Pubmed du 29/01/21

vendredi 29 janvier 2021

1. Ash RT, Park J, Suter B, Zoghbi HY, Smirnakis SM. Excessive Formation and Stabilization of Dendritic Spine Clusters in the MECP2-Duplication Syndrome Mouse Model of Autism. eNeuro. 2021 ; 8(1).

Autism-associated genetic mutations may perturb the balance between stability and plasticity of synaptic connections in the brain. Here, we report an increase in the formation and stabilization of dendritic spines in the cerebral cortex of the mouse model of MECP2-duplication syndrome, a high-penetrance form of syndromic autism. Increased stabilization is mediated entirely by spines that form cooperatively in 10-μm clusters and is observable across multiple cortical areas both spontaneously and following motor training. Excessive stability of dendritic spine clusters could contribute to behavioral rigidity and other phenotypes in syndromic autism.

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2. Bitsika V, Sharpley CF. Symptom profiles and correlates of anxiety and depression among parents of autistic girls and boys. Res Dev Disabil. 2021 ; 111 : 103874.

BACKGROUND : Although it has been reported for some time that parenting an autistic child is associated with elevated anxiety and depression, no direct comparison has been published regarding the relative anxiety and depressive states of parents of an autistic son versus an autistic daughter. AIMS : To investigate the presence of differences in anxiety and depression in parents of autistic girls and boys, and to identify if there were any meaningful child-based correlates of those states. METHODS AND PROCEDURES : A sample of 51 parents of young autistic males (M age = 10.2 yr, SD = 2.8 yr, range to 6-17 yr) and 51 parents of autistic females (M age = 10.1 yr, SD = 2.7 yr, range to 6-17 yr) completed the GAD7 and PHQ9. Autistic children were assessed for IQ and autism severity. OUTCOMES AND RESULTS : Although there were no significant differences between the two sets of parents’ GAD7 or PHQ9 total scores, there were significant and meaningful differences at the individual GAD7 and PHQ9 item level. Moreover, when examined at the within-child-sex subgroup level, different aspects of the autistic sons’ and daughters’ age and IQ were correlated with specific items from the GAD7 and PHQ9. CONCLUSIONS AND IMPLICATIONS : Because these items were somatic in nature, implications are discussed for possible treatment strategies with these parents.

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3. Caplan B, Blacher J, Eisenhower A, Baker BL, Lee SS. Gene x responsive parenting interactions in social development : Characterizing heterogeneity in autism spectrum disorder. Dev Psychobiol. 2021.

Emerging research suggests that caregiving environments and genetic variants independently contribute to social functioning in children with typical development or autism spectrum disorder (ASD). However, biologically plausible interactive models and complimentary assessment of mechanisms are needed to : (a) explain considerable social heterogeneity, (b) resolve inconsistencies in the literature, and (c) develop and select optimal treatments based on individual differences. This study examined the role of child genotypes and responsive parenting in the social development of 104 children with ASD (ages 4-7 years). We utilized a longitudinal, multi-informant design and structural equation models to evaluate : (a) the additive and interactive effects of biologically plausible candidate genes (5-HTTLPR, OXTR, DRD4) and responsive parenting in predicting prospective social development in ASD across three time points spanning 1.5 years, and (b) whether child emotion regulation mediated observed gene x environment interactions (GxEs). Responsive parenting positively predicted prospective change in child social skills ; these associations were moderated by 5-HTTLPR and DRD4 in teacher-report models, and DRD4 in parent-report models. No GxE effects were found for OXTR. Emotion regulation did not significantly mediate the GxEs involving 5-HTTLPR and DRD4. Acknowledging the complexities of GxE research, implications for future research, and targeted intervention efforts are discussed.

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4. Frazier TW, Jaini R, Busch RM, Wolf M, Sadler T, Klaas P, Hardan AY, Martinez-Agosto JA, Sahin M, Eng C. Cross-level analysis of molecular and neurobehavioral function in a prospective series of patients with germline heterozygous PTEN mutations with and without autism. Mol Autism. 2021 ; 12(1) : 5.

