1. Auffray C. {{Autism cornered: network analyses reveal mechanisms of autism spectrum disorders}}. {Molecular systems biology}. 2014;10(12):778.
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2. Banney RM, Harper-Hill K, Arnott WL. {{The Autism Diagnostic Observation Schedule and narrative assessment: Evidence for specific narrative impairments in autism spectrum disorders}}. {International journal of speech-language pathology}. 2014 Dec 26:1-13.
Purpose: The Autism Diagnostic Observation Schedule (ADOS) contains a narrative generation task in which clients tell a story from a wordless picture book; however, the resulting narrative is not usually examined for its linguistic properties. This study aimed to examine narrative generation in autism spectrum disorder (ASD) by comparing narratives elicited from children with ASD during the ADOS to those produced by language-matched typically-developing (TD) peers. Method: Participants were children with ASD (n = 11) and TD controls (n = 17). Both groups were aged 9-15 years and were matched for expressive and receptive language skills and non-verbal intelligence. Narratives were analysed for local structure elements (length, fluency, errors, semantics and syntax), cohesion and global elements (story grammar and internal state language). Results: Results indicated that the narratives of the children with ASD were syntactically less complex, contained more ambiguous pronouns and included fewer story grammar elements than their control counterparts; with further analysis showing differences between younger and older children. Conclusions: The present findings provide evidence that children with ASD exhibit subtle story generation impairments and provide preliminary support for the inclusion of narratives elicited as part of the ADOS in the assessment of specific language skills in this population.
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3. Beamer J. {{Physical Education for Students With Autism Spectrum Disorders: A Comprehensive Approach}}. {Adapted physical activity quarterly : APAQ}. 2015 Jan;32(1):83-4.
No abstract available for this article.
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4. Bickel J, Bridgemohan C, Sideridis G, Huntington N. {{Child and family characteristics associated with age of diagnosis of an autism spectrum disorder in a tertiary care setting}}. {Journal of developmental and behavioral pediatrics : JDBP}. 2015 Jan;36(1):1-7.
OBJECTIVE: To identify child and family characteristics associated with age of diagnosis of autism spectrum disorder (ASD) in a tertiary care setting using objective, standardized assessments ensuring diagnostic validity and timing. METHODS: The authors conducted a chart review of children who received their initial ASD diagnosis from 2007 to 2011. Child variables included gender, birth order, cognitive functioning, and for children </=36 months, language and adaptive assessments. Family variables included insurance, maternal age, maternal education, sibling or family member with ASD, and number of children in the house. Primary outcome was age of ASD diagnosis. The authors ran multiple regression models evaluating the impact of child and family variables on the total sample and on the subsample of children </=36 months. RESULTS: Median age of diagnosis was 2.9 years (range, 15 mo-13.8 yr; n = 591). In the total sample, significant predictors of earlier age of diagnosis were later birth order, higher maternal education, fewer children in the house, and a sibling with ASD. In a separate analysis of children </=36 months of age (n = 315) with additional data for language and adaptive assessments, significant predictors of younger age of diagnosis were higher cognitive and adaptive functioning, lower receptive and expressive language, and having a sibling with ASD. CONCLUSIONS: This study suggests that both family and child characteristics play an important role in the early identification of ASD and that predictive variables may vary based on a child’s age. Future research should help to elucidate this finding so that screening measures and policies aimed at early identification can target the most predictive factors.
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5. Edmiston EK, Merkle K, Corbett BA. {{Neural and Cortisol Responses during Play with Human and Computer Partners in Children with Autism}}. {Social cognitive and affective neuroscience}. 2014 Dec 30.
