1. Ameis SH, Daskalakis ZJ, Blumberger DM, Desarkar P, Drmic I, Mabbott DJ, Lai MC, Croarkin PE, Szatmari P. {{Repetitive Transcranial Magnetic Stimulation for the Treatment of Executive Function Deficits in Autism Spectrum Disorder: Clinical Trial Approach}}. {J Child Adolesc Psychopharmacol};2017 (Mar 27)
OBJECTIVE: Executive function (EF) deficits in patients with autism spectrum disorder (ASD) are ubiquitous and understudied. Further, there are no effective, neuroscience-based treatments to address this impairing feature of ASD. Repetitive transcranial magnetic stimulation (rTMS) has demonstrated promise in addressing EF deficits in adult neuropsychiatric disorders. This article will outline the design of a novel randomized-controlled trial of bilateral, 20 Hz, rTMS applied to the dorsolateral prefrontal cortex (DLPFC) for treatment of EF deficits in ASD that is currently ongoing. We describe prior therapeutic rTMS research for ASD and prior rTMS trials targeting EFs in adult neuropsychiatric disorders. A neurophysiological rationale for rTMS treatment of EF deficits in ASD is presented. METHODS: An ongoing protocol will enroll participants aged 16-35 with ASD and no intellectual disability. Psychotropic medications will be continued during the 4-week trial of active 20 Hz versus sham rTMS applied to the DLPFC. Twenty, active treatment sessions consisting of 25 stimulation trains at a 90% motor threshold will be administered. The primary outcome measure is the Cambridge Neuropsychological Test Automated Battery (CANTAB) spatial working memory task. At present, recruitment, enrollment, and treatment within the described clinical trial are ongoing. CONCLUSIONS: EF deficits are common and impairing symptoms of ASD. There are no evidence-based treatments for EF deficits in ASD. The protocol described here will provide important preliminary data on the feasibility and efficacy of 20 Hz rTMS to DLPFC for EF deficits in ASD.
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2. Blanken LM, Muetzel RL, Jaddoe VW, Verhulst FC, van der Lugt A, Tiemeier H, White T. {{White matter microstructure in children with autistic traits}}. {Psychiatry Res};2017 (Mar 28);263:127-134.
Autism spectrum disorder (ASD) is thought to arise from aberrant development of connections in the brain. Previous studies have identified differences in white matter microstructure in children with ASD, offering support to such hypotheses. While ASD is thought to represent the severe end of a spectrum of traits, there are no studies evaluating white matter microstructure in relation to autistic traits in children from the general population. In a population-based sample of 604 6-to-10 year-old children, we assessed the relation between a continuous measure of autistic traits and white matter microstructure, using both probabilistic tractography and Tract-Based Spatial Statistics (TBSS). Using the TBSS approach, a cluster in the left superior longitudinal fasciculus (SLF) was identified where autistic traits negatively associated with fractional anisotropy (FA). In addition, two clusters of lower axial diffusion were identified; one in the corpus callosum and another in the corticospinal tract. Part of the findings remained when excluding children with ASD and were paralleled with similar, trend-level differences in 19 children with ASD, compared to matched controls. This study showed localized associations between autistic traits on a continuum and white matter microstructure, which could indicate a continuum of the neurobiology along the spectrum of autistic symptoms.
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3. Cai Y, Wang L, Xiao R, Li X, He X, Gao J, Xu H, Fan X. {{Autism-like behavior in the BTBR mouse model of autism is improved by propofol}}. {Neuropharmacology};2017 (Mar 21);118:175-187.
Autism spectrum disorder (ASD) is a developmental disorder that is characterized by symptoms of impaired social interactions, restricted interests and repetitive behaviors. Recent studies in humans and animal-models suggest that reduced GABAergic neurotransmission in the brain may underlie autism-related behavioral symptoms. It has been shown that propofol, a commonly used anesthetic, facilitates gamma-aminobutyric acid-mediated inhibitory synaptic transmission. The present study investigated whether propofol improved autistic phenotypes in BTBR T + Itpr3tf/J (BTBR) mice, a model of idiopathic autism. We found that i.p. injection of propofol in BTBR mice significantly improved aspects of social approach and repetitive behaviors without affecting reciprocal social interactions and without any detrimental effects in C57BL/6J mice. The ability of propofol to improve autistic phenotypes in BTBR mice through GABAergic neurotransmission suggests a potential pharmacological target for interventions to treat symptoms of autism.
