ASD+ subgroup across cognitive, motor, social, language, symbolic, and speech dimensions. Findings suggest profiles of early development associated with resiliency and vulnerability to later ASD diagnosis, with multidimensional developmental lags signaling vulnerability to ASD diagnosis.

Parents play an essential role in supporting child development by providing a safe home, proper nutrition, and rich educational opportunities. In this article we focus on the role of caregiver speech in supporting development of young children with autism spectrum disorder (ASD). We review studies from typically developing children and children with autism showing that rich and responsive caregiver speech supports language development. Autism intervention studies that target caregiver speech are reviewed as are recent scientific advances from studies of typical development. The strengths and weakness of different techniques for collecting language data from caregivers and children are reviewed, and natural language samples are recommended as best practice for language research in autism. We conclude that caregivers play a powerful role in shaping their children's development and encourage researchers to adapt parent-mediated intervention studies to acknowledge individual differences in parents by using a personalized medicine approach.

Atypical communication characteristics (ACCs), such as speech delay, odd pitch, and pragmatic difficulties, are common features of autism spectrum disorder (ASD) as are the symptoms of a wide range of psychiatric disorders. Using a simple retrospective method, this study aimed to better understand the relation and stability of ACCs with a broad range of psychiatric symptoms among large, well-characterized samples of clinic-referred children and adolescents with and without ASD. Youth with ASD had higher rates and a more variable pattern of developmental change in ACCs than the non-ASD diagnostic group. Latent class analysis yielded three ACC stability subgroups within ASD: Stable ACCs, Mostly Current-Only ACCs, and Little Professors. Subgroups exhibited differences in severity of ASD symptomatology, co-occurring psychiatric symptoms, and other correlates. Our findings provide support for the clinical utility of characterizing caregiver-perceived changes in ACCs in identifying children at risk for co-occurring psychopathology and other clinically relevant variables.

This paper reviews and synthesizes key areas of research related to the etiology, development, and maintenance of internalizing symptoms in children, adolescents, and adults with autism spectrum disorder (ASD). In developing an integrated conceptual model, we draw from current conceptual models of internalizing symptoms in ASD and extend the model to include factors related to internalizing within other populations (e.g., children that have experienced early life stress, children with other neurodevelopmental conditions, typically developing children) that have not been systematically examined in ASD. Our review highlights the need for more research to understand the developmental course of internalizing symptoms, potential moderators, and the interplay between early risk and protective factors. Longitudinal studies incorporating multiple methods and both environmental and biological factors will be important in order to elucidate these mechanisms.

Anxiety disorders are common in autism spectrum disorder (ASD) and associated with social–communication impairment and repetitive behavior symptoms. The neurobiology of anxiety in ASD is unknown, but amygdala dysfunction has been implicated in both ASD and anxiety disorders. Using resting-state functional magnetic resonance imaging, we compared amygdala–prefrontal and amygdala–striatal connections across three demographically matched groups studied in the Autism Brain Imaging Data Exchange (ABIDE): ASD with a comorbid anxiety disorder (N = 25; ASD + Anxiety), ASD without a comorbid disorder (N = 68; ASD-NoAnx), and typically developing controls (N = 139; TD). Relative to ASD-NoAnx and TD controls, ASD + Anxiety individuals had decreased connectivity between the amygdala and dorsal/rostral anterior cingulate cortex (dACC/rACC). The functional connectivity of these connections was not affected in ASD-NoAnx, and amygdala connectivity with ventral ACC/medial prefrontal cortex (mPFC) circuits was not different in ASD + Anxiety or ASD-NoAnx relative to TD. Decreased amygdala–dorsomedial prefrontal cortex (dmPFC)/rACC connectivity was associated with more severe social impairment in ASD + Anxiety; amygdala–striatal connectivity was associated with restricted, repetitive behavior (RRB) symptom severity in ASD-NoAnx individuals. These findings suggest comorbid anxiety in ASD is associated with disrupted emotion-monitoring processes supported by amygdala–dACC/mPFC pathways, whereas emotion regulation systems involving amygdala–ventromedial prefrontal cortex (vmPFC) are relatively spared. Our results highlight the importance of accounting for comorbid anxiety for parsing ASD neurobiological heterogeneity.

