1. Ahlers K, Gabrielsen TP, Ellzey A, Brady A, Litchford A, Fox J, Nguyen QT, Carbone PS. {{A Pilot Project Using Pediatricians as Initial Diagnosticians in Multidisciplinary Autism Evaluations for Young Children}}. {Journal of developmental and behavioral pediatrics : JDBP}. 2018.
OBJECTIVES: Wait times for autism spectrum disorder (ASD) evaluations are long, thereby delaying access to ASD-specific services. We asked how our traditional care model (requiring all patients to see psychologists for ASD diagnostic decisions) compared to an alternative model that better utilizes the available clinicians, including initial evaluation by speech, audiology, and pediatrics (trained in Level 2 autism screening tools). Pediatricians could diagnose immediately if certain about diagnosis but could refer uncertain cases to psychology. Accuracy and time to diagnosis, charges, and parent satisfaction were our main outcome measures. METHODS: Data were gathered through record extraction (n = 244) and parent questionnaire (n = 57). We compared time to diagnosis, charges, and parent satisfaction between traditional and alternative models. Agreement between pediatrician and psychologist diagnoses was examined for a subset (n = 18). RESULTS: The alternative model’s time to diagnosis was 44% faster (85 vs 152 d) and 33% less costly overall. Diagnostic agreement was 93% for children with ASD diagnoses and 100% for children without ASD diagnoses. Pediatricians expressed higher diagnostic certainty about children with higher levels of ASD symptoms. Parents reported no differences in high satisfaction with experiences, family-centered care, and shared decision making. CONCLUSION: Efficient use of available clinicians with additional training in Level 2 autism screening resulted in improvements in time to diagnosis and reduced charges for families. Coordination of multidisciplinary teams makes this possible, with strategic sequencing of patients through workflow. Flexibility was key to not only allowing pediatricians to refer uncertain cases to psychology for diagnosis but also allowing for diagnosis by a pediatrician when symptomatic presentation clearly met diagnostic criteria.
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2. Ahmad SA, Al Thobiti TA, El Toum M, Al Harbi F. {{Florid Scurvy in an Autistic Child on a Ketogenic Diet}}. {Pediatric emergency care}. 2018.
Ketogenic diets used for treating various neurological disorders can have potentially serious adverse effects. Among these is scurvy, a rarely reported, yet potentially fatal adverse effect of the ketogenic diet caused by vitamin C deficiency. We report a case of a 5-year-old patient with autism, who presented with scurvy secondary to the dietary restrictions of a ketogenic diet. Our review of the literature showed a single previously reported case of vitamin C deficiency in a patient on ketogenic diet. We have also reviewed the clinical indications and adverse effects of ketogenic diets with special reference to scurvy. This case emphasizes the importance of vitamin supplements in patients consuming a special diet.
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3. Ahmad SF, Ansari MA, Nadeem A, Bakheet SA, Al-Ayadhi LY, Attia SM. {{Elevated IL-16 expression is associated with development of immune dysfunction in children with autism}}. {Psychopharmacology}. 2018.
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairments in communication skills and social behaviors. Several studies have suggested that neuroimmune dysfunction plays a significant role in the pathogenesis of ASD; however, its exact etiology is unknown. Interleukin-16 (IL-16), a chemoattractant, is associated with various inflammatory processes. However, its role in children with ASD is unclear. This study aimed to investigate whether IL-16 expression is associated with immune dysfunction in children with ASD. We examined IL-16 expression in CD4(+), CD8(+), CD14(+), CCR3(+), and CXCR7(+) cells in typically developing (TD) controls and children with ASD using flow cytometry in peripheral blood mononuclear cells (PBMCs). We also investigated the expression of IL-1beta(+)IL-16(+), IL-6(+)IL-16(+), and TNF-alpha(+)IL-16(+) in TD controls and children with ASD. We further explored IL-16 mRNA and protein expression using RT-PCR and western blotting. CD4(+)IL-16(+), CD8(+)IL-16(+), CD14(+)IL-16(+), CCR3(+)IL-16(+), and CXCR7(+)IL-16(+) cells increased significantly in children with ASD compared with TD controls. We also showed that expression of IL-1beta(+)IL-16(+), IL-6(+)IL-16(+), and TNF-alpha(+)IL-16(+) was elevated in children with ASD compared with TD controls. Moreover, IL-16 mRNA and protein expression was significantly induced in children with ASD compared with TD controls. These results suggest that IL-16 expression could play an essential role in immune alteration in children with ASD.
