1. Araujo DJ, Toriumi K, Escamilla CO, Kulkarni A, Anderson AG, Harper M, Usui N, Ellegood J, Lerch JP, Birnbaum SG, Tucker HO, Powell CM, Konopka G. {{Foxp1 in Forebrain Pyramidal Neurons Controls Gene Expression Required for Spatial Learning and Synaptic Plasticity}}. {J Neurosci}. 2017; 37(45): 10917-31.
Genetic perturbations of the transcription factor Forkhead Box P1 (FOXP1) are causative for severe forms of autism spectrum disorder that are often comorbid with intellectual disability. Recent work has begun to reveal an important role for FoxP1 in brain development, but the brain-region-specific contributions of Foxp1 to autism and intellectual disability phenotypes have yet to be determined fully. Here, we describe Foxp1 conditional knock-out (Foxp1(cKO)) male and female mice with loss of Foxp1 in the pyramidal neurons of the neocortex and the CA1/CA2 subfields of the hippocampus. Foxp1(cKO) mice exhibit behavioral phenotypes that are of potential relevance to autism spectrum disorder, including hyperactivity, increased anxiety, communication impairments, and decreased sociability. In addition, Foxp1(cKO) mice have gross deficits in learning and memory tasks of relevance to intellectual disability. Using a genome-wide approach, we identified differentially expressed genes in the hippocampus of Foxp1(cKO) mice associated with synaptic function and development. Furthermore, using magnetic resonance imaging, we uncovered a significant reduction in the volumes of both the entire hippocampus as well as individual hippocampal subfields of Foxp1(cKO) mice. Finally, we observed reduced maintenance of LTP in area CA1 of the hippocampus in these mutant mice. Together, these data suggest that proper expression of Foxp1 in the pyramidal neurons of the forebrain is important for regulating gene expression pathways that contribute to specific behaviors reminiscent of those seen in autism and intellectual disability. In particular, Foxp1 regulation of gene expression appears to be crucial for normal hippocampal development, CA1 plasticity, and spatial learning.SIGNIFICANCE STATEMENT Loss-of-function mutations in the transcription factor Forkhead Box P1 (FOXP1) lead to autism spectrum disorder and intellectual disability. Understanding the potential brain-region-specific contributions of FOXP1 to disease-relevant phenotypes could be a critical first step in the management of patients with these mutations. Here, we report that Foxp1 conditional knock-out (Foxp1(cKO)) mice with loss of Foxp1 in the neocortex and hippocampus display autism and intellectual-disability-relevant behaviors. We also show that these phenotypes correlate with changes in both the genomic and physiological profiles of the hippocampus in Foxp1(cKO) mice. Our work demonstrates that brain-region-specific FOXP1 expression may relate to distinct, clinically relevant phenotypes.
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2. Bonnet-Brilhault F, Malvy J, Tuller L, Prevost P, Zebib R, Ferre S, Santos CD, Roux S, Houy-Durand E, Magne R, Mofid Y, Latinus M, Wardak C, Aguillon-Hernandez N, Batty M, Gomot M. {{A strategic plan to identify key neurophysiological mechanisms and brain circuits in autism}}. {J Chem Neuroanat}. 2017.
Autism and Autism Spectrum Disorder (ASD) cover a large variety of clinical profiles which share two main dimensions: social and communication impairment and repetitive behaviors or restricted interests, which are present during childhood. There is now no doubt that genetic factors are a major component in the etiology of autism but precise physiopathological pathways are still being investigated. Furthermore, developmental trajectories combined with compensatory mechanisms will lead to various clinical and neurophysiological profiles which together constitute this Autism Spectrum Disorder. To better understand the pathophysiology of autism, comprehension of key neurophysiological mechanisms and brain circuits underlying the different bioclinical profiles is thus crucial. To achieve this goal we propose a strategy which investigates different levels of information processing from sensory perception to complex cognitive processing, taking into account the complexity of the stimulus and whether it is social or non-social in nature. In order to identify different developmental trajectories and to take into account compensatory mechanisms, we further propose that such protocols should be carried out in individuals from childhood to adulthood representing a wide variety of clinical forms.
