1. Alfaro Arenas R, Rosell Andreo J, Heine Suner D. {{A Pilot Study of Fragile X Syndrome Screening in Pregnant Women and Women Planning Pregnancy: Implementation, Acceptance, Awareness, and Geographic Factors}}. {J Genet Couns};2016 (Oct 7)
We report herein results of a study performed in the Balearic Islands which had the following goals: 1) Determine the proportion of pregnant or non-pregnant women planning pregnancy, who would choose to undergo a screening test for Fragile X Syndrome (FXS), if it is accompanied by the appropriate information; 2) Assess satisfaction and any increase in stress among women who participate in screening; 3) Collect epidemiological information about the incidence of the disease in our population; and 4) Collect demographic and health history data and assess participants’ awareness of the disease. Screening was performed on 3,731 pregnant and non-pregnant women of childbearing age and the results indicate: a very high voluntary rate of participation; a high level of self-reported satisfaction and low levels of stress because of the test; a very high incidence of premutation (1/106) in our population; and a low level of awareness about the existence of FXS (25 %). Additional findings indicate no significant correlation between self-reported health history and premutation detection, and the high premutation incidence does not seem to be specific to the indigenous Balearic population. Based on these results, we discuss the pros and cons of an implementation of preconception and pregnant women screening for FXS within a public health screening program.
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2. Cervantes PE, Matson JL, Peters WJ. {{An abbreviated scoring algorithm for the baby and infant screen for children with autism traits}}. {Dev Neurorehabil};2016 (Aug 11):1-7.
PURPOSE: Autism spectrum disorder (ASD) screening is recommended for all children aged 18-24 months. However, healthcare providers may be burdened with the responsibility of conducting these screens in addition to necessary services. Therefore, developing a time-efficient screener with sound psychometric properties is essential. METHODS: This study sought to update the abbreviated scoring algorithm of the Baby and Infant Screen for Children with aUtIsm Traits (BISCUIT) and increase its clinical utility. Six thousand and three children with ASD or atypical development enrolled in an early intervention program participated. RESULTS: A 6-item algorithm with a cutoff score of 3 was found to be optimal and yielded a sensitivity of 0.960 and a specificity of 0.864. CONCLUSION: Sensitivity and specificity estimates were similar to that of the complete BISCUIT-Part 1; thus, the 6-item algorithm can reliably differentiate children at-risk for ASD requiring further assessment. The algorithm appears to be a promising tool for early identification.
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3. Dufour MM, Lanovaz MJ. {{Comparing two methods to promote generalization of receptive identification in children with autism spectrum disorders}}. {Dev Neurorehabil};2016 (Aug 11):1-12.
PURPOSE: The purpose of our study was to compare the effects of serial and concurrent training on the generalization of receptive identification in children with autism spectrum disorders (ASD). METHODS: We taught one to three pairs of stimulus sets to nine children with ASD between the ages of three and six. One stimulus set within each pair was taught using concurrent training and the other using serial training. We alternated the training sessions within a multielement design and staggered the introduction of subsequent pairs for each participant as in a multiple baseline design. RESULTS: Overall, six participants generalized at least one stimulus set more rapidly with concurrent training whereas two participants showed generalization more rapidly with serial training. CONCLUSIONS: Our results differ from other comparison studies on the topic and indicate that practitioners should consider assessing the effects of both procedures prior to teaching receptive identification to children with ASD.
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4. Finke EH. {{Friendship: Operationalizing the Intangible to Improve Friendship-Based Outcomes for Individuals With Autism Spectrum Disorder}}. {Am J Speech Lang Pathol};2016 (Oct 7):1-10.
Purpose: Individuals with autism spectrum disorder (ASD) have social deficits that affect making and maintaining friends. Many empirically tested methods to address these social deficits are available, yet difficulties related to the establishment and maintenance of authentic friendships persist. Method: This viewpoint article (a) briefly reviews the current state of the science relative to social and friendship skills training for individuals with ASD, (b) considers the potential links (or lack thereof) between current social and friendship skill interventions for individuals with ASD and outcomes related to making and maintaining friends, (c) examines how friendship-related outcomes might be maximized, and (d) proposes a framework for intervention planning that may promote these valued outcomes. Results: There are several key concepts to consider in planning intervention targeting friendship as an outcome. These concepts include (a) equal status, (b) mutually motivating and authentic opportunities for interaction, and (c) frequent opportunities for interaction. Conclusions: There are many aspects about friendship development that cannot be controlled or contrived. Much is still to be learned about the achievement of better friendships for individuals with ASD. Reconceptualizing the way we design intervention may promote better outcomes for individuals on the autism spectrum.
