1. Aarabi M, Kessler E, Madan-Khetarpal S, Surti U, Bellissimo D, Rajkovic A, Yatsenko SA. {{Autism spectrum disorder in females with ARHGEF9 alterations and a random pattern of X chromosome inactivation}}. {European journal of medical genetics}. 2018.
Proper function of GABAergic synapses depends upon the postsynaptic compartment anchoring of neurotransmitter receptors to the membrane by gephyrin and collybistin (Cb). In humans, Cb is encoded by ARHGEF9 on Xq11.1. ARHGEF9 alterations, some inherited from unaffected mothers, have been reported in males with autism, seizures and severe neurodevelopmental abnormalities. In females, a spectrum of mild to moderate phenotype has been detected. We report two unrelated females with autism and mild intellectual disability. High resolution X-chromosome microarray analysis revealed de novo intragenic deletions in ARHGEF9 of 24kb and 56kb involving exons 5-8 and exons 3-8 and leading to truncated forms of collybistin. Peripheral blood samples revealed random X-chromosome inactivation in both patients. To explain phenotypic variability in female patients, we propose a model for disruption of collybistin and various irregular interactions in post-synaptic neurons based on X inactivation patterns. Our findings highlight the importance of ARHGEF9 integrity and suggest further research on its correlation with autism and neurobehavioral problems.
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2. Cvejic RC, Hocking DR, Wen W, Georgiou-Karistianis N, Cornish KM, Godler DE, Rogers C, Trollor JN. {{Reduced caudate volume and cognitive slowing in men at risk of fragile X-associated tremor ataxia syndrome}}. {Brain Imaging Behav}. 2018.
Fragile X-associated tremor ataxia syndrome is an inherited neurodegenerative disorder caused by premutation expansions (55-200 CGG repeats) of the FMR1 gene. There is accumulating evidence to suggest that early cognitive and brain imaging signs may be observed in some premutation carriers without motor signs of FXTAS, but few studies have examined the relationships between subcortical brain volumes and cognitive performance in this group. This study examined the relationships between caudate volume and select cognitive measures (executive function and information processing speed) in men at risk of developing FXTAS and controls with normal FMR1 alleles (<45 CGG repeats). The results showed that men with premutation alleles performed worse on measures of executive function and information processing speed, and had significantly reduced caudate volume, compared to controls. Smaller caudate volume in the premutation group was associated with slower processing speed. These findings provide preliminary evidence that early reductions in caudate volume may be associated with cognitive slowing in men with the premutation who do not present with cardinal motor signs of FXTAS. If confirmed in future studies with larger PM cohorts, these findings will have important implications for the identification of sensitive measures with potential utility for tracking cognitive decline. Lien vers le texte intégral (Open Access ou abonnement)
3. Guo C, Luo M, Wang X, Huang S, Meng Z, Shao J, Zhang X, Shao Z, Wu J, Robins DL, Jing J. {{Reliability and Validity of the Chinese Version of Modified Checklist for Autism in Toddlers, Revised, with Follow-Up (M-CHAT-R/F)}}. {J Autism Dev Disord}. 2018.
Although early detection of autism facilitates intervention, early detection strategies are not yet widespread in China. To improve the situation, the Chinese version of the Modified Checklist for Autism in Toddlers, Revised with Follow-Up (M-CHAT-R/F) was validated. The sample included 7928 toddlers, aged 16 to 30 months, screened during their routine care in six provinces of China. When the cut-off value was 3, the sensitivity and specificity of M-CHAT-R were 0.963 and 0.865. The inter-rater reliability and the test-retest reliability were also adequate (intraclass correlation coefficients were 0.853 and 0.759, both ps < .01). The Chinese version of M-CHAT-R/F is an effective tool for early detection of ASD and is applicable to early screening in China. Lien vers le texte intégral (Open Access ou abonnement)
4. Keith JM, Jamieson JP, Bennetto L. {{The Influence of Noise on Autonomic Arousal and Cognitive Performance in Adolescents with Autism Spectrum Disorder}}. {J Autism Dev Disord}. 2018.
This study examined the impact of noise on cognitive performance in autism spectrum disorder (ASD), while concurrently measuring sympathetic responses. Adolescents with and without ASD completed visually presented span tasks in a 2 x 2 experimental manipulation of noise (quiet vs. 75 dB gated broadband noise) and task difficulty (easier vs. harder). Analyses revealed a significant noise x difficulty interaction on performance, and a significant group x noise x difficulty interaction on sympathetic arousal. Correlational analyses indicated an adaptive effect of noise and increased arousal on performance in the easier condition for the control group and a detrimental effect of noise and increased arousal in the harder condition for the ASD group. Implications for sensory processing research and intervention development are discussed.
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5. Knutsen J, Crossman M, Perrin J, Shui A, Kuhlthau K. {{Sex differences in restricted repetitive behaviors and interests in children with autism spectrum disorder: An Autism Treatment Network study}}. {Autism}. 2018: 1362361318786490.