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4. Calarge CA, Schlechte JA. {{Bone Mass in Boys with Autism Spectrum Disorder}}. {J Autism Dev Disord};2017 (Mar 25)
To examine bone mass in children and adolescents with autism spectrum disorders (ASD). Risperidone-treated 5 to 17 year-old males underwent anthropometric and bone measurements, using dual-energy X-ray absorptiometry and peripheral quantitative computed tomography. Multivariable linear regression analysis models examined whether skeletal outcomes differed among participants with (n = 30) versus without ASD (n = 156). After adjusting for potential covariates, having ASD was associated with significantly lower trabecular bone mineral density and bone strength at the radius, and with marginally lower total body less head bone mineral content (p < 0.09). No differences at the lumbar spine were observed. ASD are associated with lower bone mass. Future studies should investigate interventions to optimize skeletal health in ASD. Lien vers le texte intégral (Open Access ou abonnement)
5. Chakrabarti B. {{Commentary: Critical considerations for studying low-functioning autism}}. {J Child Psychol Psychiatry};2017 (Apr);58(4):436-438.
Jack and Pelphrey provide a systematic review of neuroimaging studies in understudied populations within the autistic spectrum, focussing specifically on those with minimal verbal ability, intellectual disability and developmental regression. Despite accounting for nearly a third of the autistic spectrum, the number of studies focussing on these populations is extremely low. This review highlights a critical need for further neuroimaging research on these populations, and provides practical suggestions for overcoming the challenges posed by it. In this commentary, I discuss some of the theoretical questions that arise from the review, on the conceptualisation of the autistic spectrum as well as on optimising experimental design and analysis.
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6. Chen R, Davis LK, Guter S, Wei Q, Jacob S, Potter MH, Cox NJ, Cook EH, Sutcliffe JS, Li B. {{Leveraging blood serotonin as an endophenotype to identify de novo and rare variants involved in autism}}. {Mol Autism};2017;8:14.
BACKGROUND: Autism spectrum disorder (ASD) is one of the most highly heritable neuropsychiatric disorders, but underlying molecular mechanisms are still unresolved due to extreme locus heterogeneity. Leveraging meaningful endophenotypes or biomarkers may be an effective strategy to reduce heterogeneity to identify novel ASD genes. Numerous lines of evidence suggest a link between hyperserotonemia, i.e., elevated serotonin (5-hydroxytryptamine or 5-HT) in whole blood, and ASD. However, the genetic determinants of blood 5-HT level and their relationship to ASD are largely unknown. METHODS: In this study, pursuing the hypothesis that de novo variants (DNVs) and rare risk alleles acting in a recessive mode may play an important role in predisposition of hyperserotonemia in people with ASD, we carried out whole exome sequencing (WES) in 116 ASD parent-proband trios with most (107) probands having 5-HT measurements. RESULTS: Combined with published ASD DNVs, we identified USP15 as having recurrent de novo loss of function mutations and discovered evidence supporting two other known genes with recurrent DNVs (FOXP1 and KDM5B). Genes harboring functional DNVs significantly overlap with functional/disease gene sets known to be involved in ASD etiology, including FMRP targets and synaptic formation and transcriptional regulation genes. We grouped the probands into High-5HT and Normal-5HT groups based on normalized serotonin levels, and used network-based gene set enrichment analysis (NGSEA) to identify novel hyperserotonemia-related ASD genes based on LoF and missense DNVs. We found enrichment in the High-5HT group for a gene network module (DAWN-1) previously implicated in ASD, and this points to the TGF-beta pathway and cell junction processes. Through analysis of rare recessively acting variants (RAVs), we also found that rare compound heterozygotes (CHs) in the High-5HT group were enriched for loci in an ASD-associated gene set. Finally, we carried out rare variant group-wise transmission disequilibrium tests (gTDT) and observed significant association of rare variants in genes encoding a subset of the serotonin pathway with ASD. CONCLUSIONS: Our study identified USP15 as a novel gene implicated in ASD based on recurrent DNVs. It also demonstrates the potential value of 5-HT as an effective endophenotype for gene discovery in ASD, and the effectiveness of this strategy needs to be further explored in studies of larger sample sizes.
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7. Coretti L, Cristiano C, Florio E, Scala G, Lama A, Keller S, Cuomo M, Russo R, Pero R, Paciello O, Mattace Raso G, Meli R, Cocozza S, Calignano A, Chiariotti L, Lembo F. {{Sex-related alterations of gut microbiota composition in the BTBR mouse model of autism spectrum disorder}}. {Sci Rep};2017 (Mar 28);7:45356.