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5. Hegarty JP, 2nd, Ferguson BJ, Zamzow RM, Rohowetz LJ, Johnson JD, Christ SE, Beversdorf DQ. {{Beta-adrenergic antagonism modulates functional connectivity in the default mode network of individuals with and without autism spectrum disorder}}. {Brain Imaging Behav};2016 (Oct 6)
The beta-adrenergic antagonist propranolol benefits some social and communication domains affected in autism spectrum disorder (ASD), and these benefits appear to be associated with increased functional connectivity (FC) in the brain during task performance. FC is implicated in ASD, with the majority of studies suggesting long distance hypo-connectivity combined with regionally specific local hyper-connectivity. The objective in the current investigation was to examine the effect of propranolol on FC at rest and determine whether ASD-specific effects exist. Participants with and without ASD attended three sessions in which propranolol, nadolol (a beta-adrenergic antagonist that does not cross the blood-brain barrier), or placebo were administered. Resting-state fMRI data were acquired, and graph theory techniques were utilized to assess additional aspects of FC. Compared to placebo, propranolol administration was associated with decreased FC in the dorsal medial prefrontal cortex subnetwork of the default mode network and increased FC in the medial temporal lobe subnetwork, regardless of diagnosis. These effects were not seen with nadolol suggesting that the alterations in FC following propranolol administration were not exclusively due to peripheral cardiovascular effects. Thus, beta-adrenergic antagonism can up- or down- regulate FC, depending on the network, and alter coordinated functional activation in the brain. These changes in information processing, as demonstrated by FC, may mediate some of the clinical and behavioral effects of beta-adrenergic antagonism previously reported in patients with ASD.
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6. Ingersoll B, Berger N, Carlsen D, Hamlin T. {{Improving social functioning and challenging behaviors in adolescents with ASD and significant ID: A randomized pilot feasibility trial of reciprocal imitation training in a residential setting}}. {Dev Neurorehabil};2016 (Aug 11):1-10.
There is a lack of effective social interventions for youths with ASD and co-morbid intellectual disability (ID). A previous single-case design study indicated that reciprocal imitation training (RIT) may improve social interaction and challenging behavior in this population. The current pilot study examined the feasibility of conducting an RCT to investigate the effectiveness of RIT for improving social functioning and challenging behaviors in 20 adolescents with ASD and severe ID in a residential program. The assessment protocol was feasible. RIT was well-tolerated by the adolescents and implemented with fidelity by teaching staff. Preliminary findings indicate that treatment had moderate to large effects on social functioning and challenging behavior, with mixed findings for imitation skills. A larger RCT of RIT for this population is feasible and warranted.
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7. Krebs G, Murray K, Jassi A. {{Modified Cognitive Behavior Therapy for Severe, Treatment-Resistant Obsessive-Compulsive Disorder in an Adolescent With Autism Spectrum Disorder}}. {J Clin Psychol};2016 (Sep 22)
There is a high rate of comorbidity between obsessive-compulsive disorder (OCD) and autism spectrum disorders (ASD). Standard cognitive-behavior therapy (CBT) protocols have been shown to be less effective in treating OCD in young people with ASD than in typically developing youth. This case study describes the treatment of an adolescent boy with severe, treatment-resistant OCD and ASD using a modified CBT approach. Modifications to a standard evidence-based CBT for OCD protocol included extended psychoeducation about anxiety; regular home-based sessions; and increased involvement of systems, including family and school. Multi-informant outcome data indicated significant improvements in OCD symptoms over the course of treatment with gains being maintained over a 12-month follow-up period. These findings demonstrate the potential efficacy of modified CBT for pediatric OCD in the context of ASD.
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8. Matheis M, Matson JL, Burns CO, Jiang X, Peters WJ, Moore M, de Back KA, Estabillo J. {{Factors related to parental age of first concern in toddlers with autism spectrum disorder}}. {Dev Neurorehabil};2016 (Aug 11):1-8.
PURPOSE: The age of first concern (AOC) of parents of children with autism spectrum disorders (ASD) has substantial implications for early diagnosis and intervention. The current study sought to determine the average AOC, what types of first concerns are most common, and what factors predict earlier AOC in toddlers with ASD. METHODS: This study analyzed the predictive influence of the type of concern, symptom severity, medical diagnoses, and other independent variables on AOC among toddlers with ASD using multiple regressions. RESULTS: The mean AOC was found to be 13.97 months (SD = 7.86). The most commonly reported first concern was speech/language. First concerns related to communication, speech/language predicted later AOC, while motor concerns predicted earlier AOC. CONCLUSIONS: Concerns that are more closely related to social communication deficits characteristic of ASD predicted later AOC. The implications of these findings on screening/assessment and intervention are discussed.