Given high rates of co-occurring conditions in youth and adults with autism spectrum disorder (ASD), it is critical to examine the developmental trajectories of these symptoms of psychopathology. Using data from a cohort of participants (n = 194), most of whom were first assessed for ASD in very early childhood, we investigated the trajectories of co-occurring depressive, anxiety, and attention-deficit hyperactivity disorder (ADHD) symptoms from late childhood to adulthood. Additionally, childhood predictors and adult outcomes associated with these symptom trajectories were examined. Using group-based trajectory modeling, we found two distinct classes of individuals exhibiting each of these co-occurring symptom patterns: one class exhibited fairly low symptoms across time, and one class with elevated symptoms with varied fluctuation across time (ADHD symptoms starting high but decreasing, anxiety symptoms high and stable, and depressive symptoms fluctuating but peaking at clinically significant levels in young adulthood). All high trajectory classes were associated with age 9 adaptive skills; verbal IQ predicted higher anxiety and depressive symptom classes. After accounting for verbal IQ, all high symptom trajectory classes were negative predictors of objective adult outcomes. These findings call for wide-ranging considerations of the needs of individuals across ability levels, autism symptoms, and behavioral and emotional challenges.

Identifying developmental endophenotypes on the pathway between genetics and behavior is critical to uncovering the mechanisms underlying neurodevelopmental conditions. In this proof-of-principle study, we explored whether early disruptions in visual attention are a unique or shared candidate endophenotype of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD). We calculated the duration of the longest look (i.e., peak look) to faces in an array-based eye-tracking task for 335 14-month-old infants with and without first-degree relatives with ASD and/or ADHD. We leveraged parent-report and genotype data available for a proportion of these infants to evaluate the relation of looking behavior to familial (n = 285) and genetic liability (using polygenic scores, n = 185) as well as ASD and ADHD-relevant temperament traits at 2 years of age (shyness and inhibitory control, respectively, n = 272) and ASD and ADHD clinical traits at 6 years of age (n = 94).

Results showed that longer peak looks at the face were associated with elevated polygenic scores for ADHD (β = 0.078, p = .023), but not ASD (β = 0.002, p = .944), and with elevated ADHD traits in mid-childhood (F(1,88) = 6.401, p = .013, $\eta _p^2$=0.068; ASD: F (1,88) = 3.218, p = .076), but not in toddlerhood (ps > 0.2). This pattern of results did not emerge when considering mean peak look duration across face and nonface stimuli. Thus, alterations in attention to faces during spontaneous visual exploration may be more consistent with a developmental endophenotype of ADHD than ASD. Our work shows that dissecting paths to neurodevelopmental conditions requires longitudinal data incorporating polygenic contribution, early neurocognitive function, and clinical phenotypic variation.

Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are believed to share partially overlapping causal mechanisms suggesting that early risk markers may also overlap. Using latent profile analysis (LPA) in a sample of infants enriched for ASD and ADHD, we first examined the number of distinct groups of 3-year-old children, based on ADHD and ASD symptomatology. To investigate early predictors of ASD and ADHD symptom profiles, we next examined differences in trajectories of infant behaviors among the LPA classes spanning general development, negative affect, attention, activity level, impulsivity, and social behavior. Participants included 166 infants at familial risk for ASD (n = 89), ADHD (n = 38), or low-risk for both (n = 39) evaluated at 12, 18, 24, and 36 months of age. A three-class solution was selected reflecting a Typically Developing (TD) class (low symptoms; n = 108), an ADHD class (high ADHD/low ASD symptoms; n = 39), and an ASD class (high ASD/ADHD symptoms; n = 19). Trajectories of infant behaviors were generally suggestive of a gradient pattern of differences, with the greatest impairment within the ASD class followed by the ADHD class. These findings indicate a mixture of overlapping and distinct early markers of preschool ASD- and ADHD-like profiles that can be difficult to disentangle early in life.

Prospective longitudinal studies of idiopathic autism spectrum disorder (ASD) have provided insights into early symptoms and predictors of ASD during infancy, well before ASD can be diagnosed at age 2–3 years. However, research on the emergence of ASD in disorders with a known genetic etiology, contextualized in a developmental framework, is currently lacking. Using a biobehavioral multimethod approach, we (a) determined the rate of ASD in N = 51 preschoolers with fragile X syndrome (FXS) using a clinical best estimate (CBE) procedure with differential diagnoses of comorbid psychiatric disorders and (b) investigated trajectories of ASD symptoms and physiological arousal across infancy as predictors of ASD in preschoolers with FXS. ASD was not diagnosed if intellectual ability or psychiatric disorders better accounted for the symptoms. Our results determined that 60.7% of preschoolers with FXS met the Diagnostic and Statistical Manual of Mental Disorders (fifth edition) (DSM-5) criteria for ASD using the CBE procedure. In addition, 92% of these preschoolers presented with developmental delay and 45.4% also met criteria for psychiatric disorders, either anxiety, ADHD, or both. ASD diagnoses in preschoolers with FXS were predicted by elevated scores on traditional ASD screeners in addition to elevated autonomic arousal and avoidant eye contact from infancy.