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3. Brumback AC, Ellwood IT, Kjaerby C, Iafrati J, Robinson S, Lee AT, Patel T, Nagaraj S, Davatolhagh F, Sohal VS. {{Identifying specific prefrontal neurons that contribute to autism-associated abnormalities in physiology and social behavior}}. {Mol Psychiatry}. 2017.
Functional imaging and gene expression studies both implicate the medial prefrontal cortex (mPFC), particularly deep-layer projection neurons, as a potential locus for autism pathology. Here, we explored how specific deep-layer prefrontal neurons contribute to abnormal physiology and behavior in mouse models of autism. First, we find that across three etiologically distinct models-in utero valproic acid (VPA) exposure, CNTNAP2 knockout and FMR1 knockout-layer 5 subcortically projecting (SC) neurons consistently exhibit reduced input resistance and action potential firing. To explore how altered SC neuron physiology might impact behavior, we took advantage of the fact that in deep layers of the mPFC, dopamine D2 receptors (D2Rs) are mainly expressed by SC neurons, and used D2-Cre mice to label D2R+ neurons for calcium imaging or optogenetics. We found that social exploration preferentially recruits mPFC D2R+ cells, but that this recruitment is attenuated in VPA-exposed mice. Stimulating mPFC D2R+ neurons disrupts normal social interaction. Conversely, inhibiting these cells enhances social behavior in VPA-exposed mice. Importantly, this effect was not reproduced by nonspecifically inhibiting mPFC neurons in VPA-exposed mice, or by inhibiting D2R+ neurons in wild-type mice. These findings suggest that multiple forms of autism may alter the physiology of specific deep-layer prefrontal neurons that project to subcortical targets. Furthermore, a highly overlapping population-prefrontal D2R+ neurons-plays an important role in both normal and abnormal social behavior, such that targeting these cells can elicit potentially therapeutic effects.Molecular Psychiatry advance online publication, 7 November 2017; doi:10.1038/mp.2017.213.
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4. Cameron JL, Eagleson KL, Fox NA, Hensch TK, Levitt P. {{Social Origins of Developmental Risk for Mental and Physical Illness}}. {J Neurosci}. 2017; 37(45): 10783-91.
Adversity in early childhood exerts an enduring impact on mental and physical health, academic achievement, lifetime productivity, and the probability of interfacing with the criminal justice system. More science is needed to understand how the brain is affected by early life stress (ELS), which produces excessive activation of stress response systems broadly throughout the child’s body (toxic stress). Our research examines the importance of sex, timing and type of stress exposure, and critical periods for intervention in various brain systems across species. Neglect (the absence of sensitive and responsive caregiving) or disrupted interaction with offspring induces robust, lasting consequences in mice, monkeys, and humans. Complementary assessment of internalizing disorders and brain imaging in children suggests that early adversity can interfere with white matter development in key brain regions, which may increase risk for emotional difficulties in the long term. Neural circuits that are most plastic during ELS exposure in monkeys sustain the greatest change in gene expression, offering a mechanism whereby stress timing might lead to markedly different long-term behaviors. Rodent models reveal that disrupted maternal-infant interactions yield metabolic and behavioral outcomes often differing by sex. Moreover, ELS may further accelerate or delay critical periods of development, which reflect GABA circuit maturation, BDNF, and circadian Clock genes. Such factors are associated with several mental disorders and may contribute to a premature closure of plastic windows for intervention following ELS. Together, complementary cross-species studies are elucidating principles of adaptation to adversity in early childhood with molecular, cellular, and whole organism resolution.
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5. Chen YT, Tsou KS, Chen HL, Wong CC, Fan YT, Wu CT. {{Functional but Inefficient Kinesthetic Motor Imagery in Adolescents with Autism Spectrum Disorder}}. {J Autism Dev Disord}. 2017.
Whether action representation in individuals with autism spectrum disorder (ASD) is deficient remains controversial, as previous studies of action observation or imitation report conflicting results. Here we investigated the characteristics of action representation in adolescents with ASD through motor imagery (MI) using a hand rotation and an object rotation task. Comparable with the typically-developing group, the individuals with ASD were able to spontaneously use kinesthetic MI to perform the hand rotation task, as manifested by the significant biomechanical effects. However, the ASD group performed significantly slower only in the hand rotation task, but not in the object rotation task. The findings suggest that the adolescents with ASD showed inefficient but functional kinesthetic MI, implicating that their action representation might be preserved.