Background: Children with autism spectrum disorder (ASD) exhibit impairment in reciprocal social interactions, including play, which can manifest as failure to show social preference or discrimination between social and nonsocial stimuli. Methods: To explore mechanisms underlying these deficits, we collected salivary cortisol from forty-two children 8-to-12 years with ASD or typical development during a playground interaction with a confederate child. Participants underwent functional MRI during a Prisoner’s Dilemma game requiring cooperation or defection with a human (confederate) or computer partner. Search region of interest analyses were based on previous research (e.g., insula, amygdala, temporal parietal junction). Results: There were significant group differences in neural activation based on partner and response pattern. When playing with a human partner, children with ASD showed limited engagement of a social salience brain circuit during defection. Reduced insula activation during defection in the ASD children relative to TD children, regardless of partner type, was also a prominent finding. Insula and temporal parietal junction BOLD during defection was also associated with stress responsivity and behavior in the ASD group under playground conditions. Discussion: Children with ASD engage social salience networks less than TD children during conditions of social salience, supporting a fundamental disturbance of social engagement.
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6. Gallagher D, Voronova A, Zander MA, Cancino GI, Bramall A, Krause MP, Abad C, Tekin M, Neilsen PM, Callen DF, Scherer SW, Keller GM, Kaplan DR, Walz K, Miller FD. {{Ankrd11 Is a Chromatin Regulator Involved in Autism that Is Essential for Neural Development}}. {Developmental cell}. 2014 Dec 30.
Ankrd11 is a potential chromatin regulator implicated in neural development and autism spectrum disorder (ASD) with no known function in the brain. Here, we show that knockdown of Ankrd11 in developing murine or human cortical neural precursors caused decreased proliferation, reduced neurogenesis, and aberrant neuronal positioning. Similar cellular phenotypes and aberrant ASD-like behaviors were observed in Yoda mice carrying a point mutation in the Ankrd11 HDAC-binding domain. Consistent with a role for Ankrd11 in histone acetylation, Ankrd11 was associated with chromatin and colocalized with HDAC3, and expression and histone acetylation of Ankrd11 target genes were altered in Yoda neural precursors. Moreover, the Ankrd11 knockdown-mediated decrease in precursor proliferation was rescued by inhibiting histone acetyltransferase activity or expressing HDAC3. Thus, Ankrd11 is a crucial chromatin regulator that controls histone acetylation and gene expression during neural development, thereby providing a likely explanation for its association with cognitive dysfunction and ASD.
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7. Jonsson L, Zettergren A, Pettersson E, Hovey D, Anckarsater H, Westberg L, Lichtenstein P, Lundstrom S, Melke J. {{Association study between autistic-like traits and polymorphisms in the autism candidate regions RELN, CNTNAP2, SHANK3, and CDH9/10}}. {Molecular autism}. 2014;5(1):55.
BACKGROUND: Autistic-like traits (ALTs) are continuously distributed in the general population, with the autism spectrum disorder (ASD) at the upper extreme end. A genetic overlap has been shown between ALTs and ASD, indicating that common variation in ASD candidate genes may also influence ALTs. In our study, we have investigated the SNP rs4307059 that has been associated with both ALTs and ASD. In addition, we genotyped polymorphisms in a selection of genes involved in synaptic functioning, that is, SHANK3, RELN, and CNTNAP2, which repeatedly have been associated with ASD. The possible associations of these polymorphisms with ALTs, as well as genetic factors for neurodevelopmental problems (NDPs), were investigated in a large cohort from the general population: The Child and Adolescent Twin Study in Sweden. For analyses of ALTs and NDPs, 12,319 subjects (including 2,268 monozygotic (MZ) and 3,805 dizygotic (DZ) twin pairs) and 8,671 subjects (including 2,243 MZ and 2,044 DZ twin pairs), respectively, were included in the analyses. FINDINGS: We could not replicate the previous association between rs4307059 and social communication impairment. Moreover, common variations in CNTNAP2 (rs7794745 and rs2710102), RELN (rs362691), and SHANK3 (rs9616915) were not significantly associated with ALTs in our study. CONCLUSIONS: Our results do not suggest that the investigated genes, which previously has been found associated with ASD diagnosis, have any major influence on ALTs in children from the general population.
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8. Kryzak LA, Cengher M, Feeley KM, Fienup DM, Jones EA. {{A community support program for children with autism and their typically developing siblings: Initial investigation}}. {Journal of intellectual disabilities : JOID}. 2014 Dec 26.
