1. Abdala AP, Toward MA, Dutschmann M, Bissonnette JM, Paton JF. {{Deficiency of GABAergic synaptic inhibition in the Kolliker-Fuse area underlies respiratory dysrhythmia in a mouse model of Rett syndrome}}. {J Physiol}. 2015.
Central apnoeas and respiratory irregularity are a common feature in Rett syndrome (RTT), a neurodevelopmental disorder most often caused by mutations in the methyl-CpG-binding protein 2 gene (MECP2). We used a MECP2 deficient mouse model of RTT as a strategy to obtain insights into the neurobiology of the disease and into mechanisms essential for respiratory rhythmicity during normal breathing. Previously, we showed that, systemic administration of a GABA reuptake blocker in MECP2 deficient mice markedly reduced the occurrence of central apnoeas. Further, we found that, during central apnoeas, post-inspiratory drive (adductor motor) to the upper airways was enhanced in amplitude and duration in Mecp2 heterozygous female mice. Since pontine Kolliker-Fuse (KF) region drives post-inspiration, suppresses inspiration, and can reset the respiratory oscillator phase, we hypothesized that synaptic inhibition in this area is essential for respiratory rhythm regularity. In this study, we found that: (i) Mecp2 heterozygous mice show deficiency of GABA perisomatic bouton-like puncta and processes in the KF; (ii) blockade of GABA reuptake in the KF of RTT mice reduced breathing irregularity; (iii) conversely, blockade of GABAA receptors in the KF of healthy rats mimicked the RTT respiratory phenotype of recurrent central apnoeas and prolonged post-inspiratory activity. Our results show that reductions in synaptic inhibition within the KF induce rhythm irregularity whereas boosting GABA transmission reduces respiratory arrhythmia in a murine model of RTT. Our data suggest that manipulation of synaptic inhibition in KF may be a clinically important strategy for alleviating the life threatening respiratory disorders in RTT. This article is protected by copyright. All rights reserved.
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2. Brick DJ, Nethercott HE, Montesano S, Banuelos MG, Stover AE, Schutte SS, O’Dowd DK, Hagerman RJ, Ono M, Hessl DR, Tassone F, Schwartz PH. {{The Autism Spectrum Disorders Stem Cell Resource at Children’s Hospital of Orange County: Implications for Disease Modeling and Drug Discovery}}. {Stem Cells Transl Med}. 2015; 4(11): 1369.
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3. Chen YW, Bundy AC, Cordier R, Chien YL, Einfeld SL. {{Motivation for everyday social participation in cognitively able individuals with autism spectrum disorder}}. {Neuropsychiatr Dis Treat}. 2015; 11: 2699-709.
OBJECTIVE: The purpose of the present study was to examine motivation for the contextual nature of motivations for social participation in cognitively able adolescents and adults with autism spectrum disorder, using self-determination theory as a theoretical framework. METHODS: Fourteen Australians and 16 Taiwanese (aged 16-45 years) with Asperger’s syndrome and high functioning autism were asked to carry a device which prompted them seven times/day for 7 days, to record what they were doing, with whom, perceived difficulty and social reciprocity, and the reasons for engaging in a situation, which were then coded into degree of self-determination. RESULTS: Multilevel analyses showed that participants were more likely to be self-determined while engaging in « solitary/parallel leisure » and « social activities » than in other types of activities. Interactions with « family members » and « casual/intimate friends » were also positively associated with self-determined motivation. Further, participants were more likely to perceive higher levels of being listened to during interaction with casual/intimate friends than in interaction with other people. Global social anxiety served as a moderator for their perceptions of difficulty and social reciprocity during social engagement. CONCLUSION: The findings highlight the context-dependent motivations for social engagement of cognitively able individuals with autism spectrum disorder.
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4. Corvey K, Menear KS, Preskitt J, Goldfarb S, Menachemi N. {{Obesity, Physical Activity and Sedentary Behaviors in Children with an Autism Spectrum Disorder}}. {Matern Child Health J}. 2015.
