1. Billeci L, Narzisi A, Tonacci A, Sbriscia-Fioretti B, Serasini L, Fulceri F, Apicella F, Sicca F, Calderoni S, Muratori F. {{An integrated EEG and eye-tracking approach for the study of responding and initiating joint attention in Autism Spectrum Disorders}}. {Sci Rep}. 2017; 7(1): 13560.
Autism Spectrum Disorders (ASD) are characterised by impairment in joint attention (JA), which has two components: the response to JA and the initiation of JA. Literature suggests a correlation between JA and neural circuitries, although this link is still largely unexplored in ASD. In this pilot study, we aimed at investigating the neural correlates of responding and initiating JA in high-functioning children with ASD and evaluating the changes in brain function and visual pattern after six months of rehabilitative treatment using an integrated EEG/eye-tracking system. Our results showed that initiating and responding JA subtend both overlapping (i.e. frontal and temporal) and specialized (i.e. parietal for responding JA and occipital for initiating JA) neural circuitries. In addition, in a subgroup of subjects, we observed trends of changes in both brain activity and connectivity after rehabilitative treatment in both the two tasks, which were correlated with modifications in gaze measures. These preliminary results, if confirmed in a larger sample, suggest the feasibility of using the proposed multimodal approach to characterise JA-related brain circuitries and visual pattern in ASD individuals and to monitor longitudinal changes in response to rehabilitative intervention.
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2. Chutko LS, Yakovenko EA, Surushkina SY, Kryukova EM, Palaieva SV. {{[The efficacy of cerebrolysin in the treatment of autism spectrum disorders]}}. {Zh Nevrol Psikhiatr Im S S Korsakova}. 2017; 117(9): 71-5.
AIM: To evaluate clinical and neurophysiological changes in children with different variants of autism spectrum disorders during treatment with cerebrolysin. MATERIAL AND METHODS: Forty-three children with autism spectrum disorders, aged 4-6 years, were included in the study. To assess the degree of autism, the quantitative scale of assessing the severity of child autism CARS (‘Childhood Autism Rating Scale’) was used. A comparative analysis of the clinical picture of disease and data of the electroencephalographic examination in endogenous and exogenous (organic) variant of autism was made. RESULTS AND CONCLUSION: In children with exogenous (organic) autism, the lower scores of autistic symptom on the CARS and a greater degree of functional immaturity of the cerebral cortex, according to electroencephalographic results, were found compared to children with endogenous autism. After treatment with cerebrolysin, 27 children (62.8%) showed signs of improvement. An improvement was noted in 13 children in with endogenous autism (56.5%) and in 14 children with organic autism (70.0%). CARS scores showed a more pronounced decrease in this indicator in a subgroup of children with organic autism.
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3. French L, Kennedy EMM. {{Research Review: Early intervention for infants and young children with, or at-risk of, autism spectrum disorder: a systematic review}}. {J Child Psychol Psychiatry}. 2017.
BACKGROUND: There has been increased interest in early screening and intervention for young children with, or at risk of, autism spectrum disorder (ASD). This has generated a debate about the potential harms versus benefits of early identification and treatment. This review aims to identify the evidence base for early intervention in ASD. METHODS: A systematic review searching for randomised controlled trials (RCTs) of interventions for children up to 6 years of age with, or at risk of, ASD was undertaken. Characteristics and outcomes of included studies were collated and described in tabular format, and all included studies were rated according to the Cochrane Risk of Bias Tool. RESULTS: Forty-eight RCTs were identified, of which 40 were published since 2010. Most studies (n = 34) were undertaken in the United States. Included RCTs evaluated 32 different models of intervention. If blinding of participants and relevant personnel is overlooked as a source of bias, only six studies met criteria for low risk of bias across all domains of the Cochrane Risk of Bias Tool. The majority of studies had a relatively small sample size with only seven studies having a sample size >100. CONCLUSIONS: There has been a substantial increase in the number of RCTs evaluating early interventions in ASD. However, few studies, only 12.5% of the total, were rated as being at low risk of bias. Small sample size, unclear concealment of allocation and lack of clarity in the identification of the active ingredients in a diverse range of differently named treatment models were identified as challenges to the design, conduct and interpretation of studies. Improved co-ordination and design of studies is, therefore, required if future research in the field is to more clearly investigate the effects of early intervention for ASD.
