1. Baranek GT, Woynaroski TG, Nowell S, Turner-Brown L, DuBay M, Crais ER, Watson LR. {{Cascading effects of attention disengagement and sensory seeking on social symptoms in a community sample of infants at-risk for a future diagnosis of autism spectrum disorder}}. {Dev Cogn Neurosci};2017 (Aug 14)
Recent work suggests sensory seeking predicts later social symptomatology through reduced social orienting in infants who are at high-risk for autism spectrum disorder (ASD) based on their status as younger siblings of children diagnosed with ASD. We drew on extant longitudinal data from a community sample of at-risk infants who were identified at 12 months using the First Year Inventory, and followed to 3-5 years. We replicate findings of Damiano et al. (in this issue) that a) high-risk infants who go on to be diagnosed with ASD show heightened sensory seeking in the second year of life relative to those who do not receive a diagnosis, and b) increased sensory seeking indirectly relates to later social symptomatology via reduced social orienting. We extend previous findings to show that sensory seeking has more clinical utility later in the second year of life (20-24 months) than earlier (13-15 months). Further, this study suggests that diminished attention disengagement at 12-15 months may precede and predict increased sensory seeking at 20-24 months. Findings add support for the notion that sensory features produce cascading effects on social development in infants at risk for ASD, and suggest that reduced attention disengagement early in life may set off this cascade.
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2. Barendse EM, Schreuder LJ, Thoonen G, Hendriks MPH, Kessels RPC, Backes WH, Aldenkamp AP, Jansen JFA. {{Working memory network alterations in high-functioning adolescents with an autism spectrum disorder}}. {Psychiatry Clin Neurosci};2017 (Sep 04)
AIM: People with autism spectrum disorder (ASD) typically have deficits in the working memory (WM) system. Working memory is found to be an essential chain in successfully navigating in the social world. We hypothesize that brain networks for WM have an altered network integrity in ASD compared to controls. METHODS: 13 adolescents (1 female) with autistic disorder (n = 1), Asperger’s disorder (n = 7), and pervasive developmental disorder not otherwise specified (n = 5), and 13 typically developing control adolescents (1 female) participated in this study. Functional MRI was performed using an n-back task and in resting state. RESULTS: The analysis of the behavioral data revealed deficits in working memory performance in ASD, but only when tested to the limit. Adolescents with ASD showed lower binary global efficiency in the working memory network than the control group with n-back and resting state data. This correlated with diagnostic scores for total problems, reciprocity, and language. CONCLUSION: Adolescent with higher functioning autism have difficulty with the working memory system, which is typically compensated. Functional MRI markers of brain network organization in ASD are related to characteristics of autism as represented in diagnostic scores. Therefore, functional MRI provides neuronal correlates for memory difficulties in adolescents with ASD.
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3. Cheng M, Kato M, Tseng CH. {{Gender and autistic traits modulate implicit motor synchrony}}. {PLoS One};2017;12(9):e0184083.
Interpersonal motor synchrony during walking or dancing is universally observed across cultures, and this joint movement was modulated by physical and social parameters. However, human interactions are greatly shaped by our unique traits, and self-related factors are surprisingly little studied in the context of interpersonal motor synchrony. In this study, we investigated two such factors known to be highly associated with motor coordination: gender and autistic traits. We employed a real-world task extending our understanding beyond laboratory tasks. Participants of the same gender were paired up to walk and chat in a natural environment. A cover story was introduced so that participants would not know their walking steps were being recorded and instead believed that their location was being tracked by a global positioning system (GPS), so they would ignore the motor recording. We found that the female pairs’ steps were more synchronized than those of the males, and higher autistic tendencies (measured by the autism-spectrum quotient) attenuated synchronous steps. Those who synchronized better had higher impression rating increase for their walking partners (measured by interpersonal judgement scale) than those who synchronized less well. Our results indicated that the participants’ joint movements were shaped by predisposed traits and might share similar mechanism with social functions such as empathy.
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4. Crespi BJ. {{Shared sociogenetic basis of honey bee behavior and human risk for autism}}. {Proc Natl Acad Sci U S A};2017 (Sep 05);114(36):9502-9504.
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5. Grosberg D, Charlop MH. {{Teaching conversational speech to children with autism spectrum disorder using text-message prompting}}. {J Appl Behav Anal};2017 (Sep 04)
The present study was designed to teach conversational speech using text-message prompts to children with autism spectrum disorder (ASD) in home play settings with siblings and peers. A multiple baseline design across children was used. Children learned conversational speech through the text-message prompts, and the behavior generalized across peers and settings. Maintenance of treatment gains was seen at 1-month follow-up probes. Social validity measures indicated that parents of typically developing children viewed the participants’ conversational speech as much improved after the intervention. Results are discussed in terms of the efficacy of text-message prompts as a promising way to improve conversational speech for children with ASD.