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9. Siper PM, Zemon V, Gordon J, George-Jones J, Lurie S, Zweifach J, Tavassoli T, Wang AT, Jamison J, Buxbaum JD, Kolevzon A. {{Rapid and Objective Assessment of Neural Function in Autism Spectrum Disorder Using Transient Visual Evoked Potentials}}. {PLoS One};2016;11(10):e0164422.
OBJECTIVE: There is a critical need to identify biomarkers and objective outcome measures that can be used to understand underlying neural mechanisms in autism spectrum disorder (ASD). Visual evoked potentials (VEPs) offer a noninvasive technique to evaluate the functional integrity of neural mechanisms, specifically visual pathways, while probing for disease pathophysiology. METHODS: Transient VEPs (tVEPs) were obtained from 96 unmedicated children, including 37 children with ASD, 36 typically developing (TD) children, and 23 unaffected siblings (SIBS). A conventional contrast-reversing checkerboard condition was compared to a novel short-duration condition, which was developed to enable objective data collection from severely affected populations who are often excluded from electroencephalographic (EEG) studies. RESULTS: Children with ASD showed significantly smaller amplitudes compared to TD children at two of the earliest critical VEP components, P60-N75 and N75-P100. SIBS showed intermediate responses relative to ASD and TD groups. There were no group differences in response latency. Frequency band analyses indicated significantly weaker responses for the ASD group in bands encompassing gamma-wave activity. Ninety-two percent of children with ASD were able to complete the short-duration condition compared to 68% for the standard condition. CONCLUSIONS: The current study establishes the utility of a short-duration tVEP test for use in children at varying levels of functioning and describes neural abnormalities in children with idiopathic ASD. Implications for excitatory/inhibitory balance as well as the potential application of VEP for use in clinical trials are discussed.
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10. Yamada T, Itahashi T, Nakamura M, Watanabe H, Kuroda M, Ohta H, Kanai C, Kato N, Hashimoto RI. {{Altered functional organization within the insular cortex in adult males with high-functioning autism spectrum disorder: evidence from connectivity-based parcellation}}. {Mol Autism};2016;7:41.
BACKGROUND: The insular cortex comprises multiple functionally differentiated sub-regions, each of which has different patterns of connectivity with other brain regions. Such diverse connectivity patterns are thought to underlie a wide range of insular functions, including cognitive, affective, and sensorimotor processing, many of which are abnormal in autism spectrum disorder (ASD). Although past neuroimaging studies of ASD have shown structural and functional abnormalities in the insula, possible alterations in the sub-regional organization of the insula and the functional characteristics of each sub-region have not been examined in the ASD brain. METHODS: Resting-state functional magnetic resonance imaging (rs-fMRI) data were acquired from 36 adult males with ASD and 38 matched typically developed (TD) controls. A data-driven clustering analysis was applied to rs-fMRI data of voxels in the left and right insula to automatically group voxels with similar intrinsic connectivity pattern into a cluster. After determining the optimal number of clusters based on information theoretic measures of variation of information and mutual information, functional parcellation patterns in both the left and the right insula were compared between the TD and ASD groups. Furthermore, functional profiles of each sub-region were meta-analytically decoded using Neurosynth and were compared between the groups. RESULTS: We observed notable alterations in the anterior sector of the left insula and the middle ventral sub-region of the right insula in the ASD brain. Meta-analytic decoding revealed that whereas the anterior sector of the left insula contained two functionally differentiated sub-regions for cognitive, sensorimotor, and emotional/affective functions in TD brain, only a single functional cluster for cognitive and sensorimotor functions was identified in the anterior sector in the ASD brain. In the right insula, the middle ventral sub-region, which is primarily specialized for sensory- and auditory-related functions, showed a significant volumetric increase in the ASD brain compared with the TD brain. CONCLUSIONS: The results indicate an altered organization of sub-regions in specific parts of the left and right insula of the ASD brain. The alterations in the left and right insula may constitute neural substrates underlying abnormalities in emotional/affective and sensory functions in ASD.
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11. Zachor DA, Ben-Itzchak E. {{Specific Medical Conditions Are Associated with Unique Behavioral Profiles in Autism Spectrum Disorders}}. {Front Neurosci};2016;10:410.
