1. Billeci L, Tonacci A, Narzisi A, Manigrasso Z, Varanini M, Fulceri F, Lattarulo C, Calderoni S, Muratori F. {{Heart Rate Variability During a Joint Attention Task in Toddlers With Autism Spectrum Disorders}}. {Front Physiol};2018;9:467.
Background: Autism Spectrum Disorders (ASD) are a heterogeneous group of neurodevelopmental disorders featuring early impairments in social domain, with autonomic nervous system (ANS) unbalance possibly representing a useful marker for such disturbances. Impairments in joint attention (JA) are one of the earliest markers of social deficits in ASD. In this study, we assessed the feasibility of using wearable technologies for characterizing the ANS response in ASD toddlers during the presentation of JA stimuli. Methods: Twenty ASD toddlers and 20 age- and gender-matched typically developed (TD) children were recorded at baseline and during a JA task through an unobtrusive chest strap for electrocardiography (ECG). Specific algorithms for feature extraction, including Heart Rate (HR), Standard Deviation of the Normal-to-Normal Intervals (SDNN), Coefficient of Variation (CV), pNN10 as well as low frequency (LF) and high frequency (HF), were applied to the ECG signal and a statistical comparison between the two groups was performed. Results: As regards the single phases, SDNN (p = 0.04) and CV (p = 0.021) were increased in ASD at baseline together with increased LF absolute power (p = 0.034). Moreover, CV remained higher in ASD during the task (p = 0.03). Considering the phase and group interaction, LF increased from baseline to task in TD group (p = 0.04) while it decreased in the ASD group (p = 0.04). Conclusions: The results of this study indicate the feasibility of characterizing the ANS response in ASD toddlers through a minimally obtrusive tool. Our analysis showed an increased SDNN and CV in toddlers with ASD particularly at baseline compared to TD and lower LF during the task. These findings could suggest the possibility of using the proposed approach for evaluating physiological correlates of JA response in young children with ASD.
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2. Franchini M, Duku E, Armstrong V, Brian J, Bryson SE, Garon N, Roberts W, Roncadin C, Zwaigenbaum L, Smith IM. {{Variability in Verbal and Nonverbal Communication in Infants at Risk for Autism Spectrum Disorder: Predictors and Outcomes}}. {J Autism Dev Disord};2018 (May 16)
Early communication impairment is among the most-reported first concerns in parents of young children with autism spectrum disorder (ASD). Using a parent-report questionnaire, we derived trajectory groups for early language and gesture acquisition in siblings at high risk for ASD and in children at low risk, during their first 2 years of life. Developmental skills at 6 months were associated with trajectory group membership representing growth in receptive language and gestures. Behavioral symptoms also predicted gesture development. All communication measures were strongly related to clinical and developmental outcomes. Trajectory groups further indicated slowest language/gesture acquisition in infants with later ASD diagnoses, in particular when associated with language delay. Overall, our results confirm considerable variability in communication development in high-risk infants.
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3. Fulceri F, Guzzetta A, Athanasiadou A, Iaconianni L, Scattoni ML. {{Antenatal ultrasound value in risk calculation for Autism Spectrum Disorder: A systematic review to support future research}}. {Neurosci Biobehav Rev};2018 (May 17)
There is a growing research interest on the antenatal features of children with neurodevelopmental disorders. Indeed, it has been proved that the neurodevelopment is, at least partly, affected by processes occurring in fetal life and that the early neurodevelopmental disorders identification is essential to optimize long-term outcomes. This systematic review aims to summarize findings on antenatal ultrasound data, which are or might be considered early risk indexes of postnatal social impairments. We conducted systematic searches in Pubmed and PsychINFO databases to identify studies including fetal ultrasound measurements and postnatal neurodevelopmental outcome assessment. The bibliographic search included 3203 articles but after the assessment of the eligibility conducted by two independent researchers, only 26 studies were selected. Some alterations in ultrasound antenatal measurements (such as biophysical data, nuchal thickness and enlargement of cerebral ventricles) have been associated to autism spectrum disorder. However, data are still limited, controversial and not specific. Reported data are here discussed to strongly support studies on fetuses at high risk for autism spectrum disorder.
