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1.  Effects of a Brief Early Start Denver Model (ESDM)–Based Parent Intervention on Toddlers at Risk for Autism Spectrum Disorders: A Randomized Controlled Trial 
This study was carried out to examine the efficacy of a 12-week, low intensity (one-hour-per-week of therapist contact), parent-delivered intervention for toddlers at risk for autism spectrum disorders (ASD) ages 14–24 months and their families.
A randomized controlled trial involving 98 children and families was carried out in three different sites investigating the efficacy of a parent delivery of the Early Start Denver Model (P-ESDM) (which fosters parental use of a child-centered responsive interaction style that embeds many teaching opportunities into play) compared to community treatment as usual. Assessments were completed at baseline and 12 weeks later, immediately after the end of parent coaching sessions.
There was no effect of group assignment on parent-child interaction characteristics or on any child outcomes. Both groups of parents improved interaction skills and both groups of children demonstrated progress. Parents receiving P-ESDM demonstrated significantly stronger working alliances with their therapists than did the community group. Children in the community group received significantly more intervention hours than those in the P-ESDM group. For the group as a whole, both younger child age at the start of intervention, and a greater number of intervention hours, were positively related to degree of improvement in children’s behavior for most variables.
Parent-implemented intervention studies for early ASD have thus far not demonstrated the large effects seen in intensive treatment studies. Evidence that both younger age and more intervention hours positively affect developmental rates has implications for clinical practice, service delivery, and public policy.
PMCID: PMC3487718  PMID: 23021480
Early Start Denver Model (ESDM); early intervention; toddler; parent–child interaction; autism
2.  Autism and Deficits in Attachment Behavior 
Science (New York, N.Y.)  2005;307(5713):1201-1203.
PMCID: PMC4301420  PMID: 15731426
3.  Evidence-Based Comprehensive Treatments for Early Autism 
Early intervention for children with autism is currently a politically and scientifically complex topic. Randomized controlled trials have demonstrated positive effects in both short-term and longer term studies. The evidence suggests that early intervention programs are indeed beneficial for children with autism, often improving developmental functioning and decreasing maladaptive behaviors and symptom severity at the level of group analysis. Whether such changes lead to significant improvements in terms of greater independence and vocational and social functioning in adulthood is also unknown. Given the few randomized controlled treatment trials that have been carried out, the few models that have been tested, and the large differences in interventions that are being published, it is clear that the field is still very early in the process of determining (a) what kinds of interventions are most efficacious in early autism, (b) what variables moderate and mediate treatment gains and improved outcomes following intervention, and (c) the degree of both short-term and long-term improvements that can reasonably be expected. To examine these current research needs, the empirical studies of comprehensive treatments for young children with autism published since 1998 were reviewed. Lovaas's treatment meet Chambless and colleague's (Chambless et al., 1998; Chambless et al., 1996) criteria for “well-established” and no treatment meets the “probably efficacious” criteria, though three treatments meet criteria for “possibly efficacious” (Chambless & Hollon, 1998). Most studies were either Type 2 or 3 in terms of their methodological rigor based on Nathan and Gorman's (2002) criteria. Implications of these findings are also discussed in relation to practice guidelines as well as critical areas of research that have yet to be answered
PMCID: PMC2943764  PMID: 18444052
4.  Deferred and immediate imitation in regressive and early onset autism 
Deferred imitation has long held a privileged position in early cognitive development, considered an early marker of representational thought with links to language development and symbolic processes. Children with autism have difficulties with several abilities generally thought to be related to deferred imitation: immediate imitation, language, and symbolic play. However, few studies have examined deferred imitation in early autism. The present study examined both deferred, spontaneous imitation and immediate, elicited imitation on a set of carefully matched tasks in 36 young children with autism: 16 with early onset autism, 20 with regressive autism and two contrast groups, younger typically developing children (n = 20) and age matched children with significant developmental delays (n = 21). Analyses of co-variance controlling for differences in verbal mental age revealed significant main effects for task, but no main effect of group and no interaction of task by group. Deferred imitation scores were lower than immediate imitation scores for all groups. Imitation performance was related to overall intellectual functioning for all groups, and there were moderate and significant relations between imitation in the immediate elicited condition and in the spontaneous deferred condition for all groups. Finally, there were no differences between onset subgroups in imitation scores, suggesting that the two share a similar phenotype involving both types of imitation.
