1. Barton KS, Tabor HK, Starks H, Garrison NA, Laurino M, Burke W. {{Pathways from autism spectrum disorder diagnosis to genetic testing}}. {Genet Med}. 2017.
PurposeThis study examined challenges faced by families and health providers related to genetic testing for autism spectrum disorder (ASD).MethodsThis qualitative study of 14 parents and 15 health providers identified an unstandardized three-step process for families who pursue ASD genetic testing.ResultsStep 1 is the clinical diagnosis of ASD, confirmed by providers practicing alone or in a team. Step 2 is the offer of genetic testing to find an etiology. For those offered testing, step 3 involves the parents’ decision whether to pursue testing. Despite professional guidelines and recommendations, interviews describe considerable variability in approaches to genetic testing for ASD, a lack of consensus among providers, and questions about clinical utility. Many families in our study were unaware of the option for genetic testing; testing decisions by parents appear to be influenced by both provider recommendations and insurance coverage.ConclusionConsideration of genetic testing for ASD should take into account different views about the clinical utility of testing and variability in insurance coverage. Ideally, policy makers from the range of clinical specialties involved in ASD care should revisit policies to clarify the purpose of genetic testing for ASD and promote consensus about its appropriate use.GENETICS in MEDICINE advance online publication, 19 October 2017. doi:10.1038/gim.2017.166.
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2. Bradshaw J, Bearss K, McCracken C, Smith T, Johnson C, Lecavalier L, Swiezy N, Scahill L. {{Parent Education for Young Children With Autism and Disruptive Behavior: Response to Active Control Treatment}}. {J Clin Child Adolesc Psychol}. 2017: 1-11.
This study examines parent and child characteristics in young children with autism spectrum disorder and disruptive behavior who showed a positive response to a parent education program in a randomized clinical trial of parent training. Children with autism spectrum disorder (N = 180) were randomized to parent training (PT) or parent education program (PEP) for 6 months. Using the Clinical Global Impression-Improvement scale, masked independent evaluators rated positive response in 68.5% of children in PT compared to 39.6% in PEP. We compared baseline characteristics and change in parental stress, strain, competence, and mental health for participants who showed a positive response to PEP (PEP-R) to those who did not (PEP-NR). We also compared change in child and parent measures for PEP-R participants to those who showed a positive response to PT (PT-R). At baseline, PEP-R and PEP-NR participants did not differ on any demographic or clinical characteristics. Parents in PEP-R reported significant reductions on the Parenting Stress Index, Caregiver Strain Questionnaire, and Parent Health Questionnaire, and increases on the Parenting Sense of Competence scale. Improvements in child disruptive behavior and parental stress, strain, competence, and mental health for PEP-R participants were similar to PT-R participants. Vineland Daily Living Skills improved only for children in PT-R. PEP was an active control treatment with nearly 40% of participants showing a positive response. Change in child disruptive behavior and parental stress, strain, competence, and mental health were remarkably similar for participants independently rated with a positive response to PEP and PT.
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3. Ceolin L, Bouquier N, Vitre-Boubaker J, Rialle S, Severac D, Valjent E, Perroy J, Puighermanal E. {{Cell Type-Specific mRNA Dysregulation in Hippocampal CA1 Pyramidal Neurons of the Fragile X Syndrome Mouse Model}}. {Front Mol Neurosci}. 2017; 10: 340.
Fragile X syndrome (FXS) is a genetic disorder due to the silencing of the Fmr1 gene, causing intellectual disability, seizures, hyperactivity, and social anxiety. All these symptoms result from the loss of expression of the RNA binding protein fragile X mental retardation protein (FMRP), which alters the neurodevelopmental program to abnormal wiring of specific circuits. Aberrant mRNAs translation associated with the loss of Fmr1 product is widely suspected to be in part the cause of FXS. However, precise gene expression changes involved in this disorder have yet to be defined. The objective of this study was to identify the set of mistranslated mRNAs that could contribute to neurological deficits in FXS. We used the RiboTag approach and RNA sequencing to provide an exhaustive listing of genes whose mRNAs are differentially translated in hippocampal CA1 pyramidal neurons as the integrative result of FMRP loss and subsequent neurodevelopmental adaptations. Among genes differentially regulated between adult WT and Fmr1-/y mice, we found enrichment in FMRP-binders but also a majority of non-FMRP-binders. Interestingly, both up- and down-regulation of specific gene expression is relevant to fully understand the molecular deficiencies triggering FXS. More importantly, functional genomic analysis highlighted the importance of genes involved in neuronal connectivity. Among them, we show that Klk8 altered expression participates in the abnormal hippocampal dendritic spine maturation observed in a mouse model of FXS.
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4. Dang K, Bent S, Lawton B, Warren T, Widjaja F, McDonald MG, Breard M, O’Keefe W, Hendren RL. {{Integrating Autism Care through a School-Based Intervention Model: A Pilot Study}}. {J Clin Med}. 2017; 6(10).