Alterations of microbiota-gut-brain axis have been invoked in the pathogenesis of autism spectrum disorders (ASD). Mouse models could represent an excellent tool to understand how gut dysbiosis and related alterations may contribute to autistic phenotype. In this study we paralleled gut microbiota (GM) profiles, behavioral characteristics, intestinal integrity and immunological features of colon tissues in BTBR T + tf/J (BTBR) inbred mice, a well established animal model of ASD. Sex differences, up to date poorly investigated in animal models, were specifically addressed. Results showed that BTBR mice of both sexes presented a marked intestinal dysbiosis, alterations of behavior, gut permeability and immunological state with respect to prosocial C57BL/6j (C57) strain. Noticeably, sex-related differences were clearly detected. We identified Bacteroides, Parabacteroides, Sutterella, Dehalobacterium and Oscillospira genera as key drivers of sex-specific gut microbiota profiles associated with selected pathological traits. Taken together, our findings indicate that alteration of GM in BTBR mice shows relevant sex-associated differences and supports the use of BTBR mouse model to dissect autism associated microbiota-gut-brain axis alteration.
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8. Dinstein I, Haar S, Atsmon S, Schtaerman H. {{No evidence of early head circumference enlargements in children later diagnosed with autism in Israel}}. {Mol Autism};2017;8:15.
BACKGROUND: Large controversy exists regarding the potential existence and clinical significance of larger brain volumes in toddlers who later develop autism. Assessing this relationship is important for determining the clinical utility of early head circumference (HC) measures and for assessing the validity of the early overgrowth hypothesis of autism, which suggests that early accelerated brain development may be a hallmark of the disorder. METHODS: We performed a retrospective comparison of HC, height, and weight measurements between 66 toddlers who were later diagnosed with autism and 66 matched controls. These toddlers represent an unbiased regional sample from a single health service provider in the southern district of Israel. On average, participating toddlers had >8 measurements between birth and the age of two, which enabled us to characterize individual HC, height, and weight development with high precision and fit a negative exponential growth model to the data of each toddler with exceptional accuracy. RESULTS: The analyses revealed that HC sizes and growth rates were not significantly larger in toddlers with autism even when stratifying the autism group based on verbal capabilities at the time of diagnosis. In addition, there were no significant correlations between ADOS scores at the time of diagnosis and HC at any time-point during the first 2 years of life. CONCLUSIONS: These negative results add to accumulating evidence, which suggest that brain volume is not necessarily larger in toddlers who develop autism. We believe that conflicting results reported in other studies are due to small sample sizes, use of misleading population norms, changes in the clinical definition of autism over time, and/or inclusion of individuals with syndromic autism. While abnormally large brains may be evident in some individuals with autism and more clearly visible in MRI scans, converging evidence from this and other studies suggests that enlarged HC is not a common etiology of the entire autism population. Early HC measures, therefore, offer very limited clinical utility for assessment of autism risk in the general population.
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9. Edmiston E, Ashwood P, Van de Water J. {{Autoimmunity, Autoantibodies, and Autism Spectrum Disorder}}. {Biol Psychiatry};2017 (Mar 01);81(5):383-390.
Auism spectrum disorder (ASD) now affects one in 68 births in the United States and is the fastest growing neurodevelopmental disability worldwide. Alarmingly, for the majority of cases, the causes of ASD are largely unknown, but it is becoming increasingly accepted that ASD is no longer defined simply as a behavioral disorder, but rather as a highly complex and heterogeneous biological disorder. Although research has focused on the identification of genetic abnormalities, emerging studies increasingly suggest that immune dysfunction is a viable risk factor contributing to the neurodevelopmental deficits observed in ASD. This review summarizes the investigations implicating autoimmunity and autoantibodies in ASD.
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10. Gerencser KR, Higbee TS, Akers JS, Contreras BP. {{Evaluation of interactive computerized training to teach parents to implement photographic activity schedules with children with autism spectrum disorder}}. {J Appl Behav Anal};2017 (Mar 28)
Training parents of children with autism spectrum disorder can be a challenge due to limited resources, time, and money. Interactive computerized training (ICT)-a self-paced program that incorporates instructions, videos, and interactive questions-is one method professionals can use to disseminate trainings to broader populations. This study extends previous research on ICT by assessing the effect of ICT to teach three parents how to implement a photographic activity schedule using a systematic prompting procedure with their child. Following ICT, all parents increased their fidelity to implementation of an activity schedule during role-play sessions with an adult. Fidelity remained high during implementation with their child and maintained during a 2-week follow-up.
