1. Abu Shmais GA, Al-Ayadhi LY, Al-Dbass AM, El-Ansary AK. {{Mechanism of nitrogen metabolism-related parameters and enzyme activities in the pathophysiology of autism}}. {J Neurodev Disord}. 2012;4(1):4.
ABSTRACT: BACKGROUND: There is evidence that impaired metabolism play an important role in the etiology of many neuropsychiatric disorders. Although this has not been investigated to date, several recent studies proposed that nitrogen metabolism-related parameters may have a pathophysiological role in autism. METHODS: The study enrolled 20 Saudi boys with autism aged 4 to 12 years and 20 healthy controls matched for age and gender. Levels of creatine, urea, ammonia, gamma-aminobutyric acid (GABA), glutamate:glutamine (Glu:Gln) ratio, and enzymatic activities of glutamate dehydrogenase, 5′-nucleotidase, and adenosine deaminase (ADA) were determined in plasma samples from both groups. RESULTS: We found a significant elevation of creatine, 5′-nucleotidase, GABA, and glutamic acid and a significant decrease in the enzymatic activity of ADA and glutamine level in patients with autism compared with healthy controls. The most significant variation between the two groups was found in the Glu:Gln ratio. CONCLUSION: A raised Glu:Gln ratio together with positive correlations in creatine, GABA, and 5′-nucleotidase levels could contribute to the pathophysiology of autism, and might be useful diagnostic markers. The mechanism through which these parameters might be related to autism is discussed in detail.
Lien vers le texte intégral (Open Access ou abonnement)
2. Cascio CJ, Foss-Feig JH, Heacock JL, Newsom CR, Cowan RL, Benningfield MM, Rogers BP, Cao A. {{Response of neural reward regions to food cues in autism spectrum disorders}}. {J Neurodev Disord}. 2012;4(1):9.
ABSTRACT: BACKGROUND: One hypothesis for the social deficits that characterize autism spectrum disorders (ASD) is diminished neural reward response to social interaction and attachment. Prior research using established monetary reward paradigms as a test of non-social reward to compare with social reward may involve confounds in the ability of individuals with ASD to utilize symbolic representation of money and the abstraction required to interpret monetary gains. Thus, a useful addition to our understanding of neural reward circuitry in ASD includes a characterization of the neural response to primary rewards. METHOD: We asked 17 children with ASD and 18 children without ASD to abstain from eating for at least four hours before an MRI scan in which they viewed images of high-calorie foods. We assessed the neural reward network for increases in the blood oxygenation level dependent (BOLD) signal in response to the food images RESULTS: We found very similar patterns of increased BOLD signal to these images in the two groups; both groups showed increased BOLD signal in the bilateral amygdala, as well as in the nucleus accumbens, orbitofrontal cortex, and insula. Direct group comparisons revealed that the ASD group showed a stronger response to food cues in bilateral insula along the anterior-posterior gradient and in the anterior cingulate cortex than the control group, whereas there were no neural reward regions that showed higher activation for controls than for ASD. CONCLUSION: These results suggest that neural response to primary rewards is not diminished but in fact shows an aberrant enhancement in children with ASD.
Lien vers le texte intégral (Open Access ou abonnement)
3. Crespi BJ, Crofts HJ. {{Association testing of copy number variants in schizophrenia and autism spectrum disorders}}. {J Neurodev Disord}. 2012;4(1):15.