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4. Gangi DN, Usher LV, Messinger DS. {{An exploration of common dopaminergic variants and behavior problems in siblings at high risk for autism spectrum disorder}}. {Infant Behav Dev}. 2017; 49: 267-71.
Younger siblings of children with ASD often exhibit elevated internalizing and externalizing problems. We investigated common dopaminergic variants (DRD4 and DRD2) in relation to behavior problems at 36 months. Genotypes linked to less efficient dopaminergic functioning were associated with higher internalizing problems in high-risk siblings.
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5. Hatfield M, Falkmer M, Falkmer T, Ciccarelli M. {{Effectiveness of the BOOST-A online transition planning program for adolescents on the autism spectrum: a quasi-randomized controlled trial}}. {Child Adolesc Psychiatry Ment Health}. 2017; 11: 54.
BACKGROUND: The majority of existing transition planning programs are focused on people with a disability in general and may not meet the specific need of adolescents on the autism spectrum. In addition, these interventions focus on specific skills (e.g. job readiness or self-determination) rather than the overall transition planning process and there are methodological limitations to many of the studies determining their effectiveness. The Better OutcOmes & Successful Transitions for Autism (BOOST-A) is an online program that supports adolescents on the autism spectrum to prepare for leaving school. This study aimed to determine the effectiveness of the BOOST-A in enhancing self-determination. METHODS: A quasi-randomized controlled trial was conducted with adolescents on the autism spectrum enrolled in years 8 to 11 in Australian schools (N = 94). Participants had to have basic computer skills and the ability to write at a year 5 reading level. Participants were allocated to a control (n = 45) or intervention (n = 49) group and participants were blinded to the trial hypothesis. The intervention group used the BOOST-A for 12 months, while the control group participated in regular practice. Outcomes included self-determination, career planning and exploration, quality of life, environmental support and domain specific self-determination. Data were collected from parents and adolescents. RESULTS: There were no significant differences in overall self-determination between groups. Results indicated significant differences in favor of the intervention group in three areas: opportunity for self-determination at home as reported by parents; career exploration as reported by parents and adolescents; and transition-specific self-determination as reported by parents. CONCLUSIONS: Results provide preliminary evidence that the BOOST-A can enhance some career-readiness outcomes. Lack of significant outcomes related to self-determination at school and career planning may be due to the lack of face-to-face training and parents being the primary contacts in the study. Further research is needed to determine effectiveness of the BOOST-A related to post-secondary education and employment. Trial registration #ACTRN12615000119594.
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6. Hayes SJ, Andrew M, Foster NC, Elliott D, Gowen E, Bennett SJ. {{Sensorimotor learning and associated visual perception are intact but unrelated in autism spectrum disorder}}. {Autism Res}. 2017.
Humans show an astonishing capability to learn sensorimotor behaviours. However, data from sensorimotor learning experiments suggest the integration of efferent sensorimotor commands, afferent sensorimotor information, and visual consequences of a performed action during learning is different in autism, leading to atypical representation of internal action models. Here, we investigated the generalization of a sensorimotor internal action model formed during sensorimotor learning to a different, but associated, visual perception task. Although motor timing was generally less accurate in adults with autism, following practice with feedback both autistic adults, and controls, significantly improved performance of the movement sequence timing task by reducing timing error. In a subsequent perception task, both groups demonstrated similar temporal-discrimination accuracy (autism = 75%; control = 76%). Significant correlations between motor timing error, and temporal-discrimination during a perception task, was found for controls. No significant correlations were found for autistic adults. Our findings indicate that autistic adults demonstrated adaptation by reducing motor timing error through sensorimotor learning. However, the finding of significant correlations between motor timing error and temporal-discrimination accuracy in the control group only suggests sensorimotor processes underpinning internal action model formation operate differently in autism. Autism Res 2017. (c) 2017 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: We showed autistic adults learned a new motor skill, and visually judged moving objects, to a similar level of accuracy as a control group. Unlike the control group, there was no relationship between how well autistic adults learned the motor skill, and how well they judged objects. The lack of a relationship might be one of the reasons autistic adults interact differently in the social world.