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6. Krupp DR, Barnard RA, Duffourd Y, Evans SA, Mulqueen RM, Bernier R, Riviere JB, Fombonne E, O’Roak BJ. {{Exonic Mosaic Mutations Contribute Risk for Autism Spectrum Disorder}}. {Am J Hum Genet};2017 (Sep 07);101(3):369-390.
Genetic risk factors for autism spectrum disorder (ASD) have yet to be fully elucidated. Postzygotic mosaic mutations (PMMs) have been implicated in several neurodevelopmental disorders and overgrowth syndromes. By leveraging whole-exome sequencing data on a large family-based ASD cohort, the Simons Simplex Collection, we systematically evaluated the potential role of PMMs in autism risk. Initial re-evaluation of published single-nucleotide variant (SNV) de novo mutations showed evidence consistent with putative PMMs for 11% of mutations. We developed a robust and sensitive SNV PMM calling approach integrating complementary callers, logistic regression modeling, and additional heuristics. In our high-confidence call set, we identified 470 PMMs in children, increasing the proportion of mosaic SNVs to 22%. Probands have a significant burden of synonymous PMMs and these mutations are enriched for computationally predicted impacts on splicing. Evidence of increased missense PMM burden was not seen in the full cohort. However, missense burden signal increased in subcohorts of families where probands lacked nonsynonymous germline mutations, especially in genes intolerant to mutations. Parental mosaic mutations that were transmitted account for 6.8% of the presumed de novo mutations in the children. PMMs were identified in previously implicated high-confidence neurodevelopmental disorder risk genes, such as CHD2, CTNNB1, SCN2A, and SYNGAP1, as well as candidate risk genes with predicted functions in chromatin remodeling or neurodevelopment, including ACTL6B, BAZ2B, COL5A3, SSRP1, and UNC79. We estimate that PMMs potentially contribute risk to 3%-4% of simplex ASD case subjects and future studies of PMMs in ASD and related disorders are warranted.
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7. Lee Y, Park BY, James O, Kim SG, Park H. {{Autism Spectrum Disorder Related Functional Connectivity Changes in the Language Network in Children, Adolescents and Adults}}. {Front Hum Neurosci};2017;11:418.
Autism spectrum disorder (ASD) is a neurodevelopmental disability with global implication. Altered brain connectivity in the language network has frequently been reported in ASD patients using task-based functional magnetic resonance imaging (fMRI) compared to typically developing (TD) participants. Most of these studies have focused on a specific age group or mixed age groups with ASD. In the current study, we investigated age-related changes in functional connectivity related measure, degree centrality (DC), in the language network across three age groups with ASD (113 children, 113 adolescents and 103 adults) using resting-state fMRI data collected from the autism brain imaging data exchange repository. We identified regions with significant group-wise differences between ASD and TD groups for three age cohorts using DC based on graph theory. We found that both children and adolescents with ASD showed decreased DC in Broca’s area compared to age-matched TD groups. Adults with ASD showed decreased DC in Wernicke’s area compared to TD adults. We also observed increased DC in the left inferior parietal lobule (IPL) and left middle temporal gyrus (MTG) for children with ASD compared to TD children and for adults with ASD compared to TD adults, respectively. Overall, functional differences occurred in key language processing regions such as the left inferior frontal gyrus (IFG) and superior temporal gyrus (STG) related to language production and comprehension across three age cohorts. We explored correlations between DC values of our findings with autism diagnostic observation schedule (ADOS) scores related to severity of ASD symptoms in the ASD group. We found that DC values of the left IFG demonstrated negative correlations with ADOS scores in children and adolescents with ASD. The left STG showed significant negative correlations with ADOS scores in adults with ASD. These results might shed light on the language network regions that should be further explored for prognosis, diagnosis, and monitoring of ASD in three age groups.
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8. Maximo JO, Murdaugh DL, O’Kelley S, Kana RK. {{Changes in intrinsic local connectivity after reading intervention in children with autism}}. {Brain Lang};2017 (Sep 01);175:11-17.
