1. Beker S, Foxe JJ, Molholm S. {{Ripe for solution: Delayed development of multisensory processing in autism and its remediation}}. {Neurosci Biobehav Rev}. 2017.
Difficulty integrating inputs from different sensory sources is commonly reported in individuals with Autism Spectrum Disorder (ASD). Accumulating evidence consistently points to altered patterns of behavioral reactions and neural activity when individuals with ASD observe or act upon information arriving through multiple sensory systems. For example, impairments in the integration of seen and heard speech appear to be particularly acute, with obvious implications for interpersonal communication. Here, we explore the literature on multisensory processing in autism with a focus on developmental trajectories. While much remains to be understood, some consistent observations emerge. Broadly, sensory integration deficits are found in children with an ASD whereas these appear to be much ameliorated, or even fully recovered, in older teenagers and adults on the spectrum. This protracted delay in the development of multisensory processing raises the possibility of applying early intervention strategies focused on multisensory integration, to accelerate resolution of these functions. We also consider how dysfunctional cross-sensory oscillatory neural communication may be one key pathway to impaired multisensory processing in ASD.
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2. Bitsika V, Sharpley CF. {{Using parent- and self-reports to evaluate eating disturbances in young girls with Autism Spectrum Disorder}}. {Int J Dev Neurosci}. 2017; 65: 91-8.
BACKGROUND: Eating Disturbances (ED) often occur in Autism Spectrum Disorder (ASD) but most previous studies have relied on parent-reported data about males with ASD. Few studies have collected data from younger girls with ASD using self-reports and parents’ reports. AIMS: To compare self-reports and parents’ reports of ED in a sample of 52 young girls with ASD, a standardised scale for ED was revised for use with younger girls with ASD. METHODS: Mothers of 52 girls with ASD aged from 6 to 17 years completed the Swedish Eating Assessment for Autism spectrum disorders (SWEAA) on their daughters; the girls also completed the SWEAA as a self-report. RESULTS: The prevalence of severe ED in the sample was low (about 11%). There were minimal significant differences between mothers’ and daughters’ SWEAA responses across most SWEAA subscales. Deletion of several of the original SWEAA items produced a scale that can be used as a self-report or a carer-report with young girls with ASD. CONCLUSION: The clinical assessment of ED via self- or parent reports is suggested as a pathway to identify girls with ASD who also exhibit ED so that adequate treatment planning can be developed for them.
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3. Boone KM, Brown AK, Keim SA. {{Screening Accuracy of the Brief Infant Toddler Social-Emotional Assessment to Identify Autism Spectrum Disorder in Toddlers Born at Less Than 30 Weeks’ Gestation}}. {Child Psychiatry Hum Dev}. 2017.
Despite the higher prevalence of autism spectrum disorder (ASD) in children born preterm, valid screening tools for use in preterm populations are lacking. We aimed to evaluate the screening accuracy of the Brief Infant Toddler Social-Emotional Assessment (BITSEA) and to compare it to the Pervasive Developmental Disorders Screening Test-II, Stage 2, Developmental Clinic Screener (PDDST-II-DCS) in identifying ASD diagnosis in toddlers born at < 30 weeks' gestation. Caregivers (94% mothers) of 555 children completed questionnaires (BITSEA, PDDST-II-DCS, socio-demographics) when the children (58% male) were 18-36 months. Medical charts were abstracted 3.5 years later and showed that 4% (n = 24) of children had an ASD diagnosis. BITSEA competence (sensitivity = .74; specificity = .76) and ASD (sensitivity = .70; specificity = .73) subscales demonstrated better accuracy in identifying ASD compared to the recommended PDDST-II-DCS cut-score (sensitivity = .73; specificity = .64), specifically as it related to specificity. Additional studies are needed in other preterm populations to replicate these findings. Lien vers le texte intégral (Open Access ou abonnement)
4. Chiocchetti AG, Yousaf A, Bour HS, Haslinger D, Waltes R, Duketis E, Jarczok T, Sachse M, Biscaldi M, Degenhardt F, Herms S, Cichon S, Ackermann J, Koch I, Klauck SM, Freitag CM. {{Common functional variants of the glutamatergic system in Autism spectrum disorder with high and low intellectual abilities}}. {J Neural Transm (Vienna)}. 2017.
