5-Aminoisoquinolinone, a PARP-1 Inhibitor, Ameliorates Immune Abnormalities through Upregulation of Anti-Inflammatory and Downregulation of Inflammatory Parameters in T Cells of BTBR Mouse Model of Autism

Autism spectrum disorder (ASD) covers a range of neurodevelopmental disorders involving impairments in communication and repetitive and stereotyped patterns of behavior and reciprocal social interaction. 5-Aminoisoquinolinone (5-AIQ), a PARP-1 inhibitor, has neuroprotective and anti-inflammatory effects. We investigated the influence of 5-AIQ-treatment in BTBR T+ Itpr3tf/J (BTBR) mice as an autism model and used flow cytometry to assess the effect of 5-AIQ on FOXP3, Helios, GATA3, IL-9, IL-10 and IL-17A production by CXCR6+ and CD4+ T cells in the spleen. We also confirmed the effect of 5-AIQ treatment on expression of FOXP3, Helios, GATA3, IL-17A, IL-10, and IL-9 mRNA and protein expression levels in the brain tissue by quantitative PCR and western blotting. Our results demonstrated that 5-AIQ-treated BTBR mice had significantly increased numbers of CXCR6+FOXP3+, CXCR6+IL-10+, and CXCR6+Helios+ cells and decreased numbers of CD4+GATA3+, CD4+IL-9+, and CD4+IL-17A+ cells as compared with those in untreated BTBR mice. Our results further demonstrated that treatment with 5-AIQ in BTBR mice increased expression for FOXP3, IL-10, and Helios, and decreased expression for GATA3, IL-17A, and IL-9 mRNA. Our findings support the hypotheses that 5-AIQ has promising novel therapeutic effects on neuroimmune dysfunction in autism and is associated with modulation of Treg and Th17 cells.

The Association Between Autism Symptoms and Child Functioning in a Sample With ADHD Recruited From the Community

Objective: Although autism spectrum disorder (ASD) symptoms are associated with poorer functioning in children with attention-deficit/hyperactivity disorder (ADHD), it is unclear which ASD symptom domains are most impairing. This study investigated whether specific ASD symptom domains were associated with child functioning in children with ADHD. Method: Parents of 164 children with ADHD completed a diagnostic interview to assess ADHD and comorbidities. Parents reported on ASD symptoms (Social Communication Questionnaire) and child quality of life (Pediatric Quality of Life Inventory 4.0). Parents and teachers completed the Strengths and Difficulties Questionnaire (emotional, conduct, and peer problems). Results: Repetitive and stereotyped behaviors were independently associated with emotional ( p = .02) and conduct ( p = .03) problems, and poorer quality of life ( p = .004). Reciprocal social interaction deficits were independently associated with peer problems ( p = .03). Conclusion: Reciprocal social interaction deficits and repetitive and stereotyped behaviors are important areas that should be focused on in ADHD assessment and treatment.

Behavioural and psychological characteristics in Pitt-Hopkins syndrome: a comparison with Angelman and Cornelia de Lange syndromes

Background Pitt-Hopkins syndrome (PTHS) is a genetic neurodevelopmental disorder associated with intellectual disability. Although the genetic mechanisms underlying the disorder have been identified, description of its behavioural phenotype is in its infancy. In this study, reported behavioural and psychological characteristics of individuals with PTHS were investigated in comparison with the reported behaviour of age-matched individuals with Angelman syndrome (AS) and Cornelia de Lange syndrome (CdLS). Methods Questionnaire data were collected from parents/caregivers of individuals with PTHS (n = 24), assessing behaviours associated with autism spectrum disorder (ASD), sociability, mood, repetitive behaviour, sensory processing, challenging behaviours and overactivity and impulsivity. For most measures, data were compared to data for people with AS (n = 24) and CdLS (n = 24) individually matched by adaptive ability, age and sex. Results Individuals with PTHS evidenced significantly higher levels of difficulties with social communication and reciprocal social interaction than individuals with AS, with 21 of 22 participants with PTHS meeting criteria indicative of ASD on a screening instrument. Individuals with PTHS were reported to be less sociable with familiar and unfamiliar people than individuals with AS, but more sociable with unfamiliar people than individuals with CdLS. Data also suggested areas of atypicality in sensory experiences. Challenging behaviours were reported frequently in PTHS, with self-injury (70.8%) occurring at significantly higher rates than in AS (41.7%) and aggression (54.2%) occurring at significantly higher rates than in CdLS (25%). Individuals with PTHS also evidenced lower reported mood than individuals with AS. Conclusions Behaviours which may be characteristic of PTHS include those associated with ASD, including deficits in social communication and reciprocal social interaction. High rates of aggression and self-injurious behaviour compared to other genetic syndrome groups are of potential clinical significance and warrant further investigation. An atypical sensory profile may also be evident in PTHS. The specific aetiology of and relationships between different behavioural and psychological atypicalities in PTHS, and effective clinical management of these, present potential topics for future research.

Early childhood social communication deficits in youth at clinical high-risk for psychosis: Associations with functioning and risk

Effective social functioning requires a broad range of social communication skills that are impaired in psychosis populations. However, little is known about early childhood (4- to 5-year period) social communication during the premorbid (pre-illness) stage of psychosis. The present study utilized retrospective parent reports to examine total early childhood social communication deficits, as well as deficits in two distinct domains, reciprocal social interaction (social smiling/eye gaze) and communication (social chat/gesture), in youth at clinical high-risk (CHR) for psychosis (ages 13–21; 37.2% female). Furthermore, associations between early childhood social communication and CHR youth's current functioning (social, academic/work), symptoms (positive/negative), and risk for conversion to psychosis were examined. Compared to healthy controls, CHR individuals had greater deficits in total and communication-specific early childhood social communication. Early childhood total, communication, and reciprocal social interaction deficits were associated with worse current functioning and greater current negative symptom severity (amotivation/anhedonia) in CHR youth. Early childhood total and reciprocal social interaction deficits were also associated with increased risk for conversion. These findings inform the field's understanding of the etiology and pathophysiology of psychosis by extending the current developmental literature on premorbid deficits in psychosis populations to specific domains of social behavior in a critical developmental period.

Being social in a 3D collaborative virtual learning environment : a case study of youth with autism spectrum disorder learning social competence in iSocial

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Over the past decade 3D collaborative virtual learning has gained increasing attention from researchers and practitioners in educational technology. Learners experience of presence in collaborative activities and social interactions among learners are identified as key constructs for the social dimensions of 3D collaborative virtual learning. 3D Collaborative Virtual Learning Environments (CVLEs) are beginning to be used to support learning in a variety of disciplines, including social skills learning for individuals with Autism Spectrum Disorder (ASD). This case study explores 11 youth with ASD's experience of embodied social presence and reciprocal social interaction while learning social competence in a 3D CVLE-iSocial. The findings describe youth with ASD's 1) levels of embodied presence, embodied copresence, and embodied social presence; and 2) verbal and nonverbal reciprocal social interactions across the variety of Naturalistic Practice activities in iSocial. In addition, the results of this case study inform future design by indicating associations of design features of iSocial 3D CVLE with youth with ASD's experience of embodied social presence and characteristics of reciprocal social interaction.