1. Copping NA, Berg EL, Foley GM, Schaffler MD, Onaga BL, Buscher N, Silverman JL, Yang M. {{Touchscreen learning deficits and normal social approach behavior in the Shank3B model of Phelan-McDermid Syndrome and autism}}. {Neuroscience};2017 (Mar 14);345:155-165.
SHANK3 is a synaptic scaffolding protein localized in the postsynaptic density and has a crucial role in synaptogenesis and neural physiology. Deletions and point mutations in SHANK3 cause Phelan-McDermid Syndrome (PMS), and have also been implicated in autism spectrum disorder (ASD) and intellectual disabilities, leading to the hypothesis that reduced SHANK3 expression impairs basic brain functions that are important for social communication and cognition. Several mouse models of Shank3 deletions have been generated, varying in the specific domain deleted. Here we report impairments in cognitive function in mice heterozygous for exon 13-16 (coding for the PDZ domain) deletion. The touchscreen pairwise discrimination task was chosen by virtue of its: (a) conceptual and technical similarities to the Cambridge Neuropsychological Test Automated Battery (CANTAB) and NIH Toolbox Cognition Battery used for testing cognitive functions in humans, (b) minimal demand on motor abilities, and (c) capability to measure many aspects of learning and memory and complex cognitive functions, including cognitive flexibility. The similarity between our mouse tasks and human cognitive assays means a high translational validity in future intervention studies using preclinical models. Our study revealed that Shank3B heterozygous mice (+/-) were slower to reach criterion in the pairwise visual discrimination task, and exhibited trends toward making more errors (first trial errors) and more correction errors than wildtype mice (+/+). Open field activity was normal in +/-, ruling out hypo- or hyperactivity as potential confounds in the touchscreen test. Sociability in the three chamber test was also normal in both +/+ and +/-. These results indicate a deficit in discrimination learning in the Shank3B model of PMS and ASD, suggesting that this mouse model is a useful preclinical tool for studying neurobiological mechanisms behind cognitive impairments in PMS and ASD. The current findings are the starting point for our future research in which we will investigate multiple domains of cognition and explore pharmacological interventions.
Lien vers le texte intégral (Open Access ou abonnement)
2. de Gaulmyn A, Miljkovitch R, Montreuil M. {{Etude clinique des processus sous-jacents de l’attention conjointe de très jeunes enfants avec trouble du spectre autistique.}}. {Encephale};2017 (Mar 09)
OBJECTIVES: Symptoms in autism, a neurodevelopmental disorder, appear at an early age. Research consensus shows impairments in communication and especially joint attention, defined as the capacity to intentionally share attention between two persons or a person and an object. Recent studies in autism spectrum disorder (ASD) focus on infants’ processes associated to joint attention, such as visual and auditive regulation, attentional engagement and social motivation. The present research’s objective is to examine the role of these factors in joint attention. METHODS: A group of 50 children with ASD, aged 21 to 50 months, were selected. They went through a clinical assessment which included evaluations of development and symptoms, a scale measuring auditive and visual regulation; a grid elaborated to quantify motivation behavior towards a person and an object in two different engagement states: alone or with an adult and finally a measure of the child’s capacity to disengage from an object. A joint attention score was obtained with the Early Communication Scale for Children (ECSC). Results show: (1) an effect of visual regulation on joint attention, (2) a relation between visual regulation and joint attention partially mediated by motivation. Our results clarify the nature of the relationship between visual regulation and joint attention, with motivation modulating visual regulation in its relation to joint attention, (3) a relation between attentional disengagement and joint attention. Visual regulation, social and non-social motivation and attentional disengagement are all associated to joint attention. A clinical measure of motivation behaviors for children with ASD has been created and can be applied in clinical settings, as it is adapted to young children with ASD symptomatology and enriches diagnosis. CONCLUSIONS: Statistical analyses of our clinical observations suggest a mediation model highlighting the influence of motivation in the mechanisms underlying joint attention. The measurement of processes and mechanisms associated with social communicative skills at a very early age, here motivation and attentional disengagement processes associated with joint attention, help include these factors in early intervention programs.