The genetic architecture underlying Autism spectrum disorder (ASD) has been suggested to differ between individuals with lower (IQ 70; HIQ). Among the identified pathomechanisms, the glutamatergic signalling pathway is of specific interest in ASD. We investigated 187 common functional variants of this neurotransmitter system for association with ASD and with symptom severity in two independent samples, a German (German-ALL: N = 583 families) and the Autism Genome Project cohort (AGP-ALL: N = 2001 families), split into HIQ, and LIQ subgroups. We did not identify any association withstanding correction for multiple testing. However, we report a replicated nominal significant under-transmission (OR < 0.79, p < 0.04) of the AKAP13 rs745191-T allele in both LIQ cohorts, but not in the much larger HIQ cohorts. At the phenotypic level, we nominally replicated associations of CAMK2A-rs2241694 with non-verbal communication in both combined LIQ and HIQ ASD cohorts. Variants PLD1-rs2124147 and ADCY1-rs2461127 were nominally associated with impaired non-verbal abilities and AKAP2-rs3739456 with repetitive behaviour in both LIQ cohorts. All four LIQ-associated genes are involved in G-protein coupled signal transduction, a downstream pathway of metabotropic glutamate receptor activation. We conclude that functional common variants of glutamatergic genes do not have a strong impact on ASD, but seem to moderately affect ASD risk and phenotypic expression. Since most of our nominally replicated hits were identified in the LIQ cohort, further investigation of the glutamatergic system in this subpopulation might be warranted. Lien vers le texte intégral (Open Access ou abonnement)
5. Griswold AJ, Van Booven D, Cuccaro ML, Haines JL, Gilbert JR, Pericak-Vance MA. {{Identification of rare noncoding sequence variants in gamma-aminobutyric acid A receptor, alpha 4 subunit in autism spectrum disorder}}. {Neurogenetics}. 2017.
Alterations of the gamma-aminobutyric acid (GABA) signaling system has been strongly linked to the pathophysiology of autism spectrum disorder (ASD). Genetic associations of common variants in GABA receptor subunits, in particular GABRA4 on chromosome 4p12, with ASD have been replicated by several studies. Moreover, molecular investigations have identified altered transcriptional and translational levels of this gene and protein in brains of ASD individuals. Since the genotyped common variants are likely not the functional variants contributing to the molecular consequences or underlying ASD phenotype, this study aims to examine rare sequence variants in GABRA4, including those outside the protein coding regions of the gene. We comprehensively re-sequenced the entire protein coding and noncoding portions of the gene and putative regulatory sequences in 82 ASD individuals and 55 developmentally typical pediatric controls, all homozygous for the most significant previously associated ASD risk allele (G/G at rs1912960). We identified only a single common, coding variant, and no association of any single marker or set of variants with ASD. Functional annotation of noncoding variants identified several rare variants in putative regulatory sites. Finally, a rare variant unique to ASD cases, in an evolutionary conserved site of the 3’UTR, shows a trend toward decreasing gene expression. Hence, GABRA4 rare variants in noncoding DNA may be variants of modest physiological effects in ASD etiology.
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6. Grohmann TDA. {{A Phenomenological Account of Sensorimotor Difficulties in Autism: Intentionality, Movement, and Proprioception}}. {Psychopathology}. 2017.
During the last decades, the focus in autism research has been progressively extended. Today it offers a large amount of material on sensorimotor disturbances as well as perceptive-cognitive preferences of people with autism. However, there are more and more critical voices against an intellectualist perspective in the cognitive sciences. The « enactive approach » as well as a new « movement perspective » to autism challenge the view of autism as a mere « cognitive » disturbance. They criticize the conception of a cognizing subject which is only interested in the world in as much as she/he can extract knowledge and organize it rationally. The present paper discusses fundamental insights from this critical sensorimotor perspective to autism from a phenomenological standpoint. Several important papers have already proven the fruitful combination of phenomenology with sensorimotor-focused research in the field of autism. However, these writings generally concentrate on problems of embodied intersubjectivity as an alternative approach to leading « theory of mind » paradigms. The present article reflects on the role and dimension of sensorimotor problems in themselves and not primarily in the intersubjective encounter. The notion of body intentionality will turn out to be a central heuristic device in order to understand the subject’s relationship to the world within a holistic framework, in which the person’s way to move, feel, and perceive are manners of understanding his/her own world. Empirical findings on difficulties in proactive and anticipatory control of movement as well as research outcome on proprioception and kinesthetic feedback will provide suitable material for discussing the transformation of body intentionality in autism. Phenomenology will provide the theoretical foundation in order to understand atypical movement patterns as alternative ways for producing alternative meanings.
