Behaviors Characteristic of Autism Spectrum Disorder in Older Adults With Cognitive Impairment

Abstract Autism spectrum disorder (ASD) is commonly recognized by the time of adolescence, but is poorly understood in older adults. The possibility of late-life emergence of ASD has been poorly explored. In order to investigate late-life emergence of behaviors characteristic of ASD in MCI and AD, we surveyed caregivers of 142 older adults with neurodegenerative cognitive impairment using the Gilliam Autism Rating Scale-2. Participants with high autism index ratings (Autism ‘Possible/Very Likely’, n=23) reported significantly (statistically and clinically) younger age at onset of cognitive impairment than those who scored in the Autism ‘Unlikely’ range (n=119): 71.14±10.9 vs. 76.65±8.25 (p = 0.034). Additionally, those in Autism ‘Possible/Very Likely’ group demonstrated advanced severity of cognitive impairment, indicated by Clinical Dementia Rating Scale Sum of Boxes scores. Data demonstrate that ASD behaviors may appear de novo of degenerative dementia and such behaviors are more prevalent in those with early onset dementia. Further work elucidating a connection between ASD and dementia could shed light on subclinical forms of ASD, identify areas of shared neuroanatomic involvement between ASD and dementias, and provide valuable insights that might hasten the development of therapeutic strategies.

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Intranasal oxytocin administration ameliorates social behavioral deficits in a POGZWT/Q1038R mouse model of autism spectrum disorder

Molecular Brain ◽

10.1186/s13041-021-00769-8 ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Kohei Kitagawa ◽

Kensuke Matsumura ◽

Masayuki Baba ◽

Momoka Kondo ◽

Tomoya Takemoto ◽

...

Keyword(s):

Autism Spectrum Disorder ◽

Social Behavior ◽

Mouse Model ◽

Mouse Models ◽

De Novo ◽

Neurodevelopmental Disorder ◽

Autism Spectrum ◽

Spectrum Disorder ◽

De Novo Mutation ◽

Behavioral Deficits

AbstractAutism spectrum disorder (ASD) is a highly prevalent neurodevelopmental disorder characterized by core symptoms of impaired social behavior and communication. Recent studies have suggested that the oxytocin system, which regulates social behavior in mammals, is potentially involved in ASD. Mouse models of ASD provide a useful system for understanding the associations between an impaired oxytocin system and social behavior deficits. However, limited studies have shown the involvement of the oxytocin system in the behavioral phenotypes in mouse models of ASD. We have previously demonstrated that a mouse model that carries the ASD patient-derived de novo mutation in the pogo transposable element derived with zinc finger domain (POGZWT/Q1038R mice), showed ASD-like social behavioral deficits. Here, we have explored whether oxytocin (OXT) administration improves impaired social behavior in POGZWT/Q1038R mice and found that intranasal oxytocin administration effectively restored the impaired social behavior in POGZWT/Q1038R mice. We also found that the expression level of the oxytocin receptor gene (OXTR) was low in POGZWT/Q1038R mice. However, we did not detect significant changes in the number of OXT-expressing neurons between the paraventricular nucleus of POGZWT/Q1038R mice and that of WT mice. A chromatin immunoprecipitation assay revealed that POGZ binds to the promoter region of OXTR and is involved in the transcriptional regulation of OXTR. In summary, our study demonstrate that the pathogenic mutation in the POGZ, a high-confidence ASD gene, impairs the oxytocin system and social behavior in mice, providing insights into the development of oxytocin-based therapeutics for ASD.

