Pubmed du 11/09/19

mercredi 11 septembre 2019

1. Abraham JR, Szoko N, Barnard J, Rubin RA, Schlatzer D, Lundberg K, Li X, Natowicz MR. Proteomic Investigations of Autism Brain Identify Known and Novel Pathogenetic Processes. Sci Rep ;2019 (Sep 11) ;9(1):13118.

Autism Spectrum Disorder (ASD) is a set of heterogeneous neurodevelopmental conditions defined by impairments in social communication and restricted, repetitive behaviors, interests or activities. Only a minority of ASD cases are determined to have a definitive etiology and the pathogenesis of most ASD is poorly understood. We hypothesized that a global analysis of the proteomes of human ASD vs. control brain, heretofore not done, would provide important data with which to better understand the underlying neurobiology of autism. In this study, we characterized the proteomes of two brain regions, Brodmann area 19 (BA19) and posterior inferior cerebellum (CB), from carefully selected idiopathic ASD cases and matched controls using label-free HPLC-tandem mass spectrometry. The data revealed marked differences between ASD and control brain proteomes for both brain regions. Unlike earlier transcriptomic analyses using frontal and temporal cortex, however, our proteomic analysis did not support ASD attenuating regional gene expression differences. Bioinformatic analyses of the differentially expressed proteins between cases and controls highlighted canonical pathways involving glutamate receptor signaling and glutathione-mediated detoxification in both BA19 and CB ; other pathways such as Sertoli cell signaling and fatty acid oxidation were specifically enriched in BA19 or CB, respectively. Network analysis of both regions of ASD brain showed up-regulation of multiple pre- and post-synaptic membrane or scaffolding proteins including glutamatergic ion channels and related proteins, up-regulation of proteins involved in intracellular calcium signaling, and down-regulation of neurofilament proteins, with DLG4 and MAPT as major hub proteins in BA19 and CB protein interaction networks, respectively. Upstream regulator analysis suggests neurodegeneration-associated proteins drive the differential protein expression for ASD in both BA19 and CB. Overall, the proteomic data provide support for shared dysregulated pathways and upstream regulators for two brain regions in human ASD brain, suggesting a common ASD pathophysiology that has distinctive regional expression.

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2. Almehmadi KA, Tsilioni I, Theoharides TC. Increased Expression of miR-155p5 in Amygdala of Children With Autism Spectrum Disorder. Autism Res ;2019 (Sep 10)

MiR-155p5 is a pro-inflammatory microRNA reported to be involved in several neurol-inflammatory diseases. Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by impaired social interactions and communication, as well as stereotypic movements. Inflammation of the brain due to activation of microglia has been reported in ASD. We investigated miR-155p5 gene expression in postmortem human brain tissues [amygdala and dorsolateral prefrontal cortex regions (DLPFC)]. There was significant increase of miR-155p5 in amygdala (P </= 0.0001), but not in DLFC, in ASD children (n = 8) compared to non-ASD (n = 7) controls. The increased gene expression of miR-155p5 in amygdala of children of ASD support the presence of localized inflammation in the brain and indicates miR-155p5 may be targeted for therapy of ASD. Autism Res 2019. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY : The pathogenesis of autism spectrum disorder (ASD) is still unknown. Our data of increased gene expression of miR-155p5 in brains of children with ASD support the presence of localized inflammation in the amygdala and indicates that miR-155p5 may be targeted for therapy of ASD and other neurodegenerative diseases.

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3. Bechi M, Agostoni G, Buonocore M, Bosinelli F, Spangaro M, Bianchi L, Cocchi F, Guglielmino C, Cavallaro R, Bosia M. The Influence of Premorbid Adjustment and Autistic Traits on Social Cognitive Dysfunction in Schizophrenia. J Int Neuropsychol Soc ;2019 (Sep 11):1-10.

OBJECTIVES : Premorbid dysfunction during childhood and adolescence is well documented in patients with schizophrenia. Literature pointed out multiple premorbid trajectories leading to different patients’ cognitive status, symptomatology, and global functioning after disease onset. This study aimed at identifying groups of premorbid trajectories and disentangling between group differences in clinical and cognitive measures, focusing on theory of mind (ToM) and autistic traits (ATs). METHODS : Ninety-seven patients with schizophrenia were recruited and assessed for cognitive and ToM abilities, psychopathology, and ATs. A two-step cluster analysis identified three different groups of patients based on premorbid adjustment during childhood, adolescence, and late adolescence (i.e., stable-good, stable-poor, and "deteriorating"). RESULTS : Compared to 66 healthy controls, results showed a widespread impairment in cognitive and ToM abilities among all groups of patients, except for affective ToM and executive functions in the stable-good group. Moreover, the stable-poor group exhibited more pronounced ATs and a more severe ToM impairment, compared to the other two groups of patients. CONCLUSIONS : Our findings highlight the existence of a group of patients with poor premorbid adjustment since childhood, more pronounced ATs and a severe ToM impairment affecting those basic mentalizing skills that are usually preserved in schizophrenia. Results might have intriguing implications in identifying underpinning endophenotypes and implementing cutting-edge rehabilitation programs.

