Diminished social interaction incentive contributes to social deficits in mouse models of autism spectrum disorder

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Benjamin Rein ◽  
Zhen Yan ◽  
Zi‐Jun Wang
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Yun Li ◽  
Zhengbing Zhou ◽  
Chen Chang ◽  
Lu Qian ◽  
Chunyan Li ◽  
...  

Abstract Background Individuals with autism spectrum disorder (ASD) have social interaction deficits and difficulties in emotional regulation. The neural substrates for these socio-affective deficits are not yet clear, but one potential candidate is maldevelopment of the uncinate fasciculus (UF), a white matter tract thought to be involved in socio-affective processing. However, the developmental trajectory of the UF in young children with social interaction deficits has not been examined. The present study was designed to describe the developmental growth trajectory of the UF and the relationships between UF development and social deficits in ASD. Methods Eigenvalues of the UF were measured by diffusion tensor imaging (DTI)-based tractography in 37 children with ASD and 27 matched 2–3-year-old subjects with developmental delay (DD) at baseline (time 1) and at 2-year follow-up (time 2). Growth rates of the UF were compared between groups and associations with social deficit scores according to the Autism Diagnostic Interview-Revised (ADI-R) analyzed by Pearson’s correlations. Results At time 1, axial diffusivity (AD) of the left UF was significantly larger in the ASD group than the DD group. At time 2, left UF fractional anisotropy (FA) was significantly higher and radial diffusivity (RD) significantly lower in the ASD group than the DD group. The rate of UF growth during this 2-year interval was faster in children with ASD than DD. Significant negative correlations were found between the rise in ADI-R social deficit measures and both right UF RD and left UF mean diffusivity (MD). Conclusions Young children with ASD demonstrate UF overgrowth during the 2-year development period between 2 and 3 and 4–5 years of age, and this white matter abnormality is directly associated with the progression of social deficits. Trial registration World Health Organization class I registered international clinical trial platform, ChiCTR-ROC-17012877.


2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Kohei Kitagawa ◽  
Kensuke Matsumura ◽  
Masayuki Baba ◽  
Momoka Kondo ◽  
Tomoya Takemoto ◽  
...  

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.


2021 ◽  
pp. 1-11
Author(s):  
Denis Pavăl ◽  
Ioana Valentina Micluția

Autism spectrum disorder (ASD) comprises a group of neurodevelopmental disorders characterized by social deficits and stereotyped behaviors. Despite intensive research, its etiopathogenesis remains largely unclear. Although studies consistently reported dopaminergic anomalies, a coherent dopaminergic model of ASD was lacking until recently. In 2017, we provided a theoretical framework for a “dopamine hypothesis of ASD” which proposed that autistic behavior arises from a dysfunctional midbrain dopaminergic system. Namely, we hypothesized that malfunction of 2 critical circuits originating in the midbrain, that is, the mesocorticolimbic and nigrostriatal pathways, generates the core behavioral features of ASD. Moreover, we provided key predictions of our model along with testing means. Since then, a notable number of studies referenced our work and numerous others provided support for our model. To account for these developments, we review all these recent data and discuss their implications. Furthermore, in the light of these new insights, we further refine and reconceptualize our model, debating on the possibility that various etiologies of ASD converge upon a dysfunctional midbrain dopaminergic system. In addition, we discuss future prospects, providing new means of testing our hypothesis, as well as its limitations. Along these lines, we aimed to provide a model which, if confirmed, could provide a better understanding of the etiopathogenesis of ASD along with new therapeutic strategies.


2020 ◽  
pp. 153465012098345
Author(s):  
Mirela Cengher ◽  
Joy C. Clayborne ◽  
Adrianna E. Crouch ◽  
Julia T. O’Connor

Over 60% of children diagnosed with selective mutism are also diagnosed with Autism Spectrum Disorder. Previous research established that behavioral interventions are effective at increasing speech in children with both diagnoses. However, few studies conducted assessments to determine environmental variables that inhibit speech, and such assessments are necessary for the development of effective and efficient treatments. This case study describes an assessment that evaluated the function(s) of selective mutism. The results confirmed that the participant did not talk to avoid social interaction and that mutism occurred primarily in the presence of multiple, unfamiliar people. Our first treatment focused on increasing tolerance for social interaction, demonstrated by an increase in speech production in the presence of unfamiliar people. Our second treatment focused on increasing qualitative aspects of the participant’s speech (i.e., both responses and initiations). Finally, we taught the participant’s parents to implement the treatment in naturalistic settings, and the participant demonstrated generalization of treatment effects across people and settings. Implications for clinical practice and future research are discussed.


2014 ◽  
Vol 20 (1) ◽  
pp. 23-26 ◽  
Author(s):  
Marc Woodbury-Smith

SummaryIn medical practice it is crucial that symptom descriptions are as precise and objective as possible, which psychiatry attempts to achieve through its psychopathological lexicon. The term ‘autism spectrum disorder’ has now entered psychiatric nosology, but the symptom definitions on which it is based are not robust, potentially making reliable and valid diagnoses a problem. This is further compounded by the spectral nature of the disorder and its lack of clear diagnostic boundaries. To overcome this, there is a need for a psychopathological lexicon of 'social cognition’ and a classification system that splits rather than lumps disorders with core difficulties in social interaction.


2021 ◽  
Vol 5 (10) ◽  
pp. 57
Author(s):  
Vinícius Silva ◽  
Filomena Soares ◽  
João Sena Esteves ◽  
Cristina P. Santos ◽  
Ana Paula Pereira

Facial expressions are of utmost importance in social interactions, allowing communicative prompts for a speaking turn and feedback. Nevertheless, not all have the ability to express themselves socially and emotionally in verbal and non-verbal communication. In particular, individuals with Autism Spectrum Disorder (ASD) are characterized by impairments in social communication, repetitive patterns of behaviour, and restricted activities or interests. In the literature, the use of robotic tools is reported to promote social interaction with children with ASD. The main goal of this work is to develop a system capable of automatic detecting emotions through facial expressions and interfacing them with a robotic platform (Zeno R50 Robokind® robotic platform, named ZECA) in order to allow social interaction with children with ASD. ZECA was used as a mediator in social communication activities. The experimental setup and methodology for a real-time facial expression (happiness, sadness, anger, surprise, fear, and neutral) recognition system was based on the Intel® RealSense™ 3D sensor and on facial features extraction and multiclass Support Vector Machine classifier. The results obtained allowed to infer that the proposed system is adequate in support sessions with children with ASD, giving a strong indication that it may be used in fostering emotion recognition and imitation skills.


2019 ◽  
Vol 13 (5) ◽  
pp. 48
Author(s):  
Emad Mohammad ali ◽  
Fatimah eid ziad Al- Adwan ◽  
Yazan M. Al-Naimat

Autism Spectrum Disorder (ASD) is one of the most confusing disorders for which not only no exact cause has been identified, but also no definitive cure has been found yet. Autism is a disorder that is usually observed on the child at an early age, affecting various developmental aspects. Its development is abnormal. It shows an imbalance in its social interaction, characterized by repetition of certain behavioral patterns and challenges in verbal and nonverbal communication with others. Over the last few decades, its prevalence showed a dramatic rise; an observation that encouraged many researchers across the globe to try to explore all its aspects from etiology to diagnosis and intervention. Because of the difficulties in teaching children with autism, the families in Jordan encounter many challenges and stresses. This paper discusses the Autism Spectrum Disorder (ASD); Symptoms, Causes, Diagnosis, treatment, types and the counseling needs of the families in Jordan.


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