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Possible tics diagnosed as stereotypies in patients with severe autism spectrum disorder: a video-based evaluation

Neurological Sciences ◽

10.1007/s10072-020-04995-1 ◽

2020 ◽

Author(s):

Cristiano Termine ◽

Enzo Grossi ◽

Valentina Anelli ◽

Ledina Derhemi ◽

Andrea E. Cavanna

Keyword(s):

Autism Spectrum Disorder ◽

Rating Scale ◽

Young Patients ◽

Autism Spectrum ◽

Repetitive Behaviors ◽

Spectrum Disorder ◽

High Rate ◽

Video Recordings ◽

Significant Difference ◽

Severe Autism

Abstract Background The association of stereotypies and tics is not rare in children with severe autism spectrum disorder (ASD). The differential diagnosis between stereotypies and tics in this patient population can be difficult; however, it could be clinically relevant because of treatment implications. Methods A total of 108 video recordings of repetitive behaviors in young patients with stereotypies in the context of ASD were reviewed by a movement disorders expert and a trainee, in order to assess the prevalence of possible co-morbid tics. The Modified Rush Videotape Rating Scale (MRVS) was used to rate tic frequency and severity. Results Out of 27 patients with stereotypies (24 males; mean age 14 years), 18 (67%) reported possible tics. The most frequently observed tics were eye blinking, shoulder shrugging, neck bending, staring, and throat clearing. The mean MRVS score was 5, indicating mild tic severity. The only significant difference between patients with tics and patients without tics was the total number of stereotypies, which was higher in the subgroup of patients without tics (p = 0.01). Conclusions Expert review of video-recordings of repetitive behaviors in young patients with ASD and stereotypies suggests the possibility of a relatively high rate of co-morbid tics. These findings need to be integrated with a comprehensive clinical assessment focusing on the diagnostic re-evaluation of heterogeneous motor manifestations.

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Response (minimum clinically relevant change) in ASD symptoms after an intervention according to CARS-2: consensus from an expert elicitation procedure

European Child & Adolescent Psychiatry ◽

10.1007/s00787-021-01772-z ◽

2021 ◽

Author(s):

Lucie Jurek ◽

Matias Balthazar ◽

Sheffali Gulati ◽

Neda Novakovic ◽

María Núñez ◽

...

Keyword(s):

Autism Spectrum Disorder ◽

Rating Scale ◽

Expert Knowledge ◽

Scientific Evidence ◽

Autism Spectrum ◽

Expert Elicitation ◽

Spectrum Disorder ◽

Initial Finding ◽

Elicitation Process ◽

Core Symptoms

AbstractThe lack of consensual measures to monitor core change in Autism Spectrum Disorder (ASD) or response to interventions leads to difficulty to prove intervention efficacy on ASD core symptoms. There are no universally accepted outcome measures developed for measuring changes in core symptoms. However, the CARS (Childhood Autism Rating Scale) is one of the outcomes recommended in the EMA Guideline on the clinical development of medicinal products for the treatment of ASD. Unfortunately, there is currently no consensus on the response definition for CARS among individuals with ASD. The aim of this elicitation process was to determine an appropriate definition of a response on the CARS2 scale for interventions in patients with Autism Spectrum Disorder (ASD). An elicitation process was conducted following the Sheffield Elicitation Framework (SHELF). Five experts in the field of ASD and two experts in expert knowledge elicitation participated in an 1-day elicitation workshop. Experts in ASD were previously trained in the SHELF elicitation process and received a dossier of scientific evidence concerning the topic. The response definition was set as the mean clinically relevant improvement averaged over all patients, levels of functioning, age groups ***and clinicians. Based on the scientific evidence and expert judgment, a normal probability distribution was agreed to represent the state of knowledge of this response with expected value 4.03 and standard deviation 0.664. Considering the remaining uncertainty of the estimation and the available literature, a CARS-2 improvement of 4.5 points has been defined as a threshold to conclude to a response after an intervention. A CARS-2 improvement of 4.5 points could be used to evaluate interventions' meaningfulness in indivudals. This initial finding represents an important new benchmark and may aid decision makers in evaluating the efficacy of interventions in ASD.