Lien vers le texte intégral (Open Access ou abonnement)
3. Di Martino A, O’Connor D, Chen B, Alaerts K, Anderson JS, Assaf M, Balsters JH, Baxter L, Beggiato A, Bernaerts S, Blanken LM, Bookheimer SY, Braden BB, Byrge L, Castellanos FX, Dapretto M, Delorme R, Fair DA, Fishman I, Fitzgerald J, Gallagher L, Keehn RJ, Kennedy DP, Lainhart JE, Luna B, Mostofsky SH, Muller RA, Nebel MB, Nigg JT, O’Hearn K, Solomon M, Toro R, Vaidya CJ, Wenderoth N, White T, Craddock RC, Lord C, Leventhal B, Milham MP. {{Enhancing studies of the connectome in autism using the autism brain imaging data exchange II}}. {Sci Data};2017 (Mar 14);4:170010.
The second iteration of the Autism Brain Imaging Data Exchange (ABIDE II) aims to enhance the scope of brain connectomics research in Autism Spectrum Disorder (ASD). Consistent with the initial ABIDE effort (ABIDE I), that released 1112 datasets in 2012, this new multisite open-data resource is an aggregate of resting state functional magnetic resonance imaging (MRI) and corresponding structural MRI and phenotypic datasets. ABIDE II includes datasets from an additional 487 individuals with ASD and 557 controls previously collected across 16 international institutions. The combination of ABIDE I and ABIDE II provides investigators with 2156 unique cross-sectional datasets allowing selection of samples for discovery and/or replication. This sample size can also facilitate the identification of neurobiological subgroups, as well as preliminary examinations of sex differences in ASD. Additionally, ABIDE II includes a range of psychiatric variables to inform our understanding of the neural correlates of co-occurring psychopathology; 284 diffusion imaging datasets are also included. It is anticipated that these enhancements will contribute to unraveling key sources of ASD heterogeneity.
Lien vers le texte intégral (Open Access ou abonnement)
4. Goldman SE, Alder ML, Burgess HJ, Corbett BA, Hundley R, Wofford D, Fawkes DB, Wang L, Laudenslager ML, Malow BA. {{Characterizing Sleep in Adolescents and Adults with Autism Spectrum Disorders}}. {J Autism Dev Disord};2017 (Mar 12)
We studied 28 adolescents/young adults with autism spectrum disorders (ASD) and 13 age/sex matched individuals of typical development (TD). Structured sleep histories, validated questionnaires, actigraphy (4 weeks), and salivary cortisol and melatonin (4 days each) were collected. Compared to those with TD, adolescents/young adults with ASD had longer sleep latencies and more difficulty going to bed and falling asleep. Morning cortisol, evening cortisol, and the morning-evening difference in cortisol did not differ by diagnosis (ASD vs. TD). Dim light melatonin onsets (DLMOs) averaged across participants were not different for the ASD and TD participants. Average participant scores indicated aspects of poor sleep hygiene in both groups. Insomnia in ASD is multifactorial and not solely related to physiological factors.
Lien vers le texte intégral (Open Access ou abonnement)
5. He J, Xie Y, Kong S, Qiu W, Wang X, Wang D, Sun X, Sun D. {{Psychomotor retardation with a 1q42.11-q42.12 deletion}}. {Hereditas};2017;154:6.
A 1q42 deletion is a rare structure variation that commonly harbours various deletion breakpoints along with diversified phenotypes. In our study, we found a de novo 1q42 deletion in a boy who did not have a cleft palate or a congenital diaphragmatic hernia but presented with psychomotor retardation. A 1.9 Mb deletion located within 1q42.11-q42.12 was validated at the molecular cytogenetic level. This is the first report of a 1q42.11-q42.12 deletion in a patient with onlypsychomotor retardation. The precise break points could facilitate the discovery of potential causative genes, such as LBR, EPHX1, etc. The correlation between the psychomotor retardation and the underlying genetic factors could not only shed light on the diagnosis of psychomotor retardation at the genetic level but also provide potential therapeutic targets.
Lien vers le texte intégral (Open Access ou abonnement)
6. Lee M, Martin GE, Berry-Kravis E, Losh M. {{Erratum to: A developmental, longitudinal investigation of autism phenotypic profiles in fragile X syndrome}}. {J Neurodev Disord};2017;9:10.