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4. Ben-Sasson A, Gal E, Fluss R, Katz-Zetler N, Cermak SA. Update of a Meta-analysis of Sensory Symptoms in ASD : A New Decade of Research. J Autism Dev Disord ;2019 (Sep 9)

This meta-analysis updated evidence regarding sensory over-responsivity (SOR), under-responsivity (SUR) and seeking symptoms in individuals with autism spectrum disorders (ASDs) relative to typical controls and those with other conditions. Fifty-five questionnaire studies included 4606 individuals with ASD. Moderators tested were age, IQ, male ratio, matching group, and self-report. Compared to typical controls, effect size was large and significant for SOR, SUR, and Seeking but heterogeneous. For Seeking, age, IQ and self-report were significant moderators. Compared with developmental disorders (DDs) groups, effect size was significantly positive for SOR and Seeking ; whereas compared with other clinical groups, only SOR was significant. These findings highlight the core nature of sensory symptoms in ASD and particularly SOR. Explanatory factors are yet to be revealed.

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5. Factor RS, Swain DM, Antezana L, Muskett A, Gatto AJ, Radtke SR, Scarpa A. Teaching emotion regulation to children with autism spectrum disorder : Outcomes of the Stress and Anger Management Program (STAMP). Bull Menninger Clin ;2019 (Summer) ;83(3):235-258.

Young children with autism spectrum disorder (ASD) struggle with emotion regulation (ER), which is developmentally preceded by lability/negative affect (L/N), and their parents face unique challenges to parenting and providing assistance. The Stress and Anger Management Program (STAMP) is a cognitive-behavioral treatment designed to address ER deficits in young children with ASD through child skill-building and parent training. The current study evaluated child L/N, ER, and parental confidence outcomes in 4- to 7-year-old children with ASD (N = 23 ; 19 boys) and their parents randomly assigned to a treatment (n = 12) or a waitlist control group (n = 11). Child L/N decreased, regulation was not significantly changed, and parental confidence regarding the child’s ability to manage anger and anxiety increased from pre- to posttreatment in the treatment group, but not in the waitlist group. Implications for future interventions that address ER in children with ASD and their parents are discussed.

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6. Forsyth JK, Nachun D, Gandal MJ, Geschwind DH, Anderson AE, Coppola G, Bearden CE. Synaptic and Gene Regulatory Mechanisms in Schizophrenia, Autism, and 22q11.2 Copy Number Variant-Mediated Risk for Neuropsychiatric Disorders. Biol Psychiatry ;2019 (Jul 11)

BACKGROUND : 22q11.2 copy number variants are among the most highly penetrant genetic risk variants for developmental neuropsychiatric disorders such as schizophrenia (SCZ) and autism spectrum disorder (ASD). However, the specific mechanisms through which they confer risk remain unclear. METHODS : Using a functional genomics approach, we integrated transcriptomic data from the developing human brain, genome-wide association findings for SCZ and ASD, protein interaction data, and gene expression signatures from SCZ and ASD postmortem cortex to 1) organize genes into the developmental cellular and molecular systems within which they operate, 2) identify neurodevelopmental processes associated with polygenic risk for SCZ and ASD across the allelic frequency spectrum, and 3) elucidate pathways and individual genes through which 22q11.2 copy number variants may confer risk for each disorder. RESULTS : Polygenic risk for SCZ and ASD converged on partially overlapping neurodevelopmental modules involved in synaptic function and transcriptional regulation, with ASD risk variants additionally enriched for modules involved in neuronal differentiation during fetal development. The 22q11.2 locus formed a large protein network during development that disproportionately affected SCZ-associated and ASD-associated neurodevelopmental modules, including loading highly onto synaptic and gene regulatory pathways. SEPT5, PI4KA, and SNAP29 genes are candidate drivers of 22q11.2 synaptic pathology relevant to SCZ and ASD, and DGCR8 and HIRA are candidate drivers of disease-relevant alterations in gene regulation. CONCLUSIONS : This approach offers a powerful framework to identify neurodevelopmental processes affected by diverse risk variants for SCZ and ASD and elucidate mechanisms through which highly penetrant, multigene copy number variants contribute to disease risk.

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7. Gentles SJ, Nicholas DB, Jack SM, McKibbon KA, Szatmari P. Coming to understand the child has autism : A process illustrating parents’ evolving readiness for engaging in care. Autism ;2019 (Sep 11):1362361319874647.

We report results from a large qualitative study regarding the process of parents coming to understand the child has autism starting from the time of initial developmental concerns. Specifically, we present findings relevant to understanding how parents become motivated and prepared for engaging in care at this early stage. The study included primary data from 45 intensive interviews with 32 mothers and 9 expert professionals from urban and rural regions of Ontario, Canada. Grounded theory methods were used to guide data collection and analysis. Parents’ readiness (motivation and capacity) for engagement develops progressively at different rates as they follow individual paths of meaning making. Four optional steps account for their varied trajectories : forming an image of difference, starting to question the signs, knowing something is wrong, and being convinced it’s autism. Both the nature of the information and professional help parents seek, and the urgency with which they seek them, evolve in predictable ways depending on how far they have progressed in understanding their child has autism. Results indicate the need for sensitivity to parents’ varying awareness and readiness for involvement when engaging with them in early care, tailoring parent support interventions, and otherwise planning family-centered care pathways.