Siblings are a critical part of lifelong support for individuals with autism spectrum disorder (ASD). But siblings face their own social-emotional adjustment needs. These needs may be addressed through programs that include support groups specifically for the siblings. This study examined the effects of a community program on typical siblings’ depression, anxiety, ASD knowledge, and peer network as well as reciprocal interactions between the typical sibling and sibling with ASD. The program provided a sibling support group, a skills intervention for children with ASD, and an inclusive recreation time. Siblings reported significant decreases in depression and physiological anxiety and improvements in their peer network. Autism knowledge increased but only approached significance. Direct observations revealed improvement in reciprocal interactions by most children that did not reach statistical significance. Parents, typical siblings, and interventionists indicated positive reactions to the program and its goals and outcomes. Findings are discussed in terms of the need to continue to explore interventions for siblings of children with ASD.
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9. Langkamp DL, McManus MD, Blakemore SD. {{Telemedicine for Children with Developmental Disabilities: A More Effective Clinical Process than Office-Based Care}}. {Telemedicine journal and e-health : the official journal of the American Telemedicine Association}. 2014 Dec 29.
Abstract Background: The literature on the use of telemedicine for children with developmental disabilities (DD) is limited and mostly describes telemedicine being used to link patients with distant subspecialty multidisciplinary care. Parents generally have reported satisfaction with such care and have perceived it to be equally effective as in-person care. Here we report on the use of school-based asynchronous telemedicine to connect children with DD with primary care providers. Materials and Methods: We developed Tele-Health-Kids, a school-based program using asynchronous telemedicine to connect children with DD with their primary care physician for the care of minor illnesses. We surveyed parents at enrollment and after the child’s first telemedicine visit to assess satisfaction. We describe 4 cases that illustrate benefits, particularly for children with DD and challenging behaviors, suggesting that asynchronous telemedicine may actually be superior to traditional in-office visits in some circumstances. Results: Most parents expressed a high level of satisfaction with the program. Benefits identified include decreased stress to the child and the parents as well as increasing the likelihood of a successful medical examination due to greater cooperation by the child. Visits using asynchronous or « store and forward » telemedicine technology may be superior in some situations by allowing the visit to be performed at a pace that can be adjusted to the needs of the child with DD. Conclusions: More research in the use of asynchronous telemedicine for children and youth with DD, particularly for children with DD and challenging behaviors, is needed.
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10. Li J, Shi M, Ma Z, Zhao S, Euskirchen G, Ziskin J, Urban A, Hallmayer J, Snyder M. {{Integrated systems analysis reveals a molecular network underlying autism spectrum disorders}}. {Molecular systems biology}. 2014;10(12):774.
Autism is a complex disease whose etiology remains elusive. We integrated previously and newly generated data and developed a systems framework involving the interactome, gene expression and genome sequencing to identify a protein interaction module with members strongly enriched for autism candidate genes. Sequencing of 25 patients confirmed the involvement of this module in autism, which was subsequently validated using an independent cohort of over 500 patients. Expression of this module was dichotomized with a ubiquitously expressed subcomponent and another subcomponent preferentially expressed in the corpus callosum, which was significantly affected by our identified mutations in the network center. RNA-sequencing of the corpus callosum from patients with autism exhibited extensive gene mis-expression in this module, and our immunochemical analysis showed that the human corpus callosum is predominantly populated by oligodendrocyte cells. Analysis of functional genomic data further revealed a significant involvement of this module in the development of oligodendrocyte cells in mouse brain. Our analysis delineates a natural network involved in autism, helps uncover novel candidate genes for this disease and improves our understanding of its molecular pathology.
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11. Lind SE, Bowler DM, Raber J. {{Spatial navigation, episodic memory, episodic future thinking, and theory of mind in children with autism spectrum disorder: evidence for impairments in mental simulation?}}. {Frontiers in psychology}. 2014;5:1411.