[This corrects the article DOI: 10.1186/s11689-016-9179-0.].
Lien vers le texte intégral (Open Access ou abonnement)
7. Lemonnier E, Villeneuve N, Sonie S, Serret S, Rosier A, Roue M, Brosset P, Viellard M, Bernoux D, Rondeau S, Thummler S, Ravel D, Ben-Ari Y. {{Effects of bumetanide on neurobehavioral function in children and adolescents with autism spectrum disorders}}. {Transl Psychiatry};2017 (Mar 14);7(3):e1056.
In animal models of autism spectrum disorder (ASD), the NKCC1 chloride-importer inhibitor bumetanide restores physiological (Cl-)i levels, enhances GABAergic inhibition and attenuates electrical and behavioral symptoms of ASD. In an earlier phase 2 trial; bumetanide reduced the severity of ASD in children and adolescents (3-11 years old). Here we report the results of a multicenter phase 2B study primarily to assess dose/response and safety effects of bumetanide. Efficacy outcome measures included the Childhood Autism Rating Scale (CARS), the Social Responsive Scale (SRS) and the Clinical Global Impressions (CGI) Improvement scale (CGI-I). Eighty-eight patients with ASD spanning across the entire pediatric population (2-18 years old) were subdivided in four age groups and randomized to receive bumetanide (0.5, 1.0 or 2.0 mg twice daily) or placebo for 3 months. The mean CARS value was significantly improved in the completers group (P: 0.015). Also, 23 treated children had more than a six-point improvement in the CARS compared with only one placebo-treated individual. Bumetanide significantly improved CGI (P: 0.0043) and the SRS score by more than 10 points (P: 0.02). The most frequent adverse events were hypokalemia, increased urine elimination, loss of appetite, dehydration and asthenia. Hypokalemia occurred mainly at the beginning of the treatment at 1.0 and 2.0 mg twice-daily doses and improved gradually with oral potassium supplements. The frequency and incidence of adverse event were directly correlated with the dose of bumetanide. Therefore, bumetanide improves the core symptoms of ASD and presents a favorable benefit/risk ratio particularly at 1.0 mg twice daily.
Lien vers le texte intégral (Open Access ou abonnement)
8. Mason RA, Schnitz AG, Wills HP, Rosenbloom R, Kamps DM, Bast D. {{Impact of a Teacher-as-Coach Model: Improving Paraprofessionals Fidelity of Implementation of Discrete Trial Training for Students with Moderate-to-Severe Developmental Disabilities}}. {J Autism Dev Disord};2017 (Mar 14)
Ensuring educational progress for students with moderate-to-severe developmental disabilities requires exposure to well executed evidence-based practices. This necessitates that the special education workforce, including paraprofessionals, be well-trained. Yet evidence regarding effective training mechanisms for paraprofessionals is limited. A multiple baseline design across five teachers was used to evaluate the impact of online instructional modules and a Practice-Based Coaching (PBC) model with teacher-as-coach on their paraprofessionals’ fidelity of discrete trial training (DTT). Implementation of the instructional modules yielded little to no change in paraprofessionals’ DTT fidelity, however, a clear functional relation between PBC and improvement in paraprofessionals’ fidelity of implementation of DTT was demonstrated. Implications for future research and practice are discussed.
Lien vers le texte intégral (Open Access ou abonnement)
9. Morales-Chavez MC. {{Oral Health Assessment of a Group of Children with Autism Disorder}}. {J Clin Pediatr Dent};2017;41(2):147-149.
OBJECTIVE: The aim of this research was to determine the oral status of a group of children with autism. STUDY DESIGN: An observational transversal study was carried out in 96 pediatric patients between the ages of 2 and 16 years old with a diagnosis of autism. The patients were assessed to determine the presence of caries with Index Caries (WHO criteria) and debris and calculus with the Simplified Oral Hygiene Index, as well as the type of diet they followed. RESULTS: It was established that 41.7% of the patients had caries, with the result of an index of DMFT= 0.96 and dmft =2.41. In terms of the periodontal health 59.4% suffered from calculus. The OHI-S was 3.4. CONCLUSIONS: Children with autism exhibited a higher caries prevalence in primary teeth than in permanents. They also presented poor hygiene and an extensive presence of calculus.