Autism spectrum disorder (ASD) is a common neurodevelopmental disorder characterized by deficits in social communication and presence of restricted, repetitive behaviors, and interests. However, individuals with ASD vary significantly in their challenges and abilities in these and other developmental domains. Gene discovery in ASD has accelerated in the past decade, and genetic subtyping has yielded preliminary evidence of utility in parsing phenotypic heterogeneity through genomic subtypes. Recent advances in transcriptomics have provided additional dimensions with which to refine genetic subtyping efforts. In the current study, we investigate phenotypic differences among transcriptional subtypes defined by neurobiological spatiotemporal co-expression patterns. Of the four transcriptional subtypes examined, participants with mutations to genes typically expressed highly in all brain regions prenatally, and those with differential postnatal cerebellar expression relative to other brain regions, showed lower cognitive and adaptive skills, higher severity of social communication deficits, and later acquisition of speech and motor milestones, compared to those with mutations to genes highly expressed during the postnatal period across brain regions. These findings suggest higher-order characterization of genetic subtypes based on neurobiological expression patterns may be a promising approach to parsing phenotypic heterogeneity among those with ASD and related neurodevelopmental disorders.

To understand the complex relationships between autism spectrum disorder (ASD) and other frequently comorbid conditions, a growing number of studies have investigated the emergence of ASD during infancy. This research has suggested that symptoms of ASD and highly related comorbid conditions emerge from complex interactions between neurodevelopmental vulnerabilities and early environments, indicating that developing treatments to prevent ASD is highly challenging. However, it also suggests that attenuating the negative effects of ASD on future development once identified is possible. The present paper builds on this by conceptualizing developmental delays in nonsocial skills as the potential product of altered caregiver–infant interactions following the emergence of ASD during infancy. And, following emerging findings from caregiver–infant dyadic head-mounted eye-tracking (D-ET) research, it also suggests that a multiple pathway model of joint attention can provide mechanistic insights into how ASD alters the ability of caregiver and infant to create a context for infant learning. The potential for this view to inform early intervention is further discussed and illustrated through D-ET data collected prior to and following a brief, parent-mediated intervention for infant ASD. While promising, further research informing how a multiple pathway model of joint attention can inform ASD early intervention is needed.

Cognitive ability, externalizing symptoms, and internalizing symptoms are correlated in children. However, it is not known why they combine in the general child population over time. To address this, we used data on 17,318 children participating in the UK Millennium Cohort Study and followed-up five times between ages 3 and 14 years. We fitted three parallel-process latent growth curve models to identify the parallel unfolding of children's trajectories of internalizing symptoms, externalizing symptoms, and cognitive ability across this period. We also examined the effects of time-invariant (ethnicity, birth weight, maternal education and age at birth, and breastfeeding status) and time-varying covariates (maternal psychological distress and socioeconomic disadvantage) on the growth parameters of the trajectories. The results showed that the intercepts of the trajectories of cognitive ability and, particularly, externalizing symptoms were inversely correlated. Their linear slopes were also inversely correlated, suggesting parallel development. Internalizing symptoms were correlated positively with externalizing symptoms and inversely (and more modestly) with cognitive ability at baseline, but the slope of internalizing symptoms correlated (positively) only with the slope of externalizing symptoms. The covariates predicted 9% to 41% of the variance in the intercepts and slopes of all domains, suggesting they are important common risk factors. Overall, it appears that externalizing symptoms develop in parallel with both cognitive ability and internalizing symptoms from early childhood through to middle adolescence. Children on an increasing trajectory of externalizing symptoms are likely both increasing in internalizing symptoms and decreasing in cognitive skills as well, and are thus an important group to target for intervention.

