White matter development and language abilities during infancy in autism spectrum disorder.

White matter (WM) fiber tract differences are present in autism spectrum disorder (ASD) and could be important markers of behavior. One of the earliest phenotypic differences in ASD are language atypicalities. Although language has been linked to WM in typical development, no work has evaluated this association in early ASD. Participants came from the Infant Brain Imaging Study and included 321 infant siblings of children with ASD at high likelihood (HL) for developing ASD; 70 HL infants were later diagnosed with ASD (HL-ASD), and 251 HL infants were not diagnosed with ASD (HL-Neg). A control sample of 140 low likelihood infants not diagnosed with ASD (LL-Neg) were also included. Infants contributed expressive language, receptive language, and diffusion tensor imaging data at 6-, 12-, and 24 months. Mixed effects regression models were conducted to evaluate associations between WM and language trajectories. Trajectories of microstructural changes in the right arcuate fasciculus were associated with expressive language development. HL-ASD infants demonstrated a different developmental pattern compared to the HL-Neg and LL-Neg groups, wherein the HL-ASD group exhibited a positive association between WM fractional anisotropy and language whereas HL-Neg and LL-Neg groups showed weak or no association. No other fiber tracts demonstrated significant associations with language. In conclusion, results indicated arcuate fasciculus WM is linked to language in early toddlerhood for autistic toddlers, with the strongest associations emerging around 24 months. To our knowledge, this is the first study to evaluate associations between language and WM development during the pre-symptomatic period in ASD.

Atypical functional connectivity between the amygdala and visual, salience regions in infants with genetic liability for autism.

The amygdala undergoes a period of overgrowth in the first year of life, resulting in enlarged volume by 12 months in infants later diagnosed with ASD. The overgrowth of the amygdala may have functional consequences during infancy. We investigated whether amygdala connectivity differs in 12-month-olds at high likelihood (HL) for ASD (defined by having an older sibling with autism), compared to those at low likelihood (LL). We examined seed-based connectivity of left and right amygdalae, hypothesizing that the HL and LL groups would differ in amygdala connectivity, especially with the visual cortex, based on our prior reports demonstrating that components of visual circuitry develop atypically and are linked to genetic liability for autism. We found that HL infants exhibited weaker connectivity between the right amygdala and the left visual cortex, as well as between the left amygdala and the right anterior cingulate, with evidence that these patterns occur in distinct subgroups of the HL sample. Amygdala connectivity strength with the visual cortex was related to motor and communication abilities among HL infants. Findings indicate that aberrant functional connectivity between the amygdala and visual regions is apparent in infants with genetic liability for ASD and may have implications for early differences in adaptive behaviors.

Examining variability in Naturalistic Developmental Behavioral Intervention strategy use in caregivers of children with autism spectrum disorders.

BACKGROUND: Naturalistic Developmental Behavioral Interventions (NDBIs) for young children with autism spectrum disorder commonly involve caregiver-mediated approaches. However, to date, there is limited research on how caregivers' skills change, and, in turn, impact child outcomes. METHODS: We evaluated the NDBI strategy use of 191 caregivers prior to participation in NDBIs (or control groups) across multiple randomized controlled trials, using the Measure of NDBI Strategy Implementation, Caregiver Change (MONSI-CC). Clustering analyses were used to examine caregiver variability in NDBI strategy use at intervention entry. Generalized Linear Mixed Models were used to examine changes in caregiver strategy use over the course of intervention and its impact on changes in children's social communication. RESULTS: Using clustering analysis, we found that caregivers' baseline skills fit four profiles: limited, emerging, variable, and consistent/high, with few demographic factors distinguishing these groups. Caregivers starting with limited or emerging skills improved in their strategy use with intervention. Caregivers starting with more skills (consistent/high or variable) maintained higher skills over intervention. Children of caregivers in these groups who received target NDBIs improved in their social communication skills. CONCLUSIONS: Results suggested that caregiver skills improve through participation in NDBIs and may directly contribute to their children's outcomes, although more research on mediating factors is needed. Individualized approaches for caregivers and their children starting with differing skill profiles at intervention entry may be warranted.

Comparing narrative storytelling ability in individuals with autism and fetal alcohol spectrum disorders.

