1. Bekele E, Crittendon JA, Swanson A, Sarkar N, Warren ZE. {{Pilot clinical application of an adaptive robotic system for young children with autism}}. {Autism}. 2013 Oct 8.
It has been argued that clinical applications of advanced technology may hold promise for addressing impairments associated with autism spectrum disorders. This pilot feasibility study evaluated the application of a novel adaptive robot-mediated system capable of both administering and automatically adjusting joint attention prompts to a small group of preschool children with autism spectrum disorders (n = 6) and a control group (n = 6). Children in both groups spent more time looking at the humanoid robot and were able to achieve a high level of accuracy across trials. However, across groups, children required higher levels of prompting to successfully orient within robot-administered trials. The results highlight both the potential benefits of closed-loop adaptive robotic systems as well as current limitations of existing humanoid-robotic platforms.
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2. Callenmark B, Kjellin L, Ronnqvist L, Bolte S. {{Explicit versus implicit social cognition testing in autism spectrum disorder}}. {Autism}. 2013 Oct 8.
Although autism spectrum disorder is defined by reciprocal social-communication impairments, several studies have found no evidence for altered social cognition test performance. This study examined explicit (i.e. prompted) and implicit (i.e. spontaneous) variants of social cognition testing in autism spectrum disorder. A sample of 19 adolescents with autism spectrum disorder and 19 carefully matched typically developing controls completed the Dewey Story Test. ‘Explicit’ (multiple-choice answering format) and ‘implicit’ (free interview) measures of social cognition were obtained. Autism spectrum disorder participants did not differ from controls regarding explicit social cognition performance. However, the autism spectrum disorder group performed more poorly than controls on implicit social cognition performance in terms of spontaneous perspective taking and social awareness. Findings suggest that social cognition alterations in autism spectrum disorder are primarily implicit in nature and that an apparent absence of social cognition difficulties on certain tests using rather explicit testing formats does not necessarily mean social cognition typicality in autism spectrum disorder.
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3. Chanda S, Marro S, Wernig M, Sudhof TC. {{Neurons generated by direct conversion of fibroblasts reproduce synaptic phenotype caused by autism-associated neuroligin-3 mutation}}. {Proceedings of the National Academy of Sciences of the United States of America}. 2013 Oct 8;110(41):16622-7.
Recent studies suggest that induced neuronal (iN) cells that are directly transdifferentiated from nonneuronal cells provide a powerful opportunity to examine neuropsychiatric diseases. However, the validity of using this approach to examine disease-specific changes has not been demonstrated. Here, we analyze the phenotypes of iN cells that were derived from murine embryonic fibroblasts cultured from littermate wild-type and mutant mice carrying the autism-associated R704C substitution in neuroligin-3. We show that neuroligin-3 R704C-mutant iN cells exhibit a large and selective decrease in AMPA-type glutamate receptor-mediated synaptic transmission without changes in NMDA-type glutamate receptor- or in GABAA receptor-mediated synaptic transmission. Thus, the synaptic phenotype observed in R704C-mutant iN cells replicates the previously observed phenotype of R704C-mutant neurons. Our data show that the effect of the R704C mutation is applicable even to neurons transdifferentiated from fibroblasts and constitute a proof-of-concept demonstration that iN cells can be used for cellular disease modeling.
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4. Cutress AL, Muncer SJ. {{Parents’ views of the National Autistic Society’s EarlyBird Plus Programme}}. {Autism}. 2013 Oct 8.
Parent training interventions are recommended for parents soon after their child’s autism spectrum condition diagnosis with the aim of improving parents’ psychological well-being and coping, as well as the child’s behaviour. This report explores parents’ views of the EarlyBird Plus Programme through data collected routinely in the post-programme questionnaire. Participants’ reported increased understanding of autism and improvements in their communication with their child and their ability to manage their child’s behaviour. Parents appeared to value the opportunity to meet with other parents, and the programme seemed acceptable to the majority of parents who attended.
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5. Engelhardt CR, Mazurek MO. {{Video game access, parental rules, and problem behavior: A study of boys with autism spectrum disorder}}. {Autism}. 2013 Oct 8.
Environmental correlates of problem behavior among individuals with autism spectrum disorder remain relatively understudied. The current study examined the contribution of in-room (i.e. bedroom) access to a video game console as one potential correlate of problem behavior among a sample of 169 boys with autism spectrum disorder (ranging from 8 to 18 years of age). Parents of these children reported on (1) whether they had specific rules regulating their child’s video game use, (2) whether their child had in-room access to a variety of screen-based media devices (television, computer, and video game console), and (3) their child’s oppositional behaviors. Multivariate regression models showed that in-room access to a video game console predicted oppositional behavior while controlling for in-room access to other media devices (computer and television) and relevant variables (e.g. average number of video game hours played per day). Additionally, the association between in-room access to a video game console and oppositional behavior was particularly large when parents reported no rules on their child’s video game use. The current findings indicate that both access and parental rules regarding video games warrant future experimental and longitudinal research as they relate to problem behavior in boys with autism spectrum disorder.
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6. Frazier TW, Ratliff KR, Gruber C, Zhang Y, Law PA, Constantino JN. {{Confirmatory factor analytic structure and measurement invariance of quantitative autistic traits measured by the Social Responsiveness Scale-2}}. {Autism}. 2013 Oct 8.
Understanding the factor structure of autistic symptomatology is critical to the discovery and interpretation of causal mechanisms in autism spectrum disorder. We applied confirmatory factor analysis and assessment of measurement invariance to a large (N = 9635) accumulated collection of reports on quantitative autistic traits using the Social Responsiveness Scale, representing a broad diversity of age, severity, and reporter type. A two-factor structure (corresponding to social communication impairment and restricted, repetitive behavior) as elaborated in the updated Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-5) criteria for autism spectrum disorder exhibited acceptable model fit in confirmatory factor analysis. Measurement invariance was appreciable across age, sex, and reporter (self vs other), but somewhat less apparent between clinical and nonclinical populations in this sample comprised of both familial and sporadic autism spectrum disorders. The statistical power afforded by this large sample allowed relative differentiation of three factors among items encompassing social communication impairment (emotion recognition, social avoidance, and interpersonal relatedness) and two factors among items encompassing restricted, repetitive behavior (insistence on sameness and repetitive mannerisms). Cross-trait correlations remained extremely high, that is, on the order of 0.66-0.92. These data clarify domains of statistically significant factoral separation that may relate to partially-but not completely-overlapping biological mechanisms, contributing to variation in human social competency. Given such robust intercorrelations among symptom domains, understanding their co-emergence remains a high priority in conceptualizing common neural mechanisms underlying autistic syndromes.