ABSTRACT: BACKGROUND: Autism spectrum disorders and schizophrenia have been associated with an overlapping set of copy number variant loci, but the nature and degree of overlap in copy number variants (deletions compared to duplications) between these two disorders remains unclear. METHODS: We systematically evaluated three lines of evidence: (1) the statistical bases for associations of autism spectrum disorders and schizophrenia with a set of the primary CNVs thus far investigated, from previous studies; (2) data from case series studies on the occurrence of these CNVs in autism spectrum disorders, especially among children, and (3) data on the extent to which the CNVs were associated with intellectual disability and developmental, speech, or language delays. We also conducted new analyses of existing data on these CNVs in autism by pooling data from seven case control studies. RESULTS: Four of the CNVs considered, dup 1q21.1, dup 15q11-q13, del 16p11.2, and dup 22q11.21, showed clear statistical evidence as autism risk factors, whereas eight CNVs, del 1q21.1, del 3q29, del 15q11.2, del 15q13.3, dup 16p11.2, dup 16p13.1, del 17p12, and del 22q11.21, were strongly statistically supported as risk factors for schizophrenia. Three of the CNVs, dup 1q21.1, dup 16p11.2, and dup 16p13.1, exhibited statistical support as risk factors for both autism and schizophrenia, although for each of these CNVs statistical significance was nominal for tests involving one of the two disorders. For the CNVs that were statistically associated with schizophrenia but were not statistically associated with autism, a notable number of children with the CNVs have been diagnosed with autism or ASD; children with these CNVs also demonstrate a high incidence of intellectual disability and developmental, speech, or language delays. CONCLUSIONS: These findings suggest that although CNV loci notably overlap between autism and schizophrenia, the degree of strongly statistically supported overlap in specific CNVs at these loci remains limited. These analyses also suggest that relatively severe premorbidity to CNV-associated schizophrenia in children may sometimes be diagnosed as autism spectrum disorder.
Lien vers le texte intégral (Open Access ou abonnement)
4. Damiano CR, Aloi J, Treadway M, Bodfish JW, Dichter GS. {{Adults with autism spectrum disorders exhibit decreased sensitivity to reward parameters when making effort-based decisions}}. {J Neurodev Disord}. 2012 May 21;4(1):13.
ABSTRACT: BACKGROUND: Efficient effort expenditure to obtain rewards is critical for optimal goal-directed behavior and learning. Clinical observation suggests that individuals with autism spectrum disorders (ASD) may show dysregulated reward-based effort expenditure, but no behavioral study to date has assessed effort-based decision-making in ASD. METHODS: The current study compared a group of adults with ASD to a group of typically developing adults on the Effort Expenditure for Rewards Task (EEfRT), a behavioral measure of effort-based decision-making. In this task, participants were provided with the probability of receiving a monetary reward on a particular trial and asked to choose between either an « easy task » (less motoric effort) for a small, stable reward or a « hard task » (greater motoric effort) for a variable but consistently larger reward. RESULTS: Participants with ASD chose the hard task more frequently than did the control group, yet were less influenced by differences in reward value and probability than the control group. Additionally, effort-based decision-making was related to repetitive behavior symptoms across both groups. CONCLUSIONS: These results suggest that individuals with ASD may be more willing to expend effort to obtain a monetary reward regardless of the reward contingencies. More broadly, results suggest that behavioral choices may be less influenced by information about reward contingencies in individuals with ASD. This atypical pattern of effort-based decision-making may be relevant for understanding the heightened reward motivation for circumscribed interests in ASD.
Lien vers le texte intégral (Open Access ou abonnement)
5. Dawson G, Bernier R, Ring RH. {{Social attention: a possible early indicator of efficacy in autism clinical trials}}. {J Neurodev Disord}. 2012;4(1):11.
ABSTRACT: For decades, researchers have sought to clarify the nature of the social communication impairments in autism, highlighting impaired or atypical ‘social attention’ as a key measurable construct that helps to define the core impairment of social communication. In this paper, we provide an overview of research on social attention impairments in autism and their relation to deficiencies in neural circuitry related to social reward. We offer a framework for considering social attention as a potential moderator or mediator of response to early behavioral intervention, and as an early indicator of efficacy of behavioral and/or pharmacological treatments aimed at addressing the social impairments in autism.
Lien vers le texte intégral (Open Access ou abonnement)
6. Dichter G, Adolphs R. {{Reward processing in autism: a thematic series}}. {J Neurodev Disord}. 2012 Jul 19;4(1):20.
ABSTRACT: This thematic series presents theoretical and empirical papers focused on understanding autism from the perspective of reward processing deficits. Although the core symptoms of autism have not traditionally been conceptualized with respect to altered reward-based processes, it is clear that brain reward circuitry plays a critical role in guiding social and nonsocial learning and behavior throughout development. Additionally, brain reward circuitry may respond to social sources of information in ways that are similar to responses to primary rewards, and recent clinical data consistently suggest abnormal behavioral and neurobiologic responses to rewards in autism. This thematic series presents empirical data and review papers that highlight the utility of considering autism from the perspective of reward processing deficits. Our hope is that this novel framework may further elucidate autism pathophysiology, with the ultimate goal of yielding novel insights with potential therapeutic implications.
