1. Ansari MA, Nadeem A, Attia SM, Bakheet SA, Raish M, Ahmad SF. {{Adenosine A2A receptor modulates neuroimmune function through Th17/retinoid-related orphan receptor gamma t (RORgammat) signaling in a BTBR T+ Itpr3tf/J mouse model of autism}}. {Cell Signal};2017 (Apr 21);36:14-24.
Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by abnormal social interactions, repetitive behaviors that impair social communication, and circumscribed interests. BTBR T+tf/J (BTBR) inbred mice are generally used as a model for ASD, as they show repetitive behaviors and social deficits that resemble signs of ADS in humans. Adenosine A2A receptors (A2ARs) are considered as potential targets in the treatment of immune, inflammatory, and neurodegenerative diseases. In this study, we investigated the potential effects of the A2A adenosine receptor (A2AR) antagonist SCH 5826 (SCH) and agonist CGS 21680 (CGS) on behavior (self-grooming), hot plate test results, and expression levels of IL-17A+, RORgammat+, Foxp3+, and IL-10+ in CD4+ T spleen cells in BTBR and C57BL/6 (B6) mice. We also assessed IL-17A, RORgammat, Stat3, pStat3, Foxp3, and IL-10 mRNA and protein expression levels in the brain tissue. The CGS-treated mice showed a significantly altered self-grooming score and a reduced response to the hot plate test. The results further revealed that the SCH efficiently increased the IL-17A+ and RORgammat+ expression levels and decreased the Foxp3+ and IL-10+ expression levels in CD4+ cells. However, the treatment with CGS significantly reversed these effects. In addition, CGS significantly decreased the IL-17A, RORgammat, Stat3, and pStat3 levels and increased the Foxp3 and IL-10 mRNA and protein expression levels as compared with the BTBR control and SCH treatments. Our results clearly indicate that the CGS A2AR agonist may represent a unique target for future therapeutic strategies for neuroimmune dysfunction.
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2. Baker EK, Richdale AL, Hazi A, Prendergast LA. {{Assessing the Dim Light Melatonin Onset in Adults with Autism Spectrum Disorder and No Comorbid Intellectual Disability}}. {J Autism Dev Disord};2017 (Apr 26)
This study assessed melatonin levels and the dim light melatonin onset (DLMO) in adults with Autism Spectrum Disorder (ASD) and also investigated the relationships between melatonin and objectively measured sleep parameters. Sixteen adults with ASD (ASD-Only), 12 adults with ASD medicated for comorbid diagnoses of anxiety and/or depression (ASD-Med) and 32 controls participated in the study. Although, the timing of the DLMO did not differ between the two groups, advances and delays of the melatonin rhythm were observed in individual profiles. Overall mean melatonin levels were lower in the ASD-Med group compared to the two other groups. Lastly, greater increases in melatonin in the hour prior to sleep were associated with greater sleep efficiency in the ASD groups.
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3. Conaughton RJ, Donovan CL, March S. {{Efficacy of an internet-based CBT program for children with comorbid High Functioning Autism Spectrum Disorder and anxiety: A randomised controlled trial}}. {J Affect Disord};2017 (Apr 26);218:260-268.
BACKGROUND: All trials conducted to date on BRAVE-ONLINE for youth anxiety disorders have excluded children with High Functioning Autism Spectrum Disorder (HFASD) and therefore it is unknown whether these programs might be beneficial to HFASD children. The aim of this study was to evaluate the efficacy of BRAVE-ONLINE in HFASD children with an anxiety disorder. METHODS: Forty-two HFASD children, aged 8-12 years, with an anxiety disorder, and their parents, were randomly assigned to either the BRAVE-ONLINE condition (NET) or a waitlist control (WLC). Diagnostic interviews and parent/child questionnaires were completed at pre-treatment, post-treatment and 3-month follow-up. RESULTS: At post- assessment, compared to children in the WLC condition, children in the NET condition demonstrated a significantly greater reduction in number of anxiety diagnoses, clinical severity of diagnosis, and self and parent reported anxiety symptoms, as well as significantly greater increases in overall functioning. However, loss of primary diagnosis in this sample was lower than in previous studies. LIMITATIONS: The small sample size, coupled with attrition rates, makes it difficult to generalise the findings of the study to HFASD population and to conduct analyses regarding mediators, moderators and predictors of outcomes. CONCLUSIONS: The BRAVE-ONLINE program may be useful in reducing anxiety symptoms in HFASD children, although the effects are less strong than those found in neurotypical children for a variety of reasons.