PMCID: PMC2940420  PMID: 18221343
Autistic disorder; development; developmental delay; mental retardation; pervasive developmental disorder; preschool children; imitation
5.  Imitating actions on objects in early-onset and regressive autism: Effects and implications of task characteristics on performance 
This study was designed to examine the nature of object imitation performance in early autism. We hypothesized that imitation would be relatively preserved when behaviors on objects resulted in salient instrumental effects. We designed tasks in which, in one condition, the motor action resulted in a salient, meaningful effect on an object, whereas in the other condition, the same action resulted in a less salient effect because of differing object characteristics. The motor aspects of the tasks did not vary across conditions. Four participant groups of 2- to 5-year-olds were examined: 17 children with early-onset autism, 24 children with regressive onset autism, 22 children with developmental delays, and 22 children with typical development. Groups were matched on nonverbal skills, and differences in verbal development were examined as a moderator of imitative ability. Results revealed an interaction of group by condition, with the combined autism group failing more tasks than the combined comparison groups, and failing more tasks in the less salient condition than in the more salient condition, as hypothesized. Analyses of autism subgroups revealed these effects were primarily because of the regression onset group. Accuracy of motor performance was examined by analyzing errors. Among children passing imitative acts, there were no group differences and no condition effects in the number, type, or pattern of performance errors. Among children passing the tasks, the group with autism did not demonstrate more emulation errors (imitating the goal but not the means) than other groups. There was no evidence that either motor or attentional aspects of the tasks contributed to the poorer imitative performance of the children with autism.
PMCID: PMC2940421  PMID: 20102648
6.  Myeloid dendritic cells frequencies are increased in children with autism spectrum disorder and associated with amygdala volume and repetitive behaviors 
The pathophysiology of Autism Spectrum Disorder (ASD) is not yet known; however, studies suggest that dysfunction of the immune system affects many children with ASD. Increasing evidence points to dysfunction of the innate immune system including activation of microglia and perivascular macrophages, increases in inflammatory cytokines/chemokines in brain tissue and CSF, and abnormal peripheral monocyte cell function. Dendritic cells are major players in innate immunity and have important functions in the phagocytosis of pathogens or debris, antigen presentation, activation of naïve T cells, induction of tolerance and cytokine/chemokine production. In this study, we assessed circulating frequencies of myeloid dendritic cells (defined as Lin-1−BDCA1+CD11c+ and Lin-1−BDCA3+CD123−) and plasmacytoid dendritic cells (Lin-1− BDCA2+CD123+ or Lin-1−BDCA4+ CD11c−) in 57 children with ASD, and 29 typically developing controls of the same age, all of who were enrolled as part of the Autism Phenome Project (APP). The frequencies of dendritic cells and associations with behavioral assessment and MRI measurements of amygdala volume were compared in the same participants. The frequencies of myeloid dendritic cells were significantly increased in children with ASD compared to typically developing controls (p < 0.03). Elevated frequencies of myeloid dendritic cells were positively associated with abnormal right and left amygdala enlargement, severity of gastrointestinal symptoms and increased repetitive behaviors. The frequencies of plasmacytoid dendritic cells were also associated with amygdala volumes as well as developmental regression in children with ASD. Dendritic cells play key roles in modulating immune responses and differences in frequencies or functions of these cells may result in immune dysfunction in children with ASD. These data further implicate innate immune cells in the complex pathophysiology of ASD.