Autism spectrum disorder (ASD) is a heterogeneous group of disorders which occurs with numerous medical conditions. In previous research, subtyping in ASD has been based mostly on cognitive ability and ASD symptom severity. The aim of the current study was to investigate whether specific medical conditions in ASD are associated with unique behavioral profiles. The medical conditions included in the study were macrocephaly, microcephaly, developmental regression, food selectivity, and sleep problems. The behavioral profile was composed of cognitive ability, adaptive skills, and autism severity, and was examined in each of the aforementioned medical conditions. The study population included 1224 participants, 1043 males and 181 females (M:F ratio = 5.8:1) with a mean age of 49.9 m (SD = 29.4) diagnosed with ASD using standardized tests. Groups with and without the specific medical conditions were compared on the behavioral measures. Developmental regression was present in 19% of the population and showed a more severe clinical presentation, with lower cognitive abilities, more severe ASD symptoms, and more impaired adaptive functioning. Microcephaly was observed in 6.3% of the population and was characterized by a lower cognitive ability and more impaired adaptive functioning in comparison to the normative head circumference (HC) group. Severe food selectivity was found in 9.8% and severe sleep problems in 5.1% of the ASD population. The food selectivity and sleep problem subgroups, both showed more severe autism symptoms only as described by the parents, but not per the professional assessment, and more impaired adaptive skills. Macrocephaly was observed in 7.9% of the ASD population and did not differ from the normative HC group in any of the examined behavioral measures. Based on these findings, two unique medical-behavioral subtypes in ASD that affect inherited traits of cognition and/or autism severity were suggested. The microcephaly phenotype occurred with more impaired cognition and the developmental regression phenotype with widespread, more severe impairments in cognition and autism severity. In contrast, severe food selectivity and sleep problems represent only comorbidities to ASD that affect functioning. Defining specific subgroups in ASD with a unique biological signature and specific behavioral phenotypes may help future genetic and neuroscience research.
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12. Zhou Y, Kumari D, Sciascia N, Usdin K. {{CGG-repeat dynamics and FMR1 gene silencing in fragile X syndrome stem cells and stem cell-derived neurons}}. {Mol Autism};2016;7:42.
BACKGROUND: Fragile X syndrome (FXS), a common cause of intellectual disability and autism, results from the expansion of a CGG-repeat tract in the 5′ untranslated region of the FMR1 gene to >200 repeats. Such expanded alleles, known as full mutation (FM) alleles, are epigenetically silenced in differentiated cells thus resulting in the loss of FMRP, a protein important for learning and memory. The timing of repeat expansion and FMR1 gene silencing is controversial. METHODS: We monitored the repeat size and methylation status of FMR1 alleles with expanded CGG repeats in patient-derived induced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs) that were grown for extended period of time either as stem cells or differentiated into neurons. We used a PCR assay optimized for the amplification of large CGG repeats for sizing, and a quantitative methylation-specific PCR for the analysis of FMR1 promoter methylation. The FMR1 mRNA levels were analyzed by qRT-PCR. FMRP levels were determined by western blotting and immunofluorescence. Chromatin immunoprecipitation was used to study the association of repressive histone marks with the FMR1 gene in FXS ESCs. RESULTS: We show here that while FMR1 gene silencing can be seen in FXS embryonic stem cells (ESCs), some silenced alleles contract and when the repeat number drops below ~400, DNA methylation erodes, even when the repeat number remains >200. The resultant active alleles do not show the large step-wise expansions seen in stem cells from other repeat expansion diseases. Furthermore, there may be selection against large active alleles and these alleles do not expand further or become silenced on neuronal differentiation. CONCLUSIONS: Our data support the hypotheses that (i) large expansions occur prezygotically or in the very early embryo, (ii) large unmethylated alleles may be deleterious in stem cells, (iii) methylation can occur on alleles with >400 repeats very early in embryogenesis, and (iv) expansion and contraction may occur by different mechanisms. Our data also suggest that the threshold for stable methylation of FM alleles may be higher than previously thought. A higher threshold might explain why some carriers of FM alleles escape methylation. It may also provide a simple explanation for why silencing has not been observed in mouse models with >200 repeats.
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13. Zoghbi HY. {{Rett Syndrome and the Ongoing Legacy of Close Clinical Observation}}. {Cell};2016 (Oct 6);167(2):293-297.
This year marks the 50th anniversary of the publication of Andreas Rett’s report on 22 girls who developed a peculiar and devastating neurological disorder that later came to bear his name. On this occasion, we reflect on the progress that has occurred in understanding Rett Syndrome, development of potential treatments, and the ramifications that Rett research has had on the fields of neurobiology and genetics.
