1. Masi A, Lampit A, DeMayo MM, Glozier N, Hickie IB, Guastella AJ. {{A comprehensive systematic review and meta-analysis of pharmacological and dietary supplement interventions in paediatric autism: moderators of treatment response and recommendations for future research}}. {Psychol Med};2017 (Jan 16):1-12.
BACKGROUND: Autism spectrum disorders (ASDs) are pervasive and multifactorial neurodevelopmental conditions, characterized by impairments in social communication and interaction, and restricted, repetitive patterns of behaviour, interests or activities. Treatment options to ameliorate symptoms of ASDs are limited. Heterogeneity complicates the quest for personalized medicine in this population. Our aim was to investigate if there are baseline characteristics of patients that moderate response or trial design features that impede the identification of efficacious interventions for ASDs. METHOD: Literature searches of EMBASE, MEDLINE and PsycINFO identified 43 studies for qualitative assessment of baseline characterization of participants and 37 studies for quantitative analysis of moderators of treatment response. Criteria included blinded randomized controlled trials (RCTs) in paediatric ASD, with at least 10 participants per arm or 20 overall, of oral treatments, including pharmacological interventions and dietary supplements. RESULTS: Random-effects meta-analysis of 1997 participants (81% male) identified three moderators associated with an increase in treatment response: trials located in Europe and the Middle-East; outcome measures designated primary status; and the type of outcome measure. Inconsistent reporting of baseline symptom severity and intellectual functioning prevented analysis of these variables. Qualitative synthesis of baseline characteristics identified at least 31 variables, with only age and gender reported in all trials. Biological markers were included in six RCTs. CONCLUSIONS: Few trials reported adequate baseline characteristics to permit detailed analysis of response to treatment. Consideration of geographical location, baseline severity and intellectual function is required to ensure generalizability of results. The use of biological markers and correlates in ASD trials remains in its infancy. There is great need to improve the application of baseline characterization and incorporation of biological markers and correlates to permit selection of participants into homogeneous subgroups and to inform response to treatment in ASD.
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2. Neumeyer AM, Sokoloff NC, McDonnell E, Macklin EA, McDougle CJ, Misra M. {{Bone microarchitecture in adolescent boys with autism spectrum disorder}}. {Bone};2017 (Jan 11)
BACKGROUND: Boys with autism spectrum disorder (ASD) have lower areal bone mineral density (aBMD) than typically developing controls (TDC). Studies of volumetric BMD (vBMD) and bone microarchitecture provide information about fracture risk beyond that provided by aBMD but are currently lacking in ASD. OBJECTIVES: To assess ultradistal radius and distal tibia vBMD, bone microarchitecture and strength estimates in adolescent boys with ASD compared to TDC. DESIGN/METHODS: Cross-sectional study of 34 boys (16 ASD, 18 TDC) that assessed (i) aBMD at the whole body (WB), WB less head (WBLH), hip and spine using dual X-ray absorptiometry (DXA), (ii) vBMD and bone microarchitecture at the ultradistal radius and distal tibia using high-resolution peripheral quantitative CT (HRpQCT), and (iii) bone strength estimates (stiffness and failure load) using micro-finite element analysis (FEA). We controlled for age in all groupwise comparisons of HRpQCT and FEA measures. Activity questionnaires, food records, physical exam, and fasting levels of 25(OH) vitamin D and bone markers (C-terminal collagen crosslinks and N-terminal telopeptide (CTX and NTX) for bone resorption, N-terminal propeptide of Type 1 procollagen (P1NP) for bone formation) were obtained. RESULTS: ASD participants were slightly younger than TDC participants (13.6 vs. 14.2years, p=0.44). Tanner stage, height Z-scores and fasting serum bone marker levels did not differ between groups. ASD participants had higher BMI Z-scores, percent body fat, IGF-1 Z-scores, lower lean mass and aBMD Z-scores than TDC at the WB, WBLH, and femoral neck (P<0.1). At the radius, ASD participants had lower trabecular thickness (0.063 vs. 0.070mm, p=0.004), compressive stiffness (56.7 vs. 69.7kN/mm, p=0.030) and failure load (3.0 vs. 3.7kN, p=0.031) than TDC. ASD participants also had 61% smaller cortical area (6.6 vs. 16.4mm2, p=0.051) and thickness (0.08 vs. 0.22mm, p=0.054) compared to TDC. At the tibia, ASD participants had lower compressive stiffness (183 vs. 210kN/mm, p=0.048) and failure load (9.4 vs. 10.8kN, p=0.043) and 23% smaller cortical area (60.3 vs. 81.5mm2, p=0.078) compared to TDC. A lower proportion of ASD participants were categorized as "very physically active" (20% vs. 72%, p=0.005). Differences in physical activity, calcium intake and IGF-1 responsiveness may contribute to group differences in stiffness and failure load. CONCLUSION: Bone microarchitectural parameters are impaired in ASD, with reductions in bone strength estimates (stiffness and failure load) at the ultradistal radius and distal tibia. This may result from lower physical activity and calcium intake, and decreased IGF-1 responsiveness. Lien vers le texte intégral (Open Access ou abonnement)