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4. Davidson MM, Ellis Weismer S. {{A Discrepancy in Comprehension and Production in Early Language Development in ASD: Is it Clinically Relevant?}}. {J Autism Dev Disord};2017 (Apr 26)
This study examined the extent to which a discrepant comprehension-production profile (i.e., relatively more delayed comprehension than production) is characteristic of the early language phenotype in autism spectrum disorders (ASD) and tracked the developmental progression of the profile. Our findings indicated that a discrepant comprehension-production profile distinguished toddlers (30 months) with ASD from late talkers without ASD (91% sensitivity, 100% specificity) in groups that were comparable on expressive language, age, and socioeconomic status. Longitudinal data for children with ASD revealed that the discrepant profile steadily decreased from 30 to 44 months until there was no significant comprehension-production difference at 66 months. In conclusion, results suggest that lower comprehension than production may be an age-specific marker of toddlers with ASD.
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5. De Groot K, Van Strien JW. {{Self-Report and Brain Indicators of Impaired Emotion Regulation in the Broad Autism Spectrum}}. {J Autism Dev Disord};2017 (Apr 26)
Although not used as a diagnostic criterion, impaired emotion regulation is frequently observed in autism. The present study examined self-reported use of emotion regulation strategies in individuals scoring low or high on autistic traits. In addition, the late positive potential, which is sensitive to emotional arousal, was used to examine the effect of one strategy, reappraisal. Reporting more autistic traits was related to using more maladaptive and fewer adaptive emotion regulation strategies. Across both groups, no attenuation of the late positive potential during downregulation of unpleasant pictures was found, possibly because of the used valence-changing reappraisal operationalisation. Hence, although self-report indicated impaired emotion regulation in individuals high on autistic traits, electrophysiological findings could not confirm this.
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6. Delobel-Ayoub M, Klapouszczak D, van Bakel MME, Horridge K, Sigurdardottir S, Himmelmann K, Arnaud C. {{Prevalence and characteristics of autism spectrum disorders in children with cerebral palsy}}. {Dev Med Child Neurol};2017 (Apr 25)
AIM: To evaluate the prevalence of co-occurring autism spectrum disorders (ASDs) among children with cerebral palsy (CP), and to describe their characteristics. METHOD: The data of 1225 CP cases from four population-based registers (Iceland, Sweden, and two in France) and one population-based surveillance programme (North East England, UK) participating in the Surveillance of Cerebral Palsy in Europe Network (SCPE) were analysed. The ASD diagnoses were systematically recorded using category F84 of the International Classification of Diseases, 10th Revision. The registers provided data on children born between 1995 and 2006, while the cross-sectional survey in the UK concerned children aged 0 to 19 years, registered in 2010. RESULTS: Among the children with CP, 107 had an associated diagnosis of ASD – i.e., 8.7% of the study population (95% confidence interval 7.2-10.5). This proportion varied across centres from 4.0% to 16.7% but was independent of CP prevalence. Male sex, co-occurring epilepsy, intellectual disability, and better walking ability were associated with the coexistence of ASD. INTERPRETATION: Our findings support the need for a multidisciplinary approach to management of children with CP to adequately identify and address all facets of presentation, including ASD.