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8. Gollwitzer A, Martel C, McPartland JC, Bargh JA. Autism spectrum traits predict higher social psychological skill. Proc Natl Acad Sci U S A ;2019 (Sep 9)

Social-cognitive skills can take different forms, from accurately predicting individuals’ intentions, emotions, and thoughts (person perception or folk psychology) to accurately predicting social phenomena more generally. Past research has linked autism spectrum (AS) traits to person perception deficits in the general population. We tested whether AS traits also predict poor accuracy in terms of predicting generalized social phenomena, assessed via participants’ accuracy at predicting social psychological phenomena (e.g., social loafing, social projection, group think). We found the opposite. In a sample of approximately 6,500 participants in 104 countries, AS traits predicted slightly higher social psychological skill. A second study with 400 participants suggested that heightened systemizing underlies this relationship. Our results indicate that AS traits relate positively to a form of social cognitive skill-predicting social psychological phenomena-and highlight the importance of distinguishing between divergent types of social cognition.

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9. Hartmann K, Urbano MR, Raffaele CT, Kreiser NL, Williams TV, Qualls LR, Elkins DE. Outcomes of an emotion regulation intervention group in young adults with autism spectrum disorder. Bull Menninger Clin ;2019 (Summer) ;83(3):259-277.

Individuals on the autism spectrum experience difficulties in social relationships and emotion regulation. The aim of the present exploratory research study was to develop and explore the effectiveness of a manualized emotion regulation group intervention for autistic adults to improve emotion regulation and social communication. The group participants included seven young adults (age > 18 years) on the autism spectrum. Primary outcome measures were the Social Responsiveness Scale (SRS-2) and the Emotion Regulation Questionnaire (ERQ). Group participants reported significant improvements on the Social Communication and Interaction subscale (SCI ; t = 2.601, p = .041), the Social Awareness (AWR ; t = 3.163, p = .019), and the Social Cognition (COG ; t = 4.861, p = .003) subscales of the SRS-2 : Self Report. Overall, this study provides preliminary evidence of the effectiveness of a group treatment approach that focuses on emotion regulation to improve social interactions for young adults on the autism spectrum.

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10. Hense M, Badde S, Kohne S, Dziobek I, Roder B. Visual and Proprioceptive Influences on Tactile Spatial Processing in Adults with Autism Spectrum Disorders. Autism Res ;2019 (Sep 11)

Children with autism spectrum disorders (ASDs) often exhibit altered representations of the external world. Consistently, when localizing touch, children with ASDs were less influenced than their peers by changes of the stimulated limb’s location in external space [Wada et al., Scientific Reports 2015, 4(1), 5985]. However, given the protracted development of an external-spatial dominance in tactile processing in typically developing children, this difference might reflect a developmental delay rather than a set suppression of external space in ASDs. Here, adults with ASDs and matched control-participants completed (a) the tactile temporal order judgment (TOJ) task previously used to test external-spatial representation of touch in children with ASDs and (b) a tactile-visual cross-modal congruency (CC) task which assesses benefits of task-irrelevant visual stimuli on tactile localization in external space. In both experiments, participants localized tactile stimuli to the fingers of each hand, while holding their hands either crossed or uncrossed. Performance differences between hand postures reflect the influence of external-spatial codes. In both groups, tactile TOJ-performance markedly decreased when participants crossed their hands and CC-effects were especially large if the visual stimulus was presented at the same side of external space as the task-relevant touch. The absence of group differences was statistically confirmed using Bayesian statistical modeling : adults with ASDs weighted external-spatial codes comparable to typically developed adults during tactile and visual-tactile spatio-temporal tasks. Thus, atypicalities in the spatial coding of touch for children with ASDs appear to reflect a developmental delay rather than a stable characteristic of ASD. Autism Res 2019. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY : A touched limb’s location can be described twofold, with respect to the body (right hand) or the external world (right side). Children and adolescents with autism spectrum disorder (ASD) reportedly rely less than their peers on the external world. Here, adults with and without ASDs completed two tactile localization tasks. Both groups relied to the same degree on external world locations. This opens the possibility that the tendency to relate touch to the external world is typical in individuals with ASDs but emerges with a delay.

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11. Ho WY, Chang JC, Tyan SH, Yen YC, Lim K, Tan BSY, Ong J, Tucker-Kellogg G, Wong P, Koo E, Ling SC. FUS-mediated dysregulation of Sema5a, an autism-related gene, in FUS mice with hippocampus-dependent cognitive deficits. Hum Mol Genet ;2019 (Sep 11)