Lien vers le texte intégral (Open Access ou abonnement)
7. Hallahan BP, Daly EM, Simmons A, Moore CJ, Murphy KC, Murphy DD. {{Fragile X syndrome: a pilot proton magnetic resonance spectroscopy study in premutation carriers}}. {J Neurodev Disord}. 2012 Aug 30;4(1):23.
ABSTRACT: PurposeThere is increasing evidence that neurodevelopmental differences in people with Fragile X syndrome (FraX) may be explained by differences in glutamatergic metabolism. Premutation carriers of FraX were originally considered to be unaffected although several recent reports demonstrate neuroanatomical, cognitive, and emotional differences from controls. However there are few studies on brain metabolism in premutation carriers of FraX. METHODS: We used proton magnetic resonance spectroscopy to compare neuronal integrity of a number of brain metabolites including N-Acetyl Aspartate, Creatine + Phosphocreatinine, Choline, myoInositol, and Glutamate containing substances (Glx) in 17 male premutation carriers of FraX and 16 male healthy control individuals. RESULTS: There was no significant between-group difference in the concentration of any measured brain metabolites. However there was a differential increase in N-acetyl aspartate with aging in premutation FraX individuals compared to controls. CONCLUSIONS: This is the first 1 H-MRS study to examine premutation FraX individuals. Although we demonstrated no difference in the concentration of any of the metabolites examined between the groups, this may be due to the large age ranges included in the two samples. The differential increase in NAA levels with aging which may reflect an abnormal synaptic pruning process.
Lien vers le texte intégral (Open Access ou abonnement)
8. Hsiao MN, Tseng WL, Huang HY, Gau SS. {{Effects of autistic traits on social and school adjustment in children and adolescents: The moderating roles of age and gender}}. {Research in developmental disabilities}. 2012 Sep 6;34(1):254-65.
This study examined the associations between children’s and adolescents’ autistic-like social deficits and school and social adjustment as well as the moderating roles of age and gender in these associations. The sample consisted of 1321 students (48.7% boys) in Grade 1 to Grade 8 from northern Taiwan. Children’s and adolescents’ autistic-like social deficits were assessed using the Social Responsiveness Scale (SRS), and their school and social adjustment (i.e., academic performance, negative attitudes toward schoolwork/teachers/classmates, behavioral problems at schools, negative peer relationships, and problems with peers) were assessed using the Social Adjustment Inventory for Children and Adolescents (SAICA). Both measures were completed by the mothers of the participants. Results from the linear mixed models demonstrated that autistic-like social deficits were associated with poor academic performance, negative attitudes toward schoolwork, teachers, and classmates, behavioral problems at schools, negative peer relationships, and problematic peer interactions. Moreover, gender and/or age moderated the associations between autistic-like social deficits and school and social adjustment problems. For example, autistic-like social deficits were more strongly related to negative school attitude, school social problems, and negative peer relationships in boys than in girls. Further, autistic-like social deficits were more strongly related to problems with peers in older girls than in older boys or younger children (regardless of gender). In conclusion, the present study suggests that autistic-like social deficits may place children and adolescents at increased risk for social and school maladjustment and that the extent of maladjustment may vary with the child’s age and gender and the domains of adjustment under discussion.
Lien vers le texte intégral (Open Access ou abonnement)
9. Hu VW. {{Subphenotype-dependent disease markers for diagnosis and personalized treatment of autism spectrum disorders}}. {Disease markers}. 2012 Aug 31.
Autism spectrum disorders (ASD) are a collection of neurodevelopmental disorders that are currently diagnosed solely on the basis of abnormal reciprocal language and social development as well as stereotyped behaviors. Without genetic or molecular markers for screening, individuals with ASD are typically not diagnosed before the age of 2, with milder cases diagnosed much later. Because early diagnosis is tantamount to early behavioral intervention which has been shown to improve individual outcomes, an objective biomarker test that can diagnose at-risk children perinatally is a medical imperative. The rapidly increasing prevalence of ASD in the United States (now estimated at 1 in 88 individuals) also makes early diagnosis and intervention a public health imperative. This article reviews recent genome-wide (genomic) approaches to the identification of disease markers that may be used not only for diagnosis of ASD, but also for the informed development of novel drugs that target specific core symptoms of ASD. Because of the heterogeneity of clinical manifestations associated with the ASD population, this review also addresses the importance of dividing individuals with ASD into clinically relevant subphenotypes in the quest to identify appropriate biomarkers.