PMCID: PMC4229011  PMID: 23063420
Autism; dendritic cells; repetitive behaviors; amygdala volume; innate immunity
7.  Behavior and Sleep Problems in Children with a Family History of Autism 
The present study explores behavioral and sleep outcomes in preschool age siblings of children with autism spectrum disorders (ASD). This study focuses on behavior problems that are common in children with ASD, such as emotional reactivity, anxiety, inattention, aggression, and sleep problems. Infant siblings were recruited from families with at least one older child with ASD (high-risk group, n = 104) or families with no history of ASD (low-risk group, n = 76). As part of a longitudinal prospective study, children completed the Mullen Scales of Early Learning and the Autism Diagnostic Observation Schedule, and parents completed the Child Behavior Checklist (CBCL) and the Social Communication Questionnaire at 36 months of age. This study focuses on developmental concerns outside of ASD; therefore, only siblings who did not develop an ASD were included in analyses. Negative binomial regression analyses revealed that children in the high-risk group were more likely to have elevated behavior problems on the CBCL Anxious/Depressed and Aggression subscales. To explore sleep problems as a correlate of these behavior problems, a second series of models was specified. For both groups of children, sleep problems were associated with elevated behavior problems in each of the areas assessed (reactivity, anxiety, somatic complaints, withdrawal, attention, and aggression). These findings support close monitoring of children with a family history of ASD for both behavioral and sleep issues.
PMCID: PMC3947924  PMID: 23436793
autism; siblings; behavior problems; sleep
8.  Beyond Autism: A Baby Siblings Research Consortium Study of High-Risk Children at Three Years of Age 
First-degree relatives of persons with an autism spectrum disorder (ASD) are at increased risk for ASD-related characteristics. As little is known about the early expression of these characteristics, this study characterizes the non-ASD outcomes of 3-year-old high-risk (HR) siblings of children with ASD.
Two groups of children without ASD participated: 507 HR siblings and 324 low-risk (LR) control subjects (no known relatives with ASD). Children were enrolled at a mean age of 8 months, and outcomes were assessed at 3 years. Outcome measures were Autism Diagnostic Observation Schedule (ADOS) calibrated severity scores, and Mullen Verbal and Non-Verbal Developmental Quotients (DQ).
At 3 years, HR siblings without an ASD outcome exhibited higher mean ADOS severity scores and lower verbal and non-verbal DQs than LR controls. HR siblings were over-represented (21% HR versus 7% LR) in latent classes characterized by elevated ADOS severity and/or low to low-average DQs. The remaining HR siblings without ASD outcomes (79%) belonged to classes in which they were not differentially represented with respect to LR siblings.
Having removed a previously identified 18.7% of HR siblings with ASD outcomes from all analyses, HR siblings nevertheless exhibited higher mean levels of ASD severity and lower levels of developmental functioning than LR children. However, the latent class membership of four-fifths of the HR siblings was not significantly different from that of LR control subjects. One-fifth of HR siblings belonged to classes characterized by higher ASD severity and/or lower levels of developmental functioning. This empirically derived characterization of an early-emerging pattern of difficulties in a minority of 3-year-old HR siblings suggests the importance of developmental surveillance and early intervention for these children.
PMCID: PMC3625370  PMID: 23452686
ASD; high-risk siblings; outcome; broad autism phenotype
9.  Levels of Soluble Adhesion Molecules PECAM-1 and P-Selectin are Decreased in Children with Autism Spectrum Disorder 
Biological psychiatry  2012;72(12):1020-1025.
Although the etiopathology of Autism Spectrum Disorder (ASD) is not clear there is increasing evidence that dysfunction in the immune system affects many children with ASD. Findings of immune dysfunction in ASD include increases in inflammatory cytokines, chemokines and microglial activity in brain tissue and CSF, as well as abnormal peripheral immune cell function.
Adhesion molecules, such as platelet endothelial adhesion molecule-1 (PECAM-1), intercellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1), P-Selectin, and L-Selectin, function to facilitate leukocyte transendothelial migration. We assessed concentrations of soluble adhesion molecules, sPECAM-1, sICAM-1, sVCAM-1, sP-Selectin, and sL-Selectin in the plasma of 49 participants with ASD, and 31 typically developing controls of the same age, all of whom were enrolled as part of the Autism Phenome Project (APP). Behavioral assessment, the levels of soluble adhesion molecules, head circumference and MRI measurements of brain volume were compared in the same subjects.