BACKGROUND : PTEN is a well-established risk gene for autism spectrum disorder (ASD). Yet, little is known about how PTEN mutations and associated molecular processes influence neurobehavioral function in mutation carriers with (PTEN-ASD) and without ASD (PTEN no-ASD). The primary aim of the present study was to examine group differences in peripheral blood-derived PTEN pathway protein levels between PTEN-ASD, PTEN no-ASD, and idiopathic macrocephalic ASD patients (macro-ASD). Secondarily, associations between protein levels and neurobehavioral functions were examined in the full cohort. METHODS : Patients were recruited at four tertiary medical centers. Peripheral blood-derived protein levels from canonical PTEN pathways (PI3K/AKT and MAPK/ERK) were analyzed using Western blot analyses blinded to genotype and ASD status. Neurobehavioral measures included standardized assessments of global cognitive ability and multiple neurobehavioral domains. Analysis of variance models examined group differences in demographic, neurobehavioral, and protein measures. Bivariate correlations, structural models, and statistical learning procedures estimated associations between molecular and neurobehavioral variables. To complement patient data, Western blots for downstream proteins were generated to evaluate canonical PTEN pathways in the PTEN-m3m4 mouse model. RESULTS : Participants included 61 patients (25 PTEN-ASD, 16 PTEN no-ASD, and 20 macro-ASD). Decreased PTEN and S6 were observed in both PTEN mutation groups. Reductions in MnSOD and increases in P-S6 were observed in ASD groups. Elevated neural P-AKT/AKT and P-S6/S6 from PTEN murine models parallel our patient observations. Patient PTEN and AKT levels were independently associated with global cognitive ability, and p27 expression was associated with frontal sub-cortical functions. As a group, molecular measures added significant predictive value to several neurobehavioral domains over and above PTEN mutation status. LIMITATIONS : Sample sizes were small, precluding within-group analyses. Protein and neurobehavioral data were limited to a single evaluation. A small number of patients were excluded with invalid protein data, and cognitively impaired patients had missing data on some assessments. CONCLUSIONS : Several canonical PTEN pathway molecules appear to influence the presence of ASD and modify neurobehavioral function in PTEN mutation patients. Protein assays of the PTEN pathway may be useful for predicting neurobehavioral outcomes in PTEN patients. Future longitudinal analyses are needed to replicate these findings and evaluate within-group relationships between protein and neurobehavioral measures. TRIAL REGISTRATION : ClinicalTrials.gov Identifier NCT02461446.

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5. Holm KN, Herren AW, Taylor SL, Randol JL, Kim K, Espinal G, Martiínez-Cerdeño V, Pessah IN, Hagerman RJ, Hagerman PJ. Human Cerebral Cortex Proteome of Fragile X-Associated Tremor/Ataxia Syndrome. Frontiers in molecular biosciences. 2020 ; 7 : 600840.

Background : Fragile X-associated tremor/ataxia syndrome (FXTAS) is an adult-onset neurodegenerative disorder associated with premutation CGG-repeat expansions (55-200 repeats) in the 5’ non-coding portion of the fragile X mental retardation 1 (FMR1) gene. Core features of FXTAS include progressive tremor/ataxia, cognitive decline, variable brain volume loss, and white matter disease. The principal histopathological feature of FXTAS is the presence of central nervous system (CNS) and non-CNS intranuclear inclusions. Objective : To further elucidate the molecular underpinnings of FXTAS through the proteomic characterization of human FXTAS cortexes. Results : Proteomic analysis of FXTAS brain cortical tissue (n = 8) identified minor differences in protein abundance compared to control brains (n = 6). Significant differences in FXTAS relative to control brain predominantly involved decreased abundance of proteins, with the greatest decreases observed for tenascin-C (TNC), cluster of differentiation 38 (CD38), and phosphoserine aminotransferase 1 (PSAT1) ; proteins typically increased in other neurodegenerative diseases. Proteins with the greatest increased abundance include potentially novel neurodegeneration-related proteins and small ubiquitin-like modifier 1/2 (SUMO1/2). The FMRpolyG peptide, proposed in models of FXTAS pathogenesis but only identified in trace amounts in the earlier study of FXTAS inclusions, was not identified in any of the FXTAS or control brains in the current study. Discussion : The observed proteomic shifts, while generally relatively modest, do show a bias toward decreased protein abundance with FXTAS. Such shifts in protein abundance also suggest altered RNA binding as well as loss of cell-cell adhesion/structural integrity. Unlike other neurodegenerative diseases, the proteome of end-stage FXTAS does not suggest a strong inflammation-mediated degenerative response.