Pathological FUS inclusions are found in 10% of patients with frontotemporal dementia (FTD) and those with amyotrophic lateral sclerosis (ALS) carrying FUS mutations. Current work indicates that FUS mutations may incur gain-of-toxic functions to drive ALS pathogenesis. However, how FUS dysfunction may affect cognition remains elusive. Using a mouse model expressing wild-type human FUS mimicking the endogenous expression pattern and level within the central nervous system, we found that they developed hippocampus-mediated cognitive deficits accompanied by an age-dependent reduction in spine density and long-term potentiation (LTP) in their hippocampus. However, there were no apparent FUS aggregates, nuclear envelope defects and cytosolic FUS accumulation. These suggest that these proposed pathogenic mechanisms may not be the underlying causes for the observed cognitive deficits. Unbiased transcriptomic analysis identified expression changes in a small set of genes with preferential expression in the neurons and oligodendrocyte lineage cells. Of these, we focused on Sema5a, a gene involved in axon guidance, spine dynamics, Parkinson’s disease and autism spectrum disorders. Critically, FUS binds directly to Sema5a mRNA and regulates Sema5a expression in a FUS-dose-dependent manner. Taken together, our data suggest that FUS-driven Sema5a deregulation may underlie the cognitive deficits in FUS transgenic mice.

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12. Hunsche MC, Kerns CM. Update on the effectiveness of psychotherapy for anxiety disorders in children and adolescents with ASD. Bull Menninger Clin ;2019 (Summer) ;83(3):326-352.

A growing body of research has examined the efficacy of varying formats (individual, group, linear, modular) of cognitive-behavioral therapy (CBT) as a treatment for anxiety disorders in children and youth with autism spectrum disorders (ASD). The present review utilized Chambless and Hollon’s (1998) criteria for efficacious treatments to : (1) critically review the current evidence base for the efficacy of CBT for anxiety disorders in ASD ; and (2) provide recommendations for future research. Findings identify two probably efficacious CBT programs (one group and one individual program) and five possibly efficacious programs, but no well-established programs. Similarities and differences in the components of these programs, which range from unmodified to specifically developed for ASD populations, are highlighted. In addition, the steps required to demonstrate well-established efficacy, and ultimately effectiveness, are discussed alongside other recommendations for refined future research.

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13. Ku B, Heinonen GA, MacDonald M, Hatfield B. An inquiry into how parents of children with autism spectrum disorder interact with their children in a motor skill-based play setting. Res Dev Disabil ;2019 (Sep 11) ;94:103494.

BACKGROUND : Most studies examining parental behaviors of parents of young children with autism spectrum disorder (ASD) and typically developing (TD) children have taken place in free play settings and have primarily focused on examining social behaviors. Motor skill-based play settings, which are distinctly different from free play settings, have not been explicitly studied as it relates to parental behaviors in these environments. AIMS : The purpose of this study was to examine parental behaviors of parents of children with and without ASD in two distinctly different play settings. METHODS : Parental behaviors of eighteen parents of children with (n=9) and without ASD (n=9) were examined by observation in different play settings (free play [a social-play/traditional play based setting] and a motor skill-based play setting). The examined parental behaviors included parental encouragement, negativity, sensitivity, detachment, and intrusiveness. A 2 x 2 (group x play setting) repeated measures of ANOVA was conducted to examine the main effect of group (TD vs ASD) and play setting (a social-play based setting and a motor skill-based setting) and the interaction effect between group and play setting on parental behaviors. Post-hoc independent t-tests between groups in each setting were conducted to follow-up on significant interactions indicated in the repeated measures of ANOVA RESULTS : The repeated measures ANOVA revealed that parental encouragement showed a significant interaction effect, suggesting that the effect of group on parental encouragement depended on play setting. A post-hoc analysis revealed that parents of children with ASD showed statistically significant lower parental encouragement in a motor skill-based play setting but not in a social-play based setting compared to parents of TD children. Moreover, there was a main effect of group (parents of children with ASD vs. parents of TD children) on parental intrusiveness indicating that the mean parental intrusiveness on children with ASD was significantly higher than parents of TD children across both play settings. There were no statistically significant main or interaction effects on the other parental behaviors (parental negativity, sensitivity, and detachment) between groups. CONCLUSIONS AND IMPLICATIONS : The current study indicated parental encouragement differences between parents of children with ASD and parents of TD children varied based on the play setting. These results identify a need to examine parental behaviors, especially parental encouragement and parental intrusiveness across various types of play settings. Furthermore, as parents of children with ASD displayed lower parental encouragement in a motor skill-based play setting compared to parents of TD children, future studies are warranted to improve parental encouragement of parents of children with ASD in a motor skill-based play setting.

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14. Lena I, Mantegazza M. NaV1.2 haploinsufficiency in Scn2a knock-out mice causes an autistic-like phenotype attenuated with age. Sci Rep ;2019 (Sep 9) ;9(1):12886.

Mutations of the SCN2A gene, encoding the voltage gated sodium channel NaV1.2, have been associated to a wide spectrum of epileptic disorders ranging from benign familial neonatal-infantile seizures to early onset epileptic encephalopathies such as Ohtahara syndrome. These phenotypes may be caused by either gain-of-function or loss-of-function mutations. More recently, loss-of-function SCN2A mutations have also been identified in patients with autism spectrum disorder (ASD) without overt epileptic phenotypes. Heterozygous Scn2a knock-out mice (Scn2a(+/-)) may be a model of this phenotype. Because ASD develops in childhood, we performed a detailed behavioral characterization of Scn2a(+/-) mice comparing the juvenile/adolescent period of development and adulthood. We used tasks relevant to ASD and the different comorbidities frequently found in this disorder, such as anxiety or intellectual disability. Our data demonstrate that young Scn2a(+/-) mice display autistic-like phenotype associated to impaired memory and reduced reactivity to stressful stimuli. Interestingly, these dysfunctions are attenuated with age since adult mice show only communicative deficits. Considering the clinical data available on patients with loss-of-function SCN2A mutations, our results indicate that Scn2a(+/-) mice constitute an ASD model with construct and face validity during the juvenile/adolescent period of development. However, more information about the clinical features of adult carriers of SCN2A mutations is needed to evaluate comparatively the phenotype of adult Scn2a(+/-) mice.