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6. Dinora P, Bogenschutz M, Lynch K. {{Factors That May Influence Parent Treatment Decision Making for Young Children with Autism Spectrum Disorder}}. {J Soc Work Disabil Rehabil}. 2017.
The number of interventions available for children with Autism Spectrum Disorder (ASD) has expanded greatly in recent years, though relatively little is known about the factors that influence family caregivers as they make treatment decisions for their children. This study involved a statewide survey of parents of young children with ASD to examine the relative weights of the factors that influenced their treatment decisions. Results suggested that caregivers rely on their own intuition for much decision making, though selected professionals are also influential. Implications for professionals working with children with ASD and their families are discussed.
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7. Fatemi SH, Folsom TD, Thuras PD. {{Altered subcellular localization of fragile X mental retardation signaling partners and targets in superior frontal cortex of individuals with schizophrenia}}. {Neuroreport}. 2017; 28(16): 1066-70.
Schizophrenia is a severe, debilitating, neurodevelopmental disorder that affects 1% of the world’s population. Recent findings from our laboratory have identified reduced levels of fragile X mental retardation protein (FMRP) and several downstream FMRP targets in superior frontal cortex of individuals with schizophrenia. We hypothesized that altered subcellular expression of FMRP and its signaling partners may explain these changes. In the current study we employed subcellular fractionation and western blotting to determine levels of FMRP, phosphorylated-FMRP as well as selected signaling partners [protein phosphatase 2A catalytic subunit (PP2AC), p70 S6 kinase (p70 S6K), and amyloid-beta A4 precursor protein (APP)] in the total homogenate, nuclear, and rough endoplasmic reticulum fractions in superior frontal cortex of individuals with schizophrenia versus controls (N=12/group). In total homogenate of individuals with schizophrenia, we identified significantly lower levels of FMRP, phosphorylated-FMRP, and PP2AC. In the nuclear fraction of individuals with schizophrenia we found significantly higher levels of PP2AC, p70 S6K, APP 120 kDa, and APP 88 kDa proteins. Finally, in rough endoplasmic reticulum of individuals with schizophrenia, we identified significantly lower protein levels of p70 S6K and APP 120 kDa. These results provide evidence for a potential mechanism to explain altered FMRP expression in schizophrenia.
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8. Friedman C, Rizzolo MC. {{Correlates of Voting Participation of People with Intellectual and Developmental Disabilities}}. {J Soc Work Disabil Rehabil}. 2017.
People with intellectual and developmental disabilities (IDD) vote less frequently than nondisabled people and people with other disabilities. This study explores what factors facilitate and hinder people with IDD’s voting participation. To do so, 1,341 people with IDD were surveyed using the Personal Outcome Measures(R). Binary logistic regressions revealed significant relationships between voting participation, and support needs, residence types, guardianship statuses, and organizational supports. Along with the right supports, attention to barriers that might exist can ensure people with IDD are able to make use of their civil rights and participate in this crucial form of civic engagement.
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9. Gonzalez-Barrero AM, Nadig AS. {{Can Bilingualism Mitigate Set-Shifting Difficulties in Children With Autism Spectrum Disorders?}}. {Child Dev}. 2017.
This study investigated the effects of bilingualism on set-shifting and working memory in children with autism spectrum disorders (ASD). Bilinguals with ASD were predicted to display a specific bilingual advantage in set-shifting, but not working memory, relative to monolinguals with ASD. Forty 6- to 9-year-old children participated (20 ASD, 20 typically-developing). Set-shifting was measured using a computerized dimensional change card sort (DCCS) task, and by parent report of executive functioning in daily life. Results showed an advantage for bilingual relative to monolingual children with ASD on the DCCS task, but not for set-shifting in daily life. Working memory was similar for bilinguals and monolinguals with ASD. These findings suggest that bilingualism may mitigate some set-shifting difficulties in children with ASD.
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10. Heffernan KS, Columna L, Russo N, Myers BA, Ashby CE, Norris ML, Barreira TV. {{Brief Report: Physical Activity, Body Mass Index and Arterial Stiffness in Children with Autism Spectrum Disorder: Preliminary Findings}}. {J Autism Dev Disord}. 2017.