Lien vers le texte intégral (Open Access ou abonnement)
10. Page SC, Hamersky GR, Gallo RA, Rannals MD, Calcaterra NE, Campbell MN, Mayfield B, Briley A, Phan BN, Jaffe AE, Maher BJ. {{The schizophrenia- and autism-associated gene, transcription factor 4 regulates the columnar distribution of layer 2/3 prefrontal pyramidal neurons in an activity-dependent manner}}. {Mol Psychiatry};2017 (Mar 14)
Disruption of the laminar and columnar organization of the brain is implicated in several psychiatric disorders. Here, we show in utero gain-of-function of the psychiatric risk gene transcription factor 4 (TCF4) severely disrupts the columnar organization of medial prefrontal cortex (mPFC) in a transcription- and activity-dependent manner. This morphological phenotype was rescued by co-expression of TCF4 plus calmodulin in a calcium-dependent manner and by dampening neuronal excitability through co-expression of an inwardly rectifying potassium channel (Kir2.1). For we believe the first time, we show that N-methyl-d-aspartate (NMDA) receptor-dependent Ca2+ transients are instructive to minicolumn organization because Crispr/Cas9-mediated mutation of NMDA receptors rescued TCF4-dependent morphological phenotypes. Furthermore, we demonstrate that the transcriptional regulation by the psychiatric risk gene TCF4 enhances NMDA receptor-dependent early network oscillations. Our novel findings indicate that TCF4-dependent transcription directs the proper formation of prefrontal cortical minicolumns by regulating the expression of genes involved in early spontaneous neuronal activity, and thus our results provides insights into potential pathophysiological mechanisms of TCF4-associated psychiatric disorders.Molecular Psychiatry advance online publication, 14 March 2017; doi:10.1038/mp.2017.37.
Lien vers le texte intégral (Open Access ou abonnement)
11. Robert C, Pasquier L, Cohen D, Fradin M, Canitano R, Damaj L, Odent S, Tordjman S. {{Role of Genetics in the Etiology of Autistic Spectrum Disorder: Towards a Hierarchical Diagnostic Strategy}}. {Int J Mol Sci};2017 (Mar 12);18(3)
Progress in epidemiological, molecular and clinical genetics with the development of new techniques has improved knowledge on genetic syndromes associated with autism spectrum disorder (ASD). The objective of this article is to show the diversity of genetic disorders associated with ASD (based on an extensive review of single-gene disorders, copy number variants, and other chromosomal disorders), and consequently to propose a hierarchical diagnostic strategy with a stepwise evaluation, helping general practitioners/pediatricians and child psychiatrists to collaborate with geneticists and neuropediatricians, in order to search for genetic disorders associated with ASD. The first step is a clinical investigation involving: (i) a child psychiatric and psychological evaluation confirming autism diagnosis from different observational sources and assessing autism severity; (ii) a neuropediatric evaluation examining neurological symptoms and developmental milestones; and (iii) a genetic evaluation searching for dysmorphic features and malformations. The second step involves laboratory and if necessary neuroimaging and EEG studies oriented by clinical results based on clinical genetic and neuropediatric examinations. The identification of genetic disorders associated with ASD has practical implications for diagnostic strategies, early detection or prevention of co-morbidity, specific treatment and follow up, and genetic counseling.
Lien vers le texte intégral (Open Access ou abonnement)
12. Studenka BE, Gillam SL, Hartzheim D, Gillam RB. {{Motor and verbal perspective taking in children with Autism Spectrum Disorder: Changes in social interaction with people and tools}}. {Res Dev Disabil};2017 (Mar 09)
BACKGROUND: Children with Autism Spectrum Disorder (ASD) have difficulty communicating with others nonverbally, via mechanisms such as hand gestures, eye contact and facial expression. Individuals with ASD also have marked deficits in planning future actions (Hughes, 1996), which might contribute to impairments in non-verbal communication. Perspective taking is typically assessed using verbal scenarios whereby the participant imagines how an actor would interact in a social situation (e.g., Sally Anne task; Baron-Cohen, Leslie, & Frith, 1985). METHOD: The current project evaluated motor perspective taking in five children with ASD (8-11 years old) as they participated in a narrative intervention program over the course of about 16 weeks. The goal of the motor perspective-taking task was to facilitate the action of an experimenter either hammering with a tool or putting it away. RESULTS: Initially, children with ASD facilitated the experimenter’s action less than neurotypical control children. As the narrative intervention progressed, children with ASD exhibited increased motor facilitation that paralleled their increased use of mental state and causal language, indicating a link between verbal and motor perspective taking. CONCLUSIONS: Motoric perspective taking provides an additional way to assess understanding and communication in children with ASD and may be a valuable tool for both early assessment and diagnosis of children with ASD.