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7. Frazier TW, Youngstrom EA, Embacher R, Hardan AY, Constantino JN, Law P, Findling RL, Eng C. {{Demographic and clinical correlates of autism symptom domains and autism spectrum diagnosis}}. {Autism}. 2013 Oct 8.
Demographic and clinical factors may influence assessment of autism symptoms. This study evaluated these correlates and also examined whether social communication and interaction and restricted/repetitive behavior provided unique prediction of autism spectrum disorder diagnosis. We analyzed data from 7352 siblings included in the Interactive Autism Network registry. Social communication and interaction and restricted/repetitive behavior symptoms were obtained using caregiver-reports on the Social Responsiveness Scale. Demographic and clinical correlates were covariates in regression models predicting social communication and interaction and restricted/repetitive behavior symptoms. Logistic regression and receiver operating characteristic curve analyses evaluated the incremental validity of social communication and interaction and restricted/repetitive behavior domains over and above global autism symptoms. Autism spectrum disorder diagnosis was the strongest correlate of caregiver-reported social communication and interaction and restricted/repetitive behavior symptoms. The presence of comorbid diagnoses also increased symptom levels. Social communication and interaction and restricted/repetitive behavior symptoms provided significant, but modest, incremental validity in predicting diagnosis beyond global autism symptoms. These findings suggest that autism spectrum disorder diagnosis is by far the largest determinant of quantitatively measured autism symptoms. Externalizing (attention deficit hyperactivity disorder) and internalizing (anxiety) behavior, low cognitive ability, and demographic factors may confound caregiver-report of autism symptoms, potentially necessitating a continuous norming approach to the revision of symptom measures. Social communication and interaction and restricted/repetitive behavior symptoms may provide incremental validity in the diagnosis of autism spectrum disorder.
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8. Freuler AC, Baranek GT, Tashjian C, Watson LR, Crais ER, Turner-Brown LM. {{Parent reflections of experiences of participating in a randomized controlled trial of a behavioral intervention for infants at risk of autism spectrum disorders}}. {Autism}. 2013 Oct 8.
Background:Despite the mounting evidence of efficacy of early intervention for children with autism spectrum disorders, there is little research that considers the various perceptions and resources with which parents respond to the pressures and opportunities associated with participation in early intervention. Research is particularly lacking surrounding experiences of parents with infants who are at risk of autism spectrum disorders but do not (yet) have a diagnosed condition.Objectives:This qualitative study aimed to explore the experiences of caregivers following their participation in a randomized controlled trial of Adapted Responsive Teaching, a parent-infant relationship-focused intervention for infants at risk of autism spectrum disorders in a community sample. Parents were randomized into either the treatment group, in which they participated in the Adapted Responsive Teaching intervention, or the community services group, in which they were provided with information regarding local early intervention services and were encouraged, but not required to, seek community services as part of their inclusion in the randomized controlled trial.Methods:Semistructured interviews were conducted with families following the completion of the randomized controlled trial. Participants consisted of 13 mothers and 4 fathers. Five dyads were interviewed together for a total of 14 families. Child ages ranged from 39 to 46 months at the time of interview. Analysis was conducted on 14 interviews from 10 families who were randomized into the treatment group and 4 families randomized into the community services group. Analysis was informed by a thematic analysis approach, which involved a systematic process of coding and theme identification both across and within groups.Results:Themes that emerged across groups included Working against all odds, Value of the personal relationship, Getting the ball rolling, and Getting dad on board. One broad theme represented the data within the groups: Win-win (Adapted Responsive Teaching group) and Navigating amidst ambiguity (community services group).Conclusions:This study illuminates the personal experiences and contextual influences affecting families who are participating in the randomized controlled trial through early identification of « risk » status for autism spectrum disorders in their infants. Insights gained from these interviews may serve to refine and enhance intervention models and to enhance early intervention services for families.
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9. Garcia Dominguez L, Stieben J, Perez Velazquez JL, Shanker S. {{The Imaginary Part of Coherency in Autism: Differences in Cortical Functional Connectivity in Preschool Children}}. {PloS one}. 2013;8(10):e75941.
Cognition arises from the transient integration and segregation of activity across functionally distinct brain areas. Autism Spectrum Disorders (ASD), which encompass a wide range of developmental disabilities, have been presumed to be associated with a problem in cortical and sub-cortical dynamics of coordinated activity, often involving enhanced local but decreased long range coordination over areas of integration. In this paper we challenge this idea by presenting results from a relatively large population of ASD children and age-matched controls during a face-processing task. Over most of the explored domain, children with ASD exhibited enhanced synchronization, although finer detail reveals specific enhancement/reduction of synchrony depending on time, frequency and brain site. Our results are derived from the use of the imaginary part of coherency, a measure which is not susceptible to volume conduction artifacts and therefore presents a credible picture of coordinated brain activity. We also present evidence that this measure is a good candidate to provide features in building a classifier to be used as a potential biomarker for autism.
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10. Hanson C, Hanson S, Ramsey J, Glymour C. {{Atypical Effective Connectivity of Social Brain Networks in Individuals with Autism}}. {Brain connectivity}. 2013 Oct 4.
Failing to engage in joint attention is a strong marker of impaired social cognition associated with autism spectrum disorder (ASD). The goal of this study was to localize the source of impaired joint attention in individuals with ASD by examining both behavioral and fMRI data collected during various tasks involving eye gaze, directional cuing, and face processing. The tasks were designed to engage three brain networks associated with social cognition (face processing, Theory of Mind, and action understanding). The behavioral results indicate that even high functioning individuals with ASD perform less accurately and more slowly than neurotypical (NT) controls when processing eyes, but not when processing a directional cue (an arrow) that did not involve eyes. Behavioral differences between the neurotypical and ASD groups were consistent with differences in the effective connectivity of FACE, TOM, and ACTION networks. An Independent Multiple-sample Greedy Equivalence Search (IMaGES) was used to examine these social brain networks and found that whereas neurotypicals produced stable patterns of response across tasks designed to engage a given brain network, ASD participants did not. Moreover, ASD participants recruited all three networks in a manner highly dissimilar to that of neurotypicals. These results extend a growing literature describing disruptions in general brain connectivity in individuals with autism by targeting specific networks hypothesized to underlie the social cognitive impairments observed in these individuals.
