1. Aman MG, Findling RL, Hardan AY, Hendren RL, Melmed RD, Kehinde-Nelson O, Hsu HA, Trugman JM, Palmer RH, Graham SM, Gage AT, Perhach JL, Katz E. {{Safety and Efficacy of Memantine in Children with Autism: Randomized, Placebo-Controlled Study and Open-Label Extension}}. {J Child Adolesc Psychopharmacol};2016 (Mar 15)
OBJECTIVE: Abnormal glutamatergic neurotransmission is implicated in the pathophysiology of autism spectrum disorder (ASD). In this study, the safety, tolerability, and efficacy of the glutamatergic N-methyl-d-aspartate (NMDA) receptor antagonist memantine (once-daily extended-release [ER]) were investigated in children with autism in a randomized, placebo-controlled, 12 week trial and a 48 week open-label extension. METHODS: A total of 121 children 6-12 years of age with Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text Revision (DSM-IV-TR)-defined autistic disorder were randomized (1:1) to placebo or memantine ER for 12 weeks; 104 children entered the subsequent extension trial. Maximum memantine doses were determined by body weight and ranged from 3 to 15 mg/day. RESULTS: There was one serious adverse event (SAE) (affective disorder, with memantine) in the 12 week study and one SAE (lobar pneumonia) in the 48 week extension; both were deemed unrelated to treatment. Other AEs were considered mild or moderate and most were deemed not related to treatment. No clinically significant changes occurred in clinical laboratory values, vital signs, or electrocardiogram (ECG). There was no significant between-group difference on the primary efficacy outcome of caregiver/parent ratings on the Social Responsiveness Scale (SRS), although an improvement over baseline at Week 12 was observed in both groups. A trend for improvement at the end of the 48 week extension was observed. No improvements in the active group were observed on any of the secondary end-points, with one communication measure showing significant worsening with memantine compared with placebo (p = 0.02) after 12 weeks. CONCLUSIONS: This trial did not demonstrate clinical efficacy of memantine ER in autism; however, the tolerability and safety data were reassuring. Our results could inform future trial design in this population and may facilitate the investigation of memantine ER for other clinical applications.
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2. Bitsika V, Sharpley CF, Mills R. {{How are Sensory Features associated with seven anxiety disorders in boys with Autism Spectrum Disorder?}}. {Int J Dev Neurosci};2016 (Mar 11)
The association between Sensory Features (SF) and seven anxiety disorders was investigated using self-reports and parental reports about 140 young males with an Autism Spectrum Disorder (ASD). Although there were significant correlations between SF and self- and parent-ratings of some of the seven anxiety disorders, overall, SF was found to have an inconsistent association across the seven anxiety disorders and this was also found for the 8 symptoms of Generalised Anxiety Disorder. These data challenge the practice of assessing SF and anxiety via global measures and argue for individualized disorder-specific assessments to develop more effective diagnoses and treatments for the effects of SF.