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7. Leadbitter K, Aldred C, McConachie H, Le Couteur A, Kapadia D, Charman T, Macdonald W, Salomone E, Emsley R, Green J. {{The Autism Family Experience Questionnaire (AFEQ): An Ecologically-Valid, Parent-Nominated Measure of Family Experience, Quality of Life and Prioritised Outcomes for Early Intervention}}. {J Autism Dev Disord}. 2017.
There is a lack of measures that reflect the intervention priorities of parents of children with autism spectrum disorder (ASD) and that assess the impact of interventions on family experience and quality of life. The Autism Family Experience Questionnaire (AFEQ) was developed through focus groups and online consultation with parents, and reflected parental priorities. It was then administered to the parents of children enrolled in the Pre-school Autism Communication Trial and its 6-year follow-up study. The AFEQ showed good convergent validity with well-established measures of child adaptive functioning, parental mental health and parental wellbeing. It was sensitive to change in response to a parent-mediated intervention for young children with autism, showing treatment effect at treatment endpoint which increased at six-year follow-up.
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8. Lynch R, Diggins EL, Connors SL, Zimmerman AW, Singh K, Liu H, Talalay P, Fahey JW. {{Sulforaphane from Broccoli Reduces Symptoms of Autism: A Follow-up Case Series from a Randomized Double-blind Study}}. {Glob Adv Health Med}. 2017; 6: 2164957X17735826.
Introduction: Autism spectrum disorder (ASD) affects 1 in 68 children, is characterized by impaired social interaction and communication as well as restricted or repetitive behaviors, and varies widely with respect to its causes and presentations. There are no validated pharmacologic treatments for the core symptoms of ASD. The social, medical, and economic burdens of ASD on families and caregivers are profound. We recently showed in a small clinical trial that sulforaphane (SF) from broccoli sprouts could significantly reduce the behavioral symptoms of ASD. Methods: After we completed the intervention phase of the original trial (2011-2013), many caregivers used over-the-counter dietary SF supplements in order to attempt to maintain improvements similar to those noted during the intervention. We periodically followed the progress of study participants through the summer of 2016. Results: Families of 16 of the 26 subjects who received SF as part of the original study responded to requests for further information. Of these subjects, 6 did not continue taking SF supplements after the study. Nine of the 16 subjects are still taking an SF supplement and a 10th planned to. We present the edited testimonials of their caregivers in this case series. Conclusions: Many parents and caregivers articulated the positive effects of SF, both during the intervention phase and in the ensuing 3 years reported herein. These observations may contribute to understanding ASD and to treatments that may alleviate some of its symptoms. Diet- and supplement-based therapies deserve careful consideration for their potential to provide vital clinical as well as biochemical information about ASD.
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9. Mazzucchelli TG, Hodges J, Kane RT, Sofronoff K, Sanders MR, Einfeld S, Tonge B, Gray KM. {{Parenting and family adjustment scales (PAFAS): validation of a brief parent-report measure for use with families who have a child with a developmental disability}}. {Res Dev Disabil}. 2017; 72: 140-51.
BACKGROUND: Children with a developmental disability are three to four times more likely than their typically developing peers of developing significant emotional and behavioural problems. There is strong evidence to suggest that individual biological and psychological factors interact with family functioning to precipitate and perpetuate these problems. AIMS: This study examined the psychometric properties of a brief measure, the Parent and Family Adjustment Scales (PAFAS) for use with parents of children with a developmental disability. METHODS: A sample of 914 parents of children (M=6.27years) with a developmental disability participated in the study. Disabilities included Autism Spectrum Disorder and Intellectual Disability RESULTS: A confirmatory factor analysis supported a 16-item, four factor model of PAFAS Parenting, and an 11-item, three factor model of PAFAS Family Adjustment. The Parenting Scale measures parental consistency, coercive practices, use of encouragement and the quality of parent-child relationship. The Family Adjustment Scale measures parental emotional adjustment and partner and family support in parenting. CONCLUSIONS: The current study indicated that the PAFAS demonstrates promise as a brief measure of multiple domains of family functioning important for families who have a child with a developmental disability.
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10. Pijl MK, Rommelse NN, Hendriks M, De Korte MW, Buitelaar JK, Oosterling IJ. {{Does the Brief Observation of Social Communication Change help moving forward in measuring change in early autism intervention studies?}}. {Autism}. 2016: 1362361316669235.