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11. Herbert MR, Sage C. {{Autism and EMF? Plausibility of a pathophysiological link – Part I}}. {Pathophysiology : the official journal of the International Society for Pathophysiology / ISP}. 2013 Oct 3.
Although autism spectrum conditions (ASCs) are defined behaviorally, they also involve multileveled disturbances of underlying biology that find striking parallels in the physiological impacts of electromagnetic frequency and radiofrequency exposures (EMF/RFR). Part I of this paper will review the critical contributions pathophysiology may make to the etiology, pathogenesis and ongoing generation of core features of ASCs. We will review pathophysiological damage to core cellular processes that are associated both with ASCs and with biological effects of EMF/RFR exposures that contribute to chronically disrupted homeostasis. Many studies of people with ASCs have identified oxidative stress and evidence of free radical damage, cellular stress proteins, and deficiencies of antioxidants such as glutathione. Elevated intracellular calcium in ASCs may be due to genetics or may be downstream of inflammation or environmental exposures. Cell membrane lipids may be peroxidized, mitochondria may be dysfunctional, and various kinds of immune system disturbances are common. Brain oxidative stress and inflammation as well as measures consistent with blood-brain barrier and brain perfusion compromise have been documented. Part II of this paper will review how behaviors in ASCs may emerge from alterations of electrophysiological oscillatory synchronization, how EMF/RFR could contribute to these by de-tuning the organism, and policy implications of these vulnerabilities. Changes in brain and autonomic nervous system electrophysiological function and sensory processing predominate, seizures are common, and sleep disruption is close to universal. All of these phenomena also occur with EMF/RFR exposure that can add to system overload (‘allostatic load’) in ASCs by increasing risk, and worsening challenging biological problems and symptoms; conversely, reducing exposure might ameliorate symptoms of ASCs by reducing obstruction of physiological repair. Various vital but vulnerable mechanisms such as calcium channels may be disrupted by environmental agents, various genes associated with autism or the interaction of both. With dramatic increases in reported ASCs that are coincident in time with the deployment of wireless technologies, we need aggressive investigation of potential ASC – EMF/RFR links. The evidence is sufficient to warrant new public exposure standards benchmarked to low-intensity (non-thermal) exposure levels now known to be biologically disruptive, and strong, interim precautionary practices are advocated.
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12. Huang SF, Oi M. {{Responses to Wh-, Yes/No-, A-not-A, and choice questions in Taiwanese children with high-functioning autism spectrum disorder}}. {Clinical linguistics & phonetics}. 2013 Oct 4.
Abstract The present study investigated the hypothesis that children with high-functioning autism spectrum disorder (HFASD) have a greater difficulty in responding to Wh- than Yes/No questions across languages. Conversations between Taiwanese children and their mothers were investigated and the children’s response adequacy to maternal questions in a semi-structured setting were examined. Twelve Taiwanese children with HFASD, ranging in age from 7.1 to 14.9 years old, were compared with 12 typically developing (TD) children matched on age, sex, IQ and mean length of utterance in syllable (MLUs). Compared to TD children, HFASD children produced more inadequate or inappropriate responses to Wh- and Yes/No questions than to A-not-A and Choice questions. Taiwanese HFASD children share a greater difficulty in responding to maternal Wh-questions with their Japanese counterparts and do not show a relative ease in responding to Yes/No questions, while A-not-A and Choice questions were easier to respond to for the Taiwanese children.
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13. Karvat G, Kimchi T. {{Acetylcholine Elevation Relieves Cognitive Rigidity and Social Deficiency in a Mouse Model of Autism}}. {Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology}. 2013 Oct 7.
Autism spectrum disorders (ASD) is defined by behavioral deficits in social interaction, communication, repetitive stereotyped behaviors and restricted interests/ cognitive rigidity. Recent studies in humans and mice suggested that dysfunction of the cholinergic system may underlie autism-related behavioral symptoms. Here we tested the hypothesis that augmentation of acetylcholine in the synaptic cleft by inhibiting acetylcholinesterase may ameliorate autistic phenotypes. We first administered the acetylcholinesterase inhibitor (AChEI) Donepezil systemically by intraperitoneal (i.p.) injections. Second, the drug was injected directly into the rodent homologue of the caudate nucleus, the dorso-medial-striatum (DMS), of the inbred mouse strain BTBR T+tf/J (BTBR), a commonly-used model presenting all core autism-related phenotypes and expressing low brain acetylcholine levels. We found that i.p. injection of AChEI to BTBR mice significantly relieved autism-relevant phenotypes, including decreasing cognitive rigidity, improving social preference and enhancing social interaction, in a dose dependent manner. Microinjection of the drug directly into the DMS, but not into the ventromedial striatum, led to significant amelioration of the cognitive-rigidity and social-deficiency phenotypes. Taken together, these findings provide evidence of the key role of the cholinergic system and the DMS in the etiology of ASD, and suggest that elevated cognitive flexibility may result in enhanced social attention. The potential therapeutic effect of AChEIs in ASD patients is discussed.Neuropsychopharmacology accepted article preview online, 7 October 2013. doi:10.1038/npp.2013.274.
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14. Lazarev VV, Pontes A, Mitrofanov AA, Deazevedo LC. {{Reduced Interhemispheric Connectivity in Childhood Autism Detected by Electroencephalographic Photic Driving Coherence}}. {J Autism Dev Disord}. 2013 Oct 6.
The EEG coherence among 14 scalp points during intermittent photic stimulation at 11 fixed frequencies of 3-24 Hz was studied in 14 boys with autism, aged 6-14 years, with relatively intact verbal and intellectual functions, and 19 normally developing boys. The number of interhemispheric coherent connections pertaining to the 20 highest connections of each individual was significantly lower in autistic patients than in the control group at all the EEG beta frequencies corresponding to those of stimulation. The coefficient of coherence values between homologous occipital, parietal and central areas at the same frequencies were also lower in the autistic group in both mono- and bipolar montages due to a deficit in reactive photic driving increase. No differences between the groups were observed in the spontaneous EEG.