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3. Charrier A, Tardif C, Gepner B. {{[Slowing down the flow of facial information enhances facial scanning in children with autism spectrum disorders: A pilot eye tracking study]}}. {Encephale};2016 (Mar 16)
OBJECTIVE: Face and gaze avoidance are among the most characteristic and salient symptoms of autism spectrum disorders (ASD). Studies using eye tracking highlighted early and lifelong ASD-specific abnormalities in attention to face such as decreased attention to internal facial features. These specificities could be partly explained by disorders in the perception and integration of rapid and complex information such as that conveyed by facial movements and more broadly by biological and physical environment. Therefore, we wish to test whether slowing down facial dynamics may improve the way children with ASD attend to a face. METHODS: We used an eye tracking method to examine gaze patterns of children with ASD aged 3 to 8 (n=23) and TD controls (n=29) while viewing the face of a speaker telling a story. The story was divided into 6 sequences that were randomly displayed at 3 different speeds, i.e. a real-time speed (RT), a slow speed (S70=70% of RT speed), a very slow speed (S50=50% of RT speed). S70 and S50 were displayed thanks to software called Logiral, aimed at slowing down visual and auditory stimuli simultaneously and without tone distortion. The visual scene was divided into four regions of interest (ROI): eyes region; mouth region; whole face region; outside the face region. The total time, number and mean duration of visual fixations on the whole visual scene and the four ROI were measured between and within the two groups. RESULTS: Compared to TD children, children with ASD spent significantly less time attending to the visual scenes and, when they looked at the scene, they spent less time scanning the speaker’s face in general and her mouth in particular, and more time looking outside facial area. Within the ASD group mean duration of fixation increased on the whole scene and particularly on the mouth area, in R50 compared to RT. Children with mild autism spent more time looking at the face than the two other groups of ASD children, and spent more time attending to the face and mouth as well as longer mean duration of visual fixation on mouth and eyes, at slow speeds (S50 and/or S70) than at RT one. CONCLUSIONS: Slowing down facial dynamics enhances looking time on face, and particularly on mouth and/or eyes, in a group of 23 children with ASD and particularly in a small subgroup with mild autism. Given the crucial role of reading the eyes for emotional processing and that of lip-reading for language processing, our present result and other converging ones could pave the way for novel socio-emotional and verbal rehabilitation methods for autistic population. Further studies should investigate whether increased attention to face and particularly eyes and mouth is correlated to emotional/social and/or verbal/language improvements.
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4. Deonandan R, Liu EY, Kolisnyk B, Konkle AT. {{An Analysis of Canadian Institute for Health Research Funding for Research on Autism Spectrum Disorder}}. {Autism Res Treat};2016;2016:8106595.
We examined patterns of Canadian Institute for Health Research (CIHR) funding on autism spectrum disorder (ASD) research. From 1999 to 2013, CIHR funded 190 ASD grants worth $48 million. Biomedical research received 43% of grants (46% of dollars), clinical research 27% (41%), health services 10% (7%), and population health research 8% (3%). The greatest number of grants was given in 2009, but 2003 saw the greatest amount. Funding is clustered in a handful of provinces and institutions, favouring biomedical research and disfavouring behavioural interventions, adaptation, and institutional response. Preference for biomedical research may be due to the detriment of clinical research.
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5. Ecker C. {{The neuroanatomy of autism spectrum disorder: An overview of structural neuroimaging findings and their translatability to the clinical setting}}. {Autism};2016 (Mar 14)
Autism spectrum disorder is a complex neurodevelopmental disorder, which is accompanied by differences in brain anatomy, functioning and brain connectivity. Due to its neurodevelopmental character, and the large phenotypic heterogeneity among individuals on the autism spectrum, the neurobiology of autism spectrum disorder is inherently difficult to describe. Nevertheless, significant progress has been made in characterizing the neuroanatomical underpinnings of autism spectrum disorder across the human life span, and in identifying the molecular pathways that may be affected in autism spectrum disorder. Moreover, novel methodological frameworks for analyzing neuroimaging data are emerging that make it possible to characterize the neuroanatomy of autism spectrum disorder on the case level, and to stratify individuals based on their individual phenotypic make up. While these approaches are increasingly more often employed in the research setting, their applicability in the clinical setting remains a vision for the future. The aim of the current review is to (1) provide a general overview of recent structural neuroimaging findings examining the neuroanatomy of autism spectrum disorder across the human life span, and in males and females with the condition, (2) highlight potential neuroimaging (bio)markers that may in the future be used for the stratification of autism spectrum disorder individuals into biologically homogeneous subgroups and (3) inform treatment and intervention strategies.
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6. Estabillo JA, Matson JL, Jiang X. {{The association between familial ASD diagnosis, autism symptomatology and developmental functioning in young children}}. {Eur Child Adolesc Psychiatry};2016 (Mar 16)
Few studies have directly compared individuals with and without a relative diagnosed with ASD on various domains. The present study aimed to examine the relationship between familial ASD diagnosis and the exhibition of ASD symptoms in young children with and without ASD diagnoses. Participants included 8353 children aged 17-37 months old and their families. They were divided into four groups based on individual and family diagnosis, then compared on autism symptomatology and developmental domains. No differences were found between ASD groups on overall scores and each of the factor domains, indicating no association between family ASD diagnosis and ASD symptomatology or developmental functioning. Disparate results were found for atypically developing groups with and without relatives diagnosed with ASD. Implications of these results are discussed.