Most of the existing behavioral and cognitive intervention programs in autism spectrum disorders (ASD) have not been tested at the neurobiological level, thus falling short of finding quantifiable neurobiological changes underlying behavioral improvement. The current study takes a translational neuroimaging approach to test the impact of a structured visual imagery-based reading intervention on improving reading comprehension and assessing its underlying local neural circuitry. Behavioral and resting state functional MRI (rs-fMRI) data were collected from children with ASD who were randomly assigned to an Experimental group (ASD-EXP; n=14) and a Wait-list control group (ASD-WLC; n=14). Participants went through an established reading intervention training program (Visualizing and Verbalizing for language comprehension and thinking or V/V; 4-h per day, 10-weeks, 200h of face-to-face instruction). Local functional connectivity was examined using a connection density approach from graph theory focusing on brain areas considered part of the Reading Network. The main results are as follows: (I) the ASD-EXP group showed significant improvement, compared to the ASD-WLC group, in their reading comprehension ability evidenced from change in comprehension scores; (II) the ASD-EXP group showed increased local brain connectivity in Reading Network regions compared to the ASD-WLC group post-intervention; (III) intervention-related changes in local brain connectivity were observed in the ASD-EXP from pre to post-intervention; and (IV) improvement in language comprehension significantly predicted changes in local connectivity. The findings of this study provide novel insights into brain plasticity in children with developmental disorders using targeted intervention programs.
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9. Mirfakhraie R. {{The association between FOXP3 gene variations and autism: True or false positive?}}. {Gene};2017 (Sep 05)
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10. Morrier MJ, Ousley OY, Caceres-Gamundi GA, Segall MJ, Cubells JF, Young LJ, Andari E. {{Brief Report: Relationship Between ADOS-2, Module 4 Calibrated Severity Scores (CSS) and Social and Non-Social Standardized Assessment Measures in Adult Males with Autism Spectrum Disorder (ASD)}}. {J Autism Dev Disord};2017 (Sep 05)
The ADOS-2 Modules 1-3 now include a standardized calibrated severity score (CSS) from 1 to 10 based on the overall total raw score. Subsequent research published CSS for Module 4 (Hus, Lord, Journal of Autism and Developmental Disorders 44(8):1996-2012, 2014); however more research is needed to examine the psychometric properties of this CSS. Forty males with ASD completed an assessment battery consisting of ADOS-2 Module 4 and other clinical measures assessing core ASD symptomology and comorbidity. Pearson correlation analyses found that CSS did not correlate with measures that assessed core social deficits of ASD or general psychiatric co-morbidity, but CSS did correlate negatively with intellectual quotient. These findings provide information on the limitations and relevance of CSS to be taken into account in future clinical evaluations of ASD.
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11. Mous SE, Jiang A, Agrawal A, Constantino JN. {{Attention and motor deficits index non-specific background liabilities that predict autism recurrence in siblings}}. {J Neurodev Disord};2017 (Sep 05);9(1):32.
BACKGROUND: Recent research has demonstrated that subclinical autistic traits of parents amplify the effects of deleterious mutations in the causation of autism spectrum disorder (ASD) in their offspring. Here, we examined the extent to which two neurodevelopmental traits that are non-specific to ASD-inattention/hyperactivity and motor coordination-might contribute to ASD recurrence in siblings of ASD probands. METHODS: Data from a quantitative trait study of 114 ASD probands and their brothers, 26% of whom also had ASD, were analyzed. Autistic trait severity was ascertained using the Social Responsiveness Scale-2, attention/hyperactivity problems using the Achenbach System of Empirically Based Assessment, and motor coordination (in a subset of participants) using the Developmental Coordination Disorder Questionnaire. RESULTS: Among siblings (affected and unaffected), both categorical recurrence of ASD (Nagelkerke R 2 = 0.53) and quantitative ASD trait burden (R 2 = 0.55) were predicted by sibling ADHD and motor coordination impairment scores, even though these traits, on average, were not elevated among the unaffected siblings. CONCLUSIONS: These findings in a clinical family cohort confirm observations from general population studies that inattention/hyperactivity and motor impairment-axes of behavioral development that are non-specific to ASD, and often appreciable before ASD is typically diagnosed-jointly account for over 50% of the variation in autistic impairment of siblings, whether ascertained quantitatively or categorically. This finding within a sibling design suggests that background ASD susceptibilities that are inherited but non-specific (« BASINS ») may contribute to additive genetic liability in the same manner that ASD-specific susceptibilities (such as parental subclinical ASD traits and deleterious mutations) engender ASD risk.