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15. Li Y, Wang H, Muffat J, Cheng AW, Orlando DA, Loven J, Kwok SM, Feldman DA, Bateup HS, Gao Q, Hockemeyer D, Mitalipova M, Lewis CA, Vander Heiden MG, Sur M, Young RA, Jaenisch R. {{Global Transcriptional and Translational Repression in Human-Embryonic-Stem-Cell-Derived Rett Syndrome Neurons}}. {Cell stem cell}. 2013 Oct 3;13(4):446-58.
Rett syndrome (RTT) is caused by mutations of MECP2, a methyl CpG binding protein thought to act as a global transcriptional repressor. Here we show, using an isogenic human embryonic stem cell model of RTT, that MECP2 mutant neurons display key molecular and cellular features of this disorder. Unbiased global gene expression analyses demonstrate that MECP2 functions as a global activator in neurons but not in neural precursors. Decreased transcription in neurons was coupled with a significant reduction in nascent protein synthesis and lack of MECP2 was manifested as a severe defect in the activity of the AKT/mTOR pathway. Lack of MECP2 also leads to impaired mitochondrial function in mutant neurons. Activation of AKT/mTOR signaling by exogenous growth factors or by depletion of PTEN boosted protein synthesis and ameliorated disease phenotypes in mutant neurons. Our findings indicate a vital function for MECP2 in maintaining active gene transcription in human neuronal cells.
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16. Locke J, Rotheram-Fuller E, Xie M, Harker C, Mandell D. {{Correlation of cognitive and social outcomes among children with autism spectrum disorder in a randomized trial of behavioral intervention}}. {Autism}. 2013 Oct 8.
Although social impairments are considered the hallmark deficit of autism, many behavioral intervention studies rely on cognitive functioning as a primary outcome. Fewer studies have examined whether changes in cognition are associated with changes in social functioning. This study examined whether cognitive gains among 192 students from 47 kindergarten-through-second-grade autism support classrooms participating in a year-long behavioral intervention study were associated with gains in social functioning. Children’s gains in cognitive ability were modestly associated with independent assessors’ and teachers’ evaluations of social functioning but were not associated with changes in parent ratings. Observed social gains were not commensurate with gains in cognition, suggesting the need both for interventions that directly target social functioning and relevant field measures of social functioning.
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17. Maaswinkel H, Zhu L, Weng W. {{Assessing Social Engagement in Heterogeneous Groups of Zebrafish: A New Paradigm for Autism-Like Behavioral Responses}}. {PloS one}. 2013;8(10):e75955.
Because of its highly developed social character, zebrafish is a promising model system for the study of the genetic and neurochemical basis of altered social engagement such as is common in autism and schizophrenia. The traditional shoaling paradigm investigates social cohesion in homogeneous groups of zebrafish. However, the social dynamics of mixed groups is gaining interest from a therapeutic point of view and thus warrants animal modeling. Furthermore, mutant zebrafish are not always available in large numbers. Therefore, we developed a new paradigm that allows exploring shoaling in heterogeneous groups. The effects of MK-801, a non-competitive antagonist of the glutamate N-methyl-D-aspartate (NMDA) receptor, on social cohesion were studied to evaluate the paradigm. The drug has previously been shown to mimic aspects of autism and schizophrenia. Our results show that a single MK-801-treated zebrafish reduced social cohesion of the entire shoal drastically. Preliminary observations suggest that the social dynamics of the shoal as a whole was altered.
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18. Mari-Bauset S, Zazpe I, Mari-Sanchis A, Llopis-Gonzalez A, Morales-Suarez-Varela M. {{Food Selectivity in Autism Spectrum Disorders: A Systematic Review}}. {Journal of child neurology}. 2013 Oct 4.
Autism spectrum disorders are characterized by difficulties with reciprocal social interactions and restricted patterns of behavior and interest; one of these characteristic behaviors is food selectivity. The objective of this study was to perform a systematic review of the literature published between 1970 and 2013 concerning this eating behavior. The articles identified were analyzed in terms of sample size, study design, and criteria for assessment and intervention, as well as the results, level of evidence and grade of recommendation. The main search was conducted in Medline, Cochrane Library, Scielo, ScienceDirect, and Embase). There is empirical evidence and an overall scientific consensus supporting an association between food selectivity and autism spectrum disorders.
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19. Mazefsky CA, Schreiber DR, Olino TM, Minshew NJ. {{The association between emotional and behavioral problems and gastrointestinal symptoms among children with high-functioning autism}}. {Autism}. 2013 Oct 8.
This study investigated the association between gastrointestinal symptoms and a broad set of emotional and behavioral concerns in 95 children with high-functioning autism and IQ scores >/= 80. Gastrointestinal symptoms were assessed via the Autism Treatment Network’s Gastrointestinal Symptom Inventory, and data were gathered on autism symptom severity, adaptive behavior, and multiple internalizing and externalizing problems. The majority (61%) of children had at least one reported gastrointestinal symptom. Emotional and behavioral problems were also common but with a high degree of variability. Children with and without gastrointestinal problems did not differ in autism symptom severity, adaptive behavior, or total internalizing or externalizing problem scores. However, participants with gastrointestinal problems had significantly higher levels of affective problems. This finding is consistent with a small body of research noting a relationship between gastrointestinal problems, irritability, and mood problems in autism spectrum disorder. More research to identify the mechanisms underlying this relationship in autism spectrum disorder is warranted. Future research should include a medical assessment of gastrointestinal concerns, longitudinal design, and participants with a range of autism spectrum disorder severity in order to clarify the directionality of this relationship and to identify factors that may impact heterogeneity in the behavioral manifestation of gastrointestinal concerns.
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20. McStay RL, Dissanayake C, Scheeren A, Koot HM, Begeer S. {{Parenting stress and autism: The role of age, autism severity, quality of life and problem behaviour of children and adolescents with autism}}. {Autism}. 2013 Oct 8.