We examined the association between physical activity (PA), body mass index (BMI) and novel measures of subclinical cardiovascular disease (CVD) in 15 children with autism spectrum disorder (ASD) (mean age 7 +/- 2 years, 2 girls). PA was objectively assessed using accelerometry as time spent in moderate-vigorous physical activity (MVPA). Arterial stiffness was measured via aortic pulse wave velocity (PWV) and taken as a marker of subclinical CVD risk. MVPA was inversely associated with aortic PWV (r = – 0.46, p < 0.05). BMI percentile was positively associated with aortic PWV (r = 0.61, p < 0.05). Overall findings suggest that reduced PA and higher body mass in children with ASD are associated with increased arterial stiffness which may have a detrimental impact on overall cardiovascular health. Lien vers le texte intégral (Open Access ou abonnement)
11. Hollway JA, Mendoza-Burcham M, Andridge R, Aman MG, Handen B, Arnold LE, Lecavalier L, Williams C, Silverman L, Smith T. {{Atomoxetine, Parent Training, and Their Effects on Sleep in Youth with Autism Spectrum Disorder and Attention-Deficit/Hyperactivity Disorder}}. {J Child Adolesc Psychopharmacol}. 2017.
OBJECTIVE: Sleep disturbance is often a problem for children with either autism spectrum disorder (ASD) or attention-deficit/hyperactivity disorder (ADHD). Psychostimulant medications used to treat ADHD symptoms can exacerbate this problem. For children with ASD and ADHD, atomoxetine (ATX) is a viable alternative to psychostimulants. We investigated the effects of ATX and a manualized parent training (PT) program targeting noncompliance, on the sleep quality of children with ASD and ADHD. METHODS: Participants in a randomized clinical trial were treated with ATX + PT, ATX alone, PT alone, or placebo (PBO) alone, for 10 weeks. Fifty-four of 128 (42%) caregivers completed the Children’s Sleep Habits Questionnaire (CSHQ) at baseline and endpoint. Analysis of covariance was used to investigate possible differences between treatment groups. RESULTS: There were no significant differences between treatment groups, including PBO on the CSHQ 33-Item total score, total hours of sleep per day, and total minutes awake after sleep onset at the study endpoint. CONCLUSION: ATX appears sleep neutral. Clinicians who treat ADHD symptoms in children and adolescents with ASD may prefer ATX over psychostimulants when sleep disturbance is an issue.
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12. Ishizuka K, Tabata H, Ito H, Kushima I, Noda M, Yoshimi A, Usami M, Watanabe K, Morikawa M, Uno Y, Okada T, Mori D, Aleksic B, Ozaki N, Nagata KI. {{Possible involvement of a cell adhesion molecule, Migfilin, in brain development and pathogenesis of autism spectrum disorders}}. {J Neurosci Res}. 2017.
Migfilin, encoded by FBLIM1 at the 1p36 locus, is a multi-domain adaptor protein essential for various cellular processes such as cell morphology and migration. Small deletions and duplications at the 1p36 locus, monosomy of which results in neurodevelopmental disorders and multiple congenital anomalies, have also been identified in patients with autism spectrum disorder (ASD). However, the impact of FBLIM1, the gene within 1p36, on the pathogenesis of ASD is unknown. In this study, we performed morphological analyses of migfilin to elucidate its role in brain development. Migfilin was detected specifically in the embryonic and perinatal stages of the mouse brain. Either silencing or overexpression of migfilin in embryos following in utero electroporation disrupted Neocortical neuronal migration. Additionally, neurite elongation was impaired when migfilin was silenced in cultured mouse hippocampal neurons. We then screened FBLIM1 for rare exonic deletions/duplications in 549 Japanese ASD patients and 824 controls, detecting one case of ASD and intellectual delay that harbored a 26-kb deletion at 1p36.21 that solely included the C-terminal exon of FBLIM1. The FBLIM1 mRNA expression level in this case was reduced compared to levels in individuals without FBLIM1 deletion. Our findings indicate that tightly regulated expression of migfilin is essential for neuronal development and that FBLIM1 disruption may be related to the phenotypes associated with ASD and related neurodevelopmental disorders.