This study explored spatial navigation alongside several other cognitive abilities that are thought to share common underlying neurocognitive mechanisms (e.g., the capacity for self-projection, scene construction, or mental simulation), and which we hypothesized may be impaired in autism spectrum disorder (ASD). Twenty intellectually high-functioning children with ASD (with a mean age of ~8 years) were compared to 20 sex, age, IQ, and language ability matched typically developing children on a series of tasks to assess spatial navigation, episodic memory, episodic future thinking (also known as episodic foresight or prospection), theory of mind (ToM), relational memory, and central coherence. This is the first study to explore these abilities concurrently within the same sample. Spatial navigation was assessed using the « memory island » task, which involves finding objects within a realistic, computer simulated, three-dimensional environment. Episodic memory and episodic future thinking were assessed using a past and future event description task. ToM was assessed using the « animations » task, in which children were asked to describe the interactions between two animated triangles. Relational memory was assessed using a recognition task involving memory for items (line drawings), patterned backgrounds, or combinations of items and backgrounds. Central coherence was assessed by exploring differences in performance across segmented and unsegmented versions of block design. Children with ASD were found to show impairments in spatial navigation, episodic memory, episodic future thinking, and central coherence, but not ToM or relational memory. Among children with ASD, spatial navigation was found to be significantly negatively related to the number of repetitive behaviors. In other words, children who showed more repetitive behaviors showed poorer spatial navigation. The theoretical and practical implications of the results are discussed.
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12. Lumaban JG, Nelson DL. {{The Fragile X proteins Fmrp and Fxr2p cooperate to regulate glucose metabolism in mice}}. {Human molecular genetics}. 2014 Dec 30.
Fragile X syndrome results from loss of FMR1 expression. Individuals with the disorder exhibit not only intellectual disability, but also an array of physical and behavioral abnormalities, including sleep difficulties. Studies in mice demonstrated that Fmr1, along with its paralog Fxr2, regulate circadian behavior, and that their absence disrupts expression and cycling of essential clock mRNAs in the liver. Recent reports have identified circadian genes to be essential for normal metabolism. Here we describe the metabolic defects that arise in mice mutated for both Fmr1 and Fxr2. These mice have reduced fat deposits compared with age- and weight-matched controls. Several metabolic markers show either low levels in plasma or abnormal circadian cycling (or both). Insulin levels are consistently low regardless of light exposure and feeding conditions and the animals are extremely sensitive to injected insulin. Glucose production from introduced pyruvate and glucagon is impaired and the mice quickly clear injected glucose. These mice also have higher food intake and higher VO2 and VCO2 levels. We analyzed liver expression of genes involved in glucose homeostasis and found several that are expressed differentially in the mutant mice. These results point to the involvement of Fmr1 and Fxr2 in maintaining the normal metabolic state in mice.
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13. Martinez-Sanchis S. {{Neurobiological foundations of multisensory integration in people with autism spectrum disorders: the role of the medial prefrontal cortex}}. {Frontiers in human neuroscience}. 2014;8:970.
This review aims to relate the sensory processing problems in people with autism spectrum disorders (ASD), especially multisensory integration (MSI), to the role of the medial prefrontal cortex (mPFC) by exploring neuroanatomical findings; brain connectivity and Default Network (DN); global or locally directed attention; and temporal multisensory binding. The mPFC is part of the brain’s DN, which is deactivated when attention is focused on a particular task and activated on rest when spontaneous cognition emerges. In those with ASD, it is hypoactive and the higher the social impairment the greater the atypical activity. With an immature DN, cross-modal integration is impaired, resulting in a collection of disconnected fragments instead of a coherent global perception. The deficit in MSI may lie in the temporal synchronization of neural networks. The time interval in which the stimulation of one sensory channel could influence another would be higher, preventing integration in the typical shorter time range. Thus, the underconnectivity between distant brain areas would be involved in top-down information processes (relying on global integration of data from different sources) and would enhance low level perception processes such as over focused attention to sensory details.
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14. Newman I, Leader G, Chen JL, Mannion A. {{An analysis of challenging behavior, comorbid psychopathology, and Attention-Deficit/Hyperactivity Disorder in Fragile X Syndrome}}. {Research in developmental disabilities}. 2014 Dec 23;38C:7-17.
