1. Ahmad SF, Ansari MA, Nadeem A, Bakheet SA, Alshammari MA, Khan MR, Alsaad AMS, Attia SM. {{S3I-201, a selective Stat3 inhibitor, restores neuroimmune function through upregulation of Treg signaling in autistic BTBR T(+) Itpr3(tf)/J mice}}. {Cell Signal};2018 (Sep 10);52:127-136.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder whose symptoms include communication deficits, a lack of social skills, and stereotyped repetitive behaviors. We used BTBR T(+) Itpr3(tf)/J (BTBR) mice, a model that demonstrates most of the core behavioral features of ASD, such as decreased sociability and high levels of repetitive behaviors. Currently, there is no treatment available that is able to improve most of the ASD disorder symptoms; thus, finding novel therapies is immediately required. Stat3 inhibitors are potential targets in the treatment of several immune disorders. The aim of the present study was to investigate the effects of S3I-201, a selective Stat3 inhibitor, to determine its potential mechanism in BTBR mice. In this study, we first examined the effects of S3I-201 on repetitive behavior and marble burying. We also examined the treatment of S3I-201 on Th1 (IFN-gamma and T-bet), Th17 (IL-17A, RORgammat, Stat3, IL-21, and IL-22), and T regulatory (Treg, Foxp3 and Helios) production in spleen CD4(+) T cells. We further assessed Th1, Th17, and Treg mRNA and protein expression levels in brain tissues. S3I-201 treatment in BTBR mice significantly prevents marble burying and repetitive behavior. Furthermore, S3I-201 administration causes a considerable decrease in IFN-gamma, T-bet, IL-17A, RORgammat, Stat3, IL-21, and IL-22 levels, and increases in Foxp3 and Helios production CD4(+) T cells in BTBR mice. Additionally, S3I-201 treatment also significantly decreases Th1 and Th17 levels, and increases Treg mRNA and protein expression levels. Therefore, these results suggest that S3I-201 could be considered as a therapeutic option for ASD.

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2. Chao OY, Yunger R, Yang YM. {{Corrigendum to « Behavioral assessments of BTBR T+Itpr3tf/J mice by tests of object attention and elevated open platform: implications for an animal model of psychiatric comorbidity in autism » [Behav. Brain Res. 347 (2018) 140-147]}}. {Behav Brain Res};2018 (Sep 6)

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3. Danforth AL, Grob CS, Struble C, Feduccia AA, Walker N, Jerome L, Yazar-Klosinski B, Emerson A. {{Reduction in social anxiety after MDMA-assisted psychotherapy with autistic adults: a randomized, double-blind, placebo-controlled pilot study}}. {Psychopharmacology (Berl)};2018 (Sep 8)

RATIONALE: Standard therapeutic approaches to reduce social anxiety in autistic adults have limited effectiveness. Since 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy shows promise as a treatment for other anxiety disorders, a blinded, placebo-controlled pilot study was conducted. OBJECTIVES: To explore feasibility and safety of MDMA-assisted psychotherapy for reduction of social fear and avoidance that are common in the autistic population. METHODS: Autistic adults with marked to very severe social anxiety were randomized to receive MDMA (75 to 125 mg, n = 8) or inactive placebo (0 mg, n = 4) during two 8-h psychotherapy sessions (experimental sessions) in a controlled clinical setting. Double-blinded experimental sessions were spaced approximately 1 month apart with 3 non-drug psychotherapy sessions following each. The primary outcome was change in Leibowitz Social Anxiety Scale (LSAS) Total scores from Baseline to one month after the second experimental session. Outcomes were measured again six months after the last experimental session. RESULTS: Improvement in LSAS scores from baseline to the primary endpoint was significantly greater for MDMA group compared to the placebo group (P = 0.037), and placebo-subtracted Cohen’s d effect size was very large (d = 1.4, CI – 0.074, 2.874). Change in LSAS scores from baseline to 6-month follow-up showed similar positive results (P = 0.036), with a Cohen’s d effect size of 1.1 (CI – 0.307, 2.527). Social anxiety remained the same or continued to improve slightly for most participants in the MDMA group after completing the active treatment phase. CONCLUSIONS: This pilot trial demonstrated rapid and durable improvement in social anxiety symptoms in autistic adults following MDMA-assisted psychotherapy. Initial safety and efficacy outcomes support expansion of research into larger samples to further investigate this novel treatment for social anxiety. TRIAL REGISTRATION: clinicaltrials.gov identifier, NCT00302744.

