Pubmed du 04/02/19

lundi 4 février 2019

1. Arastoo AA, Khojastehkia H, Rahimi Z, Khafaie MA, Hosseini SA, Mansouri MT, Yosefyshad S, Abshirini M, Noshin K, Cheraghi M. Correction to : Evaluation of serum 25-Hydroxy vitamin D levels in children with autism Spectrum disorder. Italian journal of pediatrics. 2019 ; 45(1) : 22.

The original article [1] contained an error in author Mohammad Taghi Mansouri’s name.

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2. Baribeau DA, Dupuis A, Paton TA, Hammill C, Scherer SW, Schachar RJ, Arnold PD, Szatmari P, Nicolson R, Georgiades S, Crosbie J, Brian J, Iaboni A, Kushki A, Lerch JP, Anagnostou E. Structural neuroimaging correlates of social deficits are similar in autism spectrum disorder and attention-deficit/hyperactivity disorder : analysis from the POND Network. Translational psychiatry. 2019 ; 9(1) : 72.

Autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and obsessive-compulsive disorder (OCD) have been associated with difficulties recognizing and responding to social cues. Neuroimaging studies have begun to map the social brain ; however, the specific neural substrates contributing to social deficits in neurodevelopmental disorders remain unclear. Three hundred and twelve children underwent structural magnetic resonance imaging of the brain (controls = 32, OCD = 44, ADHD = 77, ASD = 159 ; mean age = 11). Their social deficits were quantified on the Social Communication Questionnaire (SCQ) and the Reading the Mind in the Eyes Test (RMET). Multivariable regression models were used to examine the structural neuroimaging correlates of social deficits, with both a region of interest and a whole-brain vertex-wise approach. For the region of interest analysis, social brain regions were grouped into three networks : (1) lateral mentalization (e.g., temporal-parietal junction), (2) frontal cognitive (e.g., orbitofrontal cortex), and (3) subcortical affective (e.g., limbic system) regions. Overall, social communication deficits on the SCQ were associated with thinner cortices in the left lateral regions and the right insula, and decreased volume in the ventral striatum, across diagnostic groups (p = 0.006 to <0.0001). Smaller subcortical volumes were associated with more severe social deficits on the SCQ in ASD and ADHD, and less severe deficits in OCD. On the RMET, larger amygdala/hippocampal volumes were associated with fewer deficits across groups. Overall, patterns of associations were similar in ASD and ADHD, supporting a common underlying biology and the blurring of the diagnostic boundaries between these disorders.

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3. Dawson G. Inappropriate Use of the Term Autism as Analogy. JAMA Pediatr. 2019.

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4. Dawson G, Sapiro G. Potential for Digital Behavioral Measurement Tools to Transform the Detection and Diagnosis of Autism Spectrum Disorder. JAMA Pediatr. 2019.

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5. Haartsen R, Jones EJH, Orekhova EV, Charman T, Johnson MH. Functional EEG connectivity in infants associates with later restricted and repetitive behaviours in autism ; a replication study. Translational psychiatry. 2019 ; 9(1) : 66.

We conducted a replication study of our prior report that increased alpha EEG connectivity at 14-months associates with later autism spectrum disorder (ASD) diagnosis, and dimensional variation in restricted interests/repetitive behaviours. 143 infants at high and low familial risk for ASD watched dynamic videos of spinning toys and women singing nursery rhymes while high-density EEG was recorded. Alpha functional connectivity (7-8 Hz) was calculated using the debiased weighted phase lag index. The final sample with clean data included low-risk infants (N = 20), and high-risk infants who at 36 months showed either typical development (N = 47), atypical development (N = 21), or met criteria for ASD (N = 13). While we did not replicate the finding that global EEG connectivity associated with ASD diagnosis, we did replicate the association between higher functional connectivity at 14 months and greater severity of restricted and repetitive behaviours at 36 months in infants who met criteria for ASD. We further showed that this association is strongest for the circumscribed interests subdomain. We propose that structural and/or functional abnormalities in frontal-striatal circuits underlie the observed association. This is the first replicated infant neural predictor of dimensional variation in later ASD symptoms.

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6. Jacob S, Wolff JJ, Steinbach MS, Doyle CB, Kumar V, Elison JT. Neurodevelopmental heterogeneity and computational approaches for understanding autism. Translational psychiatry. 2019 ; 9(1) : 63.