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4. Ghilan M, Bettio L, Noonan A, Brocardo PS, Gil-Mohapel J, Christie BR. {{Impaired Spatial Processing in a Mouse Model of Fragile X Syndrome}}. {Behav Brain Res};2018 (May 17)
Fragile X syndrome (FXS) is the most common form of inherited intellectual impairment. The Fmr1(-/y) mouse model has been previously shown to have deficits in context discrimination tasks but not in the elevated plus-maze. To further characterize this FXS mouse model and determine whether hippocampal-mediated behaviours are affected in these mice, dentate gyrus (DG)-dependent spatial processing and Cornu Ammonis 1 (CA1)-dependent temporal order discrimination tasks were evaluated. In agreement with previous findings of long-term potentiation deficits in the DG of this transgenic model of FXS, the results reported here demonstrate that Fmr1(-/y) mice perform poorly in the DG-dependent metric change spatial processing task. However, Fmr1(-/y) mice did not present deficits in the CA1-dependent temporal order discrimination task, and were able to remember the order in which objects were presented to them to the same extent as their wild-type littermate controls. These data suggest that the previously reported subregional-specific differences in hippocampal synaptic plasticity observed in the Fmr1(-/y) mouse model may manifest as selective behavioural deficits in hippocampal-dependent tasks.
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5. Kita Y, Katayama Y, Shiraishi T, Oka T, Sato T, Suyama M, Ohkawa Y, Miyata K, Oike Y, Shirane M, Nishiyama M, Nakayama KI. {{The Autism-Related Protein CHD8 Cooperates with C/EBPbeta to Regulate Adipogenesis}}. {Cell Rep};2018 (May 15);23(7):1988-2000.
The gene encoding the chromatin remodeler CHD8 is the most frequently mutated gene in individuals with autism spectrum disorder (ASD). Heterozygous mutations in CHD8 give rise to ASD that is often accompanied by macrocephaly, gastrointestinal complaints, and slender habitus. Whereas most phenotypes of CHD8 haploinsufficiency likely result from delayed neurodevelopment, the mechanism underlying slender habitus has remained unknown. Here, we show that CHD8 interacts with CCAAT/enhancer-binding protein beta (C/EBPbeta) and promotes its transactivation activity during adipocyte differentiation. Adipogenesis was impaired in Chd8-deleted preadipocytes, with the upregulation of C/EBPalpha and peroxisome-proliferator-activated receptor gamma (PPARgamma), two master regulators of this process, being attenuated in mutant cells. Furthermore, mice with CHD8 ablation in white preadipocytes had a markedly reduced white adipose tissue mass. Our findings reveal a mode of C/EBPbeta regulation by CHD8 during adipogenesis, with CHD8 deficiency resulting in a defect in the development of white adipose tissue.
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6. Lutjohann D, Lopez AM, Chuang JC, Kerksiek A, Turley SD. {{Identification of Correlative Shifts in Indices of Brain Cholesterol Metabolism in the C57BL6/Mecp2 (tm1.1Bird) Mouse, a Model for Rett Syndrome}}. {Lipids};2018 (May 17)
Rett syndrome (RS) is a pervasive neurodevelopmental disorder resulting from loss-of-function mutations in the X-linked gene methyl-Cpg-binding protein 2 (MECP2). Using a well-defined model for RS, the C57BL6/Mecp2 (tm1.1Bird) mouse, we have previously found a moderate but persistently lower rate of cholesterol synthesis, measured in vivo, in the brains of Mecp2 (-/y) mice, starting from about the third week after birth. There was no genotypic difference in the total cholesterol concentration throughout the brain at any age. This raised the question of whether the lower rate of cholesterol synthesis in the mutants was balanced by a fall in the rate at which cholesterol was converted via cholesterol 24-hydroxylase (Cyp46A1) to 24S-hydroxycholesterol (24S-OHC), the principal route through which cholesterol is ordinarily removed from the brain. Here, we show that while there were no genotypic differences in the concentrations in plasma and liver of three cholesterol precursors (lanosterol, lathosterol, and desmosterol), two plant sterols (sitosterol and campesterol), and two oxysterols (27-hydroxycholesterol [27-OHC] and 24S-OHC), the brains of the Mecp2 (-/y) mice had significantly lower concentrations of all three cholesterol precursors, campesterol, and both oxysterols, with the level of 24S-OHC being ~20% less than in their Mecp2 (+/y) controls. Together, these data suggest that coordinated regulation of cholesterol synthesis and catabolism in the central nervous system is maintained in this model for RS. Furthermore, we speculate that the adaptive changes in these two pathways conceivably resulted from a shift in the permeability of the blood-brain barrier as implied by the significantly lower campesterol and 27-OHC concentrations in the brains of the Mecp2 (-/y) mice.