BACKGROUND: Narrative discourse, or storytelling, is used in daily conversation and requires higher-level language and social communication skills that are not always captured by standardised assessments of language. Many autistic individuals and individuals with fetal alcohol spectrum disorders (FASD) have difficulties with both social communication and language skills, and narrative discourse analysis offers an ecologically relevant approach to assessing those challenges. AIMS: This study investigated narrative discourse in individuals with autism and FASD, as well as an age- and sex-matched comparison group. METHODS AND PROCEDURES: Narratives from 45 adolescents and adults, 11 with autism, 11 with FASD and 23 age- and sex-matched comparison participants were elicited using a wordless storybook. They were then transcribed orthographically, formatted to the Systematic Analyses of Language Transcript (SALT) convention and scored based on the SALT Narrative Scoring Scheme (NSS), a standardised language analysis protocol. In addition to the NSS total score, which assesses the overall structure and cohesion of the narratives produced, local and global measures of language ability were also employed. The local language measures included the number of mental state and temporal relation terms produced, while the global language measures included mean length of utterance, total different words, total words, total utterances, rate of speech, the number of mazes (e.g., repetitions, 'um', 'uh' or self-corrections) per total word and the NSS total score. OUTCOMES AND RESULTS: Using the SALT Language Sample Analysis tool, our results revealed that on global language measures, group differences were found on rate of speech, number of mazes per total words and the description of conflict/resolution in the narratives produced. The autism group produced significantly more mazes per total word and scored higher on the NSS conflict/resolution category score compared to the FASD and comparison groups. Both the autism and FASD groups spoke at a lower rate than the comparison group. On local language measures of narrative production, all groups were comparable, on average. CONCLUSIONS AND IMPLICATIONS: While many aspects of narrative discourse in the autism and FASD groups were similar to each other and to the comparison group, we observed group differences on global measures of narrative production and significant individual variability within groups, suggesting that narrative abilities considered at an individual level may provide important clinical information for intervention planning. Future research should also consider additional variables that influence narrative discourse, such as motivation, distractibility or decision-making of individual participants. WHAT THIS PAPER ADDS: What is already known on the subject Narrative discourse, or storytelling, is used in daily conversational interactions and reveals higher-level language skills that may not be well captured by standardised assessments of language. Many autistic individuals and individuals with fetal alcohol spectrum disorders (FASD) show difficulty with pragmatic and expressive language skills. What this paper adds to existing knowledge We found that many aspects of the narratives produced by the adolescents/young adults in the autism and FASD groups were comparable to each other and to the neurotypical group. However, the groups differed on three global measures of narrative production: rate of speech, number of mazes per total words and the description of conflict/resolution in the narratives produced. Also, significant variability was observed within groups, suggesting that narrative abilities should be considered at an individual level as opposed to their clinical groups. What are the potential or actual clinical implications of this work? This study showed that narrative discourse is an appropriate task that can be added to routine clinical assessments of language abilities in autistic adolescents/young adults as well as those with FASD or typical development and has the potential to reveal higher-level, real-world language skills. An important clinical implication of this study is that narrative language abilities should be considered at an individual level and individual-tailored interventions based on ability level due to the variability observed across individuals.

Quantifying latent social motivation and its associations with joint attention and language in infants at high and low likelihood for autism spectrum disorder.

Social motivation-the psychobiological predisposition for social orienting, seeking social contact, and maintaining social interaction-manifests in early infancy and is hypothesized to be foundational for social communication development in typical and atypical populations. However, the lack of infant social-motivation measures has hindered delineation of associations between infant social motivation, other early-arising social abilities such as joint attention, and language outcomes. To investigate how infant social motivation contributes to joint attention and language, this study utilizes a mixed longitudinal sample of 741 infants at high (HL = 515) and low (LL = 226) likelihood for ASD. Using moderated nonlinear factor analysis (MNLFA), we incorporated items from parent-report measures to establish a novel latent factor model of infant social motivation that exhibits measurement invariance by age, sex, and familial ASD likelihood. We then examined developmental associations between 6- and 12-month social motivation, joint attention at 12-15 months, and language at 24 months of age. On average, greater social-motivation growth from 6-12 months was associated with greater initiating joint attention (IJA) and trend-level increases in sophistication of responding to joint attention (RJA). IJA and RJA were both positively associated with 24-month language abilities. There were no additional associations between social motivation and future language in our path model. These findings substantiate a novel, theoretically driven approach to modeling social motivation and suggest a developmental cascade through which social motivation impacts other foundational skills. These findings have implications for the timing and nature of intervention targets to support social communication development in infancy. HIGHLIGHTS: We describe a novel, theoretically based model of infant social motivation wherein multiple parent-reported indicators contribute to a unitary latent social-motivation factor. Analyses revealed social-motivation factor scores exhibited measurement invariance for a longitudinal sample of infants at high and low familial ASD likelihood. Social-motivation growth from ages 6-12 months is associated with better 12-15-month joint attention abilities, which in turn are associated with greater 24-month language skills. Findings inform timing and targets of potential interventions to support healthy social communication in the first year of life.