In recent years, the emerging field of computational psychiatry has impelled the use of machine learning models as a means to further understand the pathogenesis of multiple clinical disorders. In this paper, we discuss how autism spectrum disorder (ASD) was and continues to be diagnosed in the context of its complex neurodevelopmental heterogeneity. We review machine learning approaches to streamline ASD’s diagnostic methods, to discern similarities and differences from comorbid diagnoses, and to follow developmentally variable outcomes. Both supervised machine learning models for classification outcome and unsupervised approaches to identify new dimensions and subgroups are discussed. We provide an illustrative example of how computational analytic methods and a longitudinal design can improve our inferential ability to detect early dysfunctional behaviors that may or may not reach threshold levels for formal diagnoses. Specifically, an unsupervised machine learning approach of anomaly detection is used to illustrate how community samples may be utilized to investigate early autism risk, multidimensional features, and outcome variables. Because ASD symptoms and challenges are not static within individuals across development, computational approaches present a promising method to elucidate subgroups of etiological contributions to phenotype, alternative developmental courses, interactions with biomedical comorbidities, and to predict potential responses to therapeutic interventions.

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7. Loper PL, Jr. Inappropriate Use of the Term Autism as Analogy-Reply. JAMA Pediatr. 2019.

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8. Nilsson Jobs E, Bolte S, Falck-Ytter T. Preschool Staff Spot Social Communication Difficulties, But Not Restricted and Repetitive Behaviors in Young Autistic Children. J Autism Dev Disord. 2019.

To fulfill the criteria for autism spectrum disorder (ASD), symptoms must be present across domains and contexts. We assessed preschool staff’s ratings of social communication and interaction (SCI) and restricted and repetitive behaviors (RRBs) in 3-year-old siblings of children with ASD, either diagnosed (n = 12) or not diagnosed (n = 36) with ASD, and typically developing siblings with no family history of ASD (n = 16). Ratings of SCI were more accurate than RRBs in differentiating the ASD group from the two other groups, and only the SCI ratings correlated with clinical assessment of social behavior. We conclude that while preschool staff ratings of SCI behaviors are adequate, ratings of RRBs should be treated with more caution.

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9. Oldehinkel M, Mennes M, Marquand A, Charman T, Tillmann J, Ecker C, Dell’Acqua F, Brandeis D, Banaschewski T, Baumeister S, Moessnang C, Baron-Cohen S, Holt R, Bolte S, Durston S, Kundu P, Lombardo MV, Spooren W, Loth E, Murphy DGM, Beckmann CF, Buitelaar JK. Altered Connectivity Between Cerebellum, Visual, and Sensory-Motor Networks in Autism Spectrum Disorder : Results from the EU-AIMS Longitudinal European Autism Project. Biol Psychiatry Cogn Neurosci Neuroimaging. 2018.

BACKGROUND : Resting-state functional magnetic resonance imaging-based studies on functional connectivity in autism spectrum disorder (ASD) have generated inconsistent results. Interpretation of findings is further hampered by small samples and a focus on a limited number of networks, with networks underlying sensory processing being largely underexamined. We aimed to comprehensively characterize ASD-related alterations within and between 20 well-characterized resting-state networks using baseline data from the EU-AIMS (European Autism Interventions-A Multicentre Study for Developing New Medications) Longitudinal European Autism Project. METHODS : Resting-state functional magnetic resonance imaging data was available for 265 individuals with ASD (7.5-30.3 years ; 73.2% male) and 218 typically developing individuals (6.9-29.8 years ; 64.2% male), all with IQ > 70. We compared functional connectivity within 20 networks-obtained using independent component analysis-between the ASD and typically developing groups, and related functional connectivity within these networks to continuous (overall) autism trait severity scores derived from the Social Responsiveness Scale Second Edition across all participants. Furthermore, we investigated case-control differences and autism trait-related alterations in between-network connectivity. RESULTS : Higher autism traits were associated with increased connectivity within salience, medial motor, and orbitofrontal networks. However, we did not replicate previously reported case-control differences within these networks. The between-network analysis did reveal case-control differences showing on average 1) decreased connectivity of the visual association network with somatosensory, medial, and lateral motor networks, and 2) increased connectivity of the cerebellum with these sensory and motor networks in ASD compared with typically developing subjects. CONCLUSIONS : We demonstrate ASD-related alterations in within- and between-network connectivity. The between-network alterations broadly affect connectivity between cerebellum, visual, and sensory-motor networks, potentially underlying impairments in multisensory and visual-motor integration frequently observed in ASD.