Lien vers le texte intégral (Open Access ou abonnement)
10. Kishida KT, Li J, Schwind J, Montague PR. {{New approaches to investigating social gestures in autism spectrum disorder}}. {J Neurodev Disord}. 2012;4(1):14.
ABSTRACT: The combination of economic games and human neuroimaging presents the possibility of using economic probes to identify biomarkers for quantitative features of healthy and diseased cognition. These probes span a range of important cognitive functions, but one new use is in the domain of reciprocating social exchange with other humans – a capacity perturbed in a number of psychopathologies. We summarize the use of a reciprocating exchange game to elicit neural and behavioral signatures for subjects diagnosed with autism spectrum disorder (ASD). Furthermore, we outline early efforts to capture features of social exchange in computational models and use these to identify quantitative behavioral differences between subjects with ASD and matched controls. Lastly, we summarize a number of subsequent studies inspired by the modeling results, which suggest new neural and behavioral signatures that could be used to characterize subtle deficits in information processing during interactions with other humans.
Lien vers le texte intégral (Open Access ou abonnement)
11. Knox A, Schneider A, Abucayan F, Hervey C, Tran C, Hessl D, Berry-Kravis E. {{Feasibility, reliability, and clinical validity of the Test of Attentional Performance for Children (KiTAP) in Fragile X syndrome (FXS)}}. {J Neurodev Disord}. 2012;4(1):2.
ABSTRACT: BACKGROUND: Attention and inhibition are core executive-function deficits in FRagile X syndrome (FXS). This pilot study evaluated the feasibility, reproducibility, and clinical relevance of the KiTAP, a computer-based pictorial measure of attention and inhibition with an enchanted-castle theme, in an FXS cohort. METHODS: The 8-subtest KiTAP battery (as many subtests as each could perform) was given to 36 subjects with FXS, of variable age and cognitive/behavioral functioning, and 29 were retested, with an interval of 2 to 4 weeks between sessions. Subjects were rated by parents on the Aberrant Behavior Checklist-Community Edition (ABC-C) and Behavior Assessment System for Children, Second Edition (BASC-2). Feasibility, ceiling and basal effects, and data range and distribution analyses were used to eliminate outliers and invalid data points. Reproducibility of scores was analyzed using intraclass correlation coefficients (ICCs) and validity/clinical relevance was assessed by correlating KiTAP scores with ABC-C and BASC-2 scores. RESULTS: Most of the participants with FXS were able to complete the Alertness, Distractibility, Flexibility, and Go/NoGo subtests.About 50 to 60% completed the Visual Scanning and Vigilance subtests, and 20 to 25% completed the Sustained Attention and Divided Attention subtests. A panel of seven scores from four subtests were identified as feasible for most subjects, lacked excessive ceiling, basal, or learning effects, exhibited an acceptable range and distribution of scores, had good reproducibility (ICC > 0.7), and correlated with behavioral ratings for hyperactivity or attention (P < 0.01). Only minor differences in performance on the KiTAP were seen between mental age-matched cohorts of subjects with FXS and non-FXS intellectual disability. CONCLUSIONS: The KiTAP can be administered to cohorts with FXS over a wide range of function with valid reproducible scores. With additional validation, it could represent a useful outcome measure for assessment of attention/executive-function abilities in clinical trials targeted to these core deficits in FXS.
Lien vers le texte intégral (Open Access ou abonnement)
12. Kohls G, Chevallier C, Troiani V, Schultz RT. {{Social ‘wanting’ dysfunction in autism: neurobiological underpinnings and treatment implications}}. {J Neurodev Disord}. 2012;4(1):10.