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7. Fletcher-Watson S, Apicella F, Auyeung B, Beranova S, Bonnet-Brilhault F, Canal-Bedia R, Charman T, Chericoni N, Conceicao IC, Davies K, Farroni T, Gomot M, Jones E, Kaale A, Kapica K, Kawa R, Kylliainen A, Larsen K, Lefort-Besnard J, Malvy J, Manso de Dios S, Markovska-Simoska S, Millo I, Miranda N, Pasco G, Pisula E, Raleva M, Roge B, Salomone E, Schjolberg S, Tomalski P, Vicente AM, Yirmiya N. {{Attitudes of the autism community to early autism research}}. {Autism};2016 (Mar 14)
Investigation into the earliest signs of autism in infants has become a significant sub-field of autism research. This work invokes specific ethical concerns such as use of ‘at-risk’ language, communicating study findings to parents and the future perspective of enrolled infants when they reach adulthood. This study aimed to ground this research field in an understanding of the perspectives of members of the autism community. Following focus groups to identify topics, an online survey was distributed to autistic adults, parents of children with autism and practitioners in health and education settings across 11 European countries. Survey respondents (n = 2317) were positively disposed towards early autism research, and there was significant overlap in their priorities for the field and preferred language to describe infant research participants. However, there were also differences including overall less favourable endorsement of early autism research by autistic adults relative to other groups and a dislike of the phrase ‘at-risk’ to describe infant participants, in all groups except healthcare practitioners. The findings overall indicate that the autism community in Europe is supportive of early autism research. Researchers should endeavour to maintain this by continuing to take community perspectives into account.
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8. Hedley D, Brewer N, Nevill R, Uljarevic M, Butter E, Mulick JA. {{The Relationship Between Clinicians’ Confidence and Accuracy, and the Influence of Child Characteristics, in the Screening of Autism Spectrum Disorder}}. {J Autism Dev Disord};2016 (Mar 15)
The study examined the confidence accuracy relationship, and the influence of child characteristics on clinician confidence, when predicting a diagnosis of Autism Spectrum Disorder during screening of 125 referred children aged under 3.5 years. The diagnostic process included observation, interview, language and developmental testing. Clinical judgement accuracy was compared against final diagnosis for high and low confidence levels (with confidence assessed on a 0-100 % scale). We identified a significant CA relationship with predictive accuracy highest at confidence levels of 90-100 %. Parent report of unusual behaviors was the only significant independent predictor of confidence. Clinicians’ confidence may be important when evaluating decisions to refer, or not to refer, children for further diagnostic assessment.
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9. Lloyd-Fox S, Blasi A, Elwell CE, Charman T, Murphy D, Johnson MH. {{Correction to ‘Reduced neural sensitivity to social stimuli in infants at risk for autism’}}. {Proc Biol Sci};2016 (Mar 16);283(1826)
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10. Mullins C, Fishell G, Tsien RW. {{Unifying Views of Autism Spectrum Disorders: A Consideration of Autoregulatory Feedback Loops}}. {Neuron};2016 (Mar 16);89(6):1131-1156.
Understanding the mechanisms underlying autism spectrum disorders (ASDs) is a challenging goal. Here we review recent progress on several fronts, including genetics, proteomics, biochemistry, and electrophysiology, that raise motivation for forming a viable pathophysiological hypothesis. In place of a traditionally unidirectional progression, we put forward a framework that extends homeostatic hypotheses by explicitly emphasizing autoregulatory feedback loops and known synaptic biology. The regulated biological feature can be neuronal electrical activity, the collective strength of synapses onto a dendritic branch, the local concentration of a signaling molecule, or the relative strengths of synaptic excitation and inhibition. The sensor of the biological variable (which we have termed the homeostat) engages mechanisms that operate as negative feedback elements to keep the biological variable tightly confined. We categorize known ASD-associated gene products according to their roles in such feedback loops and provide detailed commentary for exemplar genes within each module.