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15. Marro BM, Kang E, Hauschild KM, Normansell KM, Abu-Ramadan TM, Lerner MD. Social performance-based interventions promote gains in social knowledge in the absence of explicit training for youth with autism spectrum disorder. Bull Menninger Clin ;2019 (Summer) ;83(3):301-325.

Youth with autism spectrum disorder (ASD) experience deficits in social knowledge. It has long been theorized that these youth must learn these skills explicitly, and social skills interventions (SSIs) have followed suit. Recently, performance-based SSIs have emerged, which promote in vivo opportunities for social engagement without explicit instruction. Effects of performance-based SSIs on social knowledge have not been examined. This study employs two discrete samples (one lab-based, one community-based) of youth with ASD to examine the effects of performance-based interventions on social knowledge. Results largely support the efficacy and effectiveness of improving social knowledge by performance-based interventions without explicit teaching. This indicates that youth with ASD may be able to learn these aspects of social cognition implicitly, rather than exclusively explicitly. The results of the current study also suggest that SSI content, dosage, and intensity may relate to these outcomes, which are important considerations in clinical practice and future studies.

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16. Newbutt N, Bradley R, Conley I. Using Virtual Reality Head-Mounted Displays in Schools with Autistic Children : Views, Experiences, and Future Directions. Cyberpsychol Behav Soc Netw ;2019 (Sep 6)

This article seeks to place children on the autism spectrum at the center of a study examining the potential of virtual reality (VR) head-mounted displays (HMDs) used in classrooms. In doing so, we provide data that address 3 important and often overlooked research questions in the field of autism and technology, working in school-based settings with 31 autistic children from 6 to 16 years of age. First, what type of VR HMD device (and experiences therein) are preferred by children on the autism spectrum using HMDs (given possible sensory concerns). Second, how do children on the autism spectrum report the physical experience, enjoyment, and potential of VR HMDs in their classrooms ? Finally, we were interested in exploring what children on the autism spectrum would like to use VR in schools for ? Through a mixed methods approach, we found that costly and technologically advanced HMDs were preferred (namely : HTC Vive). In addition, HMDs were reported as being enjoyable, physically and visually comfortable, easy to use, and exciting, and children wanted to use them again. They identified several potential usages for HMDs, including relaxing/feeling calm, being able to explore somewhere virtually before visiting in the real world, and to develop learning opportunities in school. We discuss these findings in the context of VR in classrooms, in addition to considering limitations and implication of our findings.

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17. Ni HC, Lin HY, Chen YC, Tseng WI, Gau SS. Boys with autism spectrum disorder have distinct cortical folding patterns underpinning impaired self-regulation : a surface-based morphometry study. Brain Imaging Behav ;2019 (Sep 11)

Although impaired self-regulation (dysregulation) in autism spectrum disorder (ASD) garnered increasing awareness, the neural mechanism of dysregulation in ASD are far from conclusive. To complement our previous voxel-based morphometry findings, we estimated the cortical thickness, surface area, and local gyrification index based on the surface-based morphometry from structural MRI images in 85 ASD and 65 typically developing control (TDC) boys, aged 7-17 years. Levels of dysregulation were measured by the sum of T-scores of Attention, Aggression, and Anxiety/Depression subscales on the Child Behavior Checklist. We found both ASD and TDC shared similar relationships between dysregulation and cortical folding patterns in the left superior and inferior temporal gyri and the left premotor cortex. Significant diagnosis by dysregulation interactions in cortical folding patterns were identified over the right middle frontal and right lateral orbitofrontal regions. The statistical significance of greater local gyrification index in ASD than TDC in several brain regions disappeared when the level of dysregulation was considered. The findings of shared and distinct neural correlates underpinning dysregulation between ASD and TDC may facilitate the development of targeted interventions in the future. The present work also demonstrates that inter-subject variations in self-regulation may explain some extents of ASD-associated brain morphometric differences, likely suggesting that dysregulation is one of the yardsticks for dissecting the heterogeneity of ASD.

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18. Ong JJ. Parental satisfaction and perception of Progress in influencing the Practice of complementary health approaches in children with autism : a cross sectional survey from Negeri Sembilan, Malaysia. BMC Complement Altern Med ;2019 (Sep 9) ;19(1):250.