ABSTRACT: Most behavioral training regimens in autism spectrum disorders (ASD) rely on reward-based reinforcement strategies. Although proven to significantly increase both cognitive and social outcomes and successfully reduce aberrant behaviors, this approach fails to benefit a substantial number of affected individuals. Given the enormous amount of clinical and financial resources devoted to behavioral interventions, there is a surprisingly large gap in our knowledge of the basic reward mechanisms of learning in ASD. Understanding the mechanisms for reward responsiveness and reinforcement-based learning is urgently needed to better inform modifications that might improve current treatments. The fundamental goal of this review is to present a fine-grained literature analysis of reward function in ASD with reference to a validated neurobiological model of reward: the ‘wanting’/’liking’ framework. Despite some inconsistencies within the available literature, the evaluation across three converging sets of neurobiological data (neuroimaging, electrophysiological recordings, and neurochemical measures) reveals good evidence for disrupted reward-seeking tendencies in ASD, particularly in social contexts. This is most likely caused by dysfunction of the dopaminergic-oxytocinergic ‘wanting’ circuitry, including the ventral striatum, amygdala, and ventromedial prefrontal cortex. Such a conclusion is consistent with predictions derived from diagnostic criteria concerning the core social phenotype of ASD, which emphasize difficulties with spontaneous self-initiated seeking of social encounters (that is, social motivation). Existing studies suggest that social ‘wanting’ tendencies vary considerably between individuals with ASD, and that the degree of social motivation is both malleable and predictive of intervention response. Although the topic of reward responsiveness in ASD is very new, with much research still needed, the current data clearly point towards problems with incentive-based motivation and learning, with clear and important implications for treatment. Given the reliance of behavioral interventions on reinforcement-based learning principles, we believe that a systematic focus on the integrity of the reward system in ASD promises to yield many important clues, both to the underlying mechanisms causing ASD and to enhancing the efficacy of existing and new interventions.
Lien vers le texte intégral (Open Access ou abonnement)
13. Lin A, Tsai K, Rangel A, Adolphs R. {{Reduced social preferences in autism: evidence from charitable donations}}. {J Neurodev Disord}. 2012;4(1):8.
ABSTRACT: BACKGROUND: People with autism have abnormal preferences, ranging from an apparent lack of preference for social stimuli to unusually strong preferences for restricted sets of highly idiosyncratic stimuli. Yet the profile of preferences across social and nonsocial domains has not been mapped out in detail, and the processes responsible remain poorly understood. METHODS: To assess preferences across a range of stimuli, we measured real monetary donations to 50 charities spanning categories pertaining to people, mental health, animals, or the environment. We compared the donations made by 16 high-functioning adults with autism to those made by neurotypical controls matched on age, gender and education. We additionally collected ratings of how people evaluated the different charities. RESULTS: Compared with controls, high-functioning adults with autism donated less overall and also showed a significantly disproportionate reduction in donations to people charities compared with donations to the other charities. Furthermore, whereas controls discriminated strongly between different people charities, choosing to donate a lot of money to some and very little to others, much less discrimination was seen in the autism group. Ratings that probed how participants constructed their preferences did not differ between groups, except for a difference in the perceived impact of pictures and text information about people charities. Strikingly, there were some charities related to mental health, and autism in particular, to which the autism group donated considerably more than did the controls. CONCLUSIONS: People with autism were found to have reduced preference and sensitivity towards charities benefiting other people. The findings provide evidence for a domain-specific impairment in social cognition in autism spectrum disorder, and in particular in linking otherwise intact social knowledge to the construction of value signals on which preferences regarding other people are based.
Lien vers le texte intégral (Open Access ou abonnement)
14. Linkenauger SA, Lerner MD, Ramenzoni VC, Proffitt DR. {{A Perceptual-Motor Deficit Predicts Social and Communicative Impairments in Individuals With Autism Spectrum Disorders}}. {Autism Res}. 2012 Sep 7.
Individuals with autism spectrum disorders (ASDs) have known impairments in social and motor skills. Identifying putative underlying mechanisms of these impairments could lead to improved understanding of the etiology of core social/communicative deficits in ASDs, and identification of novel intervention targets. The ability to perceptually integrate one’s physical capacities with one’s environment (affordance perception) may be such a mechanism. This ability has been theorized to be impaired in ASDs, but this question has never been directly tested. Crucially, affordance perception has shown to be amenable to learning; thus, if it is implicated in deficits in ASDs, it may be a valuable unexplored intervention target. The present study compared affordance perception in adolescents and adults with ASDs to typically developing (TD) controls. Two groups of individuals (adolescents and adults) with ASDs and age-matched TD controls completed well-established action capability estimation tasks (reachability, graspability, and aperture passability). Their caregivers completed a measure of their lifetime social/communicative deficits. Compared with controls, individuals with ASDs showed unprecedented gross impairments in relating information about their bodies’ action capabilities to visual information specifying the environment. The magnitude of these deficits strongly predicted the magnitude of social/communicative impairments in individuals with ASDs. Thus, social/communicative impairments in ASDs may derive, at least in part, from deficits in basic perceptual-motor processes (e.g. action capability estimation). Such deficits may impair the ability to maintain and calibrate the relationship between oneself and one’s social and physical environments, and present fruitful, novel, and unexplored target for intervention. Autism Res 2012,**:**-**. (c) 2012 International Society for Autism Research, Wiley Periodicals, Inc.