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6. Imbriani G, Panico A, Grassi T, Idolo A, Serio F, Bagordo F, De Filippis G, De Giorgi D, Antonucci G, Piscitelli P, Colangelo M, Peccarisi L, Tumolo MR, De Masi R, Miani A, De Donno A. Early-Life Exposure to Environmental Air Pollution and Autism Spectrum Disorder : A Review of Available Evidence. Int J Environ Res Public Health. 2021 ; 18(3).

The number of children diagnosed with Autism Spectrum Disorder (ASD) has rapidly increased globally. Genetic and environmental factors both contribute to the development of ASD. Several studies showed linkage between prenatal, early postnatal air pollution exposure and the risk of developing ASD. We reviewed the available literature concerning the relationship between early-life exposure to air pollutants and ASD onset in childhood. We searched on Medline and Scopus for cohort or case-control studies published in English from 1977 to 2020. A total of 20 articles were selected for the review. We found a strong association between maternal exposure to particulate matter (PM) during pregnancy or in the first years of the children’s life and the risk of the ASD. This association was found to be stronger with PM(2.5) and less evident with the other pollutants. Current evidence suggest that pregnancy is the period in which exposure to environmental pollutants seems to be most impactful concerning the onset of ASD in children. Air pollution should be considered among the emerging risk factors for ASD. Further epidemiological and toxicological studies should address molecular pathways involved in the development of ASD and determine specific cause-effect associations.

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7. Javed H, Lee W, Park CH. Toward an Automated Measure of Social Engagement for Children With Autism Spectrum Disorder-A Personalized Computational Modeling Approach. Frontiers in robotics and AI. 2020 ; 7 : 43.

Social engagement is a key indicator of an individual’s socio-emotional and cognitive states. For a child with Autism Spectrum Disorder (ASD), this serves as an important factor in assessing the quality of the interactions and interventions. So far, qualitative measures of social engagement have been used extensively in research and in practice, but a reliable, objective, and quantitative measure is yet to be widely accepted and utilized. In this paper, we present our work on the development of a framework for the automated measurement of social engagement in children with ASD that can be utilized in real-world settings for the long-term clinical monitoring of a child’s social behaviors as well as for the evaluation of the intervention methods being used. We present a computational modeling approach to derive the social engagement metric based on a user study with children between the ages of 4 and 12 years. The study was conducted within a child-robot interaction setting that targets sensory processing skills in children. We collected video, audio and motion-tracking data from the subjects and used them to generate personalized models of social engagement by training a multi-channel and multi-layer convolutional neural network. We then evaluated the performance of this network by comparing it with traditional classifiers and assessed its limitations, followed by discussions on the next steps toward finding a comprehensive and accurate metric for social engagement in ASD.

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8. Javed H, Lee W, Park CH. Corrigendum : Toward an Automated Measure of Social Engagement for Children With Autism Spectrum Disorder-A Personalized Computational Modeling Approach. Frontiers in robotics and AI. 2020 ; 7 : 67.

[This corrects the article DOI : 10.3389/frobt.2020.00043.].

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9. Kostrubiec V, Kruck J. Collaborative Research Project : Developing and Testing a Robot-Assisted Intervention for Children With Autism. Frontiers in robotics and AI. 2020 ; 7 : 37.