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13. Jagla M, Schenk J, Franke GH, Hampel P. {{[Healthy Siblings of Children with Autism Spectrum Disorders. A Mixed-methods Pilot Study]}}. {Prax Kinderpsychol Kinderpsychiatr}. 2017; 66(9): 702-18.
Healthy Siblings of Children with Autism Spectrum Disorders. A Mixed-methods Pilot Study Healthy siblings of chronically ill and/or disabled children may have an increased risk of developing behavioral problems; this is particularly given for siblings of children with Autism Spectrum Disorders (ASD). Quality of life and distress of five siblings (12-15 years) of children with ASD were examined using self- and parent-proxy-reports. Guideline-based interviews were conducted with the siblings and their parents and analyzed according to Mayring. Quality of life described by the children resembled the KINDLR s standardized range of scores, but parents described a decreased quality of life. Both siblings and parents reported low to medium distress. Interviews revealed healthy children are asked by their parents to take responsibility for their siblings with ASD. Parents assumed their healthy children are less affected by the ASD of the sibling. The healthy siblings described being « annoyed » by ASD-associated behavior and partly feeling « treated unfairly ». They wished their sibling no longer « suffered » from ASD or behaved « normally ». The results of this pilot study, albeit with a small sample, show siblings do experience low to medium burden. This burden is often caused by the sibling relationship or the ASD-associated behavior. Suggestions for supporting the healthy siblings are given.
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14. Jongsma K, Spaeth E, Schicktanz S. {{Epistemic injustice in dementia and autism patient organizations – an empirical analysis}}. {AJOB Empir Bioeth}. 2017: 0.
Patient organizations (POs) represent patient collectives in health care policy. The inclusion of people with a ‘neuro-psychiatric’ condition poses a particular challenge for the organizational processes and political representation of such collectives. In recent years, new POs (POs of) have been established in the field of autism spectrum disorder and dementia that advocate a different agenda and have a different organizational structure than traditional POs (POs for). The divide between these two types of POs indicates a different standpoint with regard to who should be included on an organizational level, which voices are accepted and who should represent these voices on the political level. The inclusion and exclusion of voices needs to be normatively justified in order to be regarded legitimate representation of such a collective. With the help of Miranda Fricker’s theory of epistemic injustice, we scrutinize whether and, if so, which types of epistemic injustices (wrongdoings to a person as a knower) can be found within POs’ practices and the political field in which they operate, by analyzing 37 interviews with PO representatives, their members and policy makers. Our in-depth analysis indicates that persistent stereotypes hamper the inclusion of affected members both within POs and on the health political level. Being affected causes distrust in having the ‘capacity to know’ in a two-fold way; it is assumed that those who can represent themselves are « not affected enough » to present valuable insights into the condition and those who have difficulties to express themselves due to their condition are excluded because of their affectedness. We conclude that our analysis of the epistemic practices of POs serves as a good starting point to address these shortcomings from a theoretical and practical perspective and offers a valuable starting point for bioethics to understand unjust structures in the health political context.
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15. Kawasaki M, Kitajo K, Fukao K, Murai T, Yamaguchi Y, Funabiki Y. {{Frontal theta activation during motor synchronization in autism}}. {Sci Rep}. 2017; 7(1): 15034.
Autism is characterized by two primary characteristics: deficits in social interaction and repetitive behavioral patterns. Because interpersonal communication is extremely complicated, its underlying brain mechanisms remain unclear. Here we showed that both characteristics can be explained by a unifying underlying mechanism related to difficulties with irregularities. To address the issues, we measured electroencephalographm during a cooperative tapping task, which required participants to tap a key alternately and synchronously with constant rhythmic a PC program, a variable rhythmic PC program, or a human partner. We found that people with autism had great difficulty synchronizing tapping behavior with others, and exhibited greater than normal theta-wave (6 Hz) activity in the frontal cortex during the task, especially when their partner behaved somewhat irregularly (i.e. a variable rhythmic PC program or a human partner). Importantly, the higher theta-wave activity was related to the severity of autism, not the performance on the task. This indicates that people with autism need to use intense cognition when trying to adapt to irregular behavior and can easily become overtaxed. Difficulty adapting to irregular behavior in others is likely related to their own tendencies for repetitive and regular behaviors. Thus, while the two characteristics of autism have been comprehended separately, our unifying theory makes understanding the condition and developing therapeutic strategies more tractable.