3. Richard AE, Scheffer IE, Wilson SJ. {{Features of the broader autism phenotype in people with epilepsy support shared mechanisms between epilepsy and autism spectrum disorder}}. {Neurosci Biobehav Rev};2017 (Jan 16)
RICHARD, A.E., I.E. Scheffer and S.J. Wilson. Features of the broader autism phenotype in people with epilepsy support shared mechanisms between epilepsy and autism spectrum disorder. NEUROSCI BIOBEHAV REV 21(1) XXX-XXX, 2016.- To inform on mechanisms underlying the comorbidity of epilepsy and autism spectrum disorder (ASD), we conducted meta-analyses to test whether impaired facial emotion recognition (FER) and theory of mind (ToM), key phenotypic traits of ASD, are more common in people with epilepsy (PWE) than controls. We contrasted these findings with those of relatives of individuals with ASD (ASD-relatives) compared to controls. Furthermore, we examined the relationship of demographic (age, IQ, sex) and epilepsy-related factors (epilepsy onset age, duration, seizure laterality and origin) to FER and ToM. Thirty-one eligible studies of PWE (including 1449 individuals: 77% with temporal lobe epilepsy), and 22 of ASD-relatives (N=1295) were identified by a systematic database search. Analyses revealed reduced FER and ToM in PWE compared to controls (p <0.001), but only reduced ToM in ASD-relatives (p <0.001). ToM was poorer in PWE than ASD-relatives. Only weak associations were found between FER and ToM and epilepsy-related factors. These findings suggest shared mechanisms between epilepsy and ASD, independent of intellectual disability. Lien vers le texte intégral (Open Access ou abonnement)
4. Stancliffe RJ, Anderson LL. {{Factors associated with meeting physical activity guidelines by adults with intellectual and developmental disabilities}}. {Res Dev Disabil};2017 (Jan 16);62:1-14.
BACKGROUND: Many individuals with intellectual and developmental disabilities (IDD) have sedentary lifestyles. AIMS: (a) compare adults with IDD with the general adult population on adherence to U.S. physical activity (PA) guidelines, and (b) determine what factors predict adherence to PA guidelines by adults with IDD. METHODS: We compared adults with IDD from the 2011-2012 National Core Indicators Adult Consumer Survey (NCI-ACS) with the general U.S. population on meeting PA guidelines. We examined the association of demographic, diagnostic, mobility, health and community participation variables with meeting PA guidelines by adults with IDD. RESULTS: The rate for adults with IDD meeting PA guidelines (13.5%) was less than half that of the general population (30.8%). Among adults with IDD, at-risk groups included those with more severe disability, Down syndrome, mobility impairments, obesity, poor health, mental illness, no independent access to community exercise, and less frequent participation in community exercise. Going out for exercise was the only form of community participation associated with meeting PA guidelines. People who accessed the community for exercise independently (i.e., alone) were more likely to meet PA guidelines. CONCLUSIONS: Interventions aimed at increasing PA for people with IDD should consider these factors in their design.
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5. Velasquez F, Wiggins JL, Mattson WI, Martin DM, Lord C, Monk CS. {{The influence of 5-HTTLPR transporter genotype on amygdala-subgenual anterior cingulate cortex connectivity in autism spectrum disorder}}. {Dev Cogn Neurosci};2016 (Dec 23);24:12-20.
Social deficits in autism spectrum disorder (ASD) are linked to amygdala functioning and functional connection between the amygdala and subgenual anterior cingulate cortex (sACC) is involved in the modulation of amygdala activity. Impairments in behavioral symptoms and amygdala activation and connectivity with the sACC seem to vary by serotonin transporter-linked polymorphic region (5-HTTLPR) variant genotype in diverse populations. The current preliminary investigation examines whether amygdala-sACC connectivity differs by 5-HTTLPR genotype and relates to social functioning in ASD. A sample of 108 children and adolescents (44 ASD) completed an fMRI face-processing task. Youth with ASD and low expressing 5-HTTLPR genotypes showed significantly greater connectivity than youth with ASD and higher expressing genotypes as well as typically developing (TD) individuals with both low and higher expressing genotypes, in the comparison of happy vs. baseline faces and happy vs. neutral faces. Moreover, individuals with ASD and higher expressing genotypes exhibit a negative relationship between amygdala-sACC connectivity and social dysfunction. Altered amygdala-sACC coupling based on 5-HTTLPR genotype may help explain some of the heterogeneity in neural and social function observed in ASD. This is the first ASD study to combine genetic polymorphism analyses and functional connectivity in the context of a social task.