The present study sought to investigate the relationship between challenging behavior, comorbid psychopathology, and Attention-Deficit/Hyperactivity Disorder (AD/HD) in Fragile X Syndrome (FRAX). Additionally, this study sought to examine how such disorders are predicted by gender, presence of autism spectrum disorder (ASD), and presence of intellectual disability (ID). A total of 47 children and adolescents with FRAX were assessed. Results revealed high levels of challenging behavior and AD/HD symptoms within the sample, with some participants exhibiting symptoms of comorbid psychopathology. Further analysis revealed that challenging behavior and comorbid psychopathology were positively correlated, with stereotypy correlating most strongly with comorbid psychopathology. In addition, ASD was found to predict challenging behavior, and gender was found to predict AD/HD symptoms. The implications of these findings are discussed.
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15. Port RG, Gandal MJ, Roberts TP, Siegel SJ, Carlson GC. {{Convergence of circuit dysfunction in ASD: a common bridge between diverse genetic and environmental risk factors and common clinical electrophysiology}}. {Frontiers in cellular neuroscience}. 2014;8:414.
Most recent estimates indicate that 1 in 68 children are affected by an autism spectrum disorder (ASD). Though decades of research have uncovered much about these disorders, the pathological mechanism remains unknown. Hampering efforts is the seeming inability to integrate findings over the micro to macro scales of study, from changes in molecular, synaptic and cellular function to large-scale brain dysfunction impacting sensory, communicative, motor and cognitive activity. In this review, we describe how studies focusing on neuronal circuit function provide unique context for identifying common neurobiological disease mechanisms of ASD. We discuss how recent EEG and MEG studies in subjects with ASD have repeatedly shown alterations in ensemble population recordings (both in simple evoked related potential latencies and specific frequency subcomponents). Because these disease-associated electrophysiological abnormalities have been recapitulated in rodent models, studying circuit differences in these models may provide access to abnormal circuit function found in ASD. We then identify emerging in vivo and ex vivo techniques, focusing on how these assays can characterize circuit level dysfunction and determine if these abnormalities underlie abnormal clinical electrophysiology. Such circuit level study in animal models may help us understand how diverse genetic and environmental risks can produce a common set of EEG, MEG and anatomical abnormalities found in ASD.
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16. Rahbar MH, Samms-Vaughan M, Dickerson AS, Loveland KA, Ardjomand-Hessabi M, Bressler J, Shakespeare-Pellington S, Grove ML, Pearson DA, Boerwinkle E. {{Blood Lead Concentrations in Jamaican Children with and without Autism Spectrum Disorder}}. {International journal of environmental research and public health}. 2014;12(1):83-105.
Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder manifesting by early childhood. Lead is a toxic metal shown to cause neurodevelopmental disorders in children. Several studies have investigated the possible association between exposure to lead and ASD, but their findings are conflicting. Using data from 100 ASD cases (2-8 years of age) and their age- and sex-matched typically developing controls, we investigated the association between blood lead concentrations (BLC) and ASD in Jamaican children. We administered a questionnaire to assess demographic and socioeconomic information as well as exposure to potential lead sources. We used General Linear Models (GLM) to assess the association of BLC with ASD status as well as with sources of exposure to lead. In univariable GLM, we found a significant difference between geometric mean blood lead concentrations of ASD cases and controls (2.25 mug/dL cases vs. 2.73 mug/dL controls, p < 0.05). However, after controlling for potential confounders, there were no significant differences between adjusted geometric mean blood lead concentrations of ASD cases and controls (2.55 mug/dL vs. 2.72 mug/dL, p = 0.64). Our results do not support an association between BLC and ASD in Jamaican children. We have identified significant confounders when assessing an association between ASD and BLC.
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17. Rattazzi A. {{[The importance of early detection and early intervention for children with autism spectrum conditions]}}. {Vertex (Buenos Aires, Argentina)}. 2014 Jul-Aug;25(116):290-4.