Compared to the social communication domain, considerably less is known about the cause, development, and impact of restricted, repetitive behaviors interests and activities in children with autism spectrum disorder, including possible sex differences. This study examined sex differences in clinically identified (Autism Diagnostic Observation Schedule) restricted and repetitive behavior symptoms using the largest known sample (N = 1024) of age-matched and intelligence quotient-matched female and male children with autism spectrum disorder. More similarities than differences were observed; however, younger higher functioning and older lower functioning females presented reduced rates on the Autism Diagnostic Observation Schedule restricted and repetitive behavior subcategory unusually repetitive/excessive, stereotyped behaviors compared to similar males. These findings identify key restricted and repetitive behavior similarities and differences among young females and males with autism spectrum disorder and emphasize the need for a deeper understanding of the female autism phenotype.
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6. Lemay JF, Yohemas M, Langenberger S. {{Redesign of the autism spectrum screening and diagnostic process for children aged 12 to 36 months}}. {Paediatrics & child health}. 2018; 23(5): 308-13.
Diagnosing autism spectrum disorder (ASD) is challenging, resource-intense and time-consuming due to clinical and etiologic heterogeneity. With the rapid increase in prevalence of ASD, higher demand for diagnostic assessment often means long waitlists for families, and limited access to specialized intervention and support. In 2013, the Alberta Children’s Hospital-Autism Spectrum Disorder Diagnostic Clinic (ACH-ASDC) experienced a significant waitlist in the 12 to 36 months’ population. A Quality Improvement Project was started in 2014; one program aim was to create an efficient, sustainable and evidence-based ASD diagnostic evaluation process. The redesigned diagnostic process included: 1) pre- and postassessment parent information sessions, 2) a screening appointment and 3) standardized clinical appointment pathways. Within its first year, the new process reduced wait times to under a month without an increase in resources, leading to an efficient diagnostic process being sustained since its implementation.
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7. Lobregt-van Buuren E, Sizoo B, Mevissen L, de Jongh A. {{Eye Movement Desensitization and Reprocessing (EMDR) Therapy as a Feasible and Potential Effective Treatment for Adults with Autism Spectrum Disorder (ASD) and a History of Adverse Events}}. {J Autism Dev Disord}. 2018.
The study investigated whether EMDR is a feasible therapy for adults with ASD and a history of adverse events, and whether it is associated with reductions in symptoms of PTSD, psychological distress and autism. Participants received 6 to 8 weeks treatment as usual (TAU), followed by a maximum of 8 sessions EMDR added to TAU, and a follow-up of 6-8 weeks with TAU only. Results showed a significant reduction of symptoms of post-traumatic stress (IES-R: d = 1.16), psychological distress (BSI: d = 0.93) and autistic features (SRS-A: d = 0.39). Positive results were maintained at follow-up. The results suggest EMDR therapy to be a feasible and potentially effective treatment for individuals with ASD who suffer from the consequences of exposure to distressing events.
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8. Nakamura T, Sakaue F, Nasu-Nishimura Y, Takeda Y, Matsuura K, Akiyama T. {{The Autism-Related Protein PX-RICS Mediates GABAergic Synaptic Plasticity in Hippocampal Neurons and Emotional Learning in Mice}}. {EBioMedicine}. 2018.
GABAergic dysfunction underlies many neurodevelopmental and psychiatric disorders. GABAergic synapses exhibit several forms of plasticity at both pre- and postsynaptic levels. NMDA receptor (NMDAR)-dependent inhibitory long-term potentiation (iLTP) at GABAergic postsynapses requires an increase in surface GABAARs through promoted exocytosis; however, the regulatory mechanisms and the neuropathological significance remain unclear. Here we report that the autism-related protein PX-RICS is involved in GABAAR transport driven during NMDAR-dependent GABAergic iLTP. Chemically induced iLTP elicited a rapid increase in surface GABAARs in wild-type mouse hippocampal neurons, but not in PX-RICS/RICS-deficient neurons. This increase in surface GABAARs required the PX-RICS/GABARAP/14-3-3 complex, as revealed by gene knockdown and rescue studies. iLTP induced CaMKII-dependent phosphorylation of PX-RICS to promote PX-RICS-14-3-3 assembly. Notably, PX-RICS/RICS-deficient mice showed impaired amygdala-dependent fear learning, which was ameliorated by potentiating GABAergic activity with clonazepam. Our results suggest that PX-RICS-mediated GABAAR trafficking is a key target for GABAergic plasticity and its dysfunction leads to atypical emotional processing underlying autism.
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9. Sweeten TL, Croen LA, Windham GC, Odell JD, Stubbs EG, Torres AR. {{Brief Report: Low Rates of Herpesvirus Detection in Blood of Individuals with Autism Spectrum Disorder and Controls}}. {J Autism Dev Disord}. 2018.
Previous research indicates that infection, especially from viruses in the family Herpesviridae, may play a role in the etiology of some cases of autism spectrum disorder (ASD). Using a case-control design and the polymerase chain reaction with site-specific primers, we screened newborn and childhood blood samples for the presence of eight human herpesviruses. Herpesvirus DNA was detected in 4 of 225 ASD individuals and 2 of 235 controls, with the most frequently detected virus being HHV-6B. Although this study does not detect a significant ASD-Herpesviridae association, it is limited by the use of site-specific primers. We suggest that new techniques using bioinformatics to search next-generation sequencing databases will be more revealing of possible ASD-virus associations.
