This study examined the trajectories of autistic symptom severity in an inception cohort of 187 children with ASD assessed across four time points from diagnosis to age 10. Trajectory groups were ...derived using multivariate cluster analysis. A two trajectory/cluster solution was selected. Change in trajectory slopes revealed a
turning point
marked by plateauing in symptom reduction during the period of transition to school (age 6) for one of the two trajectories. Trajectories were labelled:
Continuously Improving
(27%) and
Improving then Plateauing
(73% of sample). Children in the two trajectories differed in levels of symptom severity, language, cognitive, and adaptive functioning skills. Study findings can inform the development of more personalized services for children with ASD transitioning into the school system.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, ODKLJ, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, VSZLJ, ZAGLJ
The emerging role of a microbiota‐gut‐brain axis in autism spectrum disorder (ASD) suggests that modulating gut microbial composition may offer a tractable approach to addressing the lifelong ...challenges of ASD. The aim of this systematic review was to provide an overview and critically evaluate the current evidence on the efficacy and safety of probiotic, prebiotic, synbiotic, and fecal microbiota transplantation therapies for core and co‐occurring behavioral symptoms in individuals with ASD. Comprehensive searches of MEDLINE, EMBASE, Scopus, Web of Science Core Collection, Cochrane Library, and Google Scholar were performed from inception to March 5, 2020, and two update searches were completed on October 25, 2020, and April 22, 2021, respectively. A total of 4306 publications were identified, of which 14 articles met the inclusion criteria. Data were extracted independently by two reviewers using a preconstructed form. Results of probiotic studies do not confirm the supposed beneficial effect of probiotics on ASD, whereas prebiotics and synbiotic combinations appear to be efficacious in selective behavioral symptoms. Evidence of the efficacy of fecal microbiota transplantation in ASD is still scarce but supports further research. Overall, the current evidence base to suggest beneficial effects of these modalities in ASD is limited and inconclusive. More clinical trials are currently looking at the use of microbial‐based therapies in ASD. With a robust double‐blind randomized controlled protocol to investigate the efficacy, these trials should provide significant and definitive results.
Lay Summary
There is a link between altered gut bacteria and autism spectrum disorder. Some people believe that modulating bacterial composition in the gut may help reduce autism symptoms, but evidence from human studies suggesting beneficial effects of probiotic, prebiotic, and combination thereof as well as fecal transplants in autism spectrum disorder is limited and inconclusive. Current data should not encourage use of these modalities. Further clinical studies are needed.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Objective To examine the association between autism spectrum disorders (ASD) and each completed week of gestation using a graphical method of presenting results at all possible categorizations of ...gestational age (GA). Study design The risk of ASD in a total of 218 110 singleton live births with complete data from Alberta, Canada between 1998 and 2004 was examined through linkage to health insurance records. The relative risk of developing ASD according to the 21 dichotomizations of shorter gestation (GA ≤23 weeks vs >23 weeks to ≤43 weeks vs >43 weeks, in 1-week increments) was calculated using log-binomial regression and adjusted for fetal sex, socioeconomic status, and birth year. Results We observed a gradual increased risk of ASD with shorter gestation. Cutoffs only between 29 and 40 weeks clearly denoted an elevated risk of developing ASD compared with longer gestation, and the risk increased with earlier GA cutoff. The results were not affected by sex or measures of fetal growth. Conclusion Our data confirm the role of shortened gestation in ASD risk. We warn against the use of prespecified or a data-driven GA cutoff, however; instead, we recommend systematically examining all plausible cutoffs for GA to avoid overstating the homogeneity of risk in children on either side of a given cutoff, as well as to increase the comparability of studies.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
In the interest of more systematically documenting the early signs of autism, and of testing specific hypotheses regarding their underlying neurodevelopmental substrates, we have initiated a ...longitudinal study of high‐risk infants, all of whom have an older sibling diagnosed with an autistic spectrum disorder. Our sample currently includes 150 infant siblings, including 65 who have been followed to age 24 months, who are the focus of this paper. We have also followed a comparison group of low‐risk infants. Our measures include a novel observational scale (the first, to our knowledge, that is designed to assess autism‐specific behavior in infants), a computerized visual orienting task, and standardized measures of temperament, cognitive and language development. Our preliminary results indicate that by 12 months of age, siblings who are later diagnosed with autism may be distinguished from other siblings and low‐risk controls on the basis of: (1) several specific behavioral markers, including atypicalities in eye contact, visual tracking, disengagement of visual attention, orienting to name, imitation, social smiling, reactivity, social interest and affect, and sensory‐oriented behaviors; (2) prolonged latency to disengage visual attention; (3) a characteristic pattern of early temperament, with marked passivity and decreased activity level at 6 months, followed by extreme distress reactions, a tendency to fixate on particular objects in the environment, and decreased expression of positive affect by 12 months; and (4) delayed expressive and receptive language. We discuss these findings in the context of various neural networks thought to underlie neurodevelopmental abnormalities in autism, including poor visual orienting. Over time, as we are able to prospectively study larger numbers and to examine interrelationships among both early‐developing behaviors and biological indices of interest, we hope this work will advance current understanding of the neurodevelopmental origins of autism.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
While it is apparent that rare variation can play an important role in the genetic architecture of autism spectrum disorders (ASDs), the contribution of common variation to the risk of developing ASD ...is less clear. To produce a more comprehensive picture, we report Stage 2 of the Autism Genome Project genome-wide association study, adding 1301 ASD families and bringing the total to 2705 families analysed (Stages 1 and 2). In addition to evaluating the association of individual single nucleotide polymorphisms (SNPs), we also sought evidence that common variants, en masse, might affect the risk. Despite genotyping over a million SNPs covering the genome, no single SNP shows significant association with ASD or selected phenotypes at a genome-wide level. The SNP that achieves the smallest P-value from secondary analyses is rs1718101. It falls in CNTNAP2, a gene previously implicated in susceptibility for ASD. This SNP also shows modest association with age of word/phrase acquisition in ASD subjects, of interest because features of language development are also associated with other variation in CNTNAP2. In contrast, allele scores derived from the transmission of common alleles to Stage 1 cases significantly predict case status in the independent Stage 2 sample. Despite being significant, the variance explained by these allele scores was small (Vm< 1%). Based on results from individual SNPs and their en masse effect on risk, as inferred from the allele score results, it is reasonable to conclude that common variants affect the risk for ASD but their individual effects are modest.