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10. Pascolini G, Majore S, Valiante M, Bottillo I, Laino L, Agolini E, Novelli A, Grammatico B, Calvani M, Grammatico P. Autism spectrum disorder in a patient with a genomic rearrangement that only involves the EPHA5 gene. Psychiatric genetics. 2019.

About one child in 68 is affected by the autism spectrum disorder (ASD), one of the most common neurodevelopmental disorders linked to intellectual disability, especially in males, intellectual disability being diagnosable in about 60-70% of autistic individuals. The biological bases of ASD are not yet fully known, but they are generally considered multifactorial, although many genes and genomic loci have been proposed to be possibly associated with this condition. In this report, we describe the case of a 14-year-old female Italian proband affected by ASD, carrying a novel approximately 270 kb interstitial microduplication, localized at the distal portion of the 4q13.1 region. The rearrangement was inherited from a mild symptomatic father and included a large part of the single EPHA5 gene, a receptor tyrosine kinase involved in the neural development, already indicated to be linked to ASD by previous Genome Wide Association Studies. This imbalance represents, to the best of our knowledge, the smallest duplication identified to date that only impacts the EPHA5 gene. We hypothesize that the duplication of this gene may alter EPHA5 expression and that this may impact the autistic phenotype of the patient.

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11. Perez Liz G, Bradstreet L, Fernandes S. Inappropriate Use of the Term Autism as Analogy. JAMA Pediatr. 2019.

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12. Peterson BS, Zargarian A, Peterson JB, Goh S, Sawardekar S, Williams SCR, Lythgoe DJ, Zelaya FO, Bansal R. Hyperperfusion of Frontal White and Subcortical Gray Matter in Autism Spectrum Disorder. Biol Psychiatry. 2018.

BACKGROUND : Our aim was to assess resting cerebral blood flow (rCBF) in children and adults with autism spectrum disorder (ASD). METHODS : We acquired pulsed arterial spin labeling magnetic resonance imaging data in 44 generally high-functioning participants with ASD simplex and 66 typically developing control subjects with comparable mean full-scale IQs. We compared rCBF values voxelwise across diagnostic groups and assessed correlations with symptom scores. We also assessed the moderating influences of participant age, sex, and IQ on our findings and the correlations of rCBF with N-acetylaspartate metabolite levels. RESULTS : We detected significantly higher rCBF values throughout frontal white matter and subcortical gray matter in participants with ASD. rCBF correlated positively with socialization deficits in participants with ASD in regions where hyperperfusion was greatest. rCBF declined with increasing IQ in the typically developing group, a correlation that was absent in participants with ASD, whose rCBF values were elevated across all IQ levels. rCBF in the ASD group correlated inversely with N-acetylaspartate metabolite levels throughout the frontal white matter, with greater rCBF accompanying lower and increasingly abnormal N-acetylaspartate levels relative to those of typically developing control subjects. CONCLUSIONS : These findings taken together suggest the presence of altered metabolism, likely of mitochondrial origin, and dysfunctional maintenance processes that support axonal functioning in ASD. These disturbances in turn likely reduce neural efficiency for cognitive and social functioning and trigger compensatory responses from supporting glial cells, which subsequently increase rCBF to affected white matter. These findings, if confirmed, suggest cellular and molecular targets for novel therapeutics that address axonal pathology and bolster glial compensatory responses in ASD.

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13. Rosenthal IA, Hutcherson CA, Adolphs R, Stanley DA. Deconstructing Theory-of-Mind Impairment in High-Functioning Adults with Autism. Current biology : CB. 2019 ; 29(3) : 513-9.e6.