The purpose of this pilot study is to determine the feasibility of monitoring the progress of children with an autism spectrum disorder (ASD) both in school and at home to promote a school-based integrated care model between parents, teachers, and medical providers. This is a prospective cohort study. To monitor progress, outcome measures were administered via an online platform developed for caregivers and teachers of children (n = 30) attending a school specializing in neurodevelopmental disorders and using an integrated medical and education program. Longitudinal analysis showed improvements in a novel scale, the Teacher Autism Progress Scale (TAPS), which was designed to measure key autism-related gains in a school environment (2.1-point improvement, p = 0.004, ES = 0.324). The TAPS showed a strong and statistically significant correlation, with improvement in aberrant behavior (r = -0.50; p = 0.008) and social responsiveness (r = -0.70; p < 0.001). The results also showed non-statistically significant improvements in aberrant behavior, social responsiveness, and quality of life over time at both school and home. To assess feasibility of ongoing progress measurement, we assessed missing data, which showed caregivers were more likely to miss surveys during summer. Results demonstrate the value and feasibility of online, longitudinal data collection in school to assist with individualized education planning and collaborative care for children with ASD. Lessons learned in this pilot will support school outcomes researchers in developing more efficacious, collaborative treatment plans between clinicians, caregivers, and teachers. Lien vers le texte intégral (Open Access ou abonnement)
5. 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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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. Hurtubise K, Carpenter C. {{Learning Experiences and Strategies of Parents of Young Children with Developmental Disabilities: Implications for Rehabilitation Professionals}}. {Phys Occup Ther Pediatr}. 2017; 37(5): 471-84.
AIM: To better understand the learning experiences of parents of children with developmental disabilities and the strategies they develop to support their caregiving role. METHODS: A qualitative secondary analysis of in-depth interviews with parents of children with developmental disability was conducted to better understand parents’ learning experiences and the strategies they developed to use this learning in supporting their children. A foundational thematic analysis process was used to identify the main themes, and the interpretive process was influenced by adult education theories. RESULTS: Findings suggest that participants are highly motivated to learn by a need to understand, to do, and to belong. They also demonstrated varying levels of cognitive, affective, and psychomotor learning. Learning style preferences are evident in participants’ narratives and in their self-reported learning strategies. CONCLUSIONS: Conceptualizing parents, as adult learners, can be helpful in designing clinical interactions and education initiatives. Knowledge of adult learning principles may enable pediatric therapists to better meet the needs of parents and fulfill their information sharing responsibilities.
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8. 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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9. Li A, MacNeill B, Curiel H, Poling A. {{Risperidone in combination with other drugs: Experimental research in individuals with autism spectrum disorder}}. {Exp Clin Psychopharmacol}. 2017; 25(5): 434-9.
Many individuals with autism spectrum disorder simultaneously receive 2 or more drugs intended to improve their behavior, but few studies have evaluated the effects of such polypharmacy. This article summarizes those studies that have systematically examined the effects of risperidone, an antipsychotic drug that is approved by the U.S. Food and Drug Administration to treat « irritability » in children and adolescents with autism spectrum disorder, in combination with another drug with respect to experimental design, assessment techniques, drug co-administered, reported effects, and participant characteristics. The drug combinations that have been evaluated do not parallel those commonly co-administered to individuals with autism spectrum disorder in the United States, and there is no compelling empirical evidence to support the practice of prescribing risperidone in combination with another drug in an attempt to benefit individuals with autism spectrum disorder. (PsycINFO Database Record
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10. McCauley JB, Harris MA, Zajic MC, Swain-Lerro LE, Oswald T, McIntyre N, Trzesniewski K, Mundy P, Solomon M. {{Self-Esteem, Internalizing Symptoms, and Theory of Mind in Youth With Autism Spectrum Disorder}}. {J Clin Child Adolesc Psychol}. 2017: 1-12.
Self-esteem is a potent indicator of mental health in typically developing (TYP) individuals. It is surprising that there have been few comprehensive investigations of self-esteem in children and adolescents with autism spectrum disorder (ASD), given that they are at high risk for comorbid mental health problems, such as depression and anxiety. The objectives of the current study were to assess how youth with ASD rate their self-esteem compared to age-matched TYP youth and to examine how self-esteem relates to internalizing psychopathology and theory of mind in the two groups. Seventy-three children and adolescents, ages 9 to 17, were administered a battery of questionnaires assessing self-esteem and internalizing symptoms, as well as tasks designed to measure theory of mind. Results indicated that youth with ASD rated their self-esteem significantly lower than did TYP youth. Self-esteem was strongly related to depression in both groups but was negatively related to theory of mind only for youth with ASD. These results may provide important insights into how individuals with ASD form evaluations of their own self-worth and illustrate how increasing self-awareness in individuals with ASD is not without risks.
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11. 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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12. Rachisan AL, Niculae AS, Tintea I, Pop B, Militaru M, Bizo A, Hrusca A. {{Association of fragile X syndrome, Robertsonian translocation (13, 22) and autism in a child}}. {Clujul Med}. 2017; 90(4): 445-8.