Lien vers le texte intégral (Open Access ou abonnement)
15. Meyza KZ, Defensor EB, Jensen AL, Corley MJ, Pearson BL, Pobbe RL, Bolivar VJ, Blanchard DC, Blanchard RJ. {{The BTBR T(+)tf/J mouse model for autism spectrum disorders-in search of biomarkers}}. {Behavioural brain research}. 2012 Aug 9.
Autism spectrum disorders (ASD) form a common group of neurodevelopmental disorders appearing to be under polygenic control, but also strongly influenced by multiple environmental factors. The brain mechanisms responsible for ASD are not understood and animal models paralleling related emotional and cognitive impairments may prove helpful in unraveling them. BTBR T(+)tf/J (BTBR) mice display behaviors consistent with the three diagnostic categories for ASD. They show impaired social interaction and communication as well as increased repetitive behaviors. This review covers much of the data available to date on BTBR behavior, neuroanatomy and physiology in search for candidate biomarkers, which could both serve as diagnostic tools and help to design effective treatments for the behavioral symptoms of ASD.
Lien vers le texte intégral (Open Access ou abonnement)
16. Newschaffer CJ, Croen LA, Fallin MD, Hertz-Picciotto I, Nguyen DV, Lee NL, Berry CA, Farzadegan H, Hess HN, Landa RJ, Levy SE, Massolo ML, Meyerer SC, Mohammed SM, Oliver MC, Ozonoff S, Pandey J, Schroeder A, Shedd-Wise KM. {{Infant siblings and the investigation of autism risk factors}}. {J Neurodev Disord}. 2012;4(1):7.
ABSTRACT: Infant sibling studies have been at the vanguard of autism spectrum disorders (ASD) research over the past decade, providing important new knowledge about the earliest emerging signs of ASD and expanding our understanding of the developmental course of this complex disorder. Studies focused on siblings of children with ASD also have unrealized potential for contributing to ASD etiologic research. Moving targeted time of enrollment back from infancy toward conception creates tremendous opportunities for optimally studying risk factors and risk biomarkers during the pre-, peri- and neonatal periods. By doing so, a traditional sibling study, which already incorporates close developmental follow-up of at-risk infants through the third year of life, is essentially reconfigured as an enriched-risk pregnancy cohort study. This review considers the enriched-risk pregnancy cohort approach of studying infant siblings in the context of current thinking on ASD etiologic mechanisms. It then discusses the key features of this approach and provides a description of the design and implementation strategy of one major ASD enriched-risk pregnancy cohort study: the Early Autism Risk Longitudinal Investigation (EARLI).
Lien vers le texte intégral (Open Access ou abonnement)
17. Panaitof SC. {{A songbird animal model for dissecting the genetic bases of autism spectrum disorder}}. {Disease markers}. 2012 Aug 31.
The neural and genetic bases of human language development and associated neurodevelopmental disorders, including autism spectrum disorder (ASD), in which language impairment represents a core deficit, are poorly understood. Given that no single animal model can fully capture the behavioral and genetic complexity of ASD, work in songbird, an experimentally tractable animal model of vocal learning, can complement the valuable tool of rodent genetic models and contribute important insights to our understanding of the communication deficits observed in ASD. Like humans, but unlike traditional laboratory animals such as rodents or non-human primates, songbirds exhibit the capacity of vocal learning, a key subcomponent of language. Human speech and birdsong reveal important parallels, highlighting similar developmental critical periods, a homologous cortico-basal ganglia-thalamic circuitry, and a critical role for social influences in the learning of vocalizations. Here I highlight recent advances in using the songbird model to probe the cellular and molecular mechanisms underlying the formation and function of neural circuitry for birdsong and, by analogy, human language, with the ultimate goal of identifying any shared or human unique biological pathways underscoring language development and its disruption in ASD.