Lien vers le texte intégral (Open Access ou abonnement)
13. Sutherland R, Hodge A, Bruck S, Costley D, Klieve H. {{Parent-reported differences between school-aged girls and boys on the autism spectrum}}. {Autism};2017 (Mar 01):1362361316668653.
More boys than girls are diagnosed with autism spectrum disorder; however, there are conflicting findings about whether they differ in their presentation. This study involved a survey of parents of school-aged children on the autism spectrum (171 parents of girls and 163 parents of boys) that was distributed via social media. The surveys provided insights regarding the characteristics of boys and girls (as perceived by parents) as well as some demographic information. There were very few differences reported regarding communication and social strengths and difficulties of boys and girls with autism. No differences were reported in the number of boys and girls on the autism spectrum with special interests or repetitive behaviours; however, significant differences were found in the types of special interests with boys and girls showing generally interests along traditional gender lines. Qualitative analysis of open comments indicated that some parents of girls on the autism spectrum described their daughter as trying to hide or mask her difficulties more but no parents of boys on the spectrum described this phenomenon.
Lien vers le texte intégral (Open Access ou abonnement)
14. Takahashi H, Nakahachi T, Stickley A, Ishitobi M, Kamio Y. {{Relationship between physiological and parent-observed auditory over-responsiveness in children with typical development and those with autism spectrum disorders}}. {Autism};2016 (Dec 01):1362361316680497.
The objective of this study was to investigate relationships between caregiver-reported sensory processing abnormalities, and the physiological index of auditory over-responsiveness evaluated using acoustic startle response measures, in children with autism spectrum disorders and typical development. Mean acoustic startle response magnitudes in response to 65-105 dB stimuli, in increments of 10 dB, were analyzed in children with autism spectrum disorders and with typical development. Average peak startle latency was also examined. We examined the relationship of these acoustic startle response measures to parent-reported behavioral sensory processing patterns in everyday situations, assessed using the Sensory Profile for all participants. Low-threshold scores on the Sensory Profile auditory section were related to acoustic startle response magnitudes at 75 and 85 dB, but not to the lower intensities of 65 dB. The peak startle latency and acoustic startle response magnitudes at low-stimuli intensities of 65 and 75 dB were significantly related to the low-threshold quadrants (sensory sensitivity and sensation avoiding) scores and to the high-threshold quadrant of sensation seeking. Our results suggest that physiological assessment provides further information regarding auditory over-responsiveness to less-intense stimuli and its relationship to caregiver-observed sensory processing abnormalities in everyday situations.
Lien vers le texte intégral (Open Access ou abonnement)
15. Wang J, Ethridge LE, Mosconi MW, White SP, Binder DK, Pedapati EV, Erickson CA, Byerly MJ, Sweeney JA. {{A resting EEG study of neocortical hyperexcitability and altered functional connectivity in fragile X syndrome}}. {J Neurodev Disord};2017;9:11.