While stress is a common experience for parents caring for a child with a developmental disability, current measures fail to distinguish between general stress in parents and the demands of parenting and perceptions of parenting skills (parenting stress). This study examined differences in ‘parenting stress’ reported by parents of children with autism and typically developing children. This study examined the role of child characteristics (age, autism severity, child quality of life and problem behaviour) on parenting stress in 150 parents of cognitively able children and adolescents with autism. The results revealed that child hyperactivity was the only factor significantly related to parenting stress in parents of children with autism, overruling measures of autism severity and child quality of life. This finding indicates the significant influence of problematic behaviours on parenting demands and perceptions of parenting skills in parents of children with autism, over other child characteristics conceived as within the parent’s control. Study implications for future research are discussed.
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21. Meyer RR. {{A review of the serotonin transporter and prenatal cortisol in the development of autism spectrum disorders}}. {Molecular autism}. 2013 Oct 8;4(1):37.
The diagnosis of autism spectrum disorder (ASD) during early childhood has a profound effect not only on young children but on their families. Aside from the physical and behavioural issues that need to be dealt with, there are significant emotional and financial costs associated with living with someone diagnosed with ASD. Understanding how autism occurs will assist in preparing families to deal with ASD, if not preventing or lessening its occurrence.Serotonin plays a vital role in the development of the brain during the prenatal and postnatal periods, yet very little is known about the serotonergic systems that affect children with ASD. This review seeks to provide an understanding of the biochemistry and physiological actions of serotonin and its termination of action through the serotonin reuptake transporter (SERT). Epidemiological studies investigating prenatal conditions that can increase the risk of ASD describe a number of factors which elevate plasma cortisol levels causing such symptoms during pregnancy such as hypertension, gestational diabetes and depression. Because cortisol plays an important role in driving dysregulation of serotonergic signalling through elevating SERT production in the developing brain, it is also necessary to investigate the physiological functions of cortisol, its action during gestation and metabolic syndromes.
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22. Patterson SY, Elder L, Gulsrud A, Kasari C. {{The association between parental interaction style and children’s joint engagement in families with toddlers with autism}}. {Autism}. 2013 Oct 8.
Purpose:This study examines the relationship between parental interaction style (responsive vs directive) and child-initiated joint engagement within caregiver-child interactions with toddlers diagnosed with autism spectrum disorders.Method:Videotaped interactions of 85 toddler-caregiver dyads were coded for child engagement and both parental responsiveness and directiveness.Results:Altogether, children spent less than one-third of the interaction jointly engaged. After controlling for child characteristics, parental style was associated with the initiator (child or parent) of joint engagement. Specifically, responsiveness predicted total time in child-initiated joint engagement, while directiveness predicted total time in parent-initiated joint engagement. Children’s social behaviours were associated with child-initiated joint engagement.Discussion:Social initiations are a key target for children with autism spectrum disorders. Results demonstrate that child initiations and global social behaviour ratings are associated with parental responsivity. Responsivity may be a critical factor to facilitate children’s initiations.
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23. Pearson A, Ropar D, de CHAF. {{A review of visual perspective taking in autism spectrum disorder}}. {Frontiers in human neuroscience}. 2013;7:652.
Impairments in social cognition are a key symptom of autism spectrum disorder (ASD). People with autism have great difficulty with understanding the beliefs and desires of other people. In recent years literature has begun to examine the link between impairments in social cognition and abilities which demand the use of spatial and social skills, such as visual perspective taking (VPT). Flavell (1977) defined two levels of perspective taking: VPT level 1 is the ability to understand that other people have a different line of sight to ourselves, whereas VPT level 2 is the understanding that two people viewing the same item from different points in space may see different things. So far, literature on whether either level of VPT is impaired or intact in autism is inconsistent. Here we review studies which have examined VPT levels 1 and 2 in people with autism with a focus on their methods. We conclude the review with an evaluation of the findings into VPT in autism and give recommendations for future research which may give a clearer insight into whether perspective taking is truly impaired in autism.
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24. Piven J, Vieland VJ, Parlier M, Thompson A, I OC, Woodbury-Smith M, Huang Y, Walters K, Fernandez B, Szatmari P. {{A molecular genetic study of autism and related phenotypes in extended pedigrees}}. {Journal of neurodevelopmental disorders}. 2013 Oct 5;5(1):30.
BACKGROUND: Efforts to uncover the risk genotypes associated with the familial nature of autism spectrum disorder (ASD) have had limited success. The study of extended pedigrees, incorporating additional ASD-related phenotypes into linkage analysis, offers an alternative approach to the search for inherited ASD susceptibility variants that complements traditional methods used to study the genetics of ASD. METHODS: We examined evidence for linkage in 19 extended pedigrees ascertained through ASD cases spread across at least two (and in most cases three) nuclear families. Both compound phenotypes (i.e., ASD and, in non-ASD individuals, the broad autism phenotype) and more narrowly defined components of these phenotypes, e.g., social and repetitive behavior, pragmatic language, and anxiety, were examined. The overarching goal was to maximize the aggregate information available on the maximum number of individuals and to disaggregate syndromic phenotypes in order to examine the genetic underpinnings of more narrowly defined aspects of ASD behavior. RESULTS: Results reveal substantial between-family locus heterogeneity and support the importance of previously reported ASD loci in inherited, familial, forms of ASD. Additional loci, not seen in the ASD analyses, show evidence for linkage to the broad autism phenotype (BAP). BAP peaks are well supported by multiple subphenotypes (including anxiety, pragmatic language, and social behavior) showing linkage to regions overlapping with the compound BAP phenotype. Whereas ‘repetitive behavior’, showing the strongest evidence for linkage (Posterior Probability of Linkage = 62% at 6p25.2-24.3, and 69% at 19p13.3), appears to be linked to novel regions not detected with other compound or narrow phenotypes examined in this study. CONCLUSIONS: These results provide support for the presence of key features underlying the complexity of the genetic architecture of ASD: substantial between-family locus heterogeneity, that the BAP appears to correspond to sets of subclinical features segregating with ASD within pedigrees, and that different features of the ASD phenotype segregate independently of one another. These findings support the additional study of larger, even more individually informative pedigrees, together with measurement of multiple, behavioral- and biomarker-based phenotypes, in both affected and non-affected individuals, to elucidate the complex genetics of familial ASD.