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7. Kouklari EC, Tsermentseli S, Monks CP. {{Hot and cool executive function in children and adolescents with autism spectrum disorder: Cross-sectional developmental trajectories}}. {Child Neuropsychol}. 2017: 1-27.
The development of executive function (EF) in autism spectrum disorder (ASD) has only been investigated using « cool »-cognitive-EF tasks. Little is known about the development of « hot »-affective-EF and whether it follows a similar developmental pathway. This study employed a cross-sectional developmental trajectories approach to examine the developmental changes in cool (working memory, inhibition, and planning) and hot EF (delay discounting and affective decision-making) of ASD participants (n = 79) and controls (n = 91) relative to age and IQ, shedding more light on the hot-cool EF organization. The developmental trajectories of some aspects of cool EF (working memory and planning) differed significantly as a function of age in ASD participants relative to controls. For both hot EFs, no significant age-related changes were found in either group. These findings extend our understanding regarding the maturation of EF from childhood through adolescence in ASD.
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8. Niturad CE, Lev D, Kalscheuer VM, Charzewska A, Schubert J, Lerman-Sagie T, Kroes HY, Oegema R, Traverso M, Specchio N, Lassota M, Chelly J, Bennett-Back O, Carmi N, Koffler-Brill T, Iacomino M, Trivisano M, Capovilla G, Striano P, Nawara M, Rzonca S, Fischer U, Bienek M, Jensen C, Hu H, Thiele H, Altmuller J, Krause R, May P, Becker F, Balling R, Biskup S, Haas SA, Nurnberg P, van Gassen KLI, Lerche H, Zara F, Maljevic S, Leshinsky-Silver E. {{Rare GABRA3 variants are associated with epileptic seizures, encephalopathy and dysmorphic features}}. {Brain}. 2017; 140(11): 2879-94.
Genetic epilepsies are caused by mutations in a range of different genes, many of them encoding ion channels, receptors or transporters. While the number of detected variants and genes increased dramatically in the recent years, pleiotropic effects have also been recognized, revealing that clinical syndromes with various degrees of severity arise from a single gene, a single mutation, or from different mutations showing similar functional defects. Accordingly, several genes coding for GABAA receptor subunits have been linked to a spectrum of benign to severe epileptic disorders and it was shown that a loss of function presents the major correlated pathomechanism. Here, we identified six variants in GABRA3 encoding the alpha3-subunit of the GABAA receptor. This gene is located on chromosome Xq28 and has not been previously associated with human disease. Five missense variants and one microduplication were detected in four families and two sporadic cases presenting with a range of epileptic seizure types, a varying degree of intellectual disability and developmental delay, sometimes with dysmorphic features or nystagmus. The variants co-segregated mostly but not completely with the phenotype in the families, indicating in some cases incomplete penetrance, involvement of other genes, or presence of phenocopies. Overall, males were more severely affected and there were three asymptomatic female mutation carriers compared to only one male without a clinical phenotype. X-chromosome inactivation studies could not explain the phenotypic variability in females. Three detected missense variants are localized in the extracellular GABA-binding NH2-terminus, one in the M2-M3 linker and one in the M4 transmembrane segment of the alpha3-subunit. Functional studies in Xenopus laevis oocytes revealed a variable but significant reduction of GABA-evoked anion currents for all mutants compared to wild-type receptors. The degree of current reduction correlated partially with the phenotype. The microduplication disrupted GABRA3 expression in fibroblasts of the affected patient. In summary, our results reveal that rare loss-of-function variants in GABRA3 increase the risk for a varying combination of epilepsy, intellectual disability/developmental delay and dysmorphic features, presenting in some pedigrees with an X-linked inheritance pattern.
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9. Ormond S, Brownlow C, Garnett MS, Rynkiewicz A, Attwood T. {{Profiling Autism Symptomatology: An Exploration of the Q-ASC Parental Report Scale in Capturing Sex Differences in Autism}}. {J Autism Dev Disord}. 2017.