BACKGROUND : Parents’ use of complementary health approaches (CHA) for children with autism spectrum disorder (ASD) are common despite the uncertain evidence of its benefit. Parents often adopt CHA due to dissatisfaction with conventional treatment. This study aimed to examine parents’ satisfaction with ASD treatment and their perception of progress in their child’s development. Parents’ use of CHA among children with ASD and the factors related were also evaluated. METHODS : Self-administered questionnaires were completed by 48 parents of children with ASD at a single tertiary referral hospital in Malaysia. Correlation analysis was used to explore associations between parental satisfaction scores, perception of progress scores and use of CHA. RESULTS : Use of CHA was reported by parents for 35.4% of children with ASD in the sample. Parents who were less satisfied with conventional treatment and parents who perceived poorer progress in their child’s development were more likely to use CHA. Strong positive relationship was found between parent satisfaction with ASD treatment scores and parent perception of progress scores, which indicates that parents who were satisfied with treatment were more likely to perceive greater progress in their child’s development. Improvement in child’s progress was most appreciated by parents in their child’s behavior (85.5%), social skills (83.3%) and motor skills (77.1%). CONCLUSION : The use of CHA was common among children with ASD. Parents were more likely to practice CHA when they were less satisfied with conventional treatment and perceived poorer progress. A larger multicenter study is required to further explore the practice of CHA among children with ASD throughout Malaysia.

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19. Patriquin MA. Evidence-based treatment and conceptualization of autism spectrum disorder : Emotion regulation, social impairment, and anxiety as targets. Bull Menninger Clin ;2019 (Summer) ;83(3):199-204.

The goal of this special issue is to highlight innovative evidence-based treatments and conceptualizations of emotion regulation difficulties, social impairment, and anxiety in autism spectrum disorder (ASD). The issue is organized into these three highly linked constructs. Targeting these constructs effectively will help to ensure positive outcomes for youth and adults with ASD. It is clear that continued research is needed that creatively addresses emotion regulation problems, social impairment, and anxiety in ASD.

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20. Reyes NM, Pickard K, Reaven J. Emotion regulation : A treatment target for autism spectrum disorder. Bull Menninger Clin ;2019 (Summer) ;83(3):205-234.

Individuals with autism spectrum disorder (ASD) tend to experience difficulties with emotion regulation (ER). Treatments designed to address ER difficulties in individuals with ASD are emerging. The authors review cognitive-behavioral therapy (CBT) and mindfulness-based treatments that have focused on ER difficulties in youth and young adults with ASD. In general, these treatments addressing ER skills have included awareness of emotions/psychoeducation about emotions, frustration tolerance, and ER skills, as well as practice and use of these skills during group therapy that sometimes includes caregivers. The results from these interventions are encouraging for individuals with high-functioning ASD because ER skills tend to improve following treatment. The inclusion of ER in other ASD treatments is discussed.

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21. Rhodus EK, Barber J, Abner EL, Duff DMC, Bardach SH, Caban-Holt A, Lightner D, Rowles GD, Schmitt FA, Jicha GA. Behaviors Characteristic of Autism Spectrum Disorder in a Geriatric Cohort With Mild Cognitive Impairment or Early Dementia. Alzheimer Dis Assoc Disord ;2019 (Sep 11)

INTRODUCTION : Autism spectrum disorder (ASD) represents a heterogenous cluster of clinical phenotypes that are classically diagnosed by the time of adolescence. The possibility of late-life emergence of ASD has been poorly explored. METHODS : To more fully characterize the possibility of late-life emergence of behaviors characteristic of ASD in mild cognitive impairment and AD, we surveyed caregivers of 142 older persons with cognitive impairment from the University of Kentucky Alzheimer’s Disease Center Longitudinal Cohort using the Gilliam Autism Rating Scale-2. RESULTS : Participants with high autism index ratings (autism "possible/very likely," n=23) reported significantly (statistically and clinically) younger age at the onset of cognitive impairment than those who scored in the autism "unlikely" range (n=119) : 71.14+/-10.9 vs. 76.65+/-8.25 (P=0.034). In addition, those in the autism "possible/very likely" group demonstrated advanced severity of cognitive impairment, indicated by the Clinical Dementia Rating Scale Sum of Boxes scores. DISCUSSION : Data demonstrate that ASD behaviors may seem de novo of degenerative dementia and such behaviors are more prevalent in those with early onset dementia. Further work elucidating a connection between ASD and dementia could shed light on subclinical forms of ASD, identify areas of shared neuroanatomic involvement between ASD and dementias, and provide valuable insights that might hasten the development of therapeutic strategies.

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22. Ribeiro R, Nicoli JR, Santos G, Lima-Santos J. Impact of vitamin deficiency on microbiota composition and immunomodulation : relevance to autistic spectrum disorders. Nutr Neurosci ;2019 (Sep 11):1-13.