The field of early autism research is in dire need of outcome measures that adequately reflect subtle changes in core autistic behaviors. This article compares the ability of a newly developed measure, the Brief Observation of Social Communication Change (BOSCC), and the Autism Diagnostic Observation Schedule (ADOS) to detect changes in core symptoms of autism in 44 toddlers. The results provide encouraging evidence for the Brief Observation of Social Communication Change as a candidate outcome measure, as reflected in sufficient inter- and intra-rater reliability, independency from other child characteristics, and sensitivity to capture change. Although the Brief Observation of Social Communication Change did not evidently outperform the Autism Diagnostic Observation Schedule on any of these quality criteria, the instrument may be better able to capture subtle, individual changes in core autistic symptoms. The promising findings warrant further study of this new instrument.
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11. Sekera ER, Rudolph HL, Carro SD, Morales MJ, Bett GCL, Rasmusson RL, Wood TD. {{Depletion of Stercobilin in Fecal Matter from a Mouse Model of Autism Spectrum Disorders}}. {Metabolomics}. 2017; 13(11).
Introduction: Autism spectrum disorders (ASD) are a group of neurodevelopmental disorders lacking a clinical biomarker for diagnosis. Emerging evidence shows that intestinal microflora from ASD subjects can be distinguished from controls, suggesting metabolite differences due to the action of intestinal microbes may provide a means for identifying potential biomarkers for ASD. Objectives: The aim of this study was to determine if quantitative differences in levels of stercobilin and stercobilinogen, metabolites produced by biological action of intestinal microflora, exist in the fecal matter between an ASD mouse model population and controls. Methods: Pairs of fecal samples were collected from two mouse groups, an ASD model group with Timothy syndrome 2 (TS2-NEO) and a gender-matched control group. After centrifugation, supernatant was spiked with an (18)O-labeled stercobilin isotopomer and subjected to solid phase extraction for processing. Extracted samples were spotted on a stainless steel plate and subjected to matrix-assisted laser desorption and ionization mass spectrometry using dihydroxybenzoic acid as the matrix (n = 5). Peak areas for bilins and (18)O-stercobilin isotopomers were determined in each fecal sample. Results: A 40-45% depletion in stercobilin in TS2-NEO fecal samples compared with controls was observed with p < 0.05; a less dramatic depletion was observed for stercobilinogen. Conclusions: The results show that stercobilin depletion in feces is observed for an ASD mouse model vs. controls. This may help to explain recent observations of a less diverse microbiome in humans with ASD and may prove helpful in developing a clinical ASD biomarker. Lien vers le texte intégral (Open Access ou abonnement)
12. Traut N, Beggiato A, Bourgeron T, Delorme R, Rondi-Reig L, Paradis AL, Toro R. {{Cerebellar Volume in Autism: Literature Meta-analysis and Analysis of the Autism Brain Imaging Data Exchange Cohort}}. {Biol Psychiatry}. 2017.
BACKGROUND: The neuroanatomical bases of autism spectrum disorder remain largely unknown. Among the most widely discussed candidate endophenotypes, differences in cerebellar volume have been often reported as statistically significant. METHODS: We aimed at objectifying this possible alteration by performing a systematic meta-analysis of the literature and an analysis of the ABIDE (Autism Brain Imaging Data Exchange) cohort. Our meta-analysis sought to determine a combined effect size of autism spectrum disorder diagnosis on different measures of the cerebellar anatomy as well as the effect of possible factors of variability across studies. We then analyzed the cerebellar volume of 328 patients and 353 control subjects from the ABIDE project. RESULTS: The meta-analysis of the literature suggested a weak but significant association between autism spectrum disorder diagnosis and increased cerebellar volume (p = .049, uncorrected), but the analysis of ABIDE did not show any relationship. The studies meta-analyzed were generally underpowered; however, the number of statistically significant findings was larger than expected. CONCLUSIONS: Although we could not provide a conclusive explanation for this excess of significant findings, our analyses would suggest publication bias as a possible reason. Finally, age, sex, and IQ were important sources of cerebellar volume variability, although independent of autism diagnosis.