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7. Muslimov IA, Eom T, Iacoangeli A, Chuang SC, Hukema RK, Willemsen R, Stefanov DG, Wong RKS, Tiedge H. {{BC RNA Mislocalization in the Fragile X Premutation}}. {eNeuro};2018 (Mar-Apr);5(2)
Fragile X premutation disorder is caused by CGG triplet repeat expansions in the 5′ untranslated region of FMR1 mRNA. The question of how expanded CGG repeats cause disease is a subject of continuing debate. Our work indicates that CGG-repeat structures compete with regulatory BC1 RNA for access to RNA transport factor hnRNP A2. As a result, BC1 RNA is mislocalized in vivo, as its synapto-dendritic presence is severely diminished in brains of CGG-repeat knock-in animals (a premutation mouse model). Lack of BC1 RNA is known to cause seizure activity and cognitive dysfunction. Our working hypothesis thus predicted that absence, or significantly reduced presence, of BC1 RNA in synapto-dendritic domains of premutation animal neurons would engender cognate phenotypic alterations. Testing this prediction, we established epileptogenic susceptibility and cognitive impairments as major phenotypic abnormalities of CGG premutation mice. In CA3 hippocampal neurons of such animals, synaptic release of glutamate elicits neuronal hyperexcitability in the form of group I metabotropic glutamate receptor-dependent prolonged epileptiform discharges. CGG-repeat knock-in animals are susceptible to sound-induced seizures and are cognitively impaired as revealed in the Attentional Set Shift Task. These phenotypic disturbances occur in young-adult premutation animals, indicating that a neurodevelopmental deficit is an early-initial manifestation of the disorder. The data are consistent with the notion that RNA mislocalization can contribute to pathogenesis.
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8. Qiu T, Guo BB, Wang LZ, Zhang H, Xu Y, Jiang XY. {{[Association between overweight/obesity in parents and autism spectrum disorders in offspring]}}. {Zhongguo Dang Dai Er Ke Za Zhi};2018 (May);20(5):383-386.
OBJECTIVE: To study the association between overweight/obesity in parents before maternal pregnancy and the development of autism spectrum disorders (ASD) in offspring. METHODS: A total of 36 children who were diagnosed with ASD (ASD group) and 72 normal children matched for sex and age (control group) were enrolled. A questionnaire survey was performed to collect the general information, including body height and body weight of parents before maternal pregnancy and maternal weight gain during pregnancy. Univariate and multivariate logistic regression analyses were used to investigate the association between overweight/obesity in parents before maternal pregnancy and ASD in offspring. RESULTS: The ASD group had a significantly higher detection rate of overweight/obesity in the father than the control group (56% vs 32%; P=0.018) before maternal pregnancy. The univariate and multivariate logistic regression analyses showed that overweight/obesity of the father before maternal pregnancy was a risk factor for ASD in offspring (OR=2.66 and 2.58 respectively; P<0.05). CONCLUSIONS: Overweight/obesity of the father before maternal pregnancy is an independent risk factor for ASD in offspring, and therefore, it is important for the father to control his body mass index within the normal range before maternal pregnancy.
9. Scott M, Falkmer M, Falkmer T, Girdler S. {{Evaluating the Effectiveness of an Autism-Specific Workplace Tool for Employers: A Randomised Controlled Trial}}. {J Autism Dev Disord};2018 (May 16)
A randomised controlled trial evaluated the effectiveness of the Integrated Employment Success Tool (IEST) in improving employers’ self-efficacy in modifying the workplace for individuals on the autism spectrum. Employers (N = 84) were randomised to the IEST or support as usual groups. Measurements of self-efficacy, knowledge and attitudes towards disability in the workplace were obtained at baseline and post-test. Results revealed a significant improvement in self-efficacy within the IEST group between baseline and post-test (p = 0.016). At post-test, there were no significant differences between groups in relation to self-efficacy in implementing autism-specific workplace modifications and employer attitudes towards disability in the workplace. Given the lack of significant outcomes, further research is needed to determine the effectiveness of the IEST for employers. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry #ACTRN12614000771651, registered 21/7/2014. Trial URL https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=366699 .