Early brain development in infants at high risk for autism spectrum disorder.

Brain enlargement has been observed in children with autism spectrum disorder (ASD), but the timing of this phenomenon, and the relationship between ASD and the appearance of behavioural symptoms, are unknown. Retrospective head circumference and longitudinal brain volume studies of two-year olds followed up at four years of age have provided evidence that increased brain volume may emerge early in development. Studies of infants at high familial risk of autism can provide insight into the early development of autism and have shown that characteristic social deficits in ASD emerge during the latter part of the first and in the second year of life. These observations suggest that prospective brain-imaging studies of infants at high familial risk of ASD might identify early postnatal changes in brain volume that occur before an ASD diagnosis. In this prospective neuroimaging study of 106 infants at high familial risk of ASD and 42 low-risk infants, we show that hyperexpansion of the cortical surface area between 6 and 12 months of age precedes brain volume overgrowth observed between 12 and 24 months in 15 high-risk infants who were diagnosed with autism at 24 months. Brain volume overgrowth was linked to the emergence and severity of autistic social deficits. A deep-learning algorithm that primarily uses surface area information from magnetic resonance imaging of the brain of 6-12-month-old individuals predicted the diagnosis of autism in individual high-risk children at 24 months (with a positive predictive value of 81% and a sensitivity of 88%). These findings demonstrate that early brain changes occur during the period in which autistic behaviours are first emerging.

Examining the factor structure and discriminative utility of the Infant Behavior Questionnaire-Revised in infant siblings of autistic children.

Using the Infant Behavior Questionnaire-Revised in a longitudinal sample of infant siblings of autistic children (HR; n = 427, 171 female, 83.4% White) and a comparison group of low-risk controls (LR, n = 200, 86 female, 81.5% White), collected between 2007 and 2017, this study identified an invariant factor structure of temperament traits across groups at 6 and 12 months. Second, after partitioning the groups by familial risk and diagnostic outcome at 24 months, results reveal an endophenotypic pattern of Positive Emotionality at both 6 and 12 months, (HR-autism spectrum disorder [ASD] < HR-no-ASD < LR). Third, increased 'Duration of Orienting' at 12 months was associated with lower scores on the 24-month developmental outcomes in HR infants. These findings may augment efforts for early identification of ASD.

Infant vocalizing and phenotypic outcomes in autism: Evidence from the first 2 years.

Infant vocalizations are early-emerging communicative markers shown to be atypical in autism spectrum disorder (ASD), but few longitudinal, prospective studies exist. In this study, 23,850 infant vocalizations from infants at low (LR)- and high (HR)-risk for ASD (HR-ASD = 23, female = 3; HR-Neg = 35, female = 13; LR = 32, female = 10; 80% White; collected from 2007 to 2017 near Philadelphia) were analyzed at 6, 12, and 24 months. At 12 months, HR-ASD infants produced fewer vocalizations than HR-Neg infants. From 6 to 24 months, HR-Neg infants demonstrated steeper vocalization growth compared to HR-ASD and LR infants. Finally, among HR infants, vocalizing at 12 months was associated with language, social phenotype, and diagnosis at age 2. Infant vocalizing is an objective behavioral marker that could facilitate earlier detection of ASD.

Social motivation in infancy is associated with familial recurrence of ASD.

Pre-diagnostic deficits in social motivation are hypothesized to contribute to autism spectrum disorder (ASD), a heritable neurodevelopmental condition. We evaluated psychometric properties of a social motivation index (SMI) using parent-report item-level data from 597 participants in a prospective cohort of infant siblings at high and low familial risk for ASD. We tested whether lower SMI scores at 6, 12, and 24 months were associated with a 24-month ASD diagnosis and whether social motivation's course differed relative to familial ASD liability. The SMI displayed good internal consistency and temporal stability. Children diagnosed with ASD displayed lower mean SMI T-scores at all ages and a decrease in mean T-scores across age. Lower group-level 6-month scores corresponded with higher familial ASD liability. Among high-risk infants, strong decline in SMI T-scores was associated with 10-fold odds of diagnosis. Infant social motivation is quantifiable by parental report, differentiates children with versus without later ASD by age 6 months, and tracks with familial ASD liability, consistent with a diagnostic and susceptibility marker of ASD. Early decrements and decline in social motivation indicate increased likelihood of ASD, highlighting social motivation's importance to risk assessment and clarification of the ontogeny of ASD.