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4. Frantz MC, Pellissier L, Pflimlin E, Loison S, Gandia J, Marsol C, Durroux T, Mouillac B, Becker J, Le Merrer J, Valencia C, Villa P, Bonnet D, Hibert M. {{LIT-001, the First Nonpeptide Oxytocin Receptor Agonist that Improves Social Interaction in a Mouse Model of Autism}}. {J Med Chem};2018 (Sep 10)

Oxytocin (OT) and its receptor (OT-R) are implicated in the aetiology of autism spectrum disorders (ASD) and OT-R is a potential target for therapeutic intervention. Very few nonpeptide oxytocin agonists have currently been reported. Their molecular and in vivo pharmacology remain to be clarified and none of them has been shown efficient in improving social interaction in animal models relevant to ASD. In an attempt to rationalize the design of centrally active nonpeptide full agonists, we studied in a systematic way the structural determinants of the affinity and efficacy of representative ligands of the V1a and V2 vasopressin receptor subtypes (V1a-R and V2-R) and of the oxytocin receptor. Our results confirm the subtlety of the structure-affinity and structure-efficacy relationships around vasopressin/oxytocin receptor ligands and lead however to the first nonpeptide OT receptor agonist active in a mouse model of ASD after peripheral i.p. administration.

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5. Ghanouni P, Jarus T, Zwicker JG, Lucyshyn J, Mow K, Ledingham A. {{Social Stories for Children with Autism Spectrum Disorder: Validating the Content of a Virtual Reality Program}}. {J Autism Dev Disord};2018 (Sep 10)

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that affects socio-emotional skills and perspective-taking abilities. Although social stories in a form of virtual reality program can help children with ASD, developing them and identifying appropriate responses might be subjective and thus challenging. Using Delphi method, and guided by general case training, we involved 63 parents and clinicians of individuals with ASD, in two rounds of online iteration to refine the stories. Scenarios that reached a 75% agreement level were accepted. This project is the first study to develop and validate a library of 75 short socio-emotional stories that illustrate various types and intensities of emotion in three social contexts of home, school, and community as the content of a virtual reality program.

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6. Gittins S, Steel D, Brunklaus A, Newsom-Davis I, Hawkins C, Aylett SE. {{Autism spectrum disorder, social communication difficulties, and developmental comorbidities in Sturge-Weber syndrome}}. {Epilepsy Behav};2018 (Sep 6);88:1-4.

Sturge-Weber syndrome (SWS) is a neurocutaneous disorder characterized by the combination of a facial naevus flammeus and pial angioma, often associated with learning difficulties and/or epilepsy. Here, we report on the neuropsychological characteristics of a cohort of 92 children with SWS seen at a national referral center between 2002 and 2015. Almost a quarter (24%) had a diagnosis of autism spectrum disorder (ASD), with 45% overall having evidence of social communication difficulties (SCD). Autism spectrum disorder was more commonly seen in those individuals with bilateral angioma (p=0.021). Significant behavioral difficulties were reported in 50% while 26% had difficulties with sleep. Difficulties with social communication, behavior, and sleep were closely associated with one another. They were not, however, significantly associated with markers of epilepsy severity and were noted to occur even in children without epilepsy. The prevalence of ASD/SCD, sleep difficulties, and behavioral disorders seen in SWS is high and reflects the complex needs of this group.

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7. Lindor E, Rinehart N, Fielding J. {{Distractor Inhibition in Autism Spectrum Disorder: Evidence of a Selective Impairment for Individuals with Co-occurring Motor Difficulties}}. {J Autism Dev Disord};2018 (Sep 10)

Although most researchers agree that individuals with Autism Spectrum Disorder (ASD) exhibit atypical attention, there is little consensus on the exact nature of their deficits. We explored whether attentional control in ASD varies as a function of motor proficiency. Nineteen children with ASD and 26 typically-developing controls completed the Movement Assessment Battery for Children and two ocular motor tasks requiring them to generate a saccade toward, and fixate, a visual target in the presence or absence of a distractor. The ASD group demonstrated poorer accuracy than typically-developing controls when distractors were present. Importantly, however, ASD symptomology was only related to poorer accuracy in individuals with motor difficulties. These findings suggest that distractor inhibition may be selectively impaired in this subgroup.