Lien vers le texte intégral (Open Access ou abonnement)
18. Pellicano E, Burr D. {{When the world becomes ‘too real’: a Bayesian explanation of autistic perception}}. {Trends in cognitive sciences}. 2012 Sep 6.
Perceptual experience is influenced both by incoming sensory information and prior knowledge about the world, a concept recently formalised within Bayesian decision theory. We propose that Bayesian models can be applied to autism – a neurodevelopmental condition with atypicalities in sensation and perception – to pinpoint fundamental differences in perceptual mechanisms. We suggest specifically that attenuated Bayesian priors – ‘hypo-priors’ – may be responsible for the unique perceptual experience of autistic people, leading to a tendency to perceive the world more accurately rather than modulated by prior experience. In this account, we consider how hypo-priors might explain key features of autism – the broad range of sensory and other non-social atypicalities – in addition to the phenomenological differences in autistic perception.
Lien vers le texte intégral (Open Access ou abonnement)
19. Provenzano G, Zunino G, Genovesi S, Sgado P, Bozzi Y. {{Mutant mouse models of autism spectrum disorders}}. {Disease markers}. 2012 Aug 31.
Autism spectrum disorders (ASDs) are a heterogeneous group of neurodevelopmental diseases characterized by a triad of specific behavioral traits: abnormal social interactions, communication deficits and stereotyped or repetitive behaviors. Several recent studies showed that ASDs have a strong genetic basis, contributing to the discovery of a number of ASD-associated genes. Due to the genetic complexity of these disorders, mouse strains with targeted deletion of ASD genes have become an essential tool to investigate the molecular and neurodevelopmental mechanisms underlying ASD. Here we will review the most relevant genetic mouse models developed by targeted inactivation of ASD-associated genes, and discuss their importance for the development of novel pharmacological therapies of these disorders.
Lien vers le texte intégral (Open Access ou abonnement)
20. Roberts EM, English PB. {{Bayesian modeling of time-dependent vulnerability to environmental hazards: an example using autism and pesticide data}}. {Statistics in medicine}. 2012 Sep 7.
Background: Flexible modeling of time-dependent effects is required when vulnerability to hazards can be expected to vary over time, but the nature of this temporal dependency cannot be specified in advance. We present an analytic approach requiring minimal a priori assumptions about temporal parameters and producing measures of uncertainty for these parameters. Methods: As a demonstration, we employ data describing autism spectrum disorders and applications of organochlorine pesticides in proximity to maternal residence before, during, and after pregnancy. We formulate a Bayesian model specifying temporal vulnerability as a flexible step function and constrain the dose-response relationship to be linear. We separately pooled information regarding hazard frequency and magnitude among cases and controls and used it as inputs for a Metropolis-within-Gibbs algorithm. To assess statistical significance, we conduct Monte Carlo simulations based on parameters calculated in the Gibbs portion of the algorithm. Results: This method delineated two discrete periods of association between hazard and outcome. The first corresponded to a previously noted period of vulnerability with the added information of wide credible intervals, suggesting a high degree of uncertainty with respect to timing. Parameters for the second, previously unobserved period displayed slightly higher precision. Assessment of model fit favored the simultaneous inclusion of both these periods, and both periods appeared statistically significant on the basis of posterior distributions of specific parameters using Monte Carlo simulations. Conclusions: This method enabled a fuller accounting of time-dependent associations between hazards and outcomes without specifying temporal structure in advance. Copyright (c) 2012 John Wiley & Sons, Ltd.
Lien vers le texte intégral (Open Access ou abonnement)
21. Rudie JD, Hernandez LM, Brown JA, Beck-Pancer D, Colich NL, Gorrindo P, Thompson PM, Geschwind DH, Bookheimer SY, Levitt P, Dapretto M. {{Autism-Associated Promoter Variant in MET Impacts Functional and Structural Brain Networks}}. {Neuron}. 2012 Sep 6;75(5):904-15.
As genes that confer increased risk for autism spectrum disorder (ASD) are identified, a crucial next step is to determine how these risk factors impact brain structure and function and contribute to disorder heterogeneity. With three converging lines of evidence, we show that a common, functional ASD risk variant in the Met Receptor Tyrosine Kinase (MET) gene is a potent modulator of key social brain circuitry in children and adolescents with and without ASD. MET risk genotype predicted atypical fMRI activation and deactivation patterns to social stimuli (i.e., emotional faces), as well as reduced functional and structural connectivity in temporo-parietal regions known to have high MET expression, particularly within the default mode network. Notably, these effects were more pronounced in individuals with ASD. These findings highlight how genetic stratification may reduce heterogeneity and help elucidate the biological basis of complex neuropsychiatric disorders such as ASD.