The Questionnaire for Autism Spectrum Conditions (Q-ASC) was developed by Attwood et al. (2011) to identify gender-sensitive profiles of autism symptomatology; prioritise and adjust the direction of clinical interventions; and support positive psychosocial outcomes and prognosis into adulthood. The current research piloted the Q-ASC with parents of 238 children with a clinical diagnosis of ASD-Level 1 (without intellectual or language impairment). Data analysis revealed eight interpretable and reliable components of the Q-ASC using Principle components analysis. Comparisons across age and gender groups found statistically significant mean differences of parent-reported characteristics. The findings from this study aim to identify improvements in the Q-ASC towards the future assessment of the sensitivity and diversity of presentations of autism among female children and adolescents.
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10. Schmitt LM, White SP, Cook EH, Sweeney JA, Mosconi MW. {{Cognitive mechanisms of inhibitory control deficits in autism spectrum disorder}}. {J Child Psychol Psychiatry}. 2017.
BACKGROUND: Inhibitory control deficits are common in autism spectrum disorder (ASD) and associated with more severe repetitive behaviors. Inhibitory control deficits may reflect slower execution of stopping processes, or a reduced ability to delay the onset of behavioral responses in contexts of uncertainty. Previous studies have documented relatively spared stopping processes in ASD, but whether inhibitory control deficits in ASD reflect failures to delay response onset has not been systematically assessed. Further, while improvements in stopping abilities and response slowing are seen through adolescence/early adulthood in health, their development in ASD is less clear. METHODS: A stop-signal test (SST) was administered to 121 individuals with ASD and 76 age and IQ-matched healthy controls (ages 5-28). This test included ‘GO trials’ in which participants pressed a button when a peripheral target appeared and interleaved ‘STOP trials’ in which they were cued to inhibit button-presses when a stop-signal appeared at variable times following the GO cue. STOP trial accuracy, RT of the stopping process (SSRT), and reaction time (RT) slowing during GO trials were examined. RESULTS: Relative to controls, individuals with ASD had reduced accuracy on STOP trials. SSRTs were similar across control and ASD participants, but RT slowing was reduced in patients compared to controls. Age-related increases in stopping ability and RT slowing were attenuated in ASD. Reduced stopping accuracy and RT slowing were associated with more severe repetitive behaviors in ASD. DISCUSSION: Our findings show that inhibitory control deficits in ASD involve failures to strategically delay behavioral response onset. These results suggest that reduced preparatory behavioral control may underpin inhibitory control deficits as well as repetitive behaviors in ASD. Typical age-related improvements in inhibitory control during late childhood/early adolescence are reduced in ASD, highlighting an important developmental window during which treatments may mitigate cognitive alterations contributing to repetitive behaviors.
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11. Song Y, Jia Z, Liu S, Liang D. {{Discourse production of mandarin-speaking children with high-functioning autism: The effect of mental and action verbs’ semantic-pragmatic features}}. {J Commun Disord}. 2017; 70: 12-24.
The present study investigated the syntactic and pragmatic performance of children with high-functioning autism (HFA) during a discourse production task with mental verbs. Children with HFA and typically developing (TD) children were matched by chronological age, verbal IQ (VIQ) and full-scale IQ (FIQ). We found that children with HFA tended to select a nominal object given a mental verb with either a nominal or clausal object. They committed few syntactic errors but generated syntactic stereotypes with mental verbs. However, this behavior was not observed with action verbs. Thus, children with HFA were specifically impaired in the argument structures of mental verbs. In pragmatic performance, children with HFA produced significantly fewer clauses or sentences with lower syntactic complexity for mental verbs than TD controls. This result might be due to the semantic-pragmatic impairment of children with HFA in the use of mental verbs. This study concludes that children with HFA were able to acquire the syntactic frames of mental verbs but were nevertheless impaired in the acquisition of pragmatic information inherent in those verbs.
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12. Stanfield AC, Philip RCM, Whalley H, Romaniuk L, Hall J, Johnstone EC, Lawrie SM. {{Dissociation of Brain Activation in Autism and Schizotypal Personality Disorder During Social Judgments}}. {Schizophr Bull}. 2017; 43(6): 1220-8.