Diagnostic shifts in autism spectrum disorder can be linked to the fuzzy nature of the diagnostic boundary: a data-driven approach.

BACKGROUND: Diagnostic shifts at early ages may provide invaluable insights into the nature of separation between autism spectrum disorder (ASD) and typical development. Recent conceptualizations of ASD suggest the condition is only fuzzily separated from non-ASD, with intermediate cases between the two. These intermediate cases may shift along a transition region over time, leading to apparent instability of diagnosis. METHODS: We used a cohort of children with high ASD risk, by virtue of having an older sibling with ASD, assessed at 24 months (N = 212) and 36 months (N = 191). We applied machine learning to empirically characterize the classification boundary between ASD and non-ASD, using variables quantifying developmental and adaptive skills. We computed the distance of children to the classification boundary. RESULTS: Children who switched diagnostic labels from 24 to 36 months, in both directions, (dynamic group) had intermediate phenotypic profiles. They were closer to the classification boundary compared to children who had stable diagnoses, both at 24 months (Cohen's d = .52) and at 36 months (d = .75). The magnitude of change in distance between the two time points was similar for the dynamic and stable groups (Cohen's d = .06), and diagnostic shifts were not associated with a large change. At the individual level, a few children in the dynamic group showed substantial change. CONCLUSIONS: Our results suggested that a diagnostic shift was largely due to a slight movement within a transition region between ASD and non-ASD. This fact highlights the need for more vigilant surveillance and intervention strategies. Young children with intermediate phenotypes may have an increased susceptibility to gain or lose their diagnosis at later ages, calling attention to the inherently dynamic nature of early ASD diagnoses.

Sex differences associated with corpus callosum development in human infants: A longitudinal multimodal imaging study.

The corpus callosum (CC) is the largest connective pathway in the human brain, linking cerebral hemispheres. There is longstanding debate in the scientific literature whether sex differences are evident in this structure, with many studies indicating the structure is larger in females. However, there are few data pertaining to this issue in infancy, during which time the most rapid developmental changes to the CC occur. In this study, we examined longitudinal brain imaging data collected from 104 infants at ages 6, 12, and 24 months. We identified sex differences in brain-size adjusted CC area and thickness characterized by a steeper rate of growth in males versus females from ages 6-24 months. In contrast to studies of older children and adults, CC size was larger for male compared to female infants. Based on diffusion tensor imaging data, we found that CC thickness is significantly associated with underlying microstructural organization. However, we observed no sex differences in the association between microstructure and thickness, suggesting that the role of factors such as axon density and/or myelination in determining CC size is generally equivalent between sexes. Finally, we found that CC length was negatively associated with nonverbal ability among females.

"If He Has it, We Know What to Do": Parent Perspectives on Familial Risk for Autism Spectrum Disorder.

OBJECTIVE: Predictive testing for familial disorders can guide healthcare and reproductive decisions. Familial disorders with onset in childhood (e.g., autism spectrum disorder [ASD]) are promising targets for presymptomatic prediction; however, little is known about parent perceptions of risk to their children in the presymptomatic period. The current study examined risk perceptions in parents of infants at high familial risk for ASD enrolled in a longitudinal study of brain and behavior development. METHODS: Semistructured interviews were conducted with 37 parents of high-risk infants during the presymptomatic window (3-15 months) that precedes an ASD diagnosis. Infants were identified as high familial risk due to having an older sibling with ASD. Parent interview responses were coded and interpreted to distill emerging themes. RESULTS: The majority of parents were aware of the increased risk of ASD for their infants, and risk perceptions were influenced by comparisons to their older child with ASD. Parents reported a variety of negative emotions in response to perceived risk, including worry, fear, and sadness, and described impacts of perceived risk on their behavior: increased vigilance to emerging symptoms, altered reproductive and healthcare decisions, and seeking ongoing assessment through research. CONCLUSIONS: Parents of children at high familial risk for childhood-onset disorders like ASD face a period of challenging uncertainty during early development. In anticipation of a future in which presymptomatic testing for ASD is made available, it is important to understand how parents react to and cope with the elevated-but still highly uncertain-risk conveyed by family history.