Autism spectrum disorders are a group of neurodevelopmental disorders characterized by social communication difficulties and restrictive and repetitive patterns of behavior, interests and activities. In Argentina in 2013, legislation introduced both at national and provincial levels generated vigorous debate in relation to early detection of autism spectrum disorders, diagnosis or « pathologization » of children, and early intervention for these children. This paper provides evidence supporting the importance of systematic screening for autism spectrum disorders in toddlers, the usefulness of the new autism spectrum disorder classification provided by DSM-5, the desirability of timely and comprehensive diagnostic assessments by interdisciplinary teams specialized in development, and the critical importance of early intervention. Early intervention takes advantage of the neuroplasticity present in early life and positively impacts prognosis of children and family quality of life. Finally, the role of parent-mediated interventions in the treatment of children with autism spectrum disorders is mentioned.
18. Simplican SC, Leader G, Kosciulek J, Leahy M. {{Defining social inclusion of people with intellectual and developmental disabilities: An ecological model of social networks and community participation}}. {Research in developmental disabilities}. 2014 Dec 23;38C:18-29.
Social inclusion is an important goal for people with intellectual and developmental disabilities, families, service providers, and policymakers; however, the concept of social inclusion remains unclear, largely due to multiple and conflicting definitions in research and policy. We define social inclusion as the interaction between two major life domains: interpersonal relationships and community participation. We then propose an ecological model of social inclusion that includes individual, interpersonal, organizational, community, and socio-political factors. We identify four areas of research that our ecological model of social inclusion can move forward: (1) organizational implementation of social inclusion; (2) social inclusion of people with intellectual and developmental disabilities living with their families, (3) social inclusion of people along a broader spectrum of disability, and (4) the potential role of self-advocacy organizations in promoting social inclusion.
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19. Stein DS, Welchons LW, Corley KB, Dickinson H, Levin AR, Nelson CA, Stein MT. {{Autism associated with early institutionalization, high intelligence, and naturalistic behavior therapy in a 7-year-old boy}}. {Journal of developmental and behavioral pediatrics : JDBP}. 2015 Jan;36(1):53-5.
CASE: Paul is a 7-year-old boy with a history of cerebral palsy and left-side weakness secondary to perinatal injury. He was adopted to the United States at 19 months from a baby home in Eastern Europe, where the caregiver to child ratio was 7:1. Paul spent most of his early developmental period in a crib. On adoption, he was nonverbal and nonambulatory, but these skills developed within 1 year. Paul was noted at 4 years of age to be struggling socially and also to exhibit restricted interests (e.g., memorizing maps and world leaders). He was referred for neuropsychological testing at age 5 and was found to have cognitive skills in the gifted range (verbal intelligence quotient, IQ =143; 99.8%) but exhibited markedly reduced social reciprocity with high levels of restricted interests and repetitive behaviors, leading to a diagnosis of autism spectrum disorder (ASD) in the context of early institutionalization. Given his cooperative and attentive presentation, high IQ, and ability to imitate, Floortime, a more naturalistic behavioral therapy for ASD, was recommended rather than traditional applied behavior analysis, which is more commonly available in the region. In addition, Paul was provided with group speech and language therapy with a social/pragmatic focus. After 1 year, Paul’s socialization improved but he struggled to initiate interactions and maintain friendships. He focused instead on his restricted interests and played alone. After 2 years of intervention, Paul presents as highly sociable with well-sustained eye gaze, interactive play, and successful friendships. Still, without direction and structure, Paul will happily draw maps for hours at a time. He is hyperlexic and working far above grade level across subjects. His mother now questions-is this still truly institutional autism or is he simply too intelligent to relate to same-age peers?
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20. Strauss K, Benvenuto A, Battan B, Siracusano M, Terribili M, Curatolo P, Fava L. {{Promoting Shared Decision Making to strengthen outcome of young children with Autism Spectrum Disorders: The role of staff competence}}. {Research in developmental disabilities}. 2014 Dec 24;38C:48-63.