Levels of sPECAM-1 and sP-Selectin were significantly reduced in the ASD group compared to typically developing controls (p < 0.02). Soluble PECAM-1 levels were negatively associated with repetitive behavior and abnormal brain growth in children with ASD (p=0.03).
As adhesion molecules modulate the permeability and signaling at the blood brain barrier as well as leukocyte infiltration into the CNS, current data suggests a role for these molecules in the complex pathophysiology of ASD.
PMCID: PMC3496806  PMID: 22717029
Autism; PECAM-1; P-Selectin; CD31; CD62-P; Adhesion
10.  Early Behavioral Intervention Is Associated With Normalized Brain Activity in Young Children With Autism 
A previously published randomized clinical trial indicated that a developmental behavioral intervention, the Early Start Denver Model (ESDM), resulted in gains in IQ, language, and adaptive behavior of children with autism spectrum disorder. This report describes a secondary outcome measurement from this trial, EEG activity.
Forty-eight 18- to 30-month-old children with autism spectrum disorder were randomized to receive the ESDM or referral to community intervention for 2 years. After the intervention (age 48 to 77 months), EEG activity (event-related potentials and spectral power) was measured during the presentation of faces versus objects. Age-matched typical children were also assessed.
The ESDM group exhibited greater improvements in autism symptoms, IQ, language, and adaptive and social behaviors than the community intervention group. The ESDM group and typical children showed a shorter Nc latency and increased cortical activation (decreased α power and increased θ power) when viewing faces, whereas the community intervention group showed the opposite pattern (shorter latency event-related potential [ERP] and greater cortical activation when viewing objects). Greater cortical activation while viewing faces was associated with improved social behavior.
This was the first trial to demonstrate that early behavioral intervention is associated with normalized patterns of brain activity, which is associated with improvements in social behavior, in young children with autism spectrum disorder.
PMCID: PMC3607427  PMID: 23101741
autism; early behavioral intervention; Early Start Denver Model; event-related potentials; brain activity
11.  Imitation from 12 to 24 months in autism and typical development: A longitudinal Rasch analysis 
Developmental psychology  2011;47(6):1565-1578.
The development of imitation during the second year of life plays an important role in domains of socio-cognitive development such as language and social learning. Deficits in imitation ability in persons with autism spectrum disorder (ASD) have also been repeatedly documented from toddlerhood into adulthood, raising the possibility that early disruptions in imitation contribute to the onset of ASD and the deficits in language and social interaction that define the disorder. This study prospectively examined the development of imitation between 12 and 24 months of age in 154 infants at familial risk for ASD and 78 typically developing infants who were all later assessed at 36 months for ASD or other developmental delays. The study established a developmental measure of imitation ability, and examined group differences over time, using an analytic Rasch measurement model. Results revealed a unidimensional latent construct of imitation and verified a reliable sequence of imitation skills that was invariant over time for all outcome groups. Results also showed that all groups displayed similar significant linear increases in imitation ability between 12 and 24 months and that these increases were related to individual growth in both expressive language and ratings of social engagement, but not fine motor development. The group of children who developed ASD by age 3 years exhibited delayed imitation development compared to the low-risk typical outcome group across all time-points, but were indistinguishable from other high-risk infants who showed other cognitive delays not related to ASD.
PMCID: PMC3712626  PMID: 21910524
imitation; autism; Rasch analysis; early identification; HGLM
12.  Onset patterns in autism: Correspondence between home video and parent report 
The onset of autism is usually conceptualized as occurring in one of two patterns, an early onset and a regressive pattern. This study examined the number and shape of trajectories of symptom onset evident in coded home movies of children with autism and examined their correspondence with parent report of onset.
Four social-communicative behaviors were coded from the home video of children with autism (n = 52) or typical development (n = 23). All home video from 6 through 24 months of age was coded (3199 segments). Latent class modeling was used to characterize trajectories and determine the optimal number needed to describe the coded home video. These trajectories were then compared to parent report of onset patterns, as defined by the Autism Diagnostic Interview-Revised.