The present work is a collaborative research aimed at testing the effectiveness of the robot-assisted intervention administered in real clinical settings by real educators. Social robots dedicated to assisting persons with autism spectrum disorder (ASD) are rarely used in clinics. In a collaborative effort to bridge the gap between innovation in research and clinical practice, a team of engineers, clinicians and researchers working in the field of psychology developed and tested a robot-assisted educational intervention for children with low-functioning ASD (N = 20) A total of 14 lessons targeting requesting and turn-taking were elaborated, based on the Pivotal Training Method and principles of Applied Analysis of Behavior. Results showed that sensory rewards provided by the robot elicited more positive reactions than verbal praises from humans. The robot was of greatest benefit to children with a low level of disability. The educators were quite enthusiastic about children’s progress in learning basic psychosocial skills from interactions with the robot. The robot nonetheless failed to act as a social mediator, as more prosocial behaviors were observed in the control condition, where instead of interacting with the robot children played with a ball. We discuss how to program robots to the distinct needs of individuals with ASD, how to harness robots’ likability in order to enhance social skill learning, and how to arrive at a consensus about the standards of excellence that need to be met in interdisciplinary co-creation research. Our intuition is that robotic assistance, obviously judged as to be positive by educators, may contribute to the dissemination of innovative evidence-based practice for individuals with ASD.

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10. Lim YH, Licari M, Spittle AJ, Watkins RE, Zwicker JG, Downs J, Finlay-Jones A. Early Motor Function of Children With Autism Spectrum Disorder : A Systematic Review. Pediatrics. 2021 ; 147(2).

CONTEXT : Early motor impairments have been reported in children with neurodevelopmental disorders (NDD), but it is not clear if early detection of motor impairments can identify children at risk for NDD or how early such impairments might be detected. OBJECTIVE : To characterize early motor function in children later diagnosed with NDD relative to typically developing children or normative data. DATA SOURCES : The Cumulative Index to Nursing and Allied Health Literature, Embase, Medline, PsycINFO, and Scopus electronic databases were searched. STUDY SELECTION : Eligible studies were required to include an examination of motor function in children (0-24 months) with later diagnosis of NDD by using standardized assessment tools. DATA EXTRACTION : Data were extracted by 4 independent researchers. The quality of the studies was assessed by using the Standard Quality Assessment Criteria for Evaluating Primary Research Papers from a Variety of Fields checklist. RESULTS : Twenty-five studies were included in this review ; in most of the studies, the authors examined children with later autism spectrum disorder (ASD). Early motor impairments were detected in children later diagnosed with ASD. The meta-analysis results indicated that differences in fine, gross, and generalized motor functions between the later ASD and typically developing groups increased with age. Motor function across different NDD groups was found to be mixed. LIMITATIONS : Results may not be applicable to children with different types of NDD not reported in this review. CONCLUSIONS : Early motor impairments are evident in children later diagnosed with ASD. More research is needed to ascertain the clinical utility of motor impairment detection as an early transdiagnostic marker of NDD risk.

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11. Lu MH, Hsueh YP. Protein synthesis as a modifiable target for autism-related dendritic spine pathophysiologies. The FEBS journal. 2021.

Autism spectrum disorder (ASD) is increasingly recognized as a condition of altered brain connectivity. As synapses are fundamental subcellular structures for neuronal connectivity, synaptic pathophysiology has become one of central themes in autism research. Reports disagree upon whether the density of dendritic spines, namely excitatory synapses, is increased or decreased in ASD and if the protein synthesis that is critical for dendritic spine formation and function is upregulated or downregulated. Here, we review recent evidence supporting a subgroup of ASD models with decreased dendritic spine density (hereafter ASD-DSD), including Nf1 and Vcp mutant mice. We discuss the relevance of branched-chain amino acid (BCAA) insufficiency in relation to unmet protein synthesis demand in ASD-DSD. In contrast to ASD-DSD, ASD models with hyperactive mammalian target of rapamycin (mTOR) may represent the opposite end of the disease spectrum, often characterized by increases in protein synthesis and dendritic spine density (denoted ASD-ISD). Finally, we propose personalized dietary leucine as a strategy tailored to balancing protein synthesis demand, thereby ameliorating dendritic spine pathophysiologies and autism-related phenotypes in susceptible patients, especially those with ASD-DSD.