We describe the case of a 6-year-old boy with both fragile X syndrome and Robertsonian Translocation (45, XY, der (13; 22) (q10; q10)). This is the first reported case of a patient with fragile X syndrome with this Robertsonian translocation. Facial features and macroorchidism were consistent with fragile X syndrome. Cognitive impairment is more significant than in his sibling with fragile X syndrome, and the patient also has a prior diagnosis of autism spectrum disorder. We emphasize the challenges in his behavioral management and outline future directions for his management.
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13. 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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14. Tseng PT, Chen YW, Stubbs B, Carvalho AF, Whiteley P, Tang CH, Yang WC, Chen TY, Li DJ, Chu CS, Liang HY, Wu CK, Yen CF, Lin PY. {{Maternal breastfeeding and autism spectrum disorder in children: A systematic review and meta-analysis}}. {Nutr Neurosci}. 2017: 1-9.
OBJECTIVES: Autism spectrum disorder (ASD) refers to a group of conditions variably affecting communicative and social interactive abilities presenting alongside behaviors with various restricted and repetitive patterns. In addition to genetic factors that influence the onset of the symptoms, there is growing interest in the potential involvement of non-genetic environmental factors. Some aspects of breastfeeding practices, including rates, timing, or optimality, have been put forward as environmental risk factors for autism. However, previous studies showed a controversial relationship between ASD and breastfeeding. METHODS: A meta-analysis on the association between maternal breastfeeding and ASD in children was conducted. We also explored potential moderating factors which might influence this association. Articles reporting the association between breastfeeding and a diagnosis of ASD were included. RESULTS: Seven articles were included in the meta-analysis. Cumulatively, children with ASD (n = 1463), either in the form of clinical diagnosis or self-report, were significantly less likely to have been breastfed than children without ASD (n = 1180) (OR = 0.61, 95% CI = 0.45-0.83, P = 0.002). Subgroup analyses revealed that results remained significant for children who were breastfed with additional supplementation. DISCUSSION: This meta-analysis provides evidence that breastfeeding (exclusively or including additional supplements) may protect against ASD. Prospective longitudinal research is required to disentangle the complex relationships and to explore potential pathophysiological mechanisms.
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15. 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.
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16. Wu WL. {{Association Among Gut Microbes, Intestinal Physiology, and Autism}}. {EBioMedicine}. 2017; 25: 11-2.
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17. Zhou JH, Wang XT, Zhou L, Xu FX, Su LD, Wang H, Jia F, Xu FQ, Chen GQ, De Zeeuw CI, Shen Y. {{Ablation of TFR1 in Purkinje Cells Inhibits mGlu1 Trafficking and Impairs Motor Coordination, But Not Autistic-Like Behaviors}}. {J Neurosci}. 2017; 37(47): 11335-52.
Group 1 metabotropic glutamate receptors (mGlu1/5s) are critical to synapse formation and participate in synaptic LTP and LTD in the brain. mGlu1/5 signaling alterations have been documented in cognitive impairment, neurodegenerative disorders, and psychiatric diseases, but underlying mechanisms for its modulation are not clear. Here, we report that transferrin receptor 1 (TFR1), a transmembrane protein of the clathrin complex, modulates the trafficking of mGlu1 in cerebellar Purkinje cells (PCs) from male mice. We show that conditional knock-out of TFR1 in PCs does not affect the cytoarchitecture of PCs, but reduces mGlu1 expression at synapses. This regulation by TFR1 acts in concert with that by Rab8 and Rab11, which modulate the internalization and recycling of mGlu1, respectively. TFR1 can bind to Rab proteins and facilitate their expression at synapses. PC ablation of TFR1 inhibits parallel fiber-PC LTD, whereas parallel fiber-LTP and PC intrinsic excitability are not affected. Finally, we demonstrate that PC ablation of TFR1 impairs motor coordination, but does not affect social behaviors in mice. Together, these findings underscore the importance of TFR1 in regulating mGlu1 trafficking and suggest that mGlu1- and mGlu1-dependent parallel fiber-LTD are associated with regulation of motor coordination, but not autistic behaviors.SIGNIFICANCE STATEMENT Group 1 metabotropic glutamate receptor (mGlu1/5) signaling alterations have been documented in cognitive impairment, neurodegenerative disorders, and psychiatric diseases. Recent work suggests that altered mGlu1 signaling in Purkinje cells (PCs) may be involved in not only motor learning, but also autistic-like behaviors. We find that conditional knock-out of transferrin receptor 1 (TFR1) in PCs reduces synaptic mGlu1 by tethering Rab8 and Rab11 in the cytosol. PC ablation of TFR1 inhibits parallel fiber-PC LTD, whereas parallel fiber-PC LTP and PC intrinsic excitability are intact. Motor coordination is impaired, but social behaviors are normal in TFR1flox/flox;pCP2-cre mice. Our data reveal a new regulator for trafficking and synaptic expression of mGlu1 and suggest that mGlu1-dependent LTD is associated with motor coordination, but not autistic-like behaviors.