A three trajectory model best fit the data from the participants with autism. One trajectory displayed low levels of social-communication across time. A second trajectory displayed high levels of social-communication early in life, followed by a significant decline over time. A third trajectory displayed initial levels of behavior that were similar to the typically developing group, but little progress in social-communication with age. There was poor correspondence between home video-based trajectories and parent report of onset.
More than two onset categories may be needed to describe the ways in which symptoms emerge in children with autism. There is low agreement between parent report and home video, suggesting that methods for improving parent report of early development must be developed.
PMCID: PMC3668453  PMID: 21784299
Autism; regression; onset; parent report
13.  Altered oscillation patterns and connectivity during picture naming in autism 
Similar behavioral deficits are shared between individuals with autism spectrum disorders (ASD) and their first-degree relatives, such as impaired face memory, object recognition, and some language aspects. Functional neuroimaging studies have reported abnormalities in ASD in at least one brain area implicated in those functions, the fusiform gyrus (FG). High frequency oscillations have also been described as abnormal in ASD in a separate line of research. The present study examined whether low- and high-frequency oscillatory power, localized in part to FG and other language-related regions, differs in ASD subjects and first-degree relatives. Twelve individuals with ASD, 16 parents of children with ASD, and 35 healthy controls participated in a picture-naming task using magnetoencephalography (MEG) to assess oscillatory power and connectivity. Relative to controls, we observed reduced evoked high-gamma activity in the right superior temporal gyrus (STG) and reduced high-beta/low-gamma evoked power in the left inferior frontal gyrus (IFG) in the ASD group. Finally, reductions in phase-locked beta-band were also seen in the ASD group relative to controls, especially in the occipital lobes (OCC). First degree relatives, in contrast, exhibited higher high-gamma band power in the left STG compared with controls, as well as increased high-beta/low-gamma evoked power in the left FG. In the left hemisphere, beta- and gamma-band functional connectivity between the IFG and FG and between STG and OCC were higher in the autism group than in controls. This suggests that, contrary to what has been previously described, reduced connectivity is not observed across all scales of observation in autism. The lack of behavioral correlation for the findings warrants some caution in interpreting the relevance of such changes for language function in ASD. Our findings in parents implicates the gamma- and beta-band ranges as potential compensatory phenomena in autism relatives.
PMCID: PMC3821038  PMID: 24265611
magnetoencephalography; gamma-band; beta-band; oscillations; functional connectivity; Granger causality; fusiform gyrus; endophenotype
14.  Telehealth for Expanding the Reach of Early Autism Training to Parents 
Autism Research and Treatment  2012;2012:121878.
Although there is consensus that parents should be involved in interventions designed for young children with autism spectrum disorder (ASD), parent participation alone does not ensure consistent, generalized gains in children's development. Barriers such as costly intervention, time-intensive sessions, and family life may prevent parents from using the intervention at home. Telehealth integrates communication technologies to provide health-related services at a distance. A 12 one-hour per week parent intervention program was tested using telehealth delivery with nine families with ASD. The goal was to examine its feasibility and acceptance for promoting child learning throughout families' daily play and caretaking interactions at home. Parents became skilled at using teachable moments to promote children's spontaneous language and imitation skills and were pleased with the support and ease of telehealth learning. Preliminary results suggest the potential of technology for helping parents understand and use early intervention practices more often in their daily interactions with children.
PMCID: PMC3512210  PMID: 23227334
15.  Recurrence Risk for Autism Spectrum Disorders: A Baby Siblings Research Consortium Study 
Pediatrics  2011;128(3):e488-e495.
The recurrence risk of autism spectrum disorders (ASD) is estimated to be between 3% and 10%, but previous research was limited by small sample sizes and biases related to ascertainment, reporting, and stoppage factors. This study used prospective methods to obtain an updated estimate of sibling recurrence risk for ASD.