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12. Massaccesi C, Groessing A, Rosenberger LA, Hartmann H, Candini M, di Pellegrino G, Frassinetti F, Silani G. Neural Correlates of Interpersonal Space Permeability and Flexibility in Autism Spectrum Disorder. Cereb Cortex. 2021.

Previous research indicates that the size of interpersonal space at which the other is perceived as intrusive (permeability) and the ability to adapt interpersonal distance based on contextual factors (flexibility) are altered in Autism Spectrum Disorder (ASD). However, the neurophysiological basis of these alterations remains poorly understood. To fill this gap, we used fMRI and assessed interpersonal space preferences of individuals with ASD before and after engaging in cooperative and non-cooperative social interactions. Compared to matched controls, ASDs showed lower comfort in response to an approaching confederate, indicating preference for larger interpersonal space in autism (altered permeability). This preference was accompanied by reduced activity in bilateral dorsal intraparietal sulcus (dIPS) and left fusiform face area (FFA), regions previously shown to be involved in interpersonal space regulation. Furthermore, we observed differences in effective connectivity among dIPS, FFA, and amygdala in ASDs compared to controls, depending on the level of experienced comfort. No differences between groups were observed in interpersonal space regulation after an experienced social interaction (flexibility). Taken together, the present findings suggest that a dysregulation of the activity and connectivity of brain areas involved in interpersonal space processing may contribute to avoidance of physical proximity and social impairments in ASD.

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13. Mepham JR, MacFabe DF, Boon FH, Foley KA, Cain DP, Ossenkopp KP. Examining the non-spatial pretraining effect on a water maze spatial learning task in rats treated with multiple intracerebroventricular (ICV) infusions of propionic acid : Contributions to a rodent model of ASD. Behav Brain Res. 2021 ; 403 : 113140.

Propionic acid (PPA) is produced by enteric gut bacteria and is a dietary short chain fatty acid. Intracerebroventricular (ICV) infusions of PPA in rodents have been shown to produce behavioural changes, including adverse effects on cognition, similar to those seen in autism spectrum disorders (ASD). Previous research has shown that repeated ICV infusions of PPA result in impaired spatial learning in a Morris water maze (MWM) as evidenced by increased search latencies, fewer direct and circle swims, and more time spent in the periphery of the maze than control rats. In the current study rats were first given non-spatial pretraining (NSP) in the water maze in order to familiarize the animals with the general requirements of the non-spatial aspects of the task before spatial training was begun. Then the effects of ICV infusions of PPA on acquisition of spatial learning were examined. PPA treated rats failed to show the positive effects of the non-spatial pretraining procedure, relative to controls, as evidenced by increased search latencies, longer distances travelled, fewer direct and circle swims, and more time spent in the periphery of the maze than PBS controls. Thus, PPA treatment blocked the effects of the pretraining procedure, likely by impairing sensorimotor components or memory of the pretraining.

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14. Quezada NT, Salas-Ortíz SF, Peralta FA, Aguayo FI, Morgado-Gallardo KP, Mac-Rae CA, Fiedler JL, Aliaga EE. Loss of Social/Non-social Context Discrimination by Movement Acceleration in the Valproate Model of Autism. Frontiers in behavioral neuroscience. 2020 ; 14 : 555610.

Autism spectrum disorder (ASD) is a neurodevelopmental alteration characterized by social/communicative deficits, repetitive/stereotyped movements, and restricted/obsessive interests. However, there is not much information about whether movement alterations in ASD comprise modifications at the basic kinematic level, such as trajectory and velocity, which may contribute to the higher level of processing that allows the perception and interpretation of actions performed by others, and hence, impact social interaction. In order to further explore possible motor alterations in ASD, we analyzed movement parameters in the Valproate (VPA) animal model of autism. We found that VPA-treated rats displayed greater movement acceleration, reduced distance between stops, spent more time in the corner of the open-field arena, and executed a number of particular behaviors ; for example, supported rearing and circling, with no major changes in distance and velocity. However, in the social interaction test, we found other alterations in the movement parameters. In addition to increased acceleration, VPA-rats displayed reduced velocity, increased stops, reduced distance/stop and lost the social/non-social area discrimination that is characteristic of control rats in acceleration and stops variables. Hence, even if prenatal VPA-treatment could have a minor effect in motor variables in a non-social context, it has a crucial effect in the capacity of the animals to adjust their kinematic variables when social/non-social context alternation is required.