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13. van Rooij D, Anagnostou E, Arango C, Auzias G, Behrmann M, Busatto GF, Calderoni S, Daly E, Deruelle C, Di Martino A, Dinstein I, Duran FLS, Durston S, Ecker C, Fair D, Fedor J, Fitzgerald J, Freitag CM, Gallagher L, Gori I, Haar S, Hoekstra L, Jahanshad N, Jalbrzikowski M, Janssen J, Lerch J, Luna B, Martinho MM, McGrath J, Muratori F, Murphy CM, Murphy DGM, O’Hearn K, Oranje B, Parellada M, Retico A, Rossa P, Rubia K, Shook D, Taylor M, Thompson PM, Tosetti M, Wallace GL, Zhou F, Buitelaar JK. {{Cortical and Subcortical Brain Morphometry Differences Between Patients With Autism Spectrum Disorder and Healthy Individuals Across the Lifespan: Results From the ENIGMA ASD Working Group}}. {Am J Psychiatry}. 2017: appiajp201717010100.
OBJECTIVE: Neuroimaging studies show structural differences in both cortical and subcortical brain regions in children and adults with autism spectrum disorder (ASD) compared with healthy subjects. Findings are inconsistent, however, and it is unclear how differences develop across the lifespan. The authors investigated brain morphometry differences between individuals with ASD and healthy subjects, cross-sectionally across the lifespan, in a large multinational sample from the Enhancing Neuroimaging Genetics Through Meta-Analysis (ENIGMA) ASD working group. METHOD: The sample comprised 1,571 patients with ASD and 1,651 healthy control subjects (age range, 2-64 years) from 49 participating sites. MRI scans were preprocessed at individual sites with a harmonized protocol based on a validated automated-segmentation software program. Mega-analyses were used to test for case-control differences in subcortical volumes, cortical thickness, and surface area. Development of brain morphometry over the lifespan was modeled using a fractional polynomial approach. RESULTS: The case-control mega-analysis demonstrated that ASD was associated with smaller subcortical volumes of the pallidum, putamen, amygdala, and nucleus accumbens (effect sizes [Cohen’s d], 0.13 to -0.13), as well as increased cortical thickness in the frontal cortex and decreased thickness in the temporal cortex (effect sizes, -0.21 to 0.20). Analyses of age effects indicate that the development of cortical thickness is altered in ASD, with the largest differences occurring around adolescence. No age-by-ASD interactions were observed in the subcortical partitions. CONCLUSIONS: The ENIGMA ASD working group provides the largest study of brain morphometry differences in ASD to date, using a well-established, validated, publicly available analysis pipeline. ASD patients showed altered morphometry in the cognitive and affective parts of the striatum, frontal cortex, and temporal cortex. Complex developmental trajectories were observed for the different regions, with a developmental peak around adolescence. These findings suggest an interplay in the abnormal development of the striatal, frontal, and temporal regions in ASD across the lifespan.
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14. Zhang S, Deng L, Jia Q, Huang S, Gu J, Zhou F, Gao M, Sun X, Feng C, Fan G. {{dbMDEGA: a database for meta-analysis of differentially expressed genes in autism spectrum disorder}}. {BMC Bioinformatics}. 2017; 18(1): 494.
BACKGROUND: Autism spectrum disorders (ASD) are hereditary, heterogeneous and biologically complex neurodevelopmental disorders. Individual studies on gene expression in ASD cannot provide clear consensus conclusions. Therefore, a systematic review to synthesize the current findings from brain tissues and a search tool to share the meta-analysis results are urgently needed. METHODS: Here, we conducted a meta-analysis of brain gene expression profiles in the current reported human ASD expression datasets (with 84 frozen male cortex samples, 17 female cortex samples, 32 cerebellum samples and 4 formalin fixed samples) and knock-out mouse ASD model expression datasets (with 80 collective brain samples). Then, we applied R language software and developed an interactive shared and updated database (dbMDEGA) displaying the results of meta-analysis of data from ASD studies regarding differentially expressed genes (DEGs) in the brain. RESULTS: This database, dbMDEGA ( https://dbmdega.shinyapps.io/dbMDEGA/ ), is a publicly available web-portal for manual annotation and visualization of DEGs in the brain from data from ASD studies. This database uniquely presents meta-analysis values and homologous forest plots of DEGs in brain tissues. Gene entries are annotated with meta-values, statistical values and forest plots of DEGs in brain samples. This database aims to provide searchable meta-analysis results based on the current reported brain gene expression datasets of ASD to help detect candidate genes underlying this disorder. CONCLUSION: This new analytical tool may provide valuable assistance in the discovery of DEGs and the elucidation of the molecular pathogenicity of ASD. This database model may be replicated to study other disorders.