Background: There are overlaps between autism and schizophrenia but these are particularly pronounced, especially in social domains, for higher functioning individuals with autism spectrum disorders (ASD) or schizotypal personality disorder (SPD). It is not known whether these overlapping social deficits result from shared or distinct brain mechanisms. We therefore compared social cognition in ASD and SPD using functional magnetic resonance imaging (fMRI). Methods: Twenty-one individuals with SPD, 28 with ASD and 33 controls were compared with respect to clinical symptoms using the Positive and Negative Syndrome Scale; social cognition, using a social judgment task and Ekman 60 faces task; and brain activation using an fMRI task of social judgment. Results: The ASD and SPD groups showed few differences in symptoms or social cognition. However, fMRI showed that, compared to ASD, the SPD group showed significantly greater activation during social compared to gender judgments in the amygdala and 3 clusters: right posterior cerebellum, extending into fusiform and inferior temporal gyri; left posterior cerebellum; and left intraparietal sulcus extending through medial portions of the temporal gyri into the fusiform gyrus (all P < .05 family-wise error corrected). Control activations lay between the ASD and SPD groups. Conclusions: Although social cognitive deficits in ASD and SPD appear superficially similar they are the result of different brain mechanisms. These findings have implications for therapeutic interventions targeted at social dysfunction in these conditions. Lien vers le texte intégral (Open Access ou abonnement)
13. Tam FI, King JA, Geisler D, Korb FM, Sareng J, Ritschel F, Steding J, Albertowski KU, Roessner V, Ehrlich S. {{Altered behavioral and amygdala habituation in high-functioning adults with autism spectrum disorder: an fMRI study}}. {Sci Rep}. 2017; 7(1): 13611.
Habituation to repeatedly presented stimuli is an important adaptive property of the nervous system. Autism spectrum disorder (ASD) has been associated with reduced neural habituation, for example in the amygdala, which may be related to social impairments. The main focus of this study was to investigate habituation effects on the level of behavioral responses as well as amygdala responses in adults with ASD during a working memory task flanked by task-irrelevant face stimuli. Twenty-two patients with high-functioning autism and 24 healthy controls (HC) were included in this functional magnetic resonance imaging (fMRI) study. We employed an established habituation index to investigate habituation effects. Suggestive of altered habituation, the habituation index showed a decrement of reaction time over the course of the experiment in the HC but not in the ASD group. Similarly, an expected pattern of habituation was evident in amygdala activation in HC but absent in ASD participants. These results provide evidence that habituation may be altered not only on a neural, but also on a behavioral level in ASD. While more research is needed to develop a better understanding of the underlying mechanisms, the current findings support the possibility that deficient habituation may be a biomarker of ASD.
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14. Vogel KR, Ainslie GR, Jansen EE, Salomons GS, Roullet JB, Gibson KM. {{In vitro modeling of experimental succinic semialdehyde dehydrogenase deficiency (SSADHD) using brain-derived neural stem cells}}. {PLoS One}. 2017; 12(10): e0186919.
We explored the utility of neural stem cells (NSCs) as an in vitro model for evaluating preclinical therapeutics in succinic semialdehyde dehydrogenase-deficient (SSADHD) mice. NSCs were obtained from aldh5a1+/+ and aldh5a1-/- mice (aldh5a1 = aldehyde dehydrogenase 5a1 = SSADH). Multiple parameters were evaluated including: (1) production of GHB (gamma-hydroxybutyrate), the biochemical hallmark of SSADHD; (2) rescue from cell death with the dual mTOR (mechanistic target of rapamycin) inhibitor, XL-765, an agent previously shown to rescue aldh5a1-/- mice from premature lethality; (3) mitochondrial number, total reactive oxygen species, and mitochondrial superoxide production, all previously documented as abnormal in aldh5a1-/- mice; (4) total ATP levels and ATP consumption; and (5) selected gene expression profiles associated with epilepsy, a prominent feature in both experimental and human SSADHD. Patterns of dysfunction were observed in all of these parameters and mirrored earlier findings in aldh5a1-/- mice. Patterns of dysregulated gene expression between hypothalamus and NSCs centered on ion channels, GABAergic receptors, and inflammation, suggesting novel pathomechanisms as well as a developmental ontogeny for gene expression potentially associated with the murine epileptic phenotype. The NSC model of SSADHD will be valuable in providing a first-tier screen for centrally-acting therapeutics and prioritizing therapeutic concepts of preclinical animal studies applicable to SSADHD.