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11. Guerin NA, Rodriguez KE, Brodhead MT, O’Haire ME. {{Assessing Preferences for Animals in Children with Autism: A New Use for Video-Based Preference Assessment}}. {Front Vet Sci};2017;4:29.
The inclusion of animals into interventions for children with autism spectrum disorder (ASD) is a growing practice known as animal-assisted intervention (AAI). The choice of the animal to include in an intervention is often solely up to the interventionist and depends on their experience, subjective judgment, and ease of access to different animals. For individuals with ASD who are non-verbal and unable to indicate preferred stimuli or activities, incorporating preference into interventions has been linked to increases in positive behaviors and enhanced quality of life. We propose that animal choice based on a participant’s preference may enhance the experience of AAI and maximize its outcomes. A common technique used to reliably determine preferred interactions and activities in interventions for children with ASD is a stimulus preference assessment. The video-based multiple-stimulus without replacement (MSWO) procedure, in particular, allows for discrimination of complex stimuli that could not feasibly be presented all at once, which is the case when choosing an animal. Based on the well-documented reliability of this technique in the field of applied behavior analysis, we propose that a future direction in AAI is utilizing video-based MSWO to guide animal selection.
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12. Iarocci G, Hutchison SM, O’Toole G. {{Second Language Exposure, Functional Communication, and Executive Function in Children With and Without Autism Spectrum Disorder (ASD)}}. {J Autism Dev Disord};2017 (Mar 24)
Parents and professionals are concerned that second language exposure may delay communication in children with ASD. In this study 174 youth (6-16 years) with and without ASD, exposed to a second language, were compared on executive function (EF) and functional communication (FC) with their peers without exposure. There were no significant differences between groups on age, IQ, and socioeconomic status. Parents reported on language exposure and rated EF and FC skills within everyday social contexts. The findings indicated that second language exposure in children with ASD is not associated with delay in cognitive and functional communication skills rather there was evidence of a reduced clinical impact as indexed by a lower percentage of children whose FC and EF ratings fell within the clinical range.
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13. Jouen AL, Narzisi A, Xavier J, Tilmont E, Bodeau N, Bono V, Ketem-Premel N, Anzalone S, Maharatna K, Chetouani M, Muratori F, Cohen D. {{GOLIAH (Gaming Open Library for Intervention in Autism at Home): a 6-month single blind matched controlled exploratory study}}. {Child Adolesc Psychiatry Ment Health};2017;11:17.
BACKGROUND: To meet the required hours of intensive intervention for treating children with autism spectrum disorder (ASD), we developed an automated serious gaming platform (11 games) to deliver intervention at home (GOLIAH) by mapping the imitation and joint attention (JA) subset of age-adapted stimuli from the Early Start Denver Model (ESDM) intervention. Here, we report the results of a 6-month matched controlled exploratory study. METHODS: From two specialized clinics, we included 14 children (age range 5-8 years) with ASD and 10 controls matched for gender, age, sites, and treatment as usual (TAU). Participants from the experimental group received in addition to TAU four 30-min sessions with GOLIAH per week at home and one at hospital for 6 months. Statistics were performed using Linear Mixed Models. RESULTS: Children and parents participated in 40% of the planned sessions. They were able to use the 11 games, and participants trained with GOLIAH improved time to perform the task in most JA games and imitation scores in most imitation games. GOLIAH intervention did not affect Parental Stress Index scores. At end-point, we found in both groups a significant improvement for Autism Diagnostic Observation Schedule scores, Vineland socialization score, Parental Stress Index total score, and Child Behavior Checklist internalizing, externalizing and total problems. However, we found no significant change for by time x group interaction. CONCLUSIONS: Despite the lack of superiority of TAU + GOLIAH versus TAU, the results are interesting both in terms of changes by using the gaming platform and lack of parental stress increase. A large randomized controlled trial with younger participants (who are the core target of ESDM model) is now discussed. This should be facilitated by computing GOLIAH for a web platform. Trial registration Clinicaltrials.gov NCT02560415.
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14. Jyotishi M, Fein D, Naigles L. {{Investigating the Grammatical and Pragmatic Origins of Wh-Questions in Children with Autism Spectrum Disorders}}. {Front Psychol};2017;8:319.