A prospective longitudinal study of infants at risk for ASD was conducted by a multisite international network, the Baby Siblings Research Consortium. Infants (n = 664) with an older biological sibling with ASD were followed from early in life to 36 months, when they were classified as having or not having ASD. An ASD classification required surpassing the cutoff of the Autism Diagnostic Observation Schedule and receiving a clinical diagnosis from an expert clinician.
A total of 18.7% of the infants developed ASD. Infant gender and the presence of >1 older affected sibling were significant predictors of ASD outcome, and there was an almost threefold increase in risk for male subjects and an additional twofold increase in risk if there was >1 older affected sibling. The age of the infant at study enrollment, the gender and functioning level of the infant's older sibling, and other demographic factors did not predict ASD outcome.
The sibling recurrence rate of ASD is higher than suggested by previous estimates. The size of the current sample and prospective nature of data collection minimized many limitations of previous studies of sibling recurrence. Clinical implications, including genetic counseling, are discussed.
PMCID: PMC3164092  PMID: 21844053
autism; recurrence; sibling risk
Brain, Behavior, and Immunity  2011;25(6):1123-1135.
Autism spectrum disorders (ASDs) are characterized by impaired language and social skills, often with restricted interests and stereotyped behaviors. A previous investigation of blood plasma from children with ASDs (mean age = 5½ years) demonstrated that 21% of samples contained autoantibodies that reacted intensely with GABAergic Golgi neurons of the cerebellum while no samples from non-sibling, typically developing children showed similar staining (Wills et al., 2009). In order to characterize the clinical features of children positive for these autoantibodies, we analyzed plasma samples from children enrolled in the Autism Phenome Project, a multidisciplinary project aimed at identifying subtypes of ASD. Plasma from male and female children (mean age = 3.2 years) was analyzed immunohistochemically for the presence of autoantibodies using histological sections of macaque monkey brain. Immunoreactivity to cerebellar Golgi neurons and other presumed interneurons was observed for some samples but there was no difference in the rate of occurrence of these autoantibodies between children with ASD and their typically developing peers. Staining of neurons, punctate profiles in the molecular layer of the dentate gyrus, and neuronal nuclei were also observed. Taken together, 42% of controls and subjects with ASD demonstrated immunoreactivity to some neural element. Interestingly, children whose plasma reacted to brain tissue had scores on the Child Behavior Checklist (CBCL) that indicated increased behavioral and emotional problems. Children whose plasma was immunoreactive with neuronal cell bodies scored higher on multiple CBCL scales. These studies indicate that additional research into the genesis and prevalence of brain-directed autoantibodies is warranted.
PMCID: PMC3313674  PMID: 21420487
Autism; autoantibody; interneurons; immunohistochemistry; Child Behavior Checklist
17.  Brief Report: Symptom Onset Patterns and Functional Outcomes in Young Children with Autism Spectrum Disorders 
This study examined the relationship between onset status and current functioning using a recently proposed onset classification system in 272 young children with autism spectrum disorder (ASD). Participants were classified into one of the following groups, based on parent report using the Autism Diagnostic Interview – Revised: Early Onset (symptoms by 12 months, no loss), Delay+Regression (symptoms by 12 months plus loss), Plateau (no early symptoms or loss), and Regression (no early symptoms, followed by loss). Findings indicate that current functioning does not differ according to onset pattern, calling into question the use of onset categorizations for prognostic purposes in children with ASD.
PMCID: PMC3265105  PMID: 21360021
autism; regression; onset; symptom; outcomes
18.  A voxel-based morphometry comparison of regional gray matter between fragile X syndrome and autism 
Psychiatry research  2009;174(2):138-145.
The phenotypic association between fragile X syndrome (FXS) and autism is well established, but no studies have directly compared whole-brain anatomy between the two disorders. We performed voxel-based morphometry analyses of MRI scans on ten individuals with FXS, ten individuals with autism, and ten healthy comparison subjects to identify volumetric changes in each disorder. Regional gray matter volumes within frontal, parietal, temporal, and cingulate gyri, as well as in the caudate nuclei and cerebellum, were larger in the FXS group relative to the autism group. In addition, volume increases in FXS were observed in frontal gyri and caudate nuclei compared to controls. The autism group exhibited volume increases in frontal and temporal gyri relative to the FXS group, and no volume increases relative to controls. Volumetric deficits relative to controls were observed in regions of the cerebellum for both groups, with additional deficits in parietal and temporal gyri for the FXS group. Our caudate nuclei and frontal gyri results may implicate dysfunction of frontostriatal circuitry in FXS. Cerebellar deficits suggest atypical development of the cerebellum contributing to the phenotype of both disorders, but further imply that unique cerebellar regions contribute to the phenotype of each disorder.