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25. Poultney CS, Goldberg AP, Drapeau E, Kou Y, Harony-Nicolas H, Kajiwara Y, De Rubeis S, Durand S, Stevens C, Rehnstrom K, Palotie A, Daly MJ, Ma’ayan A, Fromer M, Buxbaum JD. {{Identification of Small Exonic CNV from Whole-Exome Sequence Data and Application to Autism Spectrum Disorder}}. {American journal of human genetics}. 2013 Oct 3;93(4):607-19.
Copy number variation (CNV) is an important determinant of human diversity and plays important roles in susceptibility to disease. Most studies of CNV carried out to date have made use of chromosome microarray and have had a lower size limit for detection of about 30 kilobases (kb). With the emergence of whole-exome sequencing studies, we asked whether such data could be used to reliably call rare exonic CNV in the size range of 1-30 kilobases (kb), making use of the eXome Hidden Markov Model (XHMM) program. By using both transmission information and validation by molecular methods, we confirmed that small CNV encompassing as few as three exons can be reliably called from whole-exome data. We applied this approach to an autism case-control sample (n = 811, mean per-target read depth = 161) and observed a significant increase in the burden of rare (MAF </=1%) 1-30 kb CNV, 1-30 kb deletions, and 1-10 kb deletions in ASD. CNV in the 1-30 kb range frequently hit just a single gene, and we were therefore able to carry out enrichment and pathway analyses, where we observed enrichment for disruption of genes in cytoskeletal and autophagy pathways in ASD. In summary, our results showed that XHMM provided an effective means to assess small exonic CNV from whole-exome data, indicated that rare 1-30 kb exonic deletions could contribute to risk in up to 7% of individuals with ASD, and implicated a candidate pathway in developmental delay syndromes.
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26. Ruggeri B, Sarkans U, Schumann G, Persico AM. {{Biomarkers in autism spectrum disorder: the old and the new}}. {Psychopharmacology}. 2013 Oct 6.
RATIONALE: Autism spectrum disorder (ASD) is a complex heterogeneous neurodevelopmental disorder with onset during early childhood and typically a life-long course. The majority of ASD cases stems from complex, ‘multiple-hit’, oligogenic/polygenic underpinnings involving several loci and possibly gene-environment interactions. These multiple layers of complexity spur interest into the identification of biomarkers able to define biologically homogeneous subgroups, predict autism risk prior to the onset of behavioural abnormalities, aid early diagnoses, predict the developmental trajectory of ASD children, predict response to treatment and identify children at risk for severe adverse reactions to psychoactive drugs. OBJECTIVES: The present paper reviews (a) similarities and differences between the concepts of ‘biomarker’ and ‘endophenotype’, (b) established biomarkers and endophenotypes in autism research (biochemical, morphological, hormonal, immunological, neurophysiological and neuroanatomical, neuropsychological, behavioural), (c) -omics approaches towards the discovery of novel biomarker panels for ASD, (d) bioresource infrastructures and (e) data management for biomarker research in autism. RESULTS: Known biomarkers, such as abnormal blood levels of serotonin, oxytocin, melatonin, immune cytokines and lymphocyte subtypes, multiple neuropsychological, electrophysiological and brain imaging parameters, will eventually merge with novel biomarkers identified using unbiased genomic, epigenomic, transcriptomic, proteomic and metabolomic methods, to generate multimarker panels. Bioresource infrastructures, data management and data analysis using artificial intelligence networks will be instrumental in supporting efforts to identify these biomarker panels. CONCLUSIONS: Biomarker research has great heuristic potential in targeting autism diagnosis and treatment.
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27. Samuel R, Attard A, Kyriakopoulos M. {{Mental state deterioration after switching from brand-name to generic olanzapine in an adolescent with bipolar affective disorder, autism and intellectual disability: a case study}}. {BMC psychiatry}. 2013 Oct 4;13(1):244.
BACKGROUND: The appropriateness of use of generic instead of brand-name medication remains unresolved and controversial in several areas of medicine. Some evidence suggestive of variations in bioavailability and clinical effectiveness between different formulations make policy decisions occasionally difficult. The use of generic olanzapine is a widely acceptable practice on the basis of quality, safety and efficacy data and has been adopted in several countries. CASE PRESENTATION: The case of a 14 year old boy with bipolar affective disorder, autism and intellectual disability who had brand-name to generic olanzapine switch associated with rapid deterioration of his mental state is described. This clinical change was not related to any physical illness or other medication adjustment and resolved as rapidly when generic olanzapine was switched back to the brand-name formulation. CONCLUSIONS: Caution should be exercised when policy for switching from brand-name to generic psychotropic medications are made, especially when using medications off label, in extremes of age and in those patients with co-morbid complicating factors such as intellectual disability.
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28. Sarajlija A, Djuric M, Tepavcevic DK, Grkovic S, Djordjevic M. {{Vitamin D deficiency in Serbian patients with Rett syndrome}}. {The Journal of clinical endocrinology and metabolism}. 2013 Oct 8.
INTRODUCTION:Rett syndrome (RTT) is a severe neurodevelopmental disorder. Bone manifestations of RTT include osteopenia and fractures. Studies addressing serum vitamin D levels in RTT patients are scarce.GOALS:1. To determine prevalence of vitamin D deficiency in RTT patients, 2. To compare serum vitamin D levels between patients with RTT and other neurological diseases, 3. To explore correlation between demographic and clinical characteristics of RTT patients and vitamin D levels.METHODS:Demographic and clinical characteristics included age, BMI z-score, mutation status, Clinical Severity Score, presence of epilepsy, number of antiepileptic drugs (AEDs), history of fractures, scoliosis and ambulation ability. Laboratory parameters included serum 25(OH)D, PTH, calcium and alkaline phosphatase.RESULTS:The study included 35 RTT patients and 35 age-matched females with other neurological diseases. The median serum 25(OH)D in RTT group was 26.25 nmol/L, with values below 75 nmol/L in all participants. Severe deficiency (<25 nmol/L) was detected in 17/35 (48.6%) patients. Median 25(OH)D concentration was significantly lower in RTT patients than in controls. The risk for fracture by 12 years of age in RTT patients was 35.3%. Inverse correlation of 25(OH)D level to age and PTH level was detected. Patients receiving antiepileptic polytherapy had 3.3 times greater chance for severe vitamin D deficiency than patients with monotherapy.CONCLUSION:Prevalence of vitamin D deficiency in RTT patients is higher than in patients with other neurological diseases. High risk for vitamin D deficiency should be accounted for in the strategy of antiepileptic treatment in RTT, especially when polytherapy is considered.