Compared to typically developing children, children with autism (ASD) show delayed production of wh-questions. It is currently controversial the degree to which such deficits derive from social-pragmatic requirements and/or because these are complex grammatical structures. The current study employed the intermodal preferential looking (IPL) paradigm, which reduces social-pragmatic demands. The IPL paradigm can help distinguish these proposals, as successful comprehension promotes the « pragmatics-origins » argument whereas comprehension difficulties would implicate a « grammatical-origins » argument. Additionally, we tested both the linguistic and social explanations by assessing the contributions of children’s early grammatical knowledge (i.e., SVO word order) and their social-pragmatic scores on the Vineland to their later wh-question comprehension. Fourteen children with ASD and 17 TD children, matched on language level, were visited in their homes at 4-month intervals. Comprehension of wh-questions and SVO word order were tested via IPL: the wh-question video showed a costumed horse and bird serving as agents or patients of familiar transitive actions. During the test trials, they were displayed side by side with directing audios (e.g., « What did the horse tickle? », « What hugged the bird? », « Where is the horse/bird? »). Children’s eye movements were coded offline; the DV was their percent looking to the named item during test. To show comprehension, children should look longer at the named item during a where-question than during a subject-wh or object-wh question. Results indicated that TD children comprehended both subject and object wh-questions at 32 months of age. Comprehension of object-wh questions emerged chronologically later in children with ASD compared to their TD peers, but at similar levels of language. Moreover, performance on word order and social-pragmatic scores independently predicted both groups’ later performance on wh-question comprehension. Our findings indicate that both grammar and social-pragmatics are implicated in the comprehension of wh-questions. The « grammatical-origins » argument is supported because the ASD group did not reveal earlier and stable comprehension of wh-questions; furthermore, their performance on SVO word order predicted their later success in linguistic processing of wh-questions. The « pragmatic-origins » argument is also supported because children’s earlier socialization and communication scores strongly predicted their successful performance on wh-question comprehension.
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15. Manning C, Morgan MJ, Allen CT, Pellicano E. {{Susceptibility to Ebbinghaus and Muller-Lyer illusions in autistic children: a comparison of three different methods}}. {Mol Autism};2017;8:16.
BACKGROUND: Studies reporting altered susceptibility to visual illusions in autistic individuals compared to that typically developing individuals have been taken to reflect differences in perception (e.g. reduced global processing), but could instead reflect differences in higher-level decision-making strategies. METHODS: We measured susceptibility to two contextual illusions (Ebbinghaus, Muller-Lyer) in autistic children aged 6-14 years and typically developing children matched in age and non-verbal ability using three methods. In experiment 1, we used a new two-alternative-forced-choice method with a roving pedestal designed to minimise cognitive biases. Here, children judged which of two comparison stimuli was most similar in size to a reference stimulus. In experiments 2 and 3, we used methods previously used with autistic populations. In experiment 2, children judged whether stimuli were the ‘same’ or ‘different’, and in experiment 3, we used a method-of-adjustment task. RESULTS: Across all tasks, autistic children were equally susceptible to the Ebbinghaus illusion as typically developing children. Autistic children showed a heightened susceptibility to the Muller-Lyer illusion, but only in the method-of-adjustment task. This result may reflect differences in decisional criteria. CONCLUSIONS: Our results are inconsistent with theories proposing reduced contextual integration in autism and suggest that previous reports of altered susceptibility to illusions may arise from differences in decision-making, rather than differences in perception per se. Our findings help to elucidate the underlying reasons for atypical responses to perceptual illusions in autism and call for the use of methods that reduce cognitive bias when measuring illusion susceptibility.