PMCID: PMC2783567  PMID: 19853418
caudate nucleus; cerebellum; frontostriatal; inferior frontal gyrus; magnetic resonance imaging
19.  Que nous apprennent les petits frères et sœurs sur les signes précoces d’autisme?1 
L’objectif de cette revue est de présenter une synthèse des réponses que l’on peut actuellement apporter à la question de savoir quelles sont les premières caractéristiques comportementales qui prédisent le développement de l’autisme. L’article se centre sur 5 points : la présence de Troubles du Spectre Autistique (TSA) dans des groupes de frères et sœurs puînés d’enfants déjà diagnostiqués, les patterns et caractéristiques du développement moteur, les patterns et caractéristiques du développement social et émotionnel, les patterns et caractéristiques de la communication intentionnelle verbale et non verbale, et les patterns qui marquent le début de comportements pathognomoniques de TSA. La discussion porte sur les aspects inattendus des résultats et les pistes de recherche nouvelles qu’ils peuvent engendrer.
PMCID: PMC2947150  PMID: 20890377
20.  Gaze Behavior and Affect at 6-Months: Predicting Clinical Outcomes and Language Development in Typically Developing Infants and Infants At-Risk for Autism 
Developmental science  2009;12(5):798-814.
This paper presents follow-up longitudinal data to research that previously suggested the possibility of abnormal gaze behavior marked by decreased eye contact in a subgroup of 6-month-old infants at risk for autism (Merin et al., 2007). Using eye-tracking data and behavioral data recorded during a live mother-infant interaction involving the still-face procedure, the predictive utility of gaze behavior and affective behaviors at 6 months was examined using diagnostic outcome data obtained longitudinally over the following 18 months. Results revealed that none of the infants previously identified as showing lower rates of eye-contact had any signs of autism at outcome. In contrast, three infants who were diagnosed with autism demonstrated consistent gaze to the eye region and typical affective responses at 6 months. Individual differences in face scanning and affective responsivity during the live interaction were not related to any continuous measures of symptom frequency or symptom severity. In contrast, results of growth curve models for language development revealed significant relationships between face scanning and expressive language. Greater amounts of fixation to the mother’s mouth during live interaction predicted higher levels of expressive language at outcome and greater rates of growth. These findings suggest that although gaze behavior at 6 months may not provide early markers for autism as initially conceived, gaze to the mouth in particular may be useful in predicting individual differences in language development.
PMCID: PMC2732664  PMID: 19702771
autism; eye tracking; language development; early identification; speech perception
21.  A Prospective Study of the Emergence of Early Behavioral Signs of Autism 
To examine prospectively the emergence of behavioral signs of autism in the first years of life in infants at low and high risk for autism.
A prospective longitudinal design was used to compare 25 infants later diagnosed with an autism spectrum disorder (ASD) with 25 gender-matched low-risk children later determined to have typical development. Participants were evaluated at 6, 12, 18, 24, and 36 months of age. Frequencies of gaze to faces, social smiles, and directed vocalizations were coded from video and rated by examiners.
The frequency of gaze to faces, shared smiles, and vocalizations to others were highly comparable between groups at 6 months of age, but significantly declining trajectories over time were apparent in the group later diagnosed with ASD. Group differences were significant by 12 months of age on most variables. Although repeated evaluation documented loss of skills in most infants with ASD, most parents did not report a regression in their child’s development.
These results suggest that behavioral signs of autism are not present at birth, as once suggested by Kanner, but emerge over time through a process of diminishment of key social communication behaviors. More children may present with a regressive course than previously thought, but parent report methods do not capture this phenomenon well. Implications for onset classification systems and clinical screening are also discussed.