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11. Nakamura T, Arima-Yoshida F, Sakaue F, Nasu-Nishimura Y, Takeda Y, Matsuura K, Akshoomoff N, Mattson SN, Grossfeld PD, Manabe T, Akiyama T. {{PX-RICS-deficient mice mimic autism spectrum disorder in Jacobsen syndrome through impaired GABAA receptor trafficking}}. {Nat Commun};2016;7:10861.
Jacobsen syndrome (JBS) is a rare congenital disorder caused by a terminal deletion of the long arm of chromosome 11. A subset of patients exhibit social behavioural problems that meet the diagnostic criteria for autism spectrum disorder (ASD); however, the underlying molecular pathogenesis remains poorly understood. PX-RICS is located in the chromosomal region commonly deleted in JBS patients with autistic-like behaviour. Here we report that PX-RICS-deficient mice exhibit ASD-like social behaviours and ASD-related comorbidities. PX-RICS-deficient neurons show reduced surface gamma-aminobutyric acid type A receptor (GABAAR) levels and impaired GABAAR-mediated synaptic transmission. PX-RICS, GABARAP and 14-3-3zeta/theta form an adaptor complex that interconnects GABAAR and dynein/dynactin, thereby facilitating GABAAR surface expression. ASD-like behavioural abnormalities in PX-RICS-deficient mice are ameliorated by enhancing inhibitory synaptic transmission with a GABAAR agonist. Our findings demonstrate a critical role of PX-RICS in cognition and suggest a causal link between PX-RICS deletion and ASD-like behaviour in JBS patients.
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12. Richard AC, Rovelet-Lecrux A, Delaby E, Charbonnier C, Thiruvahindrapuram B, Hatchwell E, Eis PS, Afenjar A, Dussardier BG, Scherer SW, Betancur C, Campion D. {{The 22q11 PRODH/DGCR6 deletion is frequent in hyperprolinemic subjects but is not a strong risk factor for ASD}}. {Am J Med Genet B Neuropsychiatr Genet};2016 (Jan 14)
The proline dehydrogenase (PRODH) gene maps to 22q11.2 in the region deleted in the velo-cardio-facial syndrome (VCFS). A moderate to severe reduction (>50%) in PRODH activity resulting from recessive deletions and/or missense mutations has been shown to cause type 1 hyperprolinemia (HPI). Autistic features have been reported as a common clinical manifestation of HPI. Here we studied the frequency of a recurrent small 22q11.2 deletion encompassing PRODH and the neighboring DGCR6 gene in three case-control studies, one comprising HPI patients (n = 83), and the other two comprising autism spectrum disorder (ASD) patients (total of n = 2800), analyzed with high-resolution microarrays. We found that the PRODH deletion is a strong risk factor for HPI (OR = 50.7; 95%CI = 7.5-2147) but not for ASD (P = 0.4, OR = 0.6-3.3). This result indicates either that the suggested association between ASD and HPI is spurious and results from a bias leading to the preferential inclusion of patients with autistic features in HPI series, or that HPI is present in only a very small subset of ASD patients. In this latter case, a very large sample size would be required to detect an association between the PRODH deletion and ASD in a case-control study. (c) 2016 Wiley Periodicals, Inc.
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13. Valarmathi P, Kumar G, Robin S, Manonmani S, Dasgupta I, Rabindran R. {{Evaluation of virus resistance and agronomic performance of rice cultivar ASD 16 after transfer of transgene against Rice tungro bacilliform virus by backcross breeding}}. {Virus Genes};2016 (Mar 16)
Severe losses of rice yield in south and southeast Asia are caused by Rice tungro disease (RTD) induced by mixed infection of Rice tungro bacilliform virus (RTBV) and Rice tungro spherical virus (RTSV). In order to develop transgene-based resistance against RTBV, one of its genes, ORF IV, was used to generate transgenic resistance based on RNA-interference in the easily transformed rice variety Pusa Basmati-1, and the transgene was subsequently introgressed to rice variety ASD 16, a variety popular in southern India, using transgene marker-assisted selection. Here, we report the evaluation of BC3F4 and BC3F5 generation rice plants for resistance to RTBV as well as for agronomic traits under glasshouse conditions. The BC3F4 and BC3F5 generation rice plants tested showed variable levels of resistance, which was manifested by an average of twofold amelioration in height reduction, 1.5-fold decrease in the reduction in chlorophyll content, and 100- to 10,000-fold reduction in the titers of RTBV, but no reduction of RTSV titers, in three backcrossed lines when compared with the ASD 16 parent. Agronomic traits of some of the backcrossed lines recorded substantial improvements when compared with the ASD 16 parental line after inoculation by RTBV and RTSV. This work represents an important step in transferring RTD resistance to a susceptible popular rice variety, hence enhancing its yield in areas threatened by the disease.