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16. May T, Pang KC, Williams K. {{Brief Report: Sexual Attraction and Relationships in Adolescents with Autism}}. {J Autism Dev Disord};2017 (Mar 24)
Past research suggests more variation in sexual attraction in Autism Spectrum Disorder (ASD) using clinical samples. This study utilised a population representative group of 14/15 year olds from the Longitudinal Study of Australian Children. Ninety-four adolescents (73 males, 21 females) with ASD and 3454 (1685 males, 1675 females) without self-reported on sexual attraction and past sexual relationships. Females with ASD reported lower rates of heterosexual preference (adjusted odds ratio: 0.14, p < .001), higher rates of bisexuality (adjusted odds ratio: 6.05, p < .001) and uncertainty in attraction (adjusted odds ratio: 10.44, p < .001) compared with non-ASD females. ASD males reported fewer prior boyfriends/girlfriends. Findings confirm female adolescents with ASD have differences in sexual attraction compared with non-ASD females. Lien vers le texte intégral (Open Access ou abonnement)
17. Moss P, Mandy W, Howlin P. {{Child and Adult Factors Related to Quality of Life in Adults with Autism}}. {J Autism Dev Disord};2017 (Mar 25)
The WHO Quality of Life-Brief questionnaire was used to assess quality of life (QoL) among 52 adults with autism (mean age 49 years) followed-up since childhood. Overall, assessments of QOL were more positive than measures of objective social outcome (jobs, independence, relationships etc.) but correlations between caregiver and self-reports were low. Informant ratings indicated few correlations between current QoL and any child or adult factors. On self-report ratings, QoL was significantly negatively correlated with severity of repetitive behaviours in childhood; higher QoL was positively associated with better adult social outcomes. However, only a minority of adults (n = 22) could provide self-report data and findings highlight the need to develop valid measures for assessing the well-being of adults with autism.
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18. Naguy A, Yahya B. {{Rett Syndrome-Current Status and Future Directions}}. {Pediatr Neurol};2017 (Feb 04)
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19. Pfaender S, Sauer AK, Hagmeyer S, Mangus K, Linta L, Liebau S, Bockmann J, Huguet G, Bourgeron T, Boeckers TM, Grabrucker AM. {{Zinc deficiency and low enterocyte zinc transporter expression in human patients with autism related mutations in SHANK3}}. {Sci Rep};2017 (Mar 27);7:45190.
Phelan McDermid Syndrome (PMDS) is a genetic disorder characterized by features of Autism spectrum disorders. Similar to reports of Zn deficiency in autistic children, we have previously reported high incidence of Zn deficiency in PMDS. However, the underlying mechanisms are currently not well understood. Here, using inductively coupled plasma mass-spectrometry to measure the concentration of Zinc (Zn) and Copper (Cu) in hair samples from individuals with PMDS with 22q13.3 deletion including SHANK3 (SH3 and multiple ankyrin repeat domains 3), we report a high rate of abnormally low Zn/Cu ratios. To investigate possible underlying mechanisms, we generated enterocytes from PMDS patient-derived induced pluripotent stem cells and used Caco-2 cells with knockdown of SHANK3. We detected decreased expression of Zn uptake transporters ZIP2 and ZIP4 on mRNA and protein level correlating with SHANK3 expression levels, and found reduced levels of ZIP4 protein co-localizing with SHANK3 at the plasma membrane. We demonstrated that especially ZIP4 exists in a complex with SHANK3. Furthermore, we performed immunohistochemistry on gut sections from Shank3alphabeta knockout mice and confirmed a link between enterocytic SHANK3, ZIP2 and ZIP4. We conclude that apart from its well-known role in the CNS, SHANK3 might play a specific role in the GI tract.
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20. Rasga C, Quelhas AC, Byrne RM. {{How Children with Autism Reason about Other’s Intentions: False-Belief and Counterfactual Inferences}}. {J Autism Dev Disord};2017 (Mar 25)
We examine false belief and counterfactual reasoning in children with autism with a new change-of-intentions task. Children listened to stories, for example, Anne is picking up toys and John hears her say she wants to find her ball. John goes away and the reason for Anne’s action changes-Anne’s mother tells her to tidy her bedroom. We asked, ‘What will John believe is the reason that Anne is picking up toys?’ which requires a false-belief inference, and ‘If Anne’s mother hadn’t asked Anne to tidy her room, what would have been the reason she was picking up toys?’ which requires a counterfactual inference. We tested children aged 6, 8 and 10 years. Children with autism made fewer correct inferences than typically developing children at 8 years, but by 10 years there was no difference. Children with autism made fewer correct false-belief than counterfactual inferences, just like typically developing children.
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21. Sizoo BB, Kuiper E. {{Cognitive behavioural therapy and mindfulness based stress reduction may be equally effective in reducing anxiety and depression in adults with autism spectrum disorders}}. {Res Dev Disabil};2017 (Mar 22);64:47-55.