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15. Sabit H, Tombuloglu H, Rehman S, Almandil NB, Cevik E, Abdel-Ghany S, Rashwan S, Abasiyanik MF, Yee Waye MM. Gut microbiota metabolites in autistic children : An epigenetic perspective. Heliyon. 2021 ; 7(1) : e06105.

Gut microbiota has become an issue of great importance recently due to its major role in autism spectrum disorder (ASD). Over the past three decades, there has been a sustained research activity focused to explain the actual mechanism by which gut microbiota triggers/develops autism. Several genetic and epigenetic factors are involved in this disorder, with epigenetics being the most active area of research. Although the constant investigation and advancements, epigenetic implications in ASD still need a deeper functional/causal analysis. In this review, we describe the major gut microbiota metabolites and how they induce epigenetic changes in ASD along with interactions through the gut-brain axis.

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16. Shawler LA, Clayborne JC, Nasca B, O’Connor JT. An intensive telehealth assessment and treatment model for an adult with developmental disabilities. Res Dev Disabil. 2021 ; 111 : 103876.

Over the last decade, the provision of applied behavior analysis (ABA) services within a telehealth delivery format has had a flourishing literature base. Research has demonstrated that caregivers can successfully conduct functional analyses and functional communication training to treat challenging behavior with coaching from practitioners via telehealth. Previous limitations include research that has only been conducted with children, typically in 1hr, weekly meetings, so the utility of providing ABA therapy via telehealth across the lifespan is unknown. Additionally, the effects of a more intensive treatment format delivered via telehealth has not been evaluated. The purpose of the current study was to coach caregivers to conduct the assessment and treatment process for a young man with developmental disabilities using an intensive-outpatient model in a telehealth format. Functional analysis procedures led to the development of a function-based treatment to reduce challenging behavior and increase functional communication. Caregivers demonstrated high procedural integrity across all phases of the study and found the intervention highly acceptable and effective. Areas for future research and directions are discussed.

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17. Sun JW, Fan R, Wang Q, Wang QQ, Jia XZ, Ma HB. Identify abnormal functional connectivity of resting state networks in Autism spectrum disorder and apply to machine learning-based classification. Brain Res. 2021 : 147299.

Autism spectrum disorder (ASD) patients are often reported altered patterns of functional connectivity (FC) on resting-state functional magnetic resonance imaging (rsfMRI) scans. However, the results in similar brain regions were inconsistent. In this study, we first investigated statistical differences in large-scale resting-state networks (RSNs) on 192 healthy controls (HCs) and 103 ASD patients by using independent component analysis (ICA). Second, an image-based meta-analysis (IBMA) was applied to discover the consistency of spatial patterns from different sites. Last, utilizing these patterns as features, we used Support Vector Machine (SVM) classifier to identify whether a subject was suffering from ASD or not. As a result, six RSNs were obtained with ICA. In each RSN, we identified altered functional connectivity between ASD and HC across the multi-site data. We calculated the area under the receiver operating characteristic curve plots (AUC) to determine the classification performance. The AUC value of classification reaches 0.988. In conclusion, the present study indicates that intrinsic connectivity patterns produced from rsfMRI data could yield a possible biomarker of ASD and contributed to the neurobiology of ASD.

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18. White EN, Ayres KM, Snyder SK, Cagliani RR, Ledford JR. Augmentative and Alternative Communication and Speech Production for Individuals with ASD : A Systematic Review. J Autism Dev Disord. 2021.