PMCID: PMC2923050  PMID: 20410715
Autism; Onset; Infancy; Regression
22.  Atypical object exploration at 12 months of age is associated with autism in a prospective sample 
This prospective study examined object exploration behavior in 66 12-month-old infants, of whom nine were subsequently diagnosed with an autism spectrum disorder. Previous investigations differ on when the repetitive behaviors characteristic of autism are first present in early development. A task was developed that afforded specific opportunities for a range of repetitive uses of objects and was coded blind to outcome status. The autism/ASD outcome group displayed significantly more spinning, rotating, and unusual visual exploration of objects than two comparison groups. The average unusual visual exploration score of the autism/ASD group was over four standard deviations above the mean of the group with no concerns at outcome. Repetitive behaviors at 12 months were significantly related to cognitive and symptomatic status at 36 month outcome. These results suggest that repetitive or stereotyped behaviors may be present earlier than initially thought in very young children developing the autism phenotype.
PMCID: PMC2921192  PMID: 18805942
autism; diagnosis; early identification; repetitive behavior
23.  How Early Do Parent Concerns Predict Later Autism Diagnosis? 
To study the relationship between parent concerns about development in the first year and a half of life and later autism diagnostic outcomes.
Parent concerns about development were collected for infants at high and low risk for autism, using a prospective, longitudinal design. Parents were asked about developmental concerns at study intake and when their infant was 6, 12, and 18 months. Infants were then followed up until 36 months, when diagnostic status was determined.
By the time their child was 12 months, parents who have an older child with autism reported significantly more concerns in autism spectrum disorders-related areas than parents of children with typical outcomes. These concerns were significantly related to independent measures of developmental status and autism symptoms and helped predict which infants would later be diagnosed with autism or autism spectrum disorders. At 6 months, however, the concerns of parents who have an older child with autism do not predict outcome well.
Explicitly probing for parent concerns about development is useful for identifying children in need of closer monitoring and surveillance, as recommended by the American Academy of Pediatrics.
PMCID: PMC2919345  PMID: 19827218
24.  Behavioral Profiles of Affected and Unaffected Siblings of Children with Autism: Contribution of Measures of Mother–Infant Interaction and Nonverbal Communication 
We investigated whether deficits in social gaze and affect and in joint attention behaviors are evident within the first year of life among siblings of children with autism who go on to be diagnosed with autism or ASD (ASD) and siblings who are non-diagnosed (NoASD-sib) compared to low-risk controls. The ASD group did not differ from the other two groups at 6 months of age in the frequency of gaze, smiles, and vocalizations directed toward the caregiver, nor in their sensitivity to her withdrawal from interaction. However, by 12 months, infants in the ASD group exhibited lower rates of joint attention and requesting behaviors. In contrast, NoASD-sibs did not differ from comparison infants on any variables of interest at 6 and 12 months.
PMCID: PMC3044086  PMID: 20568002
Autism; Broader autism phenotype; Early identification; Mother–infant interaction; Still face procedure; Nonverbal communication
25.  Abstract Reasoning and Friendship in High Functioning Preadolescents with Autism Spectrum Disorders 
To investigate the relationship between cognitive and social functioning, 20 Israeli individuals with HFASD aged 8–12 and 22 age, maternal education, and receptive vocabulary–matched preadolescents with typical development (TYP) came to the lab with a close friend. Measures of abstract reasoning, friendship quality, and dyadic interaction during a play session were obtained. As hypothesized, individuals with HFASD were significantly impaired in abstract reasoning, and there were significant group differences in friend and observer reports of friendship quality. There also was consistency in reports between friends. Two factors—“relationship appearance” and “relationship quality” described positive aspects of the relationships. Disability status and age related to relationship appearance. Proband abstract reasoning was related to relationship quality.
PMCID: PMC3005120  PMID: 20467797
Autism spectrum disorder; Asperger Syndrome; Friendship; Abstract reasoning; Intimacy; Responsiveness

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