Anxiety and depression co-occur in 50-70% of adults with autism spectrum disorder (ASD) but treatment methods for these comorbid problems have not been systematically studied. Recently, two ASD-tailored protocols were published: mindfulness based stress reduction (MBSR) and cognitive behavioural therapy (CBT). We wanted to investigate if both methods are equally effective in reducing anxiety and depression symptoms among adults with ASD. 59 adults with ASD and anxiety or depression scores above 7 on the Hospital Anxiety and Depression Scale, gave informed consent to participate; 27 followed the CBT protocol, and 32 the MBSR treatment protocol. Anxiety and depression scores, autism symptoms, rumination, and global mood were registered at the start, at the end of the 13-week treatment period, and at 3-months follow-up. Irrational beliefs and mindful attention awareness were used as process measures during treatment and at follow-up. Results indicate that both MBSR and CBT are associated with a reduction in anxiety and depressive symptoms among adults with ASD, with a sustained effect at follow-up, but without a main effect for treatment group. A similar pattern was seen for the reduction of autistic symptoms, rumination and the improvement in global mood. There are some indications that MBSR may be preferred over CBT with respect to the treatment effect on anxiety when the scores on measures of irrational beliefs or positive global mood at baseline are high. Mindfulness and cognitive behavioral therapies are both promising treatment methods for reducing comorbid anxiety and depression in adults with ASD.
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22. Soke GN, Maenner MJ, Christensen D, Kurzius-Spencer M, Schieve LA. {{Brief Report: Estimated Prevalence of a Community Diagnosis of Autism Spectrum Disorder by Age 4 Years in Children from Selected Areas in the United States in 2010: Evaluation of Birth Cohort Effects}}. {J Autism Dev Disord};2017 (Mar 24)
We compared early-diagnosed autism spectrum disorder (ASD) (defined as diagnosis by age 4 years) between the 2002 and 2006 birth cohorts, in five sites of the Autism and Developmental Disabilities Monitoring Network. In the 2002 cohort, the prevalence/1000 of early-diagnosed ASD was half the 8-year-old prevalence (7.2 vs. 14.7, prevalence ratio [PR] 0.5 [0.4-0.6]). Overall, the prevalence of early-diagnosed ASD did not differ between birth cohorts (PR 1.1 [0.9-1.3]). However, in three sites with complete case ascertainment, the prevalence of early-diagnosed ASD was higher for those born in 2006 versus 2002 (PR 1.3 [1.1-1.5]), suggesting possible improvement in early identification. The lack of change in two sites may reflect less complete case ascertainment. Studies in more recent cohorts are needed.
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23. Stadnick N, Chlebowski C, Brookman-Frazee L. {{Caregiver-Teacher Concordance of Challenging Behaviors in Children with Autism Spectrum Disorder Served in Community Mental Health Settings}}. {J Autism Dev Disord};2017 (Mar 25)
Children with autism spectrum disorder (ASD) exhibit high rates of challenging behaviors that impair functioning and represent the primary presenting problem in mental health (MH) services. Obtaining symptom reports from multiple informants is critical for treatment planning. This study evaluated caregiver-teacher concordance of ratings of the intensity of challenging behaviors in children with ASD receiving MH services, and identified child clinical factors associated with concordance. This sample included 141 children (M = 9.07 years), their caregivers, and teachers. Caregiver-teacher concordance of challenging behaviors was low and impacted by the degree and type of child psychiatric comorbidity. Findings support need for increased attention to the range of psychiatric problems children with ASD present to tailor treatment recommendations and service delivery.
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24. Tenenbaum EJ, Amso D, Righi G, Sheinkopf SJ. {{Attempting to « Increase Intake from the Input »: Attention and Word Learning in Children with Autism}}. {J Autism Dev Disord};2017 (Mar 24)
Previous work has demonstrated that social attention is related to early language abilities. We explored whether we can facilitate word learning among children with autism by directing attention to areas of the scene that have been demonstrated as relevant for successful word learning. We tracked eye movements to faces and objects while children watched videos of a woman teaching them new words. Test trials measured participants’ recognition of these novel word-object pairings. Results indicate that for children with autism and typically developing children, pointing to the speaker’s mouth while labeling a novel object impaired performance, likely because it distracted participants from the target object. In contrast, for children with autism, holding the object close to the speaker’s mouth improved performance.