Background and Objectives Previous literature using small sample sizes and limited geographic areas report that overweight/obesity and physical inactivity occur at higher rates among children with autism spectrum disorder (ASD) compared to typically developing peers. The purpose of this study was to examine obesity, overweight, physical activity, and sedentary behavior among children and youth with and without ASD using nationally representative data and controlling for secondary conditions, including intellectual and learning disabilities, ADHD, developmental delay, and other mental, physical, and medical conditions, as well as medication use. Methods Data were collected from the 2011-2012 National Survey of Children’s Health, a cross-sectional survey of 65,680 (weighted N = 49,586,134) children aged 6-17 (1385 with ASD, weighted N = 986,352). Logistic regression was used to estimate odds ratios, adjusting for demographics and possible secondary conditions. Results Having a diagnosis of ASD was associated with higher odds of obesity (OR 1.76, CI 1.27-2.43; p = <0.001). However, after additional adjustment for possible secondary conditions, ASD diagnosis was no longer associated with obesity. Those with moderate ASD (OR 0.58, CI 0.36-0.93; p = <0.05) reported lower odds of sedentary behavior, but this association failed to achieve significance after adjustment for secondary conditions and medication use. No significant associations between ASD and overweight or physical activity were found. Conclusions These findings suggest that ASD diagnosis is not significantly associated with obesity status after adjustment for possible secondary conditions and medication use. Decision makers, clinicians, and researchers developing interventions for children with ASDs should consider how secondary conditions may impact obesity and related activities. Lien vers le texte intégral (Open Access ou abonnement)
5. Hare DJ, Gracey C, Wood C. {{Anxiety in high-functioning autism: A pilot study of experience sampling using a mobile platform}}. {Autism}. 2015.
Anxiety and stress are everyday issues for many people with high-functioning autism, and while cognitive-behavioural therapy is the treatment of choice for the management of anxiety, there are challenges in using it with people with high-functioning autism. This study used modified experience sampling techniques to examine everyday anxiety and stress in adults with high-functioning autism and to explore the feasibility of delivering real-time stress management techniques using a mobile platform. High levels of anxiety were found to be characterised by worry, confusing thoughts and being alone but was not associated with internal focus, imagery or rumination. Participants reported improved mood and less worry and anxious thinking in the active phase of the study. These results support previous studies indicating that people with high-functioning autism differ in their experience of anxiety and provided preliminary data on the feasibility of real-time stress management. The limitations of this approach are discussed together with considerations for future work in the area of developing clinical interventions on mobile platforms.
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6. Kern JK, Geier DA, Deth RC, Sykes LK, Hooker BS, Love JM, Bjorklund G, Chaigneau CG, Haley BE, Geier MR. {{Systematic Assessment of Research on Autism Spectrum Disorder and Mercury Reveals Conflicts of Interest and the Need for Transparency in Autism Research}}. {Sci Eng Ethics}. 2015.
Historically, entities with a vested interest in a product that critics have suggested is harmful have consistently used research to back their claims that the product is safe. Prominent examples are: tobacco, lead, bisphenol A, and atrazine. Research literature indicates that about 80-90 % of studies with industry affiliation found no harm from the product, while only about 10-20 % of studies without industry affiliation found no harm. In parallel to other historical debates, recent studies examining a possible relationship between mercury (Hg) exposure and autism spectrum disorder (ASD) show a similar dichotomy. Studies sponsored and supported by industry or entities with an apparent conflict of interest have most often shown no evidence of harm or no « consistent » evidence of harm, while studies without such affiliations report positive evidence of a Hg/autism association. The potentially causal relationship between Hg exposure and ASD differs from other toxic products since there is a broad coalition of entities for whom a conflict of interest arises. These include influential governmental public health entities, the pharmaceutical industry, and even the coal burning industry. This review includes a systematic literature search of original studies on the potential relationship between Hg and ASD from 1999 to date, finding that of the studies with public health and/or industry affiliation, 86 % reported no relationship between Hg and ASD. However, among studies without public health and/or industry affiliation, only 19 % find no relationship between Hg and ASD. The discrepancy in these results suggests a bias indicative of a conflict of interest.
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7. Mohamed Fel B, Zaky EA, El-Sayed AB, Elhossieny RM, Zahra SS, Salah Eldin W, Youssef WY, Khaled RA, Youssef AM. {{Assessment of Hair Aluminum, Lead, and Mercury in a Sample of Autistic Egyptian Children: Environmental Risk Factors of Heavy Metals in Autism}}. {Behav Neurol}. 2015; 2015: 545674.
Background and Aims. The etiological factors involved in the etiology of autism remain elusive and controversial, but both genetic and environmental factors have been implicated. The aim of this study was to assess the levels and possible environmental risk factors and sources of exposure to mercury, lead, and aluminum in children with autism spectrum disorder (ASD) as compared to their matched controls. Methods. One hundred ASD children were studied in comparison to 100 controls. All participants were subjected to clinical evaluation and measurement of mercury, lead, and aluminum through hair analysis which reflects past exposure. Results. The mean Levels of mercury, lead, and aluminum in hair of the autistic patients were significantly higher than controls. Mercury, lead, and aluminum levels were positively correlated with maternal fish consumptions, living nearby gasoline stations, and the usage of aluminum pans, respectively. Conclusion. Levels of mercury, lead, and aluminum in the hair of autistic children are higher than controls. Environmental exposure to these toxic heavy metals, at key times in development, may play a causal role in autism.