OBJECTIVES : Inappropriate vitamin supply is a public health problem and is related to abnormalities in brain development, immune response and, more recently, in changes of gut microbial composition. It is known that low levels of vitamin in early life are linked to increased susceptibility to neurodevelopmental disorders, such as Autism Spectrum Disorders (ASD). Unfortunately, the possible peripheral influences of vitamin deficiency that leads to alterations in the gut microbiota-immune-brain axis, one important modulator of the ASD pathology, remain unclear. This narrative review discusses how the impact of vitamin deficiency results in changes in the immune regulation and in the gut microbiota composition, trying to understand how these changes may contribute for the development and severity of ASD. METHODS : The papers were selected using Pubmed and other databases. This review discusses the following topics : (1) vitamin deficiency in alterations of central nervous system in autism, (2) the impact of low levels of vitamins in immunomodulation and how it can favor imbalance in gut microbiota composition and gastrointestinal (GI) disturbances, (3) gut microbiota imbalance/inflammation associated with the ASD pathophysiology, and (4) possible evidences of the role of vitamin deficiency in dysfunctional gut microbiota-immune-brain axis in ASD. RESULTS : Studies indicate that hypovitaminosis A, B12, D, and K have been co-related with the ASD neuropathology. Furthermore, it was shown that low levels of these vitamins favor the Th1/Th17 environment in the gut, as well as the growth of enteropathogens linked to GI disorders. DISCUSSION : GI disorders and alterations in the gut microbiota-immune-brain axis seems to be linked with ASD severity. Although unclear, hypovitaminosis appears to regulate peripherally the ASD pathophysiology by modulating the gut microbiota-immune-brain axis, however, more research is still necessary to confirm this hypothesis.

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23. Rosenbloom R, Wills HP, Mason R, Huffman JM, Mason BA. The Effects of a Technology-Based Self-monitoring Intervention on On-Task, Disruptive, and Task-Completion Behaviors for Adolescents with Autism. J Autism Dev Disord ;2019 (Sep 11)

Individuals with autism spectrum disorders (ASD) often present with difficulty in sustaining engagement, attention, and have disruptive behavior in classroom settings. Without appropriate intervention, these challenging behaviors often persist and negatively impact educational outcomes. Self-monitoring is a well-supported evidence-based practice for addressing challenging behaviors and improving pro-social behaviors for individuals with ASD. Self-monitoring procedures utilizing a handheld computer-based technology is an unobtrusive and innovative way of implementing the intervention. A withdrawal design was employed to assess the effectiveness of a technologically-delivered self-monitoring intervention (I-Connect) in improving on-task and task completion behaviors and decreasing disruptive behavior with four adolescents with ASD. Results demonstrated improvements in on-task and task completion behaviors across all four participants and disruptive behavior improved for two participants.

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24. Shepard KA, Korsak LIT, DeBartolo D, Akins MR. Axonal localization of the Fragile X family of RNA binding proteins is conserved across mammals. J Comp Neurol ;2019 (Sep 9)

Spatial segregation of proteins to neuronal axons arises in part from local translation of mRNAs that are first transported into axons in ribonucleoprotein particles (RNPs), complexes containing mRNAs and RNA binding proteins. Understanding the importance of local translation for a particular circuit requires not only identifying axonal RNPs and their mRNA cargoes, but also whether these RNPs are broadly conserved or restricted to only a few species. Fragile X granules (FXGs) are axonal RNPs containing the Fragile X related family of RNA binding proteins along with ribosomes and specific mRNAs. FXGs were previously identified in mouse, rat, and human brains in a conserved subset of neuronal circuits but with species-dependent developmental profiles. Here we asked whether FXGs are a broadly conserved feature of the mammalian brain and sought to better understand the species-dependent developmental expression pattern. We found FXGs in a conserved subset of neurons and circuits in the brains of every examined species that together include mammalian taxa separated by up to 160 million years of divergent evolution. A developmental analysis of rodents revealed that FXG expression in frontal cortex and olfactory bulb followed consistent patterns in all species examined. In contrast, FXGs in hippocampal mossy fibers increased in abundance across development for most species but decreased across development in guinea pigs and members of the Mus genus, animals that navigate particularly small home ranges in the wild. The widespread conservation of FXGs suggests that axonal translation is an ancient, conserved mechanism for regulating the proteome of mammalian axons. This article is protected by copyright. All rights reserved.

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25. Vaidya CJ, You X, Mostofsky S, Pereira F, Berl MM, Kenworthy L. Data-driven identification of subtypes of executive function across typical development, attention deficit hyperactivity disorder, and autism spectrum disorders. J Child Psychol Psychiatry ;2019 (Sep 11)

BACKGROUND : Impairment of executive function (EF), the goal-directed regulation of thoughts, actions, and emotions, drives negative outcomes and is common across neurodevelopmental disorders including attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). A primary challenge to its amelioration is heterogeneity in symptom expression within and across disorders. Parsing this heterogeneity is necessary to attain diagnostic precision, a goal of the NIMH Research Domain Criteria Initiative. We aimed to identify transdiagnostic subtypes of EF that span the normal to impaired spectrum and establish their predictive and neurobiological validity. METHODS : Community detection was applied to clinical parent-report measures in 8-14-year-old children with and without ADHD and ASD from two independent cohorts (discovery N = 320 ; replication N = 692) to identify subgroups with distinct behavioral profiles. Support vector machine (SVM) classification was used to predict subgroup membership of unseen cases. Preliminary neurobiological validation was obtained with existing functional magnetic resonance imaging (fMRI) data on a subsample (N = 84) by testing hypotheses about sensitivity of EF subgroups versus DSM categories. RESULTS : We observed three transdiagnostic EF subtypes characterized by behavioral profiles that were defined by relative weakness in : (a) flexibility and emotion regulation ; (b) inhibition ; and (c) working memory, organization, and planning. The same tripartite structure was also present in the typically developing children. SVM trained on the discovery sample and tested on the replication sample classified subgroup membership with 77.0% accuracy. Split-half SVM classification on the combined sample (N = 1,012) yielded 88.9% accuracy (this SVM is available for public use). As hypothesized, frontal-parietal engagement was better distinguished by EF subtype than DSM diagnosis and the subgroup characterized with inflexibility failed to modulate right IPL activation in response to increased executive demands. CONCLUSIONS : The observed transdiagnostic subtypes refine current diagnostic nosology and augment clinical decision-making for personalizing treatment of executive dysfunction in children.