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14. Villanueva-Bonilla C, Bonilla-Santos J, Arana-Guzman F, Ninco-Cuenca I, Quintero-Lozano A. {{[Effects of a ‘theory of mind’ cognitive development pilot programme in three children with autism: emotional component]}}. {Rev Neurol};2016 (Mar 16);62(6):267-272.
INTRODUCTION: Theory of mind is defined as the capacity to predict, understand and act when faced with other people’s behaviour, their knowledge, their intentions, their emotions and their beliefs. It is proposed as a feasible alternative for establishing a programme adapted to the characteristics of children diagnosed with autism spectrum disorder. CASE REPORTS: The effect of a ‘theory of mind’ cognitive development pilot programme on the emotional skills of three children with autism spectrum disorder is reported. Case 1: 9-year-old boy, with scarce emotional identification and expression, as well as difficulties to hold fluent and coherent conversations. Case 2: 10-year-old boy, with mechanical, not very fluent language, and difficulties to start and maintain a conversation. Case 3: 8-year-old girl who presents deficits in the non-verbal communicative behaviours used in social interaction and difficulties to adapt to situations other than everyday ones. In the three cases there is an improvement in the emotional capacities following implementation of the programme; moreover, their parents, teachers or therapists perceived positive changes in the children’s adaptive skills. CONCLUSIONS: The methodological and structural aspects of the cognitive development programme were well-suited to the children with autism who took part in the research study. Due to the preliminary nature of this study, it is suggested that future research should utilise a larger sample and a double-blind design with randomised case-controls that allow the findings to be generalised.
15. Webb SJ, Neuhaus E, Faja S. {{Face perception and learning in autism spectrum disorders}}. {Q J Exp Psychol (Hove)};2016 (Mar 16):1-17.
Autism Spectrum Disorder (ASD) is characterized by impairment in social communication and restricted and repetitive interests. While not included in the diagnostic characterization, aspects of face processing and learning have shown disruptions at all stages of development in ASD, although the exact nature and extent of the impairment vary by age and level of functioning of the ASD sample as well as by task demands. In this review, we examine the nature of face attention, perception, and learning in individuals with ASD focusing on three broad age ranges (early development, middle childhood, and adolescence/adulthood). We propose that early delays in basic face processing contribute to the atypical trajectory of social communicative skills in individuals with ASD and contribute to poor social learning throughout development. Face learning is a life-long necessity, as the social world of individual only broadens with age, and thus addressing both the source of the impairment in ASD as well as the trajectory of ability throughout the lifespan, through targeted treatments, may serve to positively impact the lives of individuals who struggle with social information and understanding.
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16. Yang ZL, Sun GL. {{[Research advances in candidate genes for autism spectrum disorder]}}. {Zhongguo Dang Dai Er Ke Za Zhi};2016 (Mar);18(3):282-287.
Autism spectrum disorder (ASD) is a kind of neurodevelopmental multigenic disorder. More than one hundred of candidate genes for ASD have been reported. The candidate gene research for ASD involves in chromosome loci and screening of candidate genes and epigenetic abnormalities for candidate genes. The reported genes encode neural adhesion molecules, ion channels, scaffold proteins, protein kinases, receptor protein and carrier protein, signaling modulate molecules and circadian relevant proteins. The research of mutation screening and expression regulation of candidate genes can help to elucidate genetic mechanisms for ASD, and may provide new approaches for the diagnosis and treatment of this disorder. This article reviews the research advance in candidate genes for ASD.