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8. Morris SL, Foster CJ, Parsons R, Falkmer M, Falkmer T, Rosalie SM. {{Differences in the use of vision and proprioception for postural control in autism spectrum disorder}}. {Neuroscience}. 2015; 307: 273-80.
BACKGROUND: People with autism spectrum disorders (ASDs) also have poorer fundamental motor skills. The development of postural control underlies both social and motor skills. All three elements are facilitated by the active use of visual information. This study compares how adults with ASD and typically developed adults (TDAs) respond to a postural illusion induced using neck vibration. Adults with ASD unlike the TDA, were not expected to correct the illusion using vision. METHODS: The study used intermittent (15off, 5on) posterior neck vibration during 200s of quiet stance to induce a postural illusion. In TDAs and only in the absence of vision this protocol induces a forward body lean. Participants (12 ASD, 20 TDA) undertook four conditions combining vibration and visual occlusion. RESULTS: As predicted, TDA were only affected by the postural illusion when vision was occluded (vibration condition: vision occluded (n=1) p=0.0001; vision available (n=3) p>0.2466). Adults with ASD were affected by the postural illusion regardless of the availability of vision (all conditions p<0.0007). CONCLUSIONS: Our findings indicated the adults with ASD did not use visual information to control standing posture. In light of existing evidence that vision-for-perception is processed typically in ASD, our findings support a specific deficit in vision-for-action. These findings may explain why individuals with ASD experience difficulties with both social and motor skills since both require vision-for-action. Further research needs to investigate the division of these visual learning pathways in order to provide more specific intervention opportunities in ASD. Lien vers le texte intégral (Open Access ou abonnement)
9. Ranger P, Ellenbroek BA. {{Perinatal Influences of Valproate on Brain and Behaviour: An Animal Model for Autism}}. {Curr Top Behav Neurosci}. 2015.
Valproic acid or valproate (VPA) is an anti-convulsant and mood stabiliser effective in treating epilepsy and bipolar disorders. Although in adults VPA is well tolerated and safe, there is convincing evidence that it has teratogenic properties, ranging from mild neurodevelopmental changes to severe congenital malformations. In particular, studies involving humans and other animals have shown that prenatal exposure to VPA can induce developmental abnormalities reminiscent of autism spectrum disorder (ASD). In this chapter, we discuss the connection between VPA and ASD, evaluate the VPA animal model of ASD, and describe the possible molecular mechanisms underlying VPA’s teratogenic properties.
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10. Russo AJ. {{Decreased Phosphorylated Protein Kinase B (Akt) in Individuals with Autism Associated with High Epidermal Growth Factor Receptor (EGFR) and Low Gamma-Aminobutyric Acid (GABA)}}. {Biomark Insights}. 2015; 10: 89-94.
Dysregulation of the PI3K/AKT/mammalian target of rapamycin (mTOR) pathway could contribute to the pathogenesis of autism spectrum disorders. In this study, phosphorylated Akt concentration was measured in 37 autistic children and 12, gender and age similar neurotypical, controls using an enzyme-linked immunosorbent assay. Akt levels were compared to biomarkers known to be associated with epidermal growth factor receptor (EGFR) and c-Met (hepatocyte growth factor (HGF) receptor) pathways and severity levels of 19 autism-related symptoms. We found phosphorylated Akt levels significantly lower in autistic children and low Akt levels correlated with high EGFR and HGF and low gamma-aminobutyric acid, but not other biomarkers. Low Akt levels also correlated significantly with increased severity of receptive language, conversational language, hypotonia, rocking and pacing, and stimming, These results suggest a relationship between decreased phosphorylated Akt and selected symptom severity in autistic children and support the suggestion that the AKT pathways may be associated with the etiology of autism.
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11. Wang T, Shan L, Du L, Feng J, Xu Z, Staal WG, Jia F. {{Serum concentration of 25-hydroxyvitamin D in autism spectrum disorder: a systematic review and meta-analysis}}. {Eur Child Adolesc Psychiatry}. 2015.
Vitamin D may play an important role in the etiology of Autism Spectrum Disorders (ASD). Vitamin D is regarded as a neuroactive steroid affecting brain development and function. It plays an essential role in myelination, which is important for connectivity in the brain. Studies have shown that decreased vitamin D levels in patients, decreased maternal vitamin D levels during pregnancy, and decreased exposure to solar UVB might increase the risk for ASD. In addition, autism symptoms and global functioning may improve after vitamin D supplementation. Here, we sought to aggregate information from previous publications on vitamin D levels and ASD, in order to achieve a higher statistical power and thereby to determine the validity of vitamin D deficiency as a risk factor for ASD. For this meta-analysis, 11 studies met the inclusion and exclusion criteria, accounting for a total of 870 ASD patients and 782 healthy controls. Levels of serum 25(OH) D in participants with ASD were significantly lower than controls, suggesting that lower vitamin D level might be a risk factor for ASD.
