Examining criterion-oriented validity of the Repetitive Behavior Scales for Early Childhood (RBS-EC) and the Video-Referenced Rating of Reciprocal Social Behavior (vrRSB)

AbstractImproved characterization of quantitative traits and dimensionally distributed complex behaviors during toddlerhood may improve early identification of autism spectrum disorder and related neurodevelopmental disorders. Parents of 205 community-ascertained toddlers (age: mean = 20.2, SD = 2.6 months) completed the Repetitive Behavior Scales for Early Childhood (RBS-EC) and the Video-Referenced Rating of Reciprocal Social Behavior (vrRSB), with longitudinal follow-up of behavioral assessments and/or another round of parent-report questionnaires. Criterion validity was examined both concurrently and longitudinally using the Infant Toddler Social Emotional Assessment (ITSEA) as a criterion anchor. Reciprocal social behavior as measured by the vrRSB was significantly associated with social competence as measured by the ITSEA, longitudinally and concurrently. Reciprocal social behavior was not associated with the externalizing subscale on the ITSEA, providing evidence of discriminant validity. Higher-order repetitive behaviors (restricted interests; rituals and routines) as measured by RBS-EC subscales were associated with the dysregulation and internalizing subscales of the ITSEA, longitudinally and concurrently. All RBS-EC subscales (excepting repetitive motor) were associated concurrently and longitudinally with the dysregulation subscale of the ITSEA. We report evidence of criterion-oriented and discriminant validity for the constructs/domains captured by the RBS-EC and vrRSB. These instruments may be particularly useful in characterizing dimensional variability across the typical-to-atypical continuum.

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Imbalanced social-communicative and restricted repetitive behavior subtypes of autism spectrum disorder exhibit different neural circuitry

Communications Biology ◽

10.1038/s42003-021-02015-2 ◽

2021 ◽

Vol 4 (1) ◽

Author(s):

Natasha Bertelsen ◽

◽

Isotta Landi ◽

Richard A. I. Bethlehem ◽

Jakob Seidlitz ◽

...

Keyword(s):

Repetitive Behavior ◽

Resting State Fmri ◽

Neural Circuitry ◽

Autism Spectrum ◽

Repetitive Behaviors ◽

Typically Developing ◽

Out Of Sample ◽

Genetic Mechanisms ◽

Social Communicative ◽

The Eu

AbstractSocial-communication (SC) and restricted repetitive behaviors (RRB) are autism diagnostic symptom domains. SC and RRB severity can markedly differ within and between individuals and may be underpinned by different neural circuitry and genetic mechanisms. Modeling SC-RRB balance could help identify how neural circuitry and genetic mechanisms map onto such phenotypic heterogeneity. Here, we developed a phenotypic stratification model that makes highly accurate (97–99%) out-of-sample SC = RRB, SC > RRB, and RRB > SC subtype predictions. Applying this model to resting state fMRI data from the EU-AIMS LEAP dataset (n = 509), we find that while the phenotypic subtypes share many commonalities in terms of intrinsic functional connectivity, they also show replicable differences within some networks compared to a typically-developing group (TD). Specifically, the somatomotor network is hypoconnected with perisylvian circuitry in SC > RRB and visual association circuitry in SC = RRB. The SC = RRB subtype show hyperconnectivity between medial motor and anterior salience circuitry. Genes that are highly expressed within these networks show a differential enrichment pattern with known autism-associated genes, indicating that such circuits are affected by differing autism-associated genomic mechanisms. These results suggest that SC-RRB imbalance subtypes share many commonalities, but also express subtle differences in functional neural circuitry and the genomic underpinnings behind such circuitry.

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Genetic architecture of reciprocal social behavior in toddlers: Implications for heterogeneity in the early origins of autism spectrum disorder

Development and Psychopathology ◽

10.1017/s0954579420000723 ◽

2020 ◽

Vol 32 (4) ◽

pp. 1190-1205

Author(s):

Natasha Marrus ◽

Julia D. Grant ◽

Brooke Harris-Olenak ◽

Jordan Albright ◽

Drew Bolster ◽

...

Keyword(s):

Autism Spectrum Disorder ◽

Social Behavior ◽

Genetic Architecture ◽

Ethnically Diverse ◽

Autism Spectrum ◽

Repetitive Behaviors ◽

Spectrum Disorder ◽

Genetic Influences ◽

Heritable Trait ◽

Birth Registries

AbstractImpairment 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.