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7. Demetriou EA, Lampit A, Quintana DS, Naismith SL, Song YJC, Pye JE, Hickie I, Guastella AJ. {{Autism spectrum disorders: a meta-analysis of executive function}}. {Mol Psychiatry};2017 (Apr 25)
Evidence of executive dysfunction in autism spectrum disorders (ASD) across development remains mixed and establishing its role is critical for guiding diagnosis and intervention. The primary objectives of this meta-analysis is to analyse executive function (EF) performance in ASD, the fractionation across EF subdomains, the clinical utility of EF measures and the influence of multiple moderators (for example, age, gender, diagnosis, measure characteristics). The Embase, Medline and PsychINFO databases were searched to identify peer-reviewed studies published since the inclusion of Autism in DSM-III (1980) up to end of June 2016 that compared EF in ASD with neurotypical controls. A random-effects model was used and moderators were tested using subgroup analysis. The primary outcome measure was Hedges’ g effect size for EF and moderator factors. Clinical sensitivity was determined by the overlap percentage statistic (OL%). Results were reported according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A total of 235 studies comprising 14 081 participants were included (N, ASD=6816, Control=7265). A moderate overall effect size for reduced EF (Hedges’ g=0.48, 95% confidence interval (CI) 0.43-0.53) was found with similar effect sizes across each domain. The majority of moderator comparisons were not significant although the overall effect of executive dysfunction has gradually reduced since the introduction of ASD. Only a small number of EF measures achieved clinical sensitivity. This study confirms a broad executive dysfunction in ASD that is relatively stable across development. The fractionation of executive dysfunction into individual subdomains was not supported, nor was diagnostic sensitivity. Development of feasible EF measures focussing on clinical sensitivity for diagnosis and treatment studies should be a priority.Molecular Psychiatry advance online publication, 25 April 2017; doi:10.1038/mp.2017.75.
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8. Erturk Cetin O, Korkmaz B, Alev G, Demirbilek V. {{EEG abnormalities and long term seizure outcome in high functioning autism}}. {Acta Neurol Belg};2017 (Apr 26)
Electroencephalographic abnormalities may occur in autistic spectrum disorders (ASD) even in the absence of clinical seizures. These abnormalities may vary from nonspecific changes to epileptiform abnormalities and are more common compared to the overall population. The level of intelligence is a significant risk factor for epilepsy in ASD. However, the relation between the functionality of the individuals with autism and the electroencephalographic (EEG) abnormalities, and the clinical significance of these abnormalities still remain relatively unclear. In this study we investigated the presence of EEG abnormalities in sixteen children diagnosed with high-functioning ASD. EEG recording was performed for at least 2 h and included at least 90 min of sleep activity. While none of the patients had clinical seizures, 5 patients (31.3%) were detected to have EEG abnormalities. Four of these were epileptiform (25%), and one patient developed seizure during follow-up. Our results support the fact that EEG abnormalities are observed at a higher rate also in ASD with a better functionality. The potential impact of EEG abnormalities on cognition and behavior, and the risk of epilepsy should be considered during long-term follow-up of these patients.
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9. Gentile I, Zappulo E, Riccio MP, Binda S, Bubba L, Pellegrinelli L, Scognamiglio D, Operto F, Margari L, Borgia G, Bravaccio C. {{Prevalence of Congenital Cytomegalovirus Infection Assessed Through Viral Genome Detection in Dried Blood Spots in Children with Autism Spectrum Disorders}}. {In Vivo};2017 (May-Jun);31(3):467-473.
BACKGROUND/AIM: Autism spectrum disorders (ASD) are neurodevelopmental disorders without a definitive etiology in most cases. Environmental factors, such as viral infections, have been linked with anomalies in brain growth, neuronal development, and functional connectivity. Congenital cytomegalovirus (CMV) infection has been associated with the onset of ASD in several case reports. The aim of this study was to evaluate the prevalence of congenital CMV infection in children with ASD and in healthy controls. PATIENTS AND METHODS: The CMV genome was tested by polymerase chain reaction (PCR) on dried blood spots collected at birth from 82 children (38 with ASD and 44 controls). RESULTS: The prevalence of congenital CMV infection was 5.3% (2/38) in cases and 0% (0/44) in controls (p=0.212). CONCLUSION: The infection rate was about 10-fold higher in patients with ASD than in the general Italian population at birth. For this reason, detection of CMV-DNA on dried blood spots could be considered in the work-up that is usually performed at ASD diagnosis to rule-out a secondary form. Given the potential prevention and treatment of CMV infection, this study could have intriguing consequences, at least for a group of patients with ASD.