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16. Kern JK, Geier DA, Deth RC, Sykes LK, Hooker BS, Love JM, Bjorklund G, Chaigneau CG, Haley BE, Geier MR. {{Systematic Assessment of Research on Autism Spectrum Disorder (ASD) and Mercury Reveals Conflicts of Interest and the Need for Transparency in Autism Research}}. {Sci Eng Ethics}. 2017.
Historically, entities with a vested interest in a product that critics have suggested is harmful have consistently used research to back their claims that the product is safe. Prominent examples are: tobacco, lead, bisphenol A, and atrazine. Research literature indicates that about 80-90% of studies with industry affiliation found no harm from the product, while only about 10-20% of studies without industry affiliation found no harm. In parallel to other historical debates, recent studies examining a possible relationship between mercury (Hg) exposure and autism spectrum disorder (ASD) show a similar dichotomy. Studies sponsored and supported by industry or entities with an apparent conflict of interest have most often shown no evidence of harm or no « consistent » evidence of harm, while studies without such affiliations report positive evidence of a Hg/autism association. The potentially causal relationship between Hg exposure and ASD differs from other toxic products since there is a broad coalition of entities for whom a conflict of interest arises. These include influential governmental public health entities, the pharmaceutical industry, and even the coal burning industry. This review includes a systematic literature search of original studies on the potential relationship between Hg and ASD from 1999 to August 2015, finding that of the studies with public health and/or industry affiliation, 86% reported no relationship between Hg and ASD. However, among studies without public health and/or industry affiliation, only 21% find no relationship between Hg and ASD. The discrepancy in these results suggests a bias indicative of a conflict of interest.
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17. Magallon-Neri E, Vila D, Santiago K, Garcia P, Canino G. {{The Prevalence of Psychiatric Disorders and Mental Health Services Utilization by Parents and Relatives Living With Individuals With Autism Spectrum Disorders in Puerto Rico}}. {J Nerv Ment Dis}. 2017.
Knowledge about prevalence rates of psychiatric disorders and mental health services use among parents and relatives of persons with autism spectrum disorder (ASD) is limited, particularly when referring to epidemiologic samples. The current study is based on an island-wide probabilistic multistage cluster sample of adult individuals (N = 3062) living in Puerto Rico. Results showed a significantly higher rate of attention deficit hyperactivity disorder and serious mental illness in parents (n = 34) or relatives (n = 34) of ASD individuals, as compared with the Puerto Rico adult population as a whole. Although not definitive because of the small sample size, the fact that the rates of mental health utilization were similar to the population sample suggests a need for greater attention by health professionals attending children with ASD to the needs for mental health services of both parents and relatives of individuals with ASD.
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18. Pantelis PC, Kennedy DP. {{Deconstructing atypical eye gaze perception in autism spectrum disorder}}. {Sci Rep}. 2017; 7(1): 14990.
The ability to discern the target of another person’s gaze is critical for social and linguistic development, but functions atypically in autism spectrum disorder (ASD). A multi-pronged approach allowed us to deconstruct this complex ability, to uncover the fundamental bases of this impairment. We analyzed performance on a novel gaze perception task with classical psychophysical metrics (precision and accuracy), principal component analysis (in the analysis of spatial biases), and Bayesian computational modeling (in the analysis of individual subjects’ use of contextual salience cues). Compared to controls, adults with ASD were less precise and less accurate in their judgments of gaze direction. Further, although nearly all controls exhibited a prototypical pattern of spatial bias in their judgments, this spatial prior was severely disrupted among a large subset of ASD participants. By contrast, Bayesian computational modeling revealed that both groups exploited contextual salience cues in their gaze judgments, and that the average strength of this contextual prior was similar for both groups. This comprehensive study revealed that although most ASD participants performed atypically in at least one aspect of gaze perception, the particular aspects disrupted varied idiosyncratically across individuals. Impairment in gaze perception in ASD likely arises via heterogeneous underlying mechanisms.
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19. Posar A, Visconti P. {{Sensory abnormalities in children with autism spectrum disorder}}. {J Pediatr (Rio J)}. 2017.