Little is known on how the conceptual description of Shared Decision Making (SDM) accomplishes clinical practice in the context of lifetime disabilities as in particular Autism Spectrum Disorders (ASD), when intervention is long-lasting and requires constant family involvement. This study aimed mainly to investigate to what extent the staff’s competence in SDM contributes to positive child and parent improvement when involving parents in Early Intensive Behavior Interventions (EIBI). It was also geared to verify whether SDM staff competence contributes to a child’s treatment responsiveness. A total of 25 young children with ASD (23 male, 3 female, age range 34-92 months, mean age 51.4+/-13.6) were included in the study. Of these, nine children were allocated to a Parent Involvement condition accompanied by SDM Staff Training (PI-SDM), and eight children to a Parent Inclusion in Treatment Delivery Only condition without SDM Staff Training (PI-DO). Nine months treatment outcomes of severity, developmental and adaptive measures were compared to Treatment As Usual (n=8). PI-SDM was associated with improvement of autistic symptoms (p</=.05), adaptive functioning (p</=.01) and developmental outcome (p</=.01), as well as parent (p</=.05) and staff competence (p</=.001). The magnitude of outcome was inferior in the PI-PO and TAU group. A Reliable Change was identified in more than 40% of children included in PI-SDM, while PI-PO (>20%) and TAU (>12%) let to little Reliable Change and partially skill deterioration. Staff’s SDM skill competence predicts reduced parental stress (beta=-.500, p</=.05) and contributes significantly to a positive treatment responder trajectory (p</=.01), besides lower severity (p</=.05), higher adaptive (p</=.01) and communication skills (p</=.05). The study indicates that parent inclusion should be conceptualized as a collaborative partnership model rather than as adherence in treatment provision, based on a target SDM staff training that may constitute an external contributor to treatment responsiveness and positive child as well as parent outcome.
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21. van de Lagemaat LN, Nijhof B, Bosch DG, Kohansal-Nodehi M, Keerthikumar S, Heimel JA. {{Age-related decreased inhibitory vs. excitatory gene expression in the adult autistic brain}}. {Frontiers in neuroscience}. 2014;8:394.
Autism spectrum disorders (ASDs) are neurodevelopmental disorders characterized by impaired social interaction and communication, and restricted behavior and interests. A disruption in the balance of excitatory and inhibitory neurotransmission has been hypothesized to underlie these disorders. Here we demonstrate that genes of both pathways are affected by ASD, and that gene expression of inhibitory and excitatory genes is altered in the cerebral cortex of adult but not younger autistic individuals. We have developed a measure for the difference in the level of excitation and inhibition based on gene expression and observe that in this measure inhibition is decreased relative to excitation in adult ASD compared to control. This difference was undetectable in young autistic brains. Given that many psychiatric features of autism are already present at an early age, this suggests that the observed imbalance in gene expression is an aging phenomenon in ASD rather than its underlying cause.
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22. Vitezic M, Bertin N, Andersson R, Lipovich L, Kawaji H, Lassmann T, Sandelin A, Heutink P, Goldowitz D, Ha T, Zhang P, Patrizi A, Fagiolini M, Forrest AR, Carninci P, Saxena A. {{CAGE-defined promoter regions of the genes implicated in Rett Syndrome}}. {BMC genomics}. 2014 Dec 24;15(1):1177.
BACKGROUND: Mutations in three functionally diverse genes cause Rett Syndrome. Although the functions of Forkhead box G1 (FOXG1), Methyl CpG binding protein 2 (MECP2) and Cyclin-dependent kinase-like 5 (CDKL5) have been studied individually, not much is known about their relation to each other with respect to expression levels and regulatory regions. Here we analyzed data from hundreds of mouse and human samples included in the FANTOM5 project, to identify transcript initiation sites, expression levels, expression correlations and regulatory regions of the three genes RESULTS: Our investigations reveal the predominantly used transcription start sites (TSSs) for each gene including novel transcription start sites for FOXG1. We show that FOXG1 expression is poorly correlated with the expression of MECP2 and CDKL5. We identify promoter shapes for each TSS, the predicted location of enhancers for each gene and the common transcription factors likely to regulate the three genes. Our data imply Polycomb Repressive Complex 2 (PRC2) mediated silencing of Foxg1 in cerebellum CONCLUSIONS: Our analyses provide a comprehensive picture of the regulatory regions of the three genes involved in Rett Syndrome.