Inferring the beliefs, desires, and intentions of other people ("theory of mind," ToM) requires specialized psychological processes that represent the minds of others as distinct from our own [1-3]. ToM is engaged ubiquitously in our everyday social behavior and features a specific developmental trajectory [4] that is notably delayed in children with autism spectrum disorder (ASD) [5, 6]. In healthy individuals, model-based analyses of social learning and decision-making have successfully elucidated specific computational components of ToM processing [7-11]. However, the use of this approach to study ToM impairment in ASD has been extremely limited [10, 12]. To better characterize specific ToM impairment in ASD, we developed a novel learning task and applied model-based analyses in high-functioning adults with ASD and matched healthy controls. After completing a charitable donation task, participants performed a "mentalizer" task in which they observed another person (the agent) complete the same charity task. The mentalizer task probed the participants’ ability to acquire and use ToM representations. To accurately predict agent behavior, participants needed to dynamically track the agent’s beliefs (true or false) about an experimental context that varied over time and use that information to infer the agent’s intentions from their actions. ASD participants were specifically impaired at using their estimates of agent belief to learn agent intentions, though their ability to track agent belief was intact and their reasoning about belief and intentions was rational. Furthermore, model parameters correlated with aspects of social functioning, e.g., ADOS severity scores [13]. Together, these results identify novel, and more specific, targets for future research.

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14. Shishido E, Ogawa S, Miyata S, Yamamoto M, Inada T, Ozaki N. Application of eye trackers for understanding mental disorders : Cases for schizophrenia and autism spectrum disorder. Neuropsychopharmacology reports. 2019.

Studies of eye movement have become an essential tool of basic neuroscience research. Measures of eye movement have been applied to higher brain functions such as cognition, social behavior, and higher-level decision-making. With the development of eye trackers, a growing body of research has described eye movements in relation to mental disorders, reporting that the basic oculomotor properties of patients with mental disorders differ from those of healthy controls. Using discrimination analysis, several independent research groups have used eye movements to differentiate patients with schizophrenia from a mixed population of patients and controls. Recently, in addition to traditional oculomotor measures, several new techniques have been applied to measure and analyze eye movement data. One research group investigated eye movements in relation to the risk of autism spectrum disorder several years prior to the emergence of verbal-behavioral abnormalities. Research on eye movement in humans in social communication is therefore considered important, but has not been well explored. Since eye movement patterns vary between patients with mental disorders and healthy controls, it is necessary to collect a large amount of eye movement data from various populations and age groups. The application of eye trackers in the clinical setting could contribute to the early treatment of mental disorders.

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15. Thompson L, Gillberg C, Landberg S, Kantzer AK, Miniscalco C, Barnevik Olsson M, Eriksson MA, Fernell E. Autism With and Without Regression : A Two-Year Prospective Longitudinal Study in Two Population-Derived Swedish Cohorts. J Autism Dev Disord. 2019.

Two community-based cohorts of children with autism spectrum disorder, examined using similar assessment protocols, were pooled (n = 301) and subdivided according to history of regression. Those with regression (n = 62), 20.5% of the combined cohort, were contrasted with those without regression (n = 241) at first assessment (age range 19-60 months) and at 2-year follow-up on a range of measures. The regression group was significantly more functionally impaired, with regard to intellectual function (p < .001), language development (p < .001), and to severity of autism (p < .01) at both T1 and T2. Only 14 (23.3%) had a clearly identified underlying etiology [24 (18.6%) in the non-regressive group]. There were no significant differences between those who had regressed ’from normal’ and those who had regressed ’from low’ functioning.

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16. van Hoorn A, Carpenter T, Oak K, Laugharne R, Ring H, Shankar R. Neuromodulation of autism spectrum disorders using vagal nerve stimulation. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia. 2019.

Influential theories propose an important role for the autonomic nervous system in social behaviour and emotion regulation. Difficulties with these capabilities occur in autism spectrum disorders (ASD). Vagus nerve stimulation (VNS) is a neuromodulation technique that stimulates autonomic pathways by means of an electrode implanted around the left vagus nerve in the neck. It is a licenced treatment for epilepsy and depression. This study searches the literature for evidence of VNS effects on behaviour in ASD. A literature search was conducted by two independent reviewers using Embase, Medline, PsycInfo and Cochrane using relevant search terms following the principals of the PRISMA guidance. The search strategy utilised a combination of text words and thesaurus terms to retrieve records relating to autism/pervasive developmental disorder and vagus nerve stimulation. No limits were applied. Supplementary searches were carried out on trials registers, and using backwards and forwards citation searching. A predesigned inclusion and exclusion criteria was administered to the identified results. From the 242 results identified search strategy 11 were found to satisfy the full search criteria and used to discuss the hypothesis. Eight studies were case series and three case reports. There is some evidence that VNS, when performed for epilepsy, may improve behaviour in people with ASD. There are indications that this occurs independently of its effects on seizure frequency and mood, although more rigorous studies are required.

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