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26. Wang J, Zhang Q, Chen Y, Yu S, Wu X, Bao X. Rett and Rett-like syndrome : Expanding the genetic spectrum to KIF1A and GRIN1 gene. Mol Genet Genomic Med ;2019 (Sep 11):e968.

BACKGROUND : This study aimed to investigate the new genetic etiologies of Rett syndrome (RTT) or Rett-like phenotypes. METHODS : Targeted next-generation sequencing (NGS) was performed on 44 Chinese patients with RTT or Rett-like phenotypes, in whom genetic analysis of MECP2, CDKL5, and FOXG1 was negative. RESULTS : The detection rate was 31.8% (14/44). A de novo pathogenic variant (c.275_276ins AA, p. Cys92*) of KIF1A was identified in a girl with all core features of typical RTT. A patient with atypical RTT was detected having de novo GRIN1 pathogenic variant (c.2337C > A, p. Val793Phe). Additionally, compound heterozygous pathogenic variants of PPT1 gene were detected in a girl, who initially displayed typical RTT features, but progressed into neuronal ceroid lipofuscinoses (NCL) afterwards. Pathogenic variants in KCNQ2, MEF2C, WDR45, TCF4, IQSEC2, and SDHA were also found in our cohort. CONCLUSIONS : It is the first time that pathogenic variants of GRIN1 and KIF1A were linked to RTT and Rett-like profiles. Our findings expanded the genetic heterogeneity of Chinese RTT or Rett-like patients, and also suggest that some patients with genetic metabolic disease such as NCL, might displayed Rett features initially, and clinical follow-up is essential for the diagnosis.

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27. Winkler M, Biswas S, Berger SM, Kuchler M, Preisendorfer L, Choo M, Fruh S, Rem PD, Enkel T, Arnold B, Komljenovic D, Sticht C, Goerdt S, Bettler B, von Bohlen Und Halbach O, Bartsch D, Geraud C. Pianp deficiency links GABAB receptor signaling and hippocampal and cerebellar neuronal cell composition to autism-like behavior. Mol Psychiatry ;2019 (Sep 11)

Pianp (also known as Leda-1) is a type I transmembrane protein with preferential expression in the mammalian CNS. Its processing is characterized by proteolytic cleavage by a range of proteases including Adam10, Adam17, MMPs, and the gamma-secretase complex. Pianp can interact with Pilralpha and the GB1a subunit of the GABAB receptor (GBR) complex. A recent case description of a boy with global developmental delay and homozygous nonsense variant in PIANP supports the hypothesis that PIANP is involved in the control of behavioral traits in mammals. To investigate the physiological functions of Pianp, constitutive, global knockout mice were generated and comprehensively analyzed. Broad assessment did not indicate malformation or malfunction of internal organs. In the brain, however, decreased sizes and altered cellular compositions of the dentate gyrus as well as the cerebellum, including a lower number of cerebellar Purkinje cells, were identified. Functionally, loss of Pianp led to impaired presynaptic GBR-mediated inhibition of glutamate release and altered gene expression in the cortex, hippocampus, amygdala, and hypothalamus including downregulation of Erdr1, a gene linked to autism-like behavior. Behavioral phenotyping revealed that Pianp deficiency leads to context-dependent enhanced anxiety and spatial learning deficits, an altered stress response, severely impaired social interaction, and enhanced repetitive behavior, which all represent characteristic features of an autism spectrum disorder-like phenotype. Altogether, Pianp represents a novel candidate gene involved in autism-like behavior, cerebellar and hippocampal pathology, and GBR signaling.

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28. Yang X, Zhou T, Zhang H, Li Y, Dong R, Liu N, Pan G, Liu Y, Gai Z. Generation of an induced pluripotent stem cell line (SDQLCHi008-A) from a patient with ASD and DD carrying an 830kb de novo deletion at chr7q11.22 including the exon 1 of AUTS2 gene. Stem Cell Res ;2019 (Aug 31) ;40:101557.

An induced pluripotent stem cell (iPSC) line was generated from human urine-derived cells of a 4year-old boy with autism spectrum disorder(ASD) and developmental delay (DD) carrying a 830kb de novo deletion at chromosome 7q11.22 disrupting the first exon and promoter region of AUTS2. The iPSC retained the original deletion of AUTS2, and had a normal karyotype, express pluripotency markers and bear differentiation potential in vitro.

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