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23. Wang Z, Magnon G, White SP, Greene R, Vaillancourt DE, Mosconi M. {{Individuals with autism spectrum disorder (ASD) show abnormalities during initial and subsequent phases of precision gripping}}. {Journal of neurophysiology}. 2014 Dec 30:jn 00661 2014.
Sensorimotor impairments are common in ASD, but they are not well understood. Here, we examined force control during initial pulses and the subsequent rise, sustained, and relaxation phases of precision gripping in 34 individuals with ASD and 25 healthy controls. Participants pressed on opposing load cells with their thumb and index finger while receiving visual feedback regarding their performance. They completed 2 and 8 sec trials during which they pressed at 15, 45 or 85% of their maximum force. Initial pulses guided by feedforward control mechanisms, sustained force output controlled by visual feedback processes, and force relaxation rates all were examined. Controls favored an initial pulse strategy characterized by a rapid increase in and then relaxation of force when the target force was low (Type 1). When the target force level or duration of trials was increased, controls transitioned to a strategy in which they more gradually increased their force, paused, and then increased their force again. Individuals with ASD showed a more persistent bias towards the Type 1 strategy at higher force levels and during longer trials and their initial force output was less accurate than that of controls. Patients showed increased force variability compared to controls when attempting to sustain a constant force level. During the relaxation phase, they showed reduced rates of force decrease. These findings suggest that both feedforward and feedback motor control mechanisms are compromised in ASD and these deficits may contribute to the dyspraxia and sensorimotor abnormalities often seen in this disorder.
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24. Wegener E, Brendel C, Fischer A, Hulsmann S, Gartner J, Huppke P. {{Characterization of the MeCP2R168X Knockin Mouse Model for Rett Syndrome}}. {PloS one}. 2014;9(12):e115444.
Rett syndrome, one of the most common causes of mental retardation in females, is caused by mutations in the X chromosomal gene MECP2. Mice deficient for MeCP2 recapitulate some of the symptoms seen in patients with Rett syndrome. It has been shown that reactivation of silent MECP2 alleles can reverse some of the symptoms in these mice. We have generated a knockin mouse model for translational research that carries the most common nonsense mutation in Rett syndrome, R168X. In this article we describe the phenotype of this mouse model. In male MeCP2R168X mice life span was reduced to 12-14 weeks and bodyweight was significantly lower than in wild type littermates. First symptoms including tremor, hind limb clasping and inactivity occurred at age 27 days. At age 6 weeks nest building, rotarod, open-field and elevated plus maze experiments showed impaired motor performance, reduced activity and decreased anxiety-like behavior. Plethysmography at the same time showed apneas and irregular breathing with reduced frequency. Female MeCP2R168X mice showed no significant abnormalities except decreased performance on the rotarod at age 9 months. In conclusion we show that the male MeCP2R168X mice have a phenotype similar to that seen in MECP2 knockout mouse models and are therefore well suited for translational research. The female mice, however, have a much milder and less constant phenotype making such research with this mouse model more challenging.
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25. Yi L, Quinn PC, Feng C, Li J, Ding H, Lee K. {{Do individuals with autism spectrum disorder process own- and other-race faces differently?}}. {Vision research}. 2014 Dec 24.
Individuals with autism spectrum disorder (ASD) process human faces in atypical ways according to previous literature. We investigated whether individuals with ASD can process face race information and respond to own- and other-race faces differentially. Chinese individuals with ASD (n=24), typically developing (TD) individuals (n=28), and individuals with intellectual disabilities (ID, n=26) were asked to recognize Chinese and Caucasian faces in an old-new face paradigm using eye tracking. In terms of recognition, the ASD and ID groups did not perform differently and displayed superior own-race recognition compared with other-race faces; TD participants displayed similar recognition of the two types of faces. In terms of eye tracking, the TD, ASD, and ID groups displayed more looking on the eyes and less looking on the nose and mouth of Caucasian faces relative to Chinese faces. Overall, individuals with ASD manifested a behavioral other-race effect and displayed the same type of cross-racial differentiation in face scanning observed in TD individuals. The findings suggest that as is the case with TD individuals, face processing of individuals with ASD is influenced by differences in visual experience with different face categories.