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29. Thabet EM. {{Ocular vestibular evoked myogenic potentials n10 response in autism spectrum disorders children with auditory hypersensitivity: an indicator of semicircular canal dehiscence}}. {European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology – Head and Neck Surgery}. 2013 Oct 8.
Sensitivity to sound is one of the most commonly reported challenges in ASD. No compelling evidence shows that hearing of ASD individuals differs physiologically from normal peers. Superior semicircular canal dehiscence was found to be more common in ASD children with auditory hypersensitivity (29 %) by means of high-resolution CT scan than the reported (14 %) in normal pediatric population by other investigators. The increased prevalence of radiographic dehiscence might be due to inability of CT scan to visualize immature bone. We wished to determine whether ocular vestibular evoked myogenic potentials in ASD children with auditory hypersensitivity produces similar responses to those obtained in adult superior canal dehiscence, and whether it could help differentiate radiographic dehiscence due to bone immaturity from true canal dehiscence syndrome. A prospective study on 14 ASD children complaining of auditory hypersensitivity served as the study group. 15 ASD children without auditory hypersensitivity, age and gender matched, served as a control group. oVEMP and high-resolution CT scan of petrous and temporal bone were performed to all participants. Mean amplitude of n10 was 1.83 +/- 0.11 and 1.79 +/- 0.09 muV in the control group with mean peak latency of 9.79 +/- 0.42 and 9.77 +/- 0.30 ms for the right and left ears, respectively. Asymmetry ratio was 2.04 +/- 1.37. In the study group, the mean amplitude of n10 was 2.07 +/- 0.46 and 1.89 +/- 0.30 muV, with mean peak latency of 9.52 +/- 0.33 and 9.59 +/- 0.21 ms for the right and left ears, respectively, with asymmetry 5.23 +/- 6.93 %. No statistically significant difference was observed for the studied parameters. In the study group, the number of ears showing an augmented amplitude (>2SD) of n10 was (N = 5). Furthermore, the study group demonstrated a radiographic SSCD in 6 ears. n10 was normal in the control group while radiographic SSCD was observed in 3 of them. Conclusion: oVEMPs show diagnostic ability in differentiating ASD children complaining of auditory hypersensitivity due to superior canal dehiscence from those with radiographic dehiscence only due to bone immaturity or atypical cortical development.
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30. Trembath D, Iacono T, Lyon K, West D, Johnson H. {{Augmentative and alternative communication supports for adults with autism spectrum disorders}}. {Autism}. 2013 Oct 8.
Many adults with autism spectrum disorders have complex communication needs and may benefit from the use of augmentative and alternative communication. However, there is a lack of research examining the specific communication needs of these adults, let alone the outcomes of interventions aimed at addressing them. The aim of this study was to explore the views and experiences of support workers and family members regarding the outcomes of providing low-technology communication aids to adults with autism spectrum disorders. The participants were six support workers and two family members of six men and women with autism spectrum disorders, who had received low-technology communication aids. Using semi-structured, in-depth interviews and following thematic analysis, the results revealed strong support for, and the potential benefits of, augmentative and alternative communication for both adults with autism spectrum disorders and their communication partners. The results also revealed inconsistencies in the actions taken to support the use of the prescribed augmentative and alternative communication systems, pointing to the clinical need to address common barriers to the provision of augmentative and alternative communication support. These barriers include organisational practices and limitations in the knowledge and skills of key stakeholders, as well as problematic attitudes.
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31. Troyb E, Orinstein A, Tyson K, Helt M, Eigsti IM, Stevens M, Fein D. {{Academic abilities in children and adolescents with a history of autism spectrum disorders who have achieved optimal outcomes}}. {Autism}. 2013 Oct 4.
This study examines the academic abilities of children and adolescents who were once diagnosed with an autism spectrum disorder, but who no longer meet diagnostic criteria for this disorder. These individuals have achieved social and language skills within the average range for their ages, receive little or no school support, and are referred to as having achieved « optimal outcomes. » Performance of 32 individuals who achieved optimal outcomes, 41 high-functioning individuals with a current autism spectrum disorder diagnosis (high-functioning autism), and 34 typically developing peers was compared on measures of decoding, reading comprehension, mathematical problem solving, and written expression. Groups were matched on age, sex, and nonverbal IQ; however, the high-functioning autism group scored significantly lower than the optimal outcome and typically developing groups on verbal IQ. All three groups performed in the average range on all subtests measured, and no significant differences were found in performance of the optimal outcome and typically developing groups. The high-functioning autism group scored significantly lower on subtests of reading comprehension and mathematical problem solving than the optimal outcome group. These findings suggest that the academic abilities of individuals who achieved optimal outcomes are similar to those of their typically developing peers, even in areas where individuals who have retained their autism spectrum disorder diagnoses exhibit some ongoing difficulty.
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32. Warreyn P, Roeyers H. {{See what I see, do as I do: Promoting joint attention and imitation in preschoolers with autism spectrum disorder}}. {Autism}. 2013 Oct 8.
Since imitation and joint attention are both important abilities for young children and since children with autism spectrum disorder show a range of problems in these domains, imitation and joint attention are important targets for intervention. In this study, we examined the possibility of promoting imitation and joint attention by means of a training programme specifically designed for low-intensity, non-residential treatment. Two matched groups of 18 children each participated in the study. The experimental group, receiving the training programme, improved significantly more on joint attention than the group receiving only treatment as usual. Only the experimental group obtained a significantly higher imitation score during the post-test compared to the pre-test. This study shows that it is possible to promote joint attention with a low-intensity treatment programme. The results concerning imitation are more modest. Future replications should involve measures of stability and generalization.
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33. Yoshimura Y, Kikuchi M, Shitamichi K, Ueno S, Munesue T, Ono Y, Tsubokawa T, Haruta Y, Oi M, Niida Y, Remijn GB, Takahashi T, Suzuki M, Higashida H, Minabe Y. {{Atypical brain lateralisation in the auditory cortex and language performance in 3- to 7-year-old children with high-functioning autism spectrum disorder: a child-customised magnetoencephalography (MEG) study}}. {Molecular autism}. 2013 Oct 8;4(1):38.