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Dance, functioning and quality of life in children with Down syndrome and autism spectrum disorder dance, functioning and quality of life in Down syndrome and autism spectrum disorder

Clinical Child Psychology and Psychiatry ◽

10.1177/13591045211061795 ◽

2021 ◽

pp. 135910452110617

Author(s):

Evanilza T. Adorno ◽

Daiany C de J. Dos Santos ◽

Beatriz M. DeJesus ◽

Adrielle A. Passos ◽

Lavínia Teixeira-Machado

Keyword(s):

Quality Of Life ◽

Autism Spectrum Disorder ◽

Down Syndrome ◽

Rating Scale ◽

Functional Independence Measure ◽

Functional Independence ◽

Autism Spectrum ◽

Spectrum Disorder ◽

Children With Down Syndrome

This study investigated dance practice in psychosocial and functional aspects, and quality of life in children with Down syndrome and autism spectrum disorder. Children with DS and ASD, between 3 and 12 years old, attended a dance program during 16 sessions/lessons, lasting 60 min, twice a week, in suitable place. Functional Independence Measure (FIM), Childhood Autism Rating Scale SF-36 quality of life survey, and Knowledge, Attitude and Practice Inquiry (KAP Inquiry) were applied before and after dance classes. Eleven participants concluded the study. Functional independence changes were observed in relation to self-care, sphincter control, locomotion, and communication domains. Children’ “quality of life” reported by parents showed changes in functional capacity, vitality, mental health, physical and social aspects, and general state of health domains. These findings suggest that regular dance practice can underlie psychosocial adjustments in children with DS and ASD.

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A de novo mosaic mutation in SPAST with two novel alternative alleles and chromosomal copy number variant in a boy with spastic paraplegia and autism spectrum disorder

European Journal of Medical Genetics ◽

10.1016/j.ejmg.2017.07.015 ◽

2017 ◽

Vol 60 (10) ◽

pp. 548-552 ◽

Cited By ~ 3

Author(s):

A.M. Matthews ◽

M. Tarailo-Graovac ◽

E.M. Price ◽

I. Blydt-Hansen ◽

A. Ghani ◽

...

Keyword(s):

Autism Spectrum Disorder ◽

Copy Number ◽

De Novo ◽

Copy Number Variant ◽

Autism Spectrum ◽

Spectrum Disorder ◽

Spastic Paraplegia ◽

Chromosomal Copy Number ◽

Chromosomal Copy

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Increased burden of deleterious variants in essential genes in autism spectrum disorder

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1613195113 ◽

2016 ◽

Vol 113 (52) ◽

pp. 15054-15059 ◽

Cited By ~ 30

Author(s):

Xiao Ji ◽

Rachel L. Kember ◽

Christopher D. Brown ◽

Maja Bućan

Keyword(s):

Autism Spectrum Disorder ◽

Large Scale ◽

De Novo ◽

Autism Spectrum ◽

Essential Genes ◽

Spectrum Disorder ◽

Model Organisms ◽

Disease Genes ◽

Priority List ◽

Human Orthologs

Autism spectrum disorder (ASD) is a heterogeneous, highly heritable neurodevelopmental syndrome characterized by impaired social interaction, communication, and repetitive behavior. It is estimated that hundreds of genes contribute to ASD. We asked if genes with a strong effect on survival and fitness contribute to ASD risk. Human orthologs of genes with an essential role in pre- and postnatal development in the mouse [essential genes (EGs)] are enriched for disease genes and under strong purifying selection relative to human orthologs of mouse genes with a known nonlethal phenotype [nonessential genes (NEGs)]. This intolerance to deleterious mutations, commonly observed haploinsufficiency, and the importance of EGs in development suggest a possible cumulative effect of deleterious variants in EGs on complex neurodevelopmental disorders. With a comprehensive catalog of 3,915 mammalian EGs, we provide compelling evidence for a stronger contribution of EGs to ASD risk compared with NEGs. By examining the exonic de novo and inherited variants from 1,781 ASD quartet families, we show a significantly higher burden of damaging mutations in EGs in ASD probands compared with their non-ASD siblings. The analysis of EGs in the developing brain identified clusters of coexpressed EGs implicated in ASD. Finally, we suggest a high-priority list of 29 EGs with potential ASD risk as targets for future functional and behavioral studies. Overall, we show that large-scale studies of gene function in model organisms provide a powerful approach for prioritization of genes and pathogenic variants identified by sequencing studies of human disease.

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