The Developmental Sequence and Relations Between Gesture and Spoken Language in Toddlers With Autism Spectrum Disorder.

In typical development, gestures precede and predict language development. This study examines the developmental sequence of expressive communication and relations between specific gestural and language milestones in toddlers with autism spectrum disorder (ASD), who demonstrate marked difficulty with gesture production and language. Communication skills across five stages (gestures, word approximations, first words, gesture-word combinations, and two-word combinations) were assessed monthly by blind raters for toddlers with ASD participating in an randomized control trial of parent-mediated treatment (N = 42, 12-30 months). Findings revealed that toddlers acquired skills following a reliable (vs. idiosyncratic) sequence and the majority of toddlers combined gestures with words before combining words in speech, but in contrast to the pattern observed in typical development, a significant subset acquired pointing after first words.

A longitudinal study of parent-reported sensory responsiveness in toddlers at-risk for autism.

BACKGROUND: Atypical sensory responsivity and sensory interests are now included in the DSM 5 diagnostic criteria for autism spectrum disorder (ASD) under the broad domain of restricted and repetitive behavior (RRB). However, relatively little is known about the emergence of sensory-related features and their relation to conventionally defined RRB in the first years of life. METHODS: Prospective, longitudinal parent-report data using the Sensory Experiences Questionnaire (SEQ) were collected for 331 high-risk toddlers (74 of whom met diagnostic criteria for ASD at age 2) and 135 low-risk controls. Longitudinal profiles for SEQ scores were compared between groups across ages 12-24 months. Associations between SEQ measures and measures of RRB subtypes (based on the Repetitive Behavior Scale, Revised) were also examined. RESULTS: Longitudinal profiles for all SEQ scores significantly differed between groups. SEQ scores were elevated for the ASD group from age 12 months, with differences becoming more pronounced across the 12-24 month interval. At both 12 and 24 months, most measures derived from the SEQ were significantly associated with all subtypes of RRB. CONCLUSIONS: These findings suggest that differences in sensory responsivity may be evident in high-risk infants later diagnosed with ASD in early toddlerhood, and that the magnitude of these differences increases over the second year of life. The high degree of association between SEQ scores and RRB supports the conceptual alignment of these features but also raises questions as to explanatory mechanisms.

Walking, Gross Motor Development, and Brain Functional Connectivity in Infants and Toddlers.

Infant gross motor development is vital to adaptive function and predictive of both cognitive outcomes and neurodevelopmental disorders. However, little is known about neural systems underlying the emergence of walking and general gross motor abilities. Using resting state fcMRI, we identified functional brain networks associated with walking and gross motor scores in a mixed cross-sectional and longitudinal cohort of infants at high and low risk for autism spectrum disorder, who represent a dimensionally distributed range of motor function. At age 12 months, functional connectivity of motor and default mode networks was correlated with walking, whereas dorsal attention and posterior cingulo-opercular networks were implicated at age 24 months. Analyses of general gross motor function also revealed involvement of motor and default mode networks at 12 and 24 months, with dorsal attention, cingulo-opercular, frontoparietal, and subcortical networks additionally implicated at 24 months. These findings suggest that changes in network-level brain-behavior relationships underlie the emergence and consolidation of walking and gross motor abilities in the toddler period. This initial description of network substrates of early gross motor development may inform hypotheses regarding neural systems contributing to typical and atypical motor outcomes, as well as neurodevelopmental disorders associated with motor dysfunction.

Joint Attention and Brain Functional Connectivity in Infants and Toddlers.

Initiating joint attention (IJA), the behavioral instigation of coordinated focus of 2 people on an object, emerges over the first 2 years of life and supports social-communicative functioning related to the healthy development of aspects of language, empathy, and theory of mind. Deficits in IJA provide strong early indicators for autism spectrum disorder, and therapies targeting joint attention have shown tremendous promise. However, the brain systems underlying IJA in early childhood are poorly understood, due in part to significant methodological challenges in imaging localized brain function that supports social behaviors during the first 2 years of life. Herein, we show that the functional organization of the brain is intimately related to the emergence of IJA using functional connectivity magnetic resonance imaging and dimensional behavioral assessments in a large semilongitudinal cohort of infants and toddlers. In particular, though functional connections spanning the brain are involved in IJA, the strongest brain-behavior associations cluster within connections between a small subset of functional brain networks; namely between the visual network and dorsal attention network and between the visual network and posterior cingulate aspects of the default mode network. These observations mark the earliest known description of how functional brain systems underlie a burgeoning fundamental social behavior, may help improve the design of targeted therapies for neurodevelopmental disorders, and, more generally, elucidate physiological mechanisms essential to healthy social behavior development.