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Sex-dependent role for EPHB2 in brain development and autism-associated behavior

Neuropsychopharmacology ◽

10.1038/s41386-021-00986-8 ◽

2021 ◽

Author(s):

Ahlem Assali ◽

Jennifer Y. Cho ◽

Evgeny Tsvetkov ◽

Abha R. Gupta ◽

Christopher W. Cowan

Keyword(s):

Pyramidal Neurons ◽

De Novo ◽

Repetitive Behavior ◽

Autism Spectrum ◽

Repetitive Behaviors ◽

Male Mice ◽

Sensory Sensitivity ◽

Hyperactivity Disorder ◽

Specific Effects ◽

Layer V

AbstractAutism spectrum disorder (ASD) is characterized by impairments in social communication and interaction and restricted, repetitive behaviors. It is frequently associated with comorbidities, such as attention-deficit hyperactivity disorder, altered sensory sensitivity, and intellectual disability. A de novo nonsense mutation in EPHB2 (Q857X) was discovered in a female patient with ASD [13], revealing EPHB2 as a candidate ASD risk gene. EPHB2 is a receptor tyrosine kinase implicated in axon guidance, synaptogenesis, and synaptic plasticity, positioning it as a plausible contributor to the pathophysiology of ASD and related disorders. In this study, we show that the Q857X mutation produced a truncated protein lacking forward signaling and that global disruption of one EphB2 allele (EphB2+/−) in mice produced several behavioral phenotypes reminiscent of ASD and common associated symptoms. EphB2+/− female, but not male, mice displayed increased repetitive behavior, motor hyperactivity, and learning and memory deficits, revealing sex-specific effects of EPHB2 hypofunction. Moreover, we observed a significant increase in the intrinsic excitability, but not excitatory/inhibitory ratio, of motor cortex layer V pyramidal neurons in EphB2+/− female, but not male, mice, suggesting a possible mechanism by which EPHB2 hypofunction may contribute to sex-specific motor-related phenotypes. Together, our findings suggest that EPHB2 hypofunction, particularly in females, is sufficient to produce ASD-associated behaviors and altered cortical functions in mice.

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SOCIAL STATUS AND GUT MICROBIAL DYSBIOSIS IN ADULTS AND CHILDREN WITH AUTISM SPECTRUM DISORDERS: A PROFOUND REVIEW OF THE AVAILABLE LITERATURE SOURCES

Journal of IMAB - Annual Proceeding (Scientific Papers) ◽

10.5272/jimab.2021273.3939 ◽

2021 ◽

Vol 27 (3) ◽

pp. 3939-3946

Author(s):

Sevginar Ibryamova ◽

◽

Veselin Petkov ◽

Tsveteslava Ignatova-Ivanova ◽

Georgi Kolev ◽

...

Keyword(s):

Autism Spectrum Disorders ◽

Behavioral Problems ◽

Autism Spectrum ◽

Repetitive Behaviors ◽

Diagnostic Methods ◽

Restricted Interests ◽

Microbial Dysbiosis ◽

Gastrointestinal Problems ◽

Adults And Children ◽

Spectrum Disorders

Autism is a complex disorder without a specific diagnosis, so the disease is defined by its specific characteristics described in the literature as cognitive defects, social, communication and behavioral problems, repetitive behaviors, unusual sensitivity to stimuli such as noise, restricted interests, and self stimulation. There are many models in the literature explaining the biology of autism, which are based on genetics, immunity, various environmental factors and diet. There is a lot of literature data that people with Autism Spectrum Disorders (ASD) often have gastrointestinal problems that also affect their behavior. ASD suffer developmental disabilities from an early age, which can be both physical and psychological. Often people suffer these problems even throughout their lives. This review aims to provide basic information on definitions, historical data, diagnostic methods, behavioral etiology, gastrointestinal and social problems in adults and children with ASD.

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Linking Autism Risk Genes to Disruption of Cortical Development

Cells ◽

10.3390/cells9112500 ◽

2020 ◽

Vol 9 (11) ◽

pp. 2500

Author(s):

Marta Garcia-Forn ◽

Andrea Boitnott ◽

Zeynep Akpinar ◽

Silvia De Rubeis

Keyword(s):

Large Scale ◽

Association Studies ◽

Neurodevelopmental Disorder ◽

Cortical Development ◽

Autism Spectrum ◽

Repetitive Behaviors ◽

Genome Wide Association Studies ◽

Restricted Interests ◽

Risk Genes ◽

Whole Exome

Autism spectrum disorder (ASD) is a prevalent neurodevelopmental disorder characterized by impairments in social communication and social interaction, and the presence of repetitive behaviors and/or restricted interests. In the past few years, large-scale whole-exome sequencing and genome-wide association studies have made enormous progress in our understanding of the genetic risk architecture of ASD. While showing a complex and heterogeneous landscape, these studies have led to the identification of genetic loci associated with ASD risk. The intersection of genetic and transcriptomic analyses have also begun to shed light on functional convergences between risk genes, with the mid-fetal development of the cerebral cortex emerging as a critical nexus for ASD. In this review, we provide a concise summary of the latest genetic discoveries on ASD. We then discuss the studies in postmortem tissues, stem cell models, and rodent models that implicate recently identified ASD risk genes in cortical development.