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6. Vivanti G, Hocking DR, Fanning P, Dissanayake C. {{The social nature of overimitation: Insights from Autism and Williams syndrome}}. {Cognition};2017 (Jan 12);161:10-18.
When imitating novel actions, typically developing preschoolers often copy components of the demonstration that are unrelated to the modeled action’s goal, a phenomenon known as ‘overimitation’. According to the social motivation account, overimitation fulfills social affiliation motives (i.e., the imitator’s drive to experience social connectedness with the demonstrator and the social context). Conversely, according to the social-cognitive account, overimitation reflects overattribution of causal relevance (i.e., the imitator’s failure to appreciate that some components of the demonstration are not relevant to the action’s outcome). Autism Spectrum Disorder (ASD) and William syndrome (WS) are characterized by reduced and enhanced spontaneous social motivation, respectively, as well as similar impairments in social-cognition, thus providing helpful test cases to understand the nature of overimitation. Using a novel eye-tracking paradigm, we examined overimitation in 31 preschoolers with ASD, 18 age- and IQ-matched peers with WS, and 19 age-matched typically developing children. We found that children with WS and typically developing children were more likely to overimitate, and to increase their attention to the model’s face during demonstration of causally irrelevant actions, compared to those with ASD. These findings will be discussed in the context of support for the social-motivational account of overimitation.
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7. Wang J, Zou Q, Han R, Li Y, Wang Y. {{Serum levels of Glial fibrillary acidic protein in Chinese children with autism spectrum disorders}}. {Int J Dev Neurosci};2017 (Jan 11)
OBJECTIVE: Glial fibrillary acidic protein (GFAP) has been studied in many neurological diseases. The purpose of this study is to investigate the potential role of GFAP in Chinese children with autism spectrum disorders (ASD) by measuring serum circulating levels of GFAP and comparing them with age and gender-matched typical development children. METHODS: A total of one hundred and fifty 2-6 years old Chinese children (75 confirmed autism cases and 75 their age-gender matched typical development children) participated in this study. Serum levels of GFAP were assayed with enzyme-linked immunosorbent assay methods, and severity of ASD was evaluated with the Childhood Autism Rating Scale (CARS) Score. RESULTS: The results indicated that the mean serum GFAP level was significantly (P<0.001) higher in autistic children as compared to controls (1.71+/-0.53ng/ml vs. 0.99+/-0.25ng/ml). There was a significant positive association between serum GFAP levels and CARS scores (r [Pearson]=0.390, P=0.001). Based on the Receiver operating characteristic (ROC) curve, the optimal cut-off value of serum GFAP levels as an indicator for auxiliary diagnosis of autism was projected to be 1.28ng/ml which yielded a sensitivity of 77.3% and a specificity of 88.4%, the area under the curve was 0.895(95%CI, 0.844-0.947). Further, an increased risk of ASD was associated with GFAP levels >1.28ng/ml (adjusted OR 9.88, 95% CI: 3.32-17.82) in the multivariate logistic analysis model. CONCLUSION: The data indicates that serum GFAP levels may be associated with severity of ASD among Chinese children, suggesting the hypothesis that increased serum levels of GFAP could be implicated in the pathophysiology of autism in Chinese children.
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8. Zhou H, Wu W, Zhang Y, He H, Yuan Z, Zhu Z, Zhao Z. {{Selective preservation of cholinergic MeCP2 rescues specific Rett-syndrome-like phenotypes in MeCP2stop mice}}. {Behav Brain Res};2017 (Jan 16);322(Pt A):51-59.
RTT is a neurodevelopmental disorder characterized by growth regression, motor dysfunction, stereotypic hand movements, and autism features. Typical Rett syndrome (RTT) is predominantly caused by mutations in X-linked MeCP2 gene which encodes methyl-CpG-binding protein 2 (MeCP2). The brain-abundant MeCP2 protein mainly functions as a transcriptional regulator for neurodevelopment-associated genes. Specific functions of MeCP2 in certain neuron types remain to be known. Although cholinergic system is an important modulating system in brain, how MeCP2 in cholinergic neurons contribute to RTT has not been clearly understood. Here we use a mouse model with selectively activated endogenous MeCP2 in cholinergic neurons in otherwise MeCP2stop mice to determine the cholinergic MeCP2 effects on rescuing the RTT-like phenotypes. We found cholinergic MeCP2 preservation could reverse some aspects of the RTT-like phenotypes in mice including hypolocomotion and increased anxiety level, and delay the onset of underweight, instead of improving the hypersocial abnormality and the poor general conditions such as short lifespan, low brain weight, and increasing severity score. Our findings suggest that selective activation of cholinergic MeCP2 is sufficient to reverse the locomotor impairment and increased anxiety-like behaviors at least in early symptomatic stage, supporting future development of RTT therapies associated with cholinergic system.