OBJECTIVE: The clinical picture of children with autism spectrum disorder is characterized by deficits of social interaction and communication, as well as by repetitive interests and activities. Sensory abnormalities are a very frequent feature that often go unnoticed due to the communication difficulties of these patients. This narrative review summarizes the main features of sensory abnormalities and the respective implications for the interpretation of several signs and symptoms of autism spectrum disorder, and therefore for its management. SOURCES: A search was performed in PubMed (United States National Library of Medicine) about the sensory abnormalities in subjects (particularly children) with autism spectrum disorder. SUMMARY OF THE FINDINGS: Sensory symptoms are common and often disabling in children with autism spectrum disorder, but are not specific for autism, being a feature frequently described also in subjects with intellectual disability. Three main sensory patterns have been described in autism spectrum disorder: hypo-responsiveness, hyper-responsiveness, and sensory seeking; to these, some authors have added a fourth pattern: enhanced perception. Sensory abnormalities may negatively impact the life of these individuals and their families. An impairment not only of unisensory modalities but also of multisensory integration is hypothesized. CONCLUSIONS: Atypical sensory reactivity of subjects with autism spectrum disorder may be the key to understand many of their abnormal behaviors, and thus it is a relevant aspect to be taken into account in their daily management in all the contexts in which they live. A formal evaluation of sensory function should be always performed in these children.
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20. Rausch A, Zhang W, Beckmann CF, Buitelaar JK, Groen WB, Haak KV. {{Connectivity-Based Parcellation of the Amygdala Predicts Social Skills in Adolescents with Autism Spectrum Disorder}}. {J Autism Dev Disord}. 2017.
Amygdala dysfunction plays a role in the social impairments in autism spectrum disorders (ASD), but it is unclear which of its subregions are abnormal in ASD. This study compared the volume and functional connectivity (FC) strength of three FC-defined amygdala subregions between ASD and controls, and assessed their relation to social skills in ASD. A subregion associated with the social perception network was enlarged in ASD (F1 = 7.842, p = .008) and its volume correlated significantly with symptom severity (social skills: r = .548, p = .009). Posthoc analysis revealed that the enlargement was driven by the vmPFC amygdala network. These findings refine our understanding of abnormal amygdala connectivity in ASD and may inform future strategies for therapeutic interventions targeting the amygdalofrontal pathway.
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21. Silva K, Lima M, Santos-Magalhaes A, Fafiaes C, de Sousa L. {{Can Dogs Assist Children with Severe Autism Spectrum Disorder in Complying with Challenging Demands? An Exploratory Experiment with a Live and a Robotic Dog}}. {J Altern Complement Med}. 2017.
OBJECTIVES: Prompted by the need to find effective ways to enhance compliance in children with autism spectrum disorder (ASD), and building on the increasing interest in dog-assisted interventions for this population, this study provides an exploratory test on whether dogs may assist children with severe ASD in complying with challenging demands while also decreasing behavioral and cardiovascular distress. DESIGN: A within-subject design was used. Depending on condition, participants were allowed to engage with a particular stimulus-their preferred toy, a live dog, or a robotic dog-before being exposed to a demanding task in which they had to wait for permission to eat a desired food item (« prohibition task »). Although inactive, the stimulus remained present during the prohibition task. SUBJECTS AND SETTINGS: Ten male children, aged between 6 and 9 years and diagnosed with severe ASD, participated in this study. All were clinically referred as having serious compliance difficulties in everyday routines. Testing occurred at participants’ homes. OUTCOME MEASURES: Participants’ emotional expressions, latency to distress, compliance levels, and behaviors that were shown during committed compliance were assessed during the prohibition task. In addition, cardiovascular reactivity to the task was monitored. RESULTS: Obtained data revealed significant differences between conditions for some of the considered measures. Latency to distress was higher in the live dog than in the toy condition. Committed compliance was higher in the live dog than in the toy and robot conditions. Quiet waiting during committed compliance was higher in the live dog condition than in the toy condition, and tension release behaviors were lower. In addition, heart rate reactivity was lower in the live dog condition than in the toy condition. CONCLUSIONS: The live dog condition appeared to have a calming effect on the participants, hypothetically facilitating compliance. Although promising, these findings are only preliminary and their clinical significance needs to be assessed in future studies.