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8. Rogers SJ, Estes A, Vismara L, Munson J, Zierhut C, Greenson J, Dawson G, Rocha M, Sugar C, Senturk D, Whelan F, Talbott M. {{Enhancing Low-Intensity Coaching in Parent Implemented Early Start Denver Model Intervention for Early Autism: A Randomized Comparison Treatment Trial}}. {J Autism Dev Disord};2018 (Sep 10)

Short-term low intensity parent implemented intervention studies for toddlers with autism spectrum disorder (ASD) have found it difficult to demonstrate significantly improved developmental scores or autism severity compared to community treatment. We conducted a randomized comparative intent-to-treat study of a parent implemented intervention to (1) test the effects of an enhanced version on parent and child learning, and (2) evaluate the sensitivity to change of proximal versus distal measures of child behavior. We randomized 45 children with ASD, 12-30 months of age, into one of two versions of parent-implemented Early Start Denver Model (P-ESDM), the basic model, in which we delivered 1.5 h of clinic-based parent coaching weekly, and an enhanced version that contained three additions: motivational interviewing, multimodal learning tools, and a weekly 1.5-h home visit. We delivered the intervention for 12 weeks and measured child and parent change frequently in multiple settings. We found a time-by-group interaction: parents in the enhanced group demonstrated significantly greater gains in interaction skills than did parents in the non-enhanced group. Both interventions were associated with significant developmental acceleration; however, child outcomes did not differ by group. We found a significant relationship between degree of change in parental interaction skill and rate of children’s improvement on our proximal measure. Parents in both groups reported satisfaction with the intervention. These findings suggest that parent skills improved more in the enhanced group than the comparison group. Children in the two groups showed similar improvements. Rate of individual parent learning was associated with greater individual child progress on a measure quite proximal to the treatment, though not on standardized assessments.

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9. Sakaguchi A, Yamashita Y, Ishii T, Uehara T, Kosaki K, Takahashi T, Takenouchi T. {{Further evidence of a causal association between AGO1, a critical regulator of MicroRNA formation, and intellectual disability/autism spectrum disorder}}. {Eur J Med Genet};2018 (Sep 10)

Among the many regulators of microRNA formation, Argonaute 1 (AGO1) plays critical roles in RNA interference, which controls a wide range of biological activities. Recent large-scale genomic studies have identified at least five patients with intellectual disability/autism spectrum disorder who had de novo mutations in AGO1, but detailed clinical information was not available. The recognizable clinical features that are associated with AGO1 mutations remain to be determined. The proposita was a 15-year-old girl with diffuse hypotonia, infrequent seizures, and intellectual disability with an intellectual quotient of 41. She had characteristic facial features consisting of telecanthus, wide nasal bridge with bulbous nasal tip, and a round face with downslanted palpebral fissures. Serial computed tomography scans showed progressive calcification in the globus pallidus that became evident during childhood. A whole exome analysis in trio revealed a de novo heterozygous mutation in AGO1, i.e., c.595G>A p.(Gly199Ser). The distinctive facial features, i.e., telecanthus, wide nasal bridge with bulbous nasal tip, and a round face with downslanted palpebral fissures, closely resembled previously reported patients who had a chromosomal microdeletion encompassing AGO1 locus. The combinatory phenotype of such characteristic facial features and radiographic features, i.e. progressive calcification in the caudate, in the presently reported patient suggest that AGO1 mutations lead to a syndromic form of intellectual disability/autism spectrum disorder. Distinctive facial features with early and progressive calcification in the globus pallidus may be suggestive of the presence of AGO1 mutations.

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10. Valagussa G, Trentin L, Signori A, Grossi E. {{Toe Walking Assessment in Autism Spectrum Disorder Subjects: A Systematic Review}}. {Autism Res};2018 (Sep 10)

There is increasing evidence that autism spectrum disorder (ASD) subjects have also motor impairments. Toe walking (TW) is a phenomenon that can be found in ASD subjects during gait, even if this condition was found not to be necessarily related only to walking, since these children often also stand and run on their tiptoes. Since persistent TW in ASD subjects may contribute to secondary shortening of the Achilles’s tendon, it becomes important to have an assessment tool and/or outcome measure for both the clinical and rehabilitative settings. The aim of this systematic review is to critically evaluate and describe the methods employed to assess toe walking in ASD subjects. The systematic review protocol was previously registered on PROSPERO. We conducted an extensive literature search in PubMed, CINAHL, PsycINFO, The Cochrane Library, and Scopus databases. There were no restrictions on the types of study design eligible for inclusion. Ten studies were included in the systematic review. Risk of bias of the included studies was conducted using the following instruments depending on the study types: STROBE Statement, Cochrane risk of bias tool, and CARE checklist. Almost all the included studies (8/10) proposed a tip-toe behavior (TTB) assessment only during walking. Nine out of ten of the included studies assessed TTB using a qualitative methodology. The results evidenced the heterogeneity of qualitative methods and a lack of a structured quantitative test to assess toe walking in ASD subjects. Autism Res 2018. (c) 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY ABSTRACT: Toe walking (TW) is a phenomenon that can be found during ASD subject’s gait. The persistence of this behavior may contribute to secondary Achilles’s tendon shortening. In this perspective it becomes important to have an assessment tool and/or outcome measure for both the clinical and rehabilitative settings. The current systematic review aimed to describe the methods employed to assess TW. The results evidenced the lack and the need of a structured quantitative test to assess TW in ASD subjects.