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10. Stauch TA, Plavnick JB, Sankar S, Gallagher AC. {{Teaching social perception skills to adolescents with autism and intellectual disabilities using video-based group instruction}}. {J Appl Behav Anal};2018 (May 17)
Few interventions focus on teaching social skills to adolescents with autism spectrum disorder (ASD) and intellectual disabilities (ID) that are consistently used during interactions with peers ( Carter et al., 2014). The present study evaluated the effects of video-based group instruction (VGI) on the acquisition of social perception skills of five adolescents with ASD or ID in a public school setting. Social perception involves observing affective behaviors of others, discriminating relevant environmental stimuli, and differentially reinforcing the affective behavior of another person. Typically developing peers supported VGI implementation as social partners for participants. A multiple probe design across behaviors demonstrated the effectiveness of VGI for teaching social perception skills. Four of five participants acquired and maintained the targeted social perception skills, and we observed some transfer to a nontreatment setting. Results of this study suggest VGI may support the acquisition of social perception among adolescents with ASD or ID.
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11. Steffenburg H, Steffenburg S, Gillberg C, Billstedt E. {{Children with autism spectrum disorders and selective mutism}}. {Neuropsychiatr Dis Treat};2018;14:1163-1169.
Background: It has been suggested that autism spectrum disorder (ASD) might be a « comorbid » condition in selective mutism (SM). Methods: In this retrospective study, we examined medical records of children with SM diagnosis (n=97) at a medical center specializing in assessment of ASD. Results: Mean age for onset of SM symptoms was 4.5 years and mean age at SM diagnosis was 8.8 years. SM was more common among girls (boy:girl ratio=2.7:1). We found that 63% of the study group had an ASD (no gender difference). The SM group with combined ASD had later onset of symptoms, higher age at diagnosis, more often a history of speech delay, and a higher proportion of borderline IQ or intellectual disability. Conclusion: The results highlight the risk of overlap between ASD and SM.
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12. Videler AC, Delescen ECJ, Ouwens MA. {{[Autism or personality disorder in older adults? Guidelines for the differential diagnosis]}}. {Tijdschr Psychiatr};2018;60(5):343-346.
Autism spectrum disorders and personality disorders are common, also in the elderly. Differential diagnosis is complex, especially if an undiagnosed autism spectrum disorder or personality disorder is suspected. We discuss two cases and conclude the article with suggestions for the differential diagnosis.
13. West KL. {{Infant Motor Development in Autism Spectrum Disorder: A Synthesis and Meta-analysis}}. {Child Dev};2018 (May 15)
Studies of infant motor development in autism spectrum disorder (ASD) have increased in recent years. This article synthesized this literature through meta-analysis to assess (a) whether infant motor ability differs in ASD relative to neurotypical controls; and (b) whether motor ability and communication are related in infants with ASD. Study 1 aggregated data from 1,953 infants with ASD (ages 3.0-42.0 months), and Study 2 included 890 infants with ASD (age 6.0-42.9 months). Study 1 revealed that infant motor ability differed significantly in ASD compared with neurotypical infants-this difference was robust to variation in measurement and design. Furthermore, this group difference amplified as age increased. Study 2 indicated that within ASD, infant motor ability and communication are related.
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14. Zeidler S, Dierckx B, Lubbers K, van Eeghen AM, Lincke CR, Kievit JA, Willemsen R, Rietman A. {{[Fragile X syndrome: new therapeutic strategies]}}. {Tijdschr Psychiatr};2018;60(5):338-342.
BACKGROUND: Fragile X syndrome (fxs) is the most common hereditary cause of intellectual disability and autism spectrum disorders. Targeted treatment is currently lacking. In the past decades an enormous amount of knowledge has been obtained concerning the involved molecular pathways, introducing potential targets for disease modifying therapy.
AIM: To present an overview of the development of targeted treatment for fxs.
METHOD: Several important publications were collected and indexed.
RESULTS: While preclinical animal model studies with targeted interventions are promising, the translation to the clinic has been disappointing.
CONCLUSION: Targeted treatment for fxs is necessary and could be applied in other causes of autism spectrum disorders and intellectual disability. Factors relating to translation, study design and outcome measures are possibly contributing to the disappointing results. The clustering of patient care in a center of expertise is required to clinically implement future therapeutic strategies and to facilitate research. In addition, this improves patient care, one example being the recent medical guideline for children with fxs.