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22. Spaniol MM, Shalev L, Kossyvaki L, Mevorach C. {{Attention Training in Autism as a Potential Approach to Improving Academic Performance: A School-Based Pilot Study}}. {J Autism Dev Disord}. 2017.
This study assessed the effectiveness of an attention intervention program (Computerized Progressive Attentional Training; CPAT) in improving academic performance of children with ASD. Fifteen 6-10 year olds with ASD attending a mainstream and a special school were assigned to an experimental (CPAT; n = 8) and active control (computer games; n = 7) group. Children were assessed pre- and post-intervention on measures of behavioural symptoms, cognitive skills and academic performance. The intervention was conducted in school twice a week for 8 weeks. Children in the CPAT group showed cognitive and academic improvements over and above the active control group, while children in both groups showed improvements in behaviour. Results suggest that attention training is a feasible approach to improving academic performance in this population.
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23. Sun JM, Kurtzberg J. {{Cell therapy for diverse central nervous system disorders: inherited metabolic diseases and autism}}. {Pediatr Res}. 2017.
The concept of utilizing human cells for the treatment of medical conditions is not new. In its simplest form, blood product transfusion as treatment of severe hemorrhage has been practiced since the 1800s. The advent of hematopoietic stem cell transplantation (HSCT) began with the development of bone marrow transplantation for hematological malignancies in the mid-1900s and is now the standard of care for many hematological disorders. In the past few decades, HSCT has expanded to additional sources of donor cells, a wider range of indications, and the development of novel cell products. This trajectory has sparked a rapidly growing interest in the pursuit of innovative cell therapies to treat presently incurable diseases, including neurological conditions. HSCT is currently an established therapy for certain neurologically devastating inherited metabolic diseases, in which engrafting donor cells provide lifelong enzyme replacement that prevents neurological deterioration and significantly extends the lives of affected children. Knowledge gained from the treatment of these rare conditions has led to refinement of the indications and timing of HSCT, the study of additional cellular products and techniques to address its limitations, and the investigation of cellular therapies without transplantation to treat more common neurological conditions, such as autism spectrum disorder.Pediatric Research advance online publication, 8 November 2017; doi:10.1038/pr.2017.254.
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24. Tora D, Gomez AM, Michaud JF, Yam PT, Charron F, Scheiffele P. {{Cellular Functions of the Autism Risk Factor PTCHD1 in Mice}}. {J Neurosci}. 2017.
The gene PTCHD1 is mutated in patients with autism spectrum disorders (ASD) and intellectual disabilities (ID) and has been hypothesized to contribute to Sonic hedgehog (Shh) signaling and synapse formation. We identify a panel of Ptchd1 interacting proteins that include postsynaptic density proteins and the retromer complex, revealing a link to critical regulators of dendritic and postsynaptic trafficking. Ptchd1 knock-out male mice exhibit cognitive alterations, including defects in a novel object recognition task. To test whether Ptchd1 is required for Shh-dependent signaling, we examined two Shh-dependent cell populations that express high levels of Ptchd1 mRNA: cerebellar granule cell precursors and dentate granule cells in the hippocampus. We find that proliferation of these neuronal precursors is not significantly altered in Ptchd1 knock-out male mice. We used whole-cell electrophysiology and anatomical methods to assess synaptic function in Ptchd1-deficient dentate granule cells. In the absence of Ptchd1, we observed profound disruption in excitatory/inhibitory balance despite normal dendritic spine density on dentate granule cells. These findings support a critical role of Ptchd1 protein in the dentate gyrus but indicate that it is not required for structural synapse formation in dentate granule cells or for Shh-dependent neuronal precursor proliferation.SIGNIFICANCE STATEMENTThe mechanisms underlying neuronal and cellular alterations resulting from Ptchd1 mutations are unknown. The results from this study support an association with dendritic trafficking complexes of Ptchd1. Loss-of-function experiments do not support a role in sonic-hedgehog-dependent signaling but reveal a disruption of synaptic transmission in the mouse dentate gyrus. The findings will help guide ongoing efforts on understanding the etiology of neurodevelopmental disorders arising from Ptchd1-deficiency.