Specific differences in visual orienting, critical in social-cognitive development, are associated with differences in white matter microstructure of the splenium.
ObjectiveThe authors sought to ...determine whether specific patterns of oculomotor functioning and visual orienting characterize 7-month-old infants who later meet criteria for an autism spectrum disorder (ASD) and to identify the neural correlates of these behaviors.MethodData were collected from 97 infants, of whom 16 were high-familial-risk infants later classified as having an ASD, 40 were high-familial-risk infants who did not later meet ASD criteria (high-risk negative), and 41 were low-risk infants. All infants underwent an eye-tracking task at a mean age of 7 months and a clinical assessment at a mean age of 25 months. Diffusion-weighted imaging data were acquired for 84 of the infants at 7 months. Primary outcome measures included average saccadic reaction time in a visually guided saccade procedure and radial diffusivity (an index of white matter organization) in fiber tracts that included corticospinal pathways and the splenium and genu of the corpus callosum.ResultsVisual orienting latencies were longer in 7-month-old infants who expressed ASD symptoms at 25 months compared with both high-risk negative infants and low-risk infants. Visual orienting latencies were uniquely associated with the microstructural organization of the splenium of the corpus callosum in low-risk infants, but this association was not apparent in infants later classified as having an ASD.ConclusionsFlexibly and efficiently orienting to salient information in the environment is critical for subsequent cognitive and social-cognitive development. Atypical visual orienting may represent an early prodromal feature of an ASD, and abnormal functional specialization of posterior cortical circuits directly informs a novel model of ASD pathogenesis.
This study investigated the extent to which sensory responsivity in infancy contributes to adaptive behavior development among toddlers at high-familial likelihood for autism. Prospective, ...longitudinal data were analyzed for 218 children, 58 of whom received an autism diagnosis. Results indicated that sensory profiles at age one year (hyperresponsivity, sensory seeking) were negatively associated with later adaptive behavior, particularly for socialization, at age 3 years regardless of diagnostic status. These results suggest that early differences in sensory responsivity may have downstream developmental consequences related to social development among young children with high-familial likelihood for autism.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Despite considerable progress in characterizing the early signs of autism spectrum disorder (ASD), more remains to be learned about how symptoms emerge in the first year of life. Parents with a new ...baby who already had at least one biological child diagnosed with ASD (high-risk) or no family history of ASD (low-risk) completed two measures when their baby was 9 months of age, the Autism Parent Screen for Infants (APSI) questionnaire and the interview-based Parent Concerns Form. Children underwent a blinded independent diagnostic assessment for ASD at age 3 years. Total scores on the APSI and the Parent Concerns Form were both able to independently differentiate high-risk children who were later diagnosed with ASD from other high-risk and low-risk children who were not. Using logistic regression, we found that the total score on the APSI predicted ASD outcomes at age 3 with 70% accuracy, but the Parent Concerns Form did not contribute any unique variance when the APSI was already in the model. The results suggest that the APSI identifies early features predictive of ASD in high-risk infants and can be used to flag them for targeted follow-up and screening.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, ODKLJ, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, VSZLJ, ZAGLJ
Mutations in
SHANK3, which encodes a synaptic scaffolding protein, have been described in subjects with an autism spectrum disorder (ASD). To assess the quantitative contribution of
SHANK3 to the ...pathogenesis of autism, we determined the frequency of DNA sequence and copy-number variants in this gene in 400 ASD-affected subjects ascertained in Canada. One de novo mutation and two gene deletions were discovered, indicating a contribution of 0.75% in this cohort. One additional
SHANK3 deletion was characterized in two ASD-affected siblings from another collection, which brings the total number of published mutations in unrelated ASD-affected families to seven. The combined data provide support that haploinsufficiency of
SHANK3 can cause a monogenic form of autism in sufficient frequency to warrant consideration in clinical diagnostic testing.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Social-emotional behavior in autism spectrum disorder (ASD) was examined among high-risk (HR; siblings of children diagnosed with ASD) and low-risk (LR; no family history of ASD) toddlers. Caregivers ...completed the Infant-Toddler Social Emotional Assessment (ITSEA) at 18 months, and blind diagnostic assessment for ASD was conducted at 36 months. Results indicated impairment in social-emotional functioning among HR toddlers subsequently diagnosed with ASD compared to other HR and LR toddlers, such that ITSEA domains (Internalizing, Dysregulation, Competence) and subdomains predicted later ASD symptoms and diagnosis. Receiver operating curves of optimal ITSEA cutoffs ranged from 0.23 to 0.44 for sensitivity, and 0.74 to 0.89 for specificity. Although classification accuracy for ASD was limited, group differences highlight the importance of considering social-emotional development when assessing ASD risk.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, ODKLJ, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, VSZLJ, ZAGLJ
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