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11. Zhao X, Li X, Song Y, Shi W. {{Autistic Traits and Prosocial Behaviour in the General Population: Test of the Mediating Effects of Trait Empathy and State Empathic Concern}}. {J Autism Dev Disord};2018 (Sep 10)

Although the core characteristics associated with autistic traits are impaired social interactions, there are few studies examining how autistic traits translate into prosocial behaviour in daily life. The current study explored the effect of autistic traits on prosocial behaviour and the mediating role of multimodal empathy (trait empathy and state empathic concern). The results showed that autistic traits reduced prosocial behaviour directly and indirectly through complex mediation by multimodal empathy. The findings revealed the internal mechanism of autistic traits impeding prosocial behaviour and expanded our understandings of social behaviour in autism spectrum conditions (ASCs) and autistic traits in the general population. Furthermore, the results have implications for social adaptability interventions for individuals with ASCs and high levels of autistic traits.

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12. Zhao Y, Zhou C, Yu H, Zhang W, Cheng F, Yu H, Zhou D, Li B, Liu J, Dai J, Zhong J, Chen M, Huang T, Pan R, Duan S, Hu Z. {{Association between the methylation of six apoptosisassociated genes with autism spectrum disorder}}. {Mol Med Rep};2018 (Sep 10)

Excessive apoptosis hinders the process of brain maturation and is regarded as one of the principal risk factors for the development of autism spectrum disorder (ASD). The aim of the present study was to investigate the association between the methylation of six apoptosisassociated genes [transforming growth factor beta 1 (TGFB1), BCL2 associated X, apoptosis regulator, insulin like growth factor binding protein 3, protein kinase C beta 1, presenilin 2 and CC motif chemokine ligand 2] and ASD. Using quantitative methylationspecific polymerase chain reaction technology, DNA methylation levels were detected in 42 autistic and 26 control subjects. The logistic regression analysis results demonstrated that of the six genes, only TGFB1 was significantly hypomethylated in peripheral blood samples from children with autism compared with control samples (mean percentage of methylated reference, 0.011% vs. 0.019%; ageadjusted P=0.028). In addition, TGFB1 methylation was identified to be positively associated with the interaction ability score from the Autism Behavior Checklist (r=0.452; P=0.035). These data suggested that decreased TGFB1 methylation may contribute to the development of ASD.

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13. Zhou W, Li S. {{Decreased levels of serum retinoic acid in chinese children with autism spectrum disorder}}. {Psychiatry Res};2018 (Aug 25);269:469-473.

Previous studies framed a possible link of retinoic acid (RA) regulation in brain to autism spectrum disorders (ASD) etiology. The aim of this study was to measure serum levels of RA in relation to the degree of the severity of autism. Serum RA levels were measured by enzyme-linked immunosorbent assay (ELISA) colorimetric detection Kit in 81 children with autism and 81 age-sex matched typical development children. The severity of autistic symptomatology was measured by the Childhood Autism Rating Scale (CARS) score using the Chinese version. The serum levels of RA in the children with ASD (1.68+/-0.52ng/ml) were significantly lower than those of control subjects (2.13+/-0.71ng/ml) (P<0.001). At admission, 57 children (70.4%) had a severe autism. In those children, the mean serum RA levels were lower than in those children with mild to moderate autism (1.57+/-0.47ng/ml VS. 1.95+/-0.55ng/ml; P=0.003). Furthermore, in multivariate model, low RA level was associated with having/the presence of ASD (adjusted odd ratio[OR] 0.516; P=0.003) and severe ASD (OR 0.415; P=0.015) after adjusted for confounding factors. The data suggested that serum RA levels were reduced in the group with ASD, and the levels negative correlated significantly with the severity of autism. Lien vers le texte intégral (Open Access ou abonnement)