BACKGROUND: Cortical hyperexcitability due to abnormal fast-spiking inhibitory interneuron function has been documented in fmr1 KO mice, a mouse model of the fragile X syndrome which is the most common single gene cause of autism and intellectual disability. METHODS: We collected resting state dense-array electroencephalography data from 21 fragile X syndrome (FXS) patients and 21 age-matched healthy participants. RESULTS: FXS patients exhibited greater gamma frequency band power, which was correlated with social and sensory processing difficulties. Second, FXS patients showed increased spatial spreading of phase-synchronized high frequency neural activity in the gamma band. Third, we observed increased negative theta-to-gamma but decreased alpha-to-gamma band amplitude coupling, and the level of increased theta power was inversely related to the level of resting gamma power in FXS. CONCLUSIONS: Increased theta band power and coupling from frontal sources may represent a mechanism providing compensatory inhibition of high-frequency gamma band activity, potentially contributing to the widely varying level of neurophysiological and behavioral abnormalities and treatment response seen in full-mutation FXS patients. These findings extend preclinical observations and provide new mechanistic insights into brain alterations and their variability across FXS patients. Electrophysiological measures may provide useful translational biomarkers for advancing drug development and individualizing treatments for neurodevelopmental disorders with associated neuronal hyperexcitability.
Lien vers le texte intégral (Open Access ou abonnement)
16. Zamzow RM, Lit L, Hamilton S, Beversdorf DQ. {{Characterizing Autism-Relevant Social Behavior in Poodles via Owner Report}}. {J Comp Psychol};2017 (Mar 13)
Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by deficits in social communication and the presence of restricted, repetitive behaviors. It can be difficult to model the complex behavioral features of this disorder with rodent models, which have limited similarity to human behaviors. The domestic dog may be a promising model of complex human behavior, including core features of ASD. The present study examines ASD-relevant social behavior in Miniature and Standard Poodles using an owner-report questionnaire with questions adapted from the Autism Diagnostic Observation Schedule (Lord, Rutter, DiLavore, & Risi, 2000). A previous study identified 3 behavioral constructs examined by this questionnaire: initiation of reciprocal social behaviors, response to social interaction, and communication. In the present study, confirmatory and experimental factor analyses used to assess how collected data fit with the previous model revealed moderate model fit and a similar factorial structure. Between-breed comparisons across these factors and at the individual question level revealed differences between Miniature and Standard Poodles in showing behaviors. Cluster analyses used to group dogs within each breed according to social behavior identified smaller subgroups of dogs with less social behavior across all 3 factors compared with the average within each breed. Within- and between-breed differences in social behavior warrant investigation of genetic variation underlying this complex trait as it relates to ASD-relevant behavior. (PsycINFO Database Record
Lien vers le texte intégral (Open Access ou abonnement)
17. Zilkha N, Kuperman Y, Kimchi T. {{High-fat diet exacerbates cognitive rigidity and social deficiency in the BTBR mouse model of autism}}. {Neuroscience};2017 (Mar 14);345:142-154.
The global increase in rates of obesity has been accompanied by a similar surge in the number of autism diagnoses. Accumulating epidemiological evidence suggest a possible link between overweight and the risk for autism spectrum disorders (ASD), as well as autism severity. In laboratory animals, several studies have shown a connection between various environmental factors, including diet-induced obesity, and the development of autism-related behaviors. However, the effect of high-fat or imbalanced diet on a pre-existing autism-like phenotype is unclear. In this study, we employed the BTBR inbred mouse strain, a well-established mouse model for autism, to assess the impact of inadequate fattening nutrition on the autism-related behavioral phenotype. Male mice were fed by high-fat diet (HFD) or control balanced diet (control) from weaning onward, and tested in a series of behavioral assays as adults. In addition, we measured the hypothalamic expression levels of several genes involved in oxytocin and dopamine signaling, in search of a possible neurobiological underlying mechanism. As an internal control, we also employed similar metabolic and behavioral measures on neurotypical C57 mice. Compared to control-fed mice, BTBR mice fed by HFD showed marked aggravation in autism-related behaviors, manifested in increased cognitive rigidity and diminished preference for social novelty. Moreover, the total autism composite (severity) score was higher in the HFD group, and positively correlated with higher body weight. Finally, we revealed negative correlations associating dopamine signaling factors in the hypothalamus, to autism-related severity and body weight. In contrast, we found no significant effects of HFD on autism-related behaviors of C57 mice, though the metabolic effects of the diet were similar for both strains. Our results indicate a direct causative link between diet-induced obesity and worsening of a pre-existing autism-related behavior and emphasize the need for adequate nutrition in ASD patients. These findings might also implicate the involvement of hypothalamic dopamine in mediating this effect.