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10. Gogou M, Kolios G. {{The effect of dietary supplements on clinical aspects of autism spectrum disorder: A systematic review of the literature}}. {Brain Dev};2017 (Apr 21)
BACKGROUND: Autism spectrum disorder is associated with significant social and financial burden and no definite treatment for this entity has been identified, yet. In recent years there has been an increasing interest in the use of dietary interventions as a complementary therapeutic option for these patients. OBJECTIVE: The aim of this systematic review is to provide high evidence level literature data about the effect of dietary supplements on clinical aspects of children with autism. METHODS: A comprehensive literature search was conducted using Pubmed as the medical database source. Randomized controlled trials conducted in pediatric populations and including measures of clinical outcomes were considered. RESULTS: A total of 17 eligible prospective studies were selected. Types of dietary supplements evaluated in these studies included amino acids, fatty acids and vitamins/minerals. N-acetylcysteine was shown to exert a beneficial effect on symptoms of irritability. On the other hand, literature data about the efficacy of d-cycloserine and pyridoxine-magnesium supplements was controversial. No significant effect was identified for fatty acids, N,N-dimethylglycine and inositol. Literature data about ascorbic acid and methyl B12 was few, although some encouraging results were found. No serious adverse events were reported in the vast majority of the studies, while the prevalence of adverse reactions was similar between treatment and placebo groups. CONCLUSIONS: The use of dietary supplements in children with autism seems to be a safe practice with encouraging data about their clinical efficacy. More studies are needed to further investigate this issue.
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11. Golovin RM, Broadie K. {{Neural Circuits: Reduced Inhibition in Fragile X Syndrome}}. {Curr Biol};2017 (Apr 24);27(8):R298-R300.
The Drosophila Fragile X Syndrome model has long generated insights into this devastating neurological disease state. A recent study of olfactory neural circuitry shows that decreased lateral inhibition onto projection neurons relaying sensory input into higher brain centers causes impaired behavior.
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12. Goodwin A, Matthews NL, Smith CJ. {{The Effects of Early Language on Age at Diagnosis and Functioning at School Age in Children with Autism Spectrum Disorder}}. {J Autism Dev Disord};2017 (Apr 26)
Research suggests that toddlers with no language delay (NLD) should have better outcomes than those with language delay (LD). However, the predictive utility of language milestones relative to co-varying factors such as age at diagnosis, IQ, and ASD symptomatology is unclear. This study compared school-aged children with ASD and NLD (n = 59) to a well-matched group with ASD and LD (n = 59). The LD group was diagnosed at younger ages and their historical ASD symptoms were more severe than the NLD group. The groups were similar in current ASD symptoms and adaptive functioning at school age. Language milestones were correlated with adaptive functioning, but IQ and social symptoms of ASD were stronger predictors of functioning at school age. Therefore, language milestones may not be the best indicators of prognosis for children who are diagnosed after toddlerhood.
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13. Martinez K, Merchan-Naranjo J, Pina-Camacho L, Aleman-Gomez Y, Boada L, Fraguas D, Moreno C, Arango C, Janssen J, Parellada M. {{Atypical age-dependency of executive function and white matter microstructure in children and adolescents with autism spectrum disorders}}. {Eur Child Adolesc Psychiatry};2017 (Apr 26)
Executive function (EF) performance is associated with measurements of white matter microstructure (WMS) in typical individuals. Impaired EF is a hallmark symptom of autism spectrum disorders (ASD) but it is unclear how impaired EF relates to variability in WMS. Twenty-one male youth (8-18 years) with ASD and without intellectual disability and twenty-one typical male participants (TP) matched for age, intelligence quotient, handedness, race and parental socioeconomic status were recruited. Five EF domains were assessed and several DTI-based measurements of WMS [fractional anisotropy (FA), mean diffusivity (MD) and radial diffusivity (RD)] were estimated for eighteen white matter tracts. The ASD group had lower scores for attention (F = 8.37, p = 0.006) and response inhibition (F = 13.09, p = 0.001). Age-dependent changes of EF performance and WMS measurements were present in TP but attenuated in the ASD group. The strongest diagnosis-by-age effect was found for forceps minor, left anterior thalamic radiation and left cingulum angular bundle (all p’s Lien vers le texte intégral (Open Access ou abonnement)
14. Murshid EZ. {{Effectiveness of a preparatory aid in facilitating oral assessment in a group of Saudi children with autism spectrum disorders in Central Saudi Arabia}}. {Saudi Med J};2017 (May);38(5):533-540.
