Acute or chronic oxytocin administration relieves social deficits in two mouse models of autism spectrum disorder

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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The Dopamine Hypothesis of Autism Spectrum Disorder Revisited: Current Status and Future Prospects

Developmental Neuroscience ◽

10.1159/000515751 ◽

2021 ◽

pp. 1-11

Author(s):

Denis Pavăl ◽

Ioana Valentina Micluția

Keyword(s):

Autism Spectrum Disorder ◽

Dopaminergic System ◽

Autism Spectrum ◽

Spectrum Disorder ◽

Current Status ◽

Social Deficits ◽

Future Prospects ◽

Autistic Behavior ◽

Stereotyped Behaviors ◽

Dopamine Hypothesis

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.

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Structural neuroimaging correlates of social deficits are similar in autism spectrum disorder and attention-deficit/hyperactivity disorder: analysis from the POND Network

Translational Psychiatry ◽

10.1038/s41398-019-0382-0 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 16

Author(s):

Danielle A. Baribeau ◽

Annie Dupuis ◽

Tara A. Paton ◽

Christopher Hammill ◽

Stephen W. Scherer ◽

...

Keyword(s):

Autism Spectrum Disorder ◽

Attention Deficit Hyperactivity Disorder ◽

Attention Deficit ◽

Autism Spectrum ◽

Spectrum Disorder ◽

Social Deficits ◽

Structural Neuroimaging ◽

Hyperactivity Disorder

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Gut Bacteria Shared by Children and Their Mothers Associate with Developmental Level and Social Deficits in Autism Spectrum Disorder

mSphere ◽

10.1128/msphere.01044-20 ◽

2020 ◽

Vol 5 (6) ◽

Author(s):

Yu Chen ◽

Hui Fang ◽

Chunyan Li ◽

Guojun Wu ◽

Ting Xu ◽

...

Keyword(s):

Autism Spectrum Disorder ◽

Gut Microbiota ◽

Autism Spectrum ◽

Gut Bacteria ◽

Spectrum Disorder ◽

Developmental Level ◽

Social Deficits ◽

Microbial Structure

Gut microbiota may contribute to the pathogenesis and development of autism spectrum disorder. The maternal gut microbiota influences offspring gut microbial structure and composition.

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Diagnosis of Autism Spectrum Disorder in Adolescents with Complex Clinical Presentations: A Montreal Case Series

Adolescent Psychiatry ◽

10.2174/2210676609666181204125951 ◽

2019 ◽

Vol 9 (1) ◽

pp. 33-43

Author(s):

Nicolas Garel ◽

Patricia Garel

Keyword(s):

Mental Health ◽

Autism Spectrum Disorder ◽

Autism Spectrum Disorders ◽

Young Children ◽

Autism Spectrum ◽

Spectrum Disorder ◽

Social Deficits ◽

High Functioning ◽

Intellectual Abilities ◽

Spectrum Disorders

Background: Despite increased attention and recognition of autism spectrum disorders, many patients suffering from these disorders remain undiagnosed or are diagnosed late due to their subtle clinical presentation. The challenge for clinicians working in the field of mental health is not in screening and diagnosing young children showing typical signs of autism spectrum disorders, but rather in identifying patients at the high-functioning end of the spectrum whose intellectual abilities mask their social deficits. Objective: Because therapeutic interventions differ radically once the diagnosis of ASD has been made, it is important to understand the trajectory of those adolescents and identify clues that could help raise the diagnosis of ASD earlier. Methods: Records of eight adolescents with a late diagnosis of ASD were retrospectively reviewed to identify relevant clinical features that were overlooked in childhood and early adolescence. Results: The patients were previously misdiagnosed with multiple mental health disorders. These cases showed striking similarities in terms of developmental history, reasons for misdiagnosis, and the clinical picture at the time of ASD recognition. The cases were characterized by complex and fluctuating symptomatology, including depression, anxiety, behavioural problems, self-injurious behaviour and suicidal thoughts. Their Autism Spectrum Disorder (ASD) went previously undiagnosed due to the individual’s intelligence and learning abilities, which masked their social deficits and developmental irregularities. Signs of ASD were continuously present since childhood in all the eight cases. Once the developmental histories and the psychiatric evaluation of these adolescents were done by psychiatrists with appropriate knowledge of autism, the diagnosis of ASD was made. Conclusion: The ASD hypothesis should be raised in the presence of confusing symptoms that do not respond to usual treatment and are accompanied by an irregular developmental background. It is indeed a difficult diagnosis to make; however, the focused clinician can note subtle signs of ASD despite the intellectual learning of social codes. Family history, developmental irregularities, rigidity, difficulty in spontaneously understanding emotions, discomfort in groups and the need to be alone are significant indicators to recognize. Once the diagnosis has been considered, it must be confirmed or rejected by an experienced multidisciplinary team. The challenge for clinicians working in the field of mental health is not in screening and diagnosing young children showing typical signs of ASD, but rather in identifying patients who are at high-functioning end of the spectrum whose intellectual abilities mask their social deficits.

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C-65 Transdiagnostic Factors of Social Impairment in Comorbid Autism Spectrum Disorder and Attention Deficit Hyperactivity Disorder

Archives of Clinical Neuropsychology ◽

10.1093/arclin/acz034.227 ◽

2019 ◽

Vol 34 (6) ◽

pp. 1094-1094

Author(s):

A Garagozzo ◽

L Katz ◽

M Scott ◽

S Hunter

Keyword(s):

Autism Spectrum Disorder ◽

Motor Skills ◽

Autism Spectrum ◽

Spectrum Disorder ◽

Motor Dysfunction ◽

Social Impairment ◽

Motor Deficits ◽

Social Deficits ◽

Functional Communication ◽

Children With Adhd

Abstract Objective Comorbid Autism Spectrum Disorder (ASD) and ADHD are associated with greater symptom severity, including social impairment. Furthering work by Lerner, Pothoff, and Hunter (2015), we sought to identify unique and shared factors that contribute to parent-reported social deficits in children with ADHD, ASD, and ADHD+ASD. We hypothesized attention, hyperactivity, and motor skills would predict social deficits in ADHD, while functional communication and motor skills would predict social deficits in ASD; and additively, all factors would predict social deficits in ADHD+ASD. Method Utilizing a clinical database, we identified 236 participants (4-21 years; Mage = 10.6; 71% male; 28% African American; FSIQ M = 94.31) with diagnoses of ADHD, ASD, and ADHD+ASD. We examined FSIQ from the WISC-4/5, WPPSI-3, or DAS-2, motor skills and social impairment from the SIB-R and attention, hyperactivity, and functional communication from the BASC-2/3. Results Using hierarchical linear regression and controlling for FSIQ, hypotheses were partially supported. FSIQ was controlled for in each group. For ADHD, hyperactivity, functional communication, and motor skills contributed significantly to the model (p < .001), while for ASD, motor skills contributed significantly to the model (p < .001). For ASD + ADHD, functional communication and motor skills contributed significantly to the model (p < .001) Conclusion Results support previous findings that motor deficits and functional communication are associated with social impairment in children with ADHD and ASD, independently and comorbidly. This suggests that targeting motor dysfunction and functional communication concurrently may be effective for improving social interaction skills in children with ADHD +ASD.

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