Naturalistic Language Recordings Reveal "Hypervocal" Infants at High Familial Risk for Autism.

Children's early language environments are related to later development. Little is known about this association in siblings of children with autism spectrum disorder (ASD), who often experience language delays or have ASD. Fifty-nine 9-month-old infants at high or low familial risk for ASD contributed full-day in-home language recordings. High-risk infants produced more vocalizations than low-risk peers; conversational turns and adult words did not differ by group. Vocalization differences were driven by a subgroup of "hypervocal" infants. Despite more vocalizations overall, these infants engaged in less social babbling during a standardized clinic assessment, and they experienced fewer conversational turns relative to their rate of vocalizations. Two ways in which these individual and environmental differences may relate to subsequent development are discussed.

Beyond Social Skills: Supporting Peer Relationships and Friendships for School-Aged Children with Autism Spectrum Disorder.

Social impairments are the sine qua non of autism spectrum disorder (ASD). However, children with ASD are capable of forming reciprocal friendships and many people with ASD have a strong desire for friends. Developing and maintaining friendships is associated with many important outcomes, including improved quality of life, mental health, and academic achievement. Children with ASD often attend groups to improve social skills, but strategies for building and maintaining friendships are not consistently addressed or measured following intervention. In this article, our objective is to build an understanding of peer relationships and friendships in school-aged children with ASD and how to best support them. In this article, we describe characteristics of peer relationships and friendships for children with ASD. We discuss current research findings on intervention to improve social skills, peer relationships, and friendships in school-aged children with ASD. Finally, we give suggestions for clinical practice and future research.

Splenium development and early spoken language in human infants.

The association between developmental trajectories of language-related white matter fiber pathways from 6 to 24 months of age and individual differences in language production at 24 months of age was investigated. The splenium of the corpus callosum, a fiber pathway projecting through the posterior hub of the default mode network to occipital visual areas, was examined as well as pathways implicated in language function in the mature brain, including the arcuate fasciculi, uncinate fasciculi, and inferior longitudinal fasciculi. The hypothesis that the development of neural circuitry supporting domain-general orienting skills would relate to later language performance was tested in a large sample of typically developing infants. The present study included 77 infants with diffusion weighted MRI scans at 6, 12 and 24 months and language assessment at 24 months. The rate of change in splenium development varied significantly as a function of language production, such that children with greater change in fractional anisotropy (FA) from 6 to 24 months produced more words at 24 months. Contrary to findings from older children and adults, significant associations between language production and FA in the arcuate, uncinate, or left inferior longitudinal fasciculi were not observed. The current study highlights the importance of tracing brain development trajectories from infancy to fully elucidate emerging brain-behavior associations while also emphasizing the role of the splenium as a key node in the structural network that supports the acquisition of spoken language.

Altered corpus callosum morphology associated with autism over the first 2 years of life.

Numerous brain imaging studies indicate that the corpus callosum is smaller in older children and adults with autism spectrum disorder. However, there are no published studies examining the morphological development of this connective pathway in infants at-risk for the disorder. Magnetic resonance imaging data were collected from 270 infants at high familial risk for autism spectrum disorder and 108 low-risk controls at 6, 12 and 24 months of age, with 83% of infants contributing two or more data points. Fifty-seven children met criteria for ASD based on clinical-best estimate diagnosis at age 2 years. Corpora callosa were measured for area, length and thickness by automated segmentation. We found significantly increased corpus callosum area and thickness in children with autism spectrum disorder starting at 6 months of age. These differences were particularly robust in the anterior corpus callosum at the 6 and 12 month time points. Regression analysis indicated that radial diffusivity in this region, measured by diffusion tensor imaging, inversely predicted thickness. Measures of area and thickness in the first year of life were correlated with repetitive behaviours at age 2 years. In contrast to work from older children and adults, our findings suggest that the corpus callosum may be larger in infants who go on to develop autism spectrum disorder. This result was apparent with or without adjustment for total brain volume. Although we did not see a significant interaction between group and age, cross-sectional data indicated that area and thickness differences diminish by age 2 years. Regression data incorporating diffusion tensor imaging suggest that microstructural properties of callosal white matter, which includes myelination and axon composition, may explain group differences in morphology.