This review evaluated the effects of augmentative and alternative communication (AAC) on speech development in children with autism spectrum disorders (ASD) ; replicated, updated, and extended the systematic review by Schlosser and Wendt (American Journal of Speech-Language Pathology 17:212-230, 2008). Twenty-five single case design articles and three group design articles published between 1975 and May 2020 met inclusion criteria related to participant characteristics, intervention type, design, and visual analysis of dependent variable outcomes. Overall, AAC resulted in improved speech production ; however, speech gains that did occur did not surpass AAC use.

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19. Yang JQ, Yang CH, Yin BQ. Combined the GABA-A and GABA-B receptor agonists attenuates autistic behaviors in a prenatal valproic acid-induced mouse model of autism. Behav Brain Res. 2021 ; 403 : 113094.

Autism spectrum disorder (ASD) is an immensely challenging developmental disorder characterized primarily by two core behavioral symptoms of social communication deficits and restricted/repetitive behaviors. Investigating the etiological process and identifying an appropriate therapeutic target remain as formidable challenges to overcome ASD due to numerous risk factors and complex symptoms associated with the disorder. Among the various mechanisms that contribute to ASD, the maintenance of excitation and inhibition balance emerged as a key factor to regulate proper functioning of neuronal circuitry. In this study, we employed prenatally exposed to valproic acid (VPA) to establish a validated ASD mouse model and found impaired inhibitory gamma-aminobutyric acid (GABAergic) neurotransmission through a presynaptic mechanism in these model mice, which was accompanied with decreased GABA release and GABA-A and GABA-B receptor subunits expression. And acute administration of individual GABA-A or GABA-B receptor agonists partially reversed autistic-like behaviors in the model mice. Furthermore, acute administration of the combined GABA-A and GABA-B receptor agonists palliated sociability deficits, anxiety and repetitive behaviors in the animal model of autistic-like behaviors, demonstrating the therapeutic potential of above cocktail in the treatment of ASD.

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20. Yang T, Liu J, Zhang Y, Zhang Q, Shangguan L, Li Z, Luo X, Gong J. Coping style predicts sense of security and mediates the relationship between autistic traits and social anxiety : Moderation by a polymorphism of the FKBP5 gene. Behav Brain Res. 2021 ; 404 : 113142.

The mechanism underlying the relationship between autistic traits and social anxiety still remains unknown. It is therefore necessary to investigate potential psychological and biological mechanisms. A total of 2695 college students were samples for this research during 2017-2018. The assessed variables included demographic characteristics and measures of autistic traits, sense of security, coping styles, and social anxiety. Blood samples were collected from which DNA was extracted. Regression analysis indicated that autistic traits and negative coping were positively associated with social anxiety ; furthermore, positive coping, interpersonal security, and sense of control were negatively associated with social anxiety. Further analyses demonstrated that the relationship between autistic traits and social anxiety was mediated by coping styles (both positive coping and negative coping) and sense of security (both interpersonal security and sense of control), and coping style predicted the sense of security. The FK506 binding protein 5 (FKBP5) gene rs3800373 moderated the association between autistic traits and social anxiety. The present study is the first to demonstrate that both coping style and sense of security play an intermediate role between autistic traits and social anxiety in a sample of Chinese college students ; moreover, the FKBP5 gene moderates this association between autistic traits and social anxiety.

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21. Zheng S, Kim H, Salzman E, Ankenman K, Bent S. Improving Social Knowledge and Skills among Adolescents with Autism : Systematic Review and Meta-Analysis of UCLA PEERS® for Adolescents. J Autism Dev Disord. 2021.

UCLA PEERS® for Adolescents is a widely applied program among a number of social skills training programs developed over the years. We synthesized current research evidence on the PEERS program to evaluate the treatment effect on four commonly used outcome measures. 12 studies met inclusion criteria for the review and nine met the criteria for meta-analysis. Results showed moderate to large pooled effects across measures and informants in favor of the PEERS program, with the largest effect seen in social knowledge improvement and the smallest effect in the frequency of get-togethers. The heterogeneity of effects across studies were examined and the limitations of the current evidence were discussed.

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