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Delineating Repetitive Behavior Profiles across the Lifespan in Fragile X Syndrome

Brain Sciences ◽

10.3390/brainsci10040239 ◽

2020 ◽

Vol 10 (4) ◽

pp. 239

Author(s):

Debra L. Reisinger ◽

Rebecca C. Shaffer ◽

Nicole Tartaglia ◽

Elizabeth Berry-Kravis ◽

Craig A. Erickson

Keyword(s):

Fragile X Syndrome ◽

Fragile X ◽

Repetitive Behavior ◽

Autism Spectrum ◽

Repetitive Behaviors ◽

Motor Behaviors ◽

Sensory Motor ◽

Adolescents And Adults ◽

Males And Females ◽

The Impact

Restricted repetitive behaviors (RRBs) are a core area of impairment in autism spectrum disorder (ASD), but also affect several other neurodevelopmental disorders including fragile X syndrome (FXS). Current literature has begun to describe the RRB profile in FXS up through adolescence; however, little is known about the subtypes of RRBs in adolescents and adults. Further, literature on the RRB profile of females with FXS is limited. The present study examines the RRB profile across subtypes and specific items in both males and females with FXS while assessing for differences based on age, ASD diagnosis and the impact of IQ. Participants included 154 individuals with FXS (ages 2 to 50 years old). Results revealed a peak in RRB severity in FXS between 7–12 years for the majority of RRB subscales with the exception of Sensory-Motor behaviors peaking between 2 and 12 years before declining. Distinct RRB profiles in males and females with FXS emerged in addition to significant overlap among the item and subscale levels of RRBs across gender. Further, an added diagnosis of ASD significantly increased rates of RRBs across all subscale levels, but not necessarily across all items. Lastly, IQ did not solely account for the presence of RRBs in FXS, with Sensory-Motor behaviors being driven by comorbid ASD in males with FXS, and Restricted Interest behaviors being driven by comorbid ASD regardless of gender. These findings build on the current understanding of RRBs in FXS based on gender and comorbid ASD and lay important groundwork for the development of targeted behavioral and pharmacological treatments.

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Translational animal models of autism and neurodevelopmental disorders

Dialogues in Clinical Neuroscience ◽

10.31887/dcns.2012.14.3/jcrawley ◽

2012 ◽

Vol 14 (3) ◽

pp. 293-305 ◽

Cited By ~ 31

Keyword(s):

Mouse Models ◽

De Novo ◽

Single Gene ◽

Neurodevelopmental Disorder ◽

Gene Mutations ◽

Autism Spectrum ◽

Repetitive Behaviors ◽

Restricted Interests ◽

Homologous Genes ◽

Biological Outcomes

Autism is a neurodevelopmental disorder whose diagnosis is based on three behavioral criteria: unusual reciprocal social interactions, deficits in communication, and stereotyped repetitive behaviors with restricted interests. A large number of de novo single gene mutations and chromosomal deletions are associated with autism spectrum disorders. Based on the strong genetic evidence, mice with targeted mutations in homologous genes have been generated as translational research tools. Mouse models of autism have revealed behavioral and biological outcomes of mutations in risk genes. The field is now poised to employ the most robust phenotypes in the most replicable mouse models for preclinical screening of novel therapeutics.

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Spatial and Temporal Gene Function Studies in Rodents: Towards Gene-Based Therapies for Autism Spectrum Disorder

Genes ◽

10.3390/genes13010028 ◽

2021 ◽

Vol 13 (1) ◽

pp. 28

Author(s):

Iris W. Riemersma ◽

Robbert Havekes ◽

Martien J. H. Kas

Keyword(s):