Lien vers le texte intégral (Open Access ou abonnement)
22. Sepeta L, Tsuchiya N, Davies MS, Sigman M, Bookheimer SY, Dapretto M. {{Abnormal social reward processing in autism as indexed by pupillary responses to happy faces}}. {J Neurodev Disord}. 2012;4(1):17.
ABSTRACT: BACKGROUND: Individuals with Autism Spectrum Disorders (ASD) typically show impaired eye contact during social interactions. From a young age, they look less at faces than typically developing (TD) children and tend to avoid direct gaze. However, the reason for this behavior remains controversial; ASD children might avoid eye contact because they perceive the eyes as aversive or because they do not find social engagement through mutual gaze rewarding. METHODS: We monitored pupillary diameter as a measure of autonomic response in children with ASD (n = 20, mean age = 12.4) and TD controls (n = 18, mean age = 13.7) while they looked at faces displaying different emotions. Each face displayed happy, fearful, angry or neutral emotions with the gaze either directed to or averted from the subjects. RESULTS: Overall, children with ASD and TD controls showed similar pupillary responses; however, they differed significantly in their sensitivity to gaze direction for happy faces. Specifically, pupillary diameter increased among TD children when viewing happy faces with direct gaze as compared to those with averted gaze, whereas children with ASD did not show such sensitivity to gaze direction. We found no group differences in fixation that could explain the differential pupillary responses. There was no effect of gaze direction on pupil diameter for negative affect or neutral faces among either the TD or ASD group. CONCLUSIONS: We interpret the increased pupillary diameter to happy faces with direct gaze in TD children to reflect the intrinsic reward value of a smiling face looking directly at an individual. The lack of this effect in children with ASD is consistent with the hypothesis that individuals with ASD may have reduced sensitivity to the reward value of social stimuli.
Lien vers le texte intégral (Open Access ou abonnement)
23. Sizoo B, van der Reijden M. {{[Reaction on ‘The ethical duty to treat children and adolescents with autism and catatonia’]}}. {Tijdschrift voor psychiatrie}. 2012;54(9):843-4.
24. Voineagu I. {{Autism: From genetics to biomarkers}}. {Disease markers}. 2012 Sep 6.
Lien vers le texte intégral (Open Access ou abonnement)
25. Watson KK, Platt ML. {{Of mice and monkeys: using non-human primate models to bridge mouse- and human-based investigations of autism spectrum disorders}}. {J Neurodev Disord}. 2012 Jul 30;4(1):21.
ABSTRACT: The autism spectrum disorders (ASDs) arise from a diverse array of genetic and environmental origins that disrupt the typical developmental trajectory of neural connectivity and synaptogenesis. ASDs are marked by dysfunctional social behavior and cognition, among other deficits. Greater understanding of the biological substrates of typical social behavior in animal models will further our understanding of the etiology of ASDs. Despite the precision and tractability of molecular genetic models of ASDs in rodents, these organisms lack the complexity of human social behavior, thus limiting their impact on understanding ASDs to basic mechanisms. Non-human primates (NHPs) provide an attractive, complementary model for ASDs, due in part to the complexity and dynamics of social structures, reliance on vision for social signaling, and deep homology in brain circuitry mediating social behavior and reward. This knowledge is based on a rich literature, compiled over 50 years of observing primate behavior in the wild, which, in the case of rhesus macaques, is complemented by a large body of research characterizing neuronal activity during cognitive behavior. Several recent developments in this field are directly relevant to ASDs, including how the brain represents the perceptual features of social stimuli; how social information influences attention processes in the brain; and how the value of social interaction is computed. Because the symptoms of ASDs may represent extreme manifestations of traits that vary in intensity within the general population, we will additionally discuss ways in which nonhuman primates also show variation in social behavior and reward sensitivity. In cases where variation in species typical behavior is analogous to similar variations in human behavior, we believe that study of the neural circuitry underlying this variation will provide important insights into the systems level mechanisms contributing to ASD pathology.