BACKGROUND: Magnetoencephalography (MEG) is used to measure the auditory evoked magnetic field (AEF), which reflects language-related performance. In young children, however, the simultaneous quantification of the bilateral auditory-evoked response during binaural hearing is difficult using conventional adult-sized MEG systems. Recently, a child-customised MEG device has facilitated the acquisition of bi-hemispheric recordings, even in young children. Using the child-customised MEG device, we previously reported that language-related performance was reflected in the strength of the early component (P50m) of the auditory evoked magnetic field (AEF) in typically developing (TD) young children (2 to 5 years old) [Eur J Neurosci 2012, 35:644–650]. The aim of this study was to investigate how this neurophysiological index in each hemisphere is correlated with language performance in autism spectrum disorder (ASD) and TD children. METHODS: We used magnetoencephalography (MEG) to measure the auditory evoked magnetic field (AEF), which reflects language-related performance. We investigated the P50m that is evoked by voice stimuli (/ne/) bilaterally in 33 young children (3 to 7 years old) with ASD and in 30 young children who were typically developing (TD). The children were matched according to their age (in months) and gender. Most of the children with ASD were high-functioning subjects. RESULTS: The results showed that the children with ASD exhibited significantly less leftward lateralisation in their P50m intensity compared with the TD children. Furthermore, the results of a multiple regression analysis indicated that a shorter P50m latency in both hemispheres was specifically correlated with higher language-related performance in the TD children, whereas this latency was not correlated with non-verbal cognitive performance or chronological age. The children with ASD did not show any correlation between P50m latency and language-related performance; instead, increasing chronological age was a significant predictor of shorter P50m latency in the right hemisphere. CONCLUSIONS: Using a child-customised MEG device, we studied the P50m component that was evoked through binaural human voice stimuli in young ASD and TD children to examine differences in auditory cortex function that are associated with language development. Our results suggest that there is atypical brain function in the auditory cortex in young children with ASD, regardless of language development.
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34. Yu AC, Abrego-Collier C, Sonderegger M. {{Phonetic Imitation from an Individual-Difference Perspective: Subjective Attitude, Personality and « Autistic » Traits}}. {PloS one}. 2013;8(9):e74746.
NUMEROUS STUDIES HAVE DOCUMENTED THE PHENOMENON OF PHONETIC IMITATION: the process by which the production patterns of an individual become more similar on some phonetic or acoustic dimension to those of her interlocutor. Though social factors have been suggested as a motivator for imitation, few studies has established a tight connection between language-external factors and a speaker’s likelihood to imitate. The present study investigated the phenomenon of phonetic imitation using a within-subject design embedded in an individual-differences framework. Participants were administered a phonetic imitation task, which included two speech production tasks separated by a perceptual learning task, and a battery of measures assessing traits associated with Autism-Spectrum Condition, working memory, and personality. To examine the effects of subjective attitude on phonetic imitation, participants were randomly assigned to four experimental conditions, where the perceived sexual orientation of the narrator (homosexual vs. heterosexual) and the outcome (positive vs. negative) of the story depicted in the exposure materials differed. The extent of phonetic imitation by an individual is significantly modulated by the story outcome, as well as by the participant’s subjective attitude toward the model talker, the participant’s personality trait of openness and the autistic-like trait associated with attention switching.
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35. Zachor DA, Curatolo P, Participants of the Italian-Israeli Consensus C. {{Recommendations for early diagnosis and intervention in autism spectrum disorders: An Italian-Israeli consensus conference}}. {European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society}. 2013 Sep 25.
On April 2013 experts in the field of autism from Italy and Israel convened in Jerusalem to discuss and finalize clinical recommendations for early diagnosis and intervention in Autism Spectrum Disorders (ASDs). In this paper, we summarize the results of this Italian-Israeli consensus conference. ASDs constitute a class of severe and heterogeneous neurodevelopmental conditions caused by atypical brain development beginning during early prenatal life, reflecting many genetic, neurobiological and environmental influences. The first clinical signs of ASDs begin to be evident in children between 12 and 18 months of age, often after a period of relatively typical postnatal development. Recent longitudinal studies reveal substantial diversity in developmental trajectories through childhood and adolescence. Some intervention approaches have been demonstrated to be effective in improving core symptoms of ASDs, even if the heterogeneity and developmental nature of the disorder make it implausible that only one specific treatment will be best for all children with ASDs. More randomized control trials (RCTs) on early intervention are needed to identify the most effective strategies and provide the most efficient allocation of resources during the critical early intervention time period. Future research should focus on linking biological phenotypes with specific genotypes, thus establishing a foundation for the development of diagnostic screening tools and individualization of treatments.
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36. Zikopoulos B, Barbas H. {{Altered neural connectivity in excitatory and inhibitory cortical circuits in autism}}. {Frontiers in human neuroscience}. 2013;7:609.
Converging evidence from diverse studies suggests that atypical brain connectivity in autism affects in distinct ways short- and long-range cortical pathways, disrupting neural communication and the balance of excitation and inhibition. This hypothesis is based mostly on functional non-invasive studies that show atypical synchronization and connectivity patterns between cortical areas in children and adults with autism. Indirect methods to study the course and integrity of major brain pathways at low resolution show changes in fractional anisotropy (FA) or diffusivity of the white matter in autism. Findings in post-mortem brains of adults with autism provide evidence of changes in the fine structure of axons below prefrontal cortices, which communicate over short- or long-range pathways with other cortices and subcortical structures. Here we focus on evidence of cellular and axon features that likely underlie the changes in short- and long-range communication in autism. We review recent findings of changes in the shape, thickness, and volume of brain areas, cytoarchitecture, neuronal morphology, cellular elements, and structural and neurochemical features of individual axons in the white matter, where pathology is evident even in gross images. We relate cellular and molecular features to imaging and genetic studies that highlight a variety of polymorphisms and epigenetic factors that primarily affect neurite growth and synapse formation and function in autism. We report preliminary findings of changes in autism in the ratio of distinct types of inhibitory neurons in prefrontal cortex, known to shape network dynamics and the balance of excitation and inhibition. Finally we present a model that synthesizes diverse findings by relating them to developmental events, with a goal to identify common processes that perturb development in autism and affect neural communication, reflected in altered patterns of attention, social interactions, and language.