Autism Spectrum Disorder ◽

Gene Function ◽

Current Knowledge ◽

Developmental Trajectories ◽

Autism Spectrum ◽

Synaptic Function ◽

Repetitive Behaviors ◽

Spectrum Disorder ◽

Restricted Interests ◽

Highly Correlated

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition that is characterized by differences in social interaction, repetitive behaviors, restricted interests, and sensory differences beginning early in life. Especially sensory symptoms are highly correlated with the severity of other behavioral differences. ASD is a highly heterogeneous condition on multiple levels, including clinical presentation, genetics, and developmental trajectories. Over a thousand genes have been implicated in ASD. This has facilitated the generation of more than two hundred genetic mouse models that are contributing to understanding the biological underpinnings of ASD. Since the first symptoms already arise during early life, it is especially important to identify both spatial and temporal gene functions in relation to the ASD phenotype. To further decompose the heterogeneity, ASD-related genes can be divided into different subgroups based on common functions, such as genes involved in synaptic function. Furthermore, finding common biological processes that are modulated by this subgroup of genes is essential for possible patient stratification and the development of personalized early treatments. Here, we review the current knowledge on behavioral rodent models of synaptic dysfunction by focusing on behavioral phenotypes, spatial and temporal gene function, and molecular targets that could lead to new targeted gene-based therapy.

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Social (Pragmatic) Communication Disorder: Another name for the Broad Autism Phenotype?

Autism ◽

10.1177/1362361318822503 ◽

2019 ◽

Vol 23 (8) ◽

pp. 1982-1992 ◽

Cited By ~ 4

Author(s):

Judy Flax ◽

Christine Gwin ◽

Sherri Wilson ◽

Yuli Fradkin ◽

Steve Buyske ◽

...

Keyword(s):

Autism Spectrum Disorder ◽

Social Communication ◽

Repetitive Behavior ◽

Family Members ◽

Autism Spectrum ◽

Spectrum Disorder ◽

Communication Disorder ◽

Restricted Interests ◽

Communication Impairment ◽

Pragmatic Communication

The Diagnostic and Statistical Manual of Mental Disorders’ (5th ed.) Social (Pragmatic) Communication Disorder is meant to capture the social elements of communication dysfunction in children who do not meet autism spectrum disorder criteria. It is unclear whether Social (Pragmatic) Communication Disorder captures these elements without overlapping with Autism Spectrum Disorder or the Diagnostic and Statistical Manual of Mental Disorders’ (5th ed.) Language Disorder. Standardized behavioral assessments administered during a family genetics study were used to evaluate the social communication impairment and the restricted interests and repetitive behaviors in persons with autism spectrum disorder, language impairment, or neither. Social communication impairment and restricted interests and repetitive behavior were significantly correlated in all family members regardless of affection status. Rates of social communication impairment and restricted interests and repetitive behavior were highest in individuals with autism spectrum disorder. One-third of family members with language impairment presented with at least mild/moderate levels of social communication impairment (36.6%) and restricted interests and repetitive behavior (43.3%). A subset of unaffected members also presented with mild/moderate levels of social communication impairment (parents = 10.1%, siblings 11.6%) and restricted interests and repetitive behavior (parents = 14.0%, siblings = 22.1%). The majority of child family members with mild/moderate levels of social communication impairment had similar restricted interest and repetitive behavior levels reflecting criteria representing the Broad Autism Phenotype. These data suggest that social pragmatic communication disorder does not capture the profiles of children who have both social communication impairment and restricted interests and repetitive behavior but are in need of clinical services.

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Development of a Robotic Motor Skills Assessment System for Children With Autism

2017 Design of Medical Devices Conference ◽

10.1115/dmd2017-3447 ◽

2017 ◽

Author(s):

Guru Subramani ◽

Aubrey M. Fisher ◽

Moria F. Bittmann ◽

Andrea H. Mason ◽

Brittany G. Travers ◽

...

Keyword(s):

Social Interactions ◽

Motor Skills ◽

Upper Limb ◽

Children With Autism ◽

Autism Spectrum ◽

Repetitive Behaviors ◽

Assessment System ◽

Skills Assessment ◽

Robot Arm ◽

Restricted Interests

Autism is a developmental disorder characterized by atypical social interactions and repetitive behaviors/restricted interests[1]. It is found that children with autism also experience delayed or impaired motor skills development [2]. It would be advantageous to develop methods that precisely evaluate these motor skills impairments. The use of robots for evaluating upper limb motor competency have been looked at in the stroke literature [3]. We would like to leverage robotic tools for motor skills assessment but with focus for children with autism spectrum disorder. Robotic methodologies provide a unique way of testing upper limb motor skills. For instance, if a person holds on to the end of a robot arm and moves the robot arm in space, the robot can apply forces and prevent or assist the person with these motions. In this fashion, the robot can apply perturbations in a repeatable and precise manner with high fidelity. Since individuals with autism have anxieties interacting with other individuals[4], using an impersonal robot would alleviate the anxiety of social interactions. These individuals learn motor skills best with consistent repetition and strong reinforcement, qualities that robots provide. Therefore, a robot based evaluation strategy and therapy paradigm for children with Autism would be beneficial for the community.

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