OBJECTIVES: To evaluate the effectiveness of a specially-designed dental book (preparatory aid) on the behavior of a group of Autism Spectrum Disorder (ASD) Saudi children during their first dental visit to the College of Dentistry, King Saud University, Riyadh, Saudi Arabia. Methods: A cross-sectional double-blinded pre-and post clinical study consisting of 2 parts; a survey targeting the parents, and a clinical oral examination of their ASD children was conducted between January and June of 2016. Results: A total of 40 children (75% males and 25% females) with an average age of 6.1 years were included. Approximately 47.5% children acted positively during the dental procedure. The dental book had a positive effect on the behavior of 37.5% children according to their parents’ evaluation and highly effective in enhancing the parents’ dental knowledge (67.5%). Conclusion: Parents expressed positive opinions regarding the use of preparatory aids in the dental environment. Approximately half of the ASD children benefit from the preparatory aid used according to the parents’ opinion, and the follow up survey showed improvement in the parent’s dental knowledge and oral hygiene practices.
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15. Van der Merwe C, Bornman J, Donohue D, Harty M. {{The attitudes of typically developing adolescents towards their sibling with autism spectrum disorder}}. {S Afr J Commun Disord};2017 (Apr 26);64(1):e1-e7.
BACKGROUND: Understanding how the cognitive, emotional and behavioural components of sibling attitudes interact with one another at various stages of a sibling’s lifespan will allow clinicians to provide better support to children with autism spectrum disorder (ASD) and their families. However, no research exists which focusses on describing the attitudes of adolescent siblings of children with ASD within the South African context towards their sibling with an ASD. The primary aim of this study was to investigate how typically developing adolescents recall their past attitudes and describe their present attitudes towards their sibling with an ASD. METHODS: Thirty typically developing adolescents who have siblings with ASD were selected to complete the survey instrument, the Lifespan Sibling Relationship Scale, using a cross-sectional design. RESULTS: Results indicate that the measure has internal consistency within this sample. Wilcoxon signed-ranks tests were used to test for significant differences between the mean values for the two self-reported time periods. Friedman analysis of variances (ANOVAs) was used to test for significant differences in the three components of attitudes, namely affect, behaviour and cognition. Results indicate that participants held more positive attitudes towards their siblings with ASD as adolescents compared with when they were younger and that adolescents rated their current emotions towards and beliefs about their sibling with ASD to be more positive than their current interaction experiences. CONCLUSION: As siblings’ attitudes appear to change over time, clinicians should use a lifespan approach to sibling attitudes when designing and implementing supports for siblings of children with ASD.
16. Wink LK, Adams R, Pedapati EV, Dominick KC, Fox E, Buck C, Erickson CA. {{Brief Report: Metformin for Antipsychotic-Induced Weight Gain in Youth with Autism Spectrum Disorder}}. {J Autism Dev Disord};2017 (Apr 26)
Antipsychotic treatment in youth with autism spectrum disorder (ASD) is becoming increasingly common, placing individuals at risk for antipsychotic-induced weight gain and associated complications. Metformin hydrochloride, a biguanide medication FDA-approved for treatment of type-2 diabetes in youth, may hold promise for treatment of antipsychotic-induced weight gain in youth with ASD. In this report we assess the long-term impact of metformin on antipsychotic-associated weight gain in a naturalistic sample of 53 youth with ASD. Results indicate that treatment with metformin stabilized BMI z-score over a nearly 2 year mean treatment period. Further work is indicated to determine the safety and efficacy of metformin treatment in youth with ASD, as well as predictors of response as a treatment for antipsychotic-induced weight gain.