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25. Wang J, Wang Q, Peng J, Nie D, Zhao F, Kim M, Zhang H, Wee CY, Wang S, Shen D. {{Multi-task diagnosis for autism spectrum disorders using multi-modality features: A multi-center study}}. {Hum Brain Mapp};2017 (Mar 27)
Autism spectrum disorder (ASD) is a neurodevelopment disease characterized by impairment of social interaction, language, behavior, and cognitive functions. Up to now, many imaging-based methods for ASD diagnosis have been developed. For example, one may extract abundant features from multi-modality images and then derive a discriminant function to map the selected features toward the disease label. A lot of recent works, however, are limited to single imaging centers. To this end, we propose a novel multi-modality multi-center classification (M3CC) method for ASD diagnosis. We treat the classification of each imaging center as one task. By introducing the task-task and modality-modality regularizations, we solve the classification for all imaging centers simultaneously. Meanwhile, the optimal feature selection and the modeling of the discriminant functions can be jointly conducted for highly accurate diagnosis. Besides, we also present an efficient iterative optimization solution to our formulated problem and further investigate its convergence. Our comprehensive experiments on the ABIDE database show that our proposed method can significantly improve the performance of ASD diagnosis, compared to the existing methods. Hum Brain Mapp, 2017. (c) 2017 Wiley Periodicals, Inc.
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26. Wang S, Adolphs R. {{Reduced specificity in emotion judgment in people with autism spectrum disorder}}. {Neuropsychologia};2017 (Mar 24);99:286-295.
There is a conflicting literature on facial emotion processing in autism spectrum disorder (ASD): both typical and atypical performance have been reported, and inconsistencies in the literature may stem from different processes examined (emotion judgment, face perception, fixations) as well as differences in participant populations. Here we conducted a detailed investigation of the ability to discriminate graded emotions shown in morphs of fear-happy faces, in a well-characterized high-functioning sample of participants with ASD and matched controls. Signal detection approaches were used in the analyses, and concurrent high-resolution eye-tracking was collected. Although people with ASD had typical thresholds for categorical fear and confidence judgments, their psychometric specificity to detect emotions across the entire range of intensities was reduced. However, fixation patterns onto the stimuli were typical and could not account for the reduced specificity of emotion judgment. Together, our results argue for a subtle and specific deficit in emotion perception in ASD that, from a signal detection perspective, is best understood as a reduced specificity due to increased noise in central processing of the face stimuli.
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27. Wang Z, Kwon M, Mohanty S, Schmitt LM, White SP, Christou EA, Mosconi MW. {{Increased Force Variability Is Associated with Altered Modulation of the Motorneuron Pool Activity in Autism Spectrum Disorder (ASD)}}. {Int J Mol Sci};2017 (Mar 25);18(4)
Force control deficits have been repeatedly documented in autism spectrum disorder (ASD). They are associated with worse social and daily living skill impairments in patients suggesting that developing a more mechanistic understanding of the central and peripheral processes that cause them may help guide the development of treatments that improve multiple outcomes in ASD. The neuromuscular mechanisms underlying force control deficits are not yet understood. Seventeen individuals with ASD and 14 matched healthy controls completed an isometric index finger abduction test at 60% of their maximum voluntary contraction (MVC) during recording of the first dorsal interosseous (FDI) muscle to determine the neuromuscular processes associated with sustained force variability. Central modulation of the motorneuron pool activation of the FDI muscle was evaluated at delta (0-4 Hz), alpha (4-10 Hz), beta (10-35 Hz) and gamma (35-60 Hz) frequency bands. ASD patients showed greater force variability than controls when attempting to maintain a constant force. Relative to controls, patients also showed increased central modulation of the motorneuron pool at beta and gamma bands. For controls, reduced force variability was associated with reduced delta frequency modulation of the motorneuron pool activity of the FDI muscle and increased modulation at beta and gamma bands. In contrast, delta, beta, and gamma frequency oscillations were not associated with force variability in ASD. These findings suggest that alterations of central mechanisms that control motorneuron pool firing may underlie the common and often impairing symptoms of ASD.
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28. Ziermans T, Swaab H, Stockmann A, de Bruin E, van Rijn S. {{Formal Thought Disorder and Executive Functioning in Children and Adolescents with Autism Spectrum Disorder: Old Leads and New Avenues}}. {J Autism Dev Disord};2017 (Mar 24)
Formal thought disorder (FTD) is a disruption in the flow of thought and a common feature in psychotic disorders and autism spectrum disorder (ASD). Executive dysfunction has often been associated with FTD, yet for ASD convincing evidence is lacking. This study investigated FTD and three core executive functions in 50 young children and adolescents with high-functioning ASD and 56 matched controls. Higher overall levels of FTD marked ASD compared to controls. Furthermore, in ASD decreased performance on verbal working memory was correlated with increased FTD ratings and explained a significant amount of variance of objective and subjective FTD. Verbal working memory is currently the most promising target executive function for understanding the development of idiosyncratic thought disorders in ASD.