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12. Sadleir LG, Mountier EI, Gill D, Davis S, Joshi C, DeVile C, Kurian MA, Mandelstam S, Wirrell E, Nickels KC, Murali HR, Carvill G, Myers CT, Mefford HC, Scheffer IE. {{Not all SCN1A epileptic encephalopathies are Dravet syndrome: Early profound Thr226Met phenotype}}. {Neurology};2017 (Sep 05);89(10):1035-1042.
OBJECTIVE: To define a distinct SCN1A developmental and epileptic encephalopathy with early onset, profound impairment, and movement disorder. METHODS: A case series of 9 children were identified with a profound developmental and epileptic encephalopathy and SCN1A mutation. RESULTS: We identified 9 children 3 to 12 years of age; 7 were male. Seizure onset was at 6 to 12 weeks with hemiclonic seizures, bilateral tonic-clonic seizures, or spasms. All children had profound developmental impairment and were nonverbal and nonambulatory, and 7 of 9 required a gastrostomy. A hyperkinetic movement disorder occurred in all and was characterized by dystonia and choreoathetosis with prominent oral dyskinesia and onset from 2 to 20 months of age. Eight had a recurrent missense SCN1A mutation, p.Thr226Met. The remaining child had the missense mutation p.Pro1345Ser. The mutation arose de novo in 8 of 9; for the remaining case, the mother was negative and the father was unavailable. CONCLUSIONS: Here, we present a phenotype-genotype correlation for SCN1A. We describe a distinct SCN1A phenotype, early infantile SCN1A encephalopathy, which is readily distinguishable from the well-recognized entities of Dravet syndrome and genetic epilepsy with febrile seizures plus. This disorder has an earlier age at onset, profound developmental impairment, and a distinctive hyperkinetic movement disorder, setting it apart from Dravet syndrome. Remarkably, 8 of 9 children had the recurrent missense mutation p.Thr226Met.
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13. Shibutani M, Horii T, Shoji H, Morita S, Kimura M, Terawaki N, Miyakawa T, Hatada I. {{Arid1b Haploinsufficiency Causes Abnormal Brain Gene Expression and Autism-Related Behaviors in Mice}}. {Int J Mol Sci};2017 (Aug 30);18(9)
Autism spectrum disorder (ASD) is a neurodevelopmental disorder with core symptoms that include poor social communication, restricted interests, and repetitive behaviors. Several ASD mouse models exhibit impaired social interaction, anxiety-like behavior, and elevated perseveration. Large-scale whole exome sequencing studies identified many genes putatively associated with ASD. Like chromodomain helicase DNA binding protein 8 (CHD8), the most frequently mutated gene in individuals with ASD, the candidate gene AT-rich interaction domain 1B (ARID1B) encodes a chromatin remodeling factor. Arid1b heterozygous knockout (hKO) mice exhibited ASD-like traits related to social behavior, anxiety, and perseveration, in addition to associated features reported in some cases of ASD, such as reduced weight, impaired motor coordination, and hydrocephalus. Hydrocephalus was present in 5 of 91 hKO mice, while it was not observed in wild-type littermates (0 of 188). Genome-wide gene expression patterns in Arid1b hKO mice were similar to those in ASD patients and Chd8-haploinsufficient mice, an ASD model, and to developmental changes in gene expression in fast-spiking cells in the mouse brain. Our results suggest that Arid1b haploinsufficiency causes ASD-like phenotypes in mice.
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14. Shpigler HY, Saul MC, Corona F, Block L, Cash Ahmed A, Zhao SD, Robinson GE. {{Deep evolutionary conservation of autism-related genes}}. {Proc Natl Acad Sci U S A};2017 (Sep 05);114(36):9653-9658.
E. O. Wilson proposed in Sociobiology that similarities between human and animal societies reflect common mechanistic and evolutionary roots. When introduced in 1975, this controversial hypothesis was beyond science’s ability to test. We used genomic analyses to determine whether superficial behavioral similarities in humans and the highly social honey bee reflect common molecular mechanisms. Here, we report that gene expression signatures for individual bees unresponsive to various salient social stimuli are significantly enriched for autism spectrum disorder-related genes. These signatures occur in the mushroom bodies, a high-level integration center of the insect brain. Furthermore, our finding of enrichment was unique to autism spectrum disorders; brain gene expression signatures from other honey bee behaviors do not show this enrichment, nor do datasets from other human behavioral and health conditions. These results demonstrate deep conservation for genes associated with a human social pathology and individual differences in insect social behavior, thus providing an example of how comparative genomics can be used to test sociobiological theory.