Although child maltreatment is a major public health concern, which adversely affects psychological and physical development, we know relatively little concerning psychophysiological and personality factors that may modify risk in children exposed to maltreatment. Using a three-wave, short-term prospective design, we examined the influence of individual differences in two disparate psychophysiological measures of risk (i.e., resting frontal brain electrical activity and respiratory sinus arrhythmia) on the trajectories of extraversion and neuroticism in a sample of female adolescents (N = 55; M age = 14.02 years) exposed to child maltreatment. Adolescents exposed to child maltreatment with relatively higher left frontal absolute alpha power (i.e., lower brain activity) at rest exhibited increasing trajectories of extraversion, and adolescents exposed to child maltreatment with relatively lower respiratory sinus arrhythmia at rest displayed increasing trajectories of neuroticism over 1 year. Individual differences in psychophysiological measures indexing resting central and peripheral nervous system activity may therefore differentially influence personality characteristics in adolescent females exposed to child maltreatment.

Social withdrawal and social anxiety are believed to have a bidirectional influence on one another, but it is unknown if their relationship is bidirectional, especially within person, and if peer experiences influence this relationship. We investigated temporal sequencing and the strength of effects between social withdrawal and social anxiety, and the roles of peer victimization and acceptance in the pathways. Participants were 2,772 adolescents from the population-based and clinically referred cohorts of the Tracking Adolescents' Individual Lives Survey. Self- and parent-reported withdrawal, and self-reported social anxiety, peer victimization, and perceived peer acceptance were assessed at 11, 13, and 16 years. Random-intercept cross-lagged panel models were used to investigate within-person associations between these variables. There was no feedback loop between withdrawal and social anxiety. Social withdrawal did not predict social anxiety at any age. Social anxiety at 11 years predicted increased self-reported withdrawal at 13 years. Negative peer experiences predicted increased self- and parent-reported withdrawal at 13 years and increased parent-reported withdrawal at 16 years. In turn, self-reported withdrawal at 13 years predicted negative peer experiences at 16 years. In conclusion, adolescents became more withdrawn when they became more socially anxious or experienced greater peer problems, and increasing withdrawal predicted greater victimization and lower acceptance.

There is an extensive literature describing the detrimental effects of adverse childhood experiences (ACE; e.g., abuse, neglect, and household dysfunction) on physical and mental health. However, few large-scale studies have explored these associations longitudinally in urban minority cohorts or assessed links to broader measures of well-being such as educational attainment, occupation, and crime. Although adversity and resilience have long been of interest in developmental psychology, protective and promotive factors have been understudied in the ACE literature. This paper investigates the psychosocial processes through which ACEs contribute to outcomes, in addition to exploring ways to promote resilience to ACEs in vulnerable populations. Follow-up data were analyzed for 87% of the original 1,539 participants in the Chicago Longitudinal Study (N = 1,341), a prospective investigation of the impact of an Early Childhood Education program and early experiences on life-course well-being. Findings suggest that ACEs impact well-being in low-socioeconomic status participants above and beyond the effects of demographic risk and poverty, and point to possible mechanisms of transmission of ACE effects. Results also identify key areas across the ecological system that may promote resilience to ACEs, and speak to the need to continue to support underserved communities in active ways.

The Young Adolescent Project (YAP) is an ongoing longitudinal study investigating the effects of abuse and neglect on adolescent development. It is a multidisciplinary study guided by a developmental, ecological perspective, and designed to consider the physical, social, and psychological effects of childhood maltreatment through the transition from childhood to adolescence. Four waves of data collection have been completed, ranging from early (Mean age = 10.95) to late adolescence (Mean age = 18.24). Members of the maltreated group (n = 303) were selected from new cases that had been opened by the Department of Child and Family Services, whereas the comparison group (n = 151) were not involved with child welfare but lived in the same neighborhoods as the maltreated group. The study assessed a wide variety of domains including physical development (e.g., height, weight, body mass, pubertal development); physiological reactivity (e.g., cortisol); cognitive abilities; mental health (e.g., symptoms of depression, anxiety, trauma, and aggression); risk behavior (e.g., sexual activity, delinquency, or substance use); social development (e.g., self-esteem, competence, and social support); family environment; and exposure to community violence. Overall, our findings demonstrated the pervasive and persistent adverse effects of child maltreatment both within and across domains, but they also identified maltreated youth with positive functioning. Our hope is that this work will help move us toward identifying targets for intervention to cultivate resilience and positive adaptation after early maltreatment experiences.