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4. Dawson G, Campbell K, Hashemi J, Lippmann SJ, Smith V, Carpenter K, Egger H, Espinosa S, Vermeer S, Baker J, Sapiro G. {{Atypical postural control can be detected via computer vision analysis in toddlers with autism spectrum disorder}}. {Scientific reports}. 2018; 8(1): 17008.
Evidence suggests that differences in motor function are an early feature of autism spectrum disorder (ASD). One aspect of motor ability that develops during childhood is postural control, reflected in the ability to maintain a steady head and body position without excessive sway. Observational studies have documented differences in postural control in older children with ASD. The present study used computer vision analysis to assess midline head postural control, as reflected in the rate of spontaneous head movements during states of active attention, in 104 toddlers between 16-31 months of age (Mean = 22 months), 22 of whom were diagnosed with ASD. Time-series data revealed robust group differences in the rate of head movements while the toddlers watched movies depicting social and nonsocial stimuli. Toddlers with ASD exhibited a significantly higher rate of head movement as compared to non-ASD toddlers, suggesting difficulties in maintaining midline position of the head while engaging attentional systems. The use of digital phenotyping approaches, such as computer vision analysis, to quantify variation in early motor behaviors will allow for more precise, objective, and quantitative characterization of early motor signatures and potentially provide new automated methods for early autism risk identification.
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5. Dempsey J, Dempsey AG. {{Autism Spectrum Disorder Severity, Developmental Delays, and Overweight/Obese Weight Status}}. {The Journal of pediatrics}. 2018.
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6. Drozd HP, Karathanasis SF, Molosh AI, Lukkes JL, Clapp DW, Shekhar A. {{From bedside to bench and back: Translating ASD models}}. {Progress in brain research}. 2018; 241: 113-58.
Autism spectrum disorders (ASD) represent a heterogeneous group of disorders defined by deficits in social interaction/communication and restricted interests, behaviors, or activities. Models of ASD, developed based on clinical data and observations, are used in basic science, the « bench, » to better understand the pathophysiology of ASD and provide therapeutic options for patients in the clinic, the « bedside. » Translational medicine creates a bridge between the bench and bedside that allows for clinical and basic science discoveries to challenge one another to improve the opportunities to bring novel therapies to patients. From the clinical side, biomarker work is expanding our understanding of possible mechanisms of ASD through measures of behavior, genetics, imaging modalities, and serum markers. These biomarkers could help to subclassify patients with ASD in order to better target treatments to a more homogeneous groups of patients most likely to respond to a candidate therapy. In turn, basic science has been responding to developments in clinical evaluation by improving bench models to mechanistically and phenotypically recapitulate the ASD phenotypes observed in clinic. While genetic models are identifying novel therapeutics targets at the bench, the clinical efforts are making progress by defining better outcome measures that are most representative of meaningful patient responses. In this review, we discuss some of these challenges in translational research in ASD and strategies for the bench and bedside to bridge the gap to achieve better benefits to patients.
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7. Garg S, Green J. {{Studying child development in genetic models of ASD}}. {Progress in brain research}. 2018; 241: 159-92.
This chapter approaches the early development in autism spectrum disorder (ASD) through comparative study of some key monogenic syndromic models of ASD in humans. Using this method, as well as referring to relevant work in idiopathic ASD, we address three complimentary areas: (i) patterns of ASD behavioral phenotype expression across genetic syndromes, as a way of addressing gene-phenotype correlations; (ii) longitudinal developmental trajectories toward autism in early childhood, as a way of addressing developmental specificity; and (iii) experimental intervention trials, for treatment and mechanism discovery. The comparative approach does not highlight striking phenotypic specificity, but early studies were often limited and more methodologically sophisticated recent studies may suggest subtle distinctions. Longitudinal studies are at an early stage but can build on the substantive work on early prodromal development of idiopathic ASD. Translational intervention trials to date have not found candidate treatments and we argue that a new generation of more ambitious experimental mechanism trials is needed. This field now has the opportunity to combine comparative prospective longitudinal developmental studies with in-depth cross-syndrome phenotyping and linked ambitious targeted mechanistic interventions in a way that could be mutually informing and maximize the potential of syndromic models to illuminate the pathophysiology of ASD.
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8. Gonzalez-Barrero AM, Nadig A. {{Bilingual children with autism spectrum disorders: The impact of amount of language exposure on vocabulary and morphological skills at school age}}. {Autism research : official journal of the International Society for Autism Research}. 2018.
Studies of bilingual children with Autism Spectrum Disorders (ASD) have focused on early language development using parent report measures. However, the effect of bilingual exposure on more complex linguistic abilities is unknown. In the current study, we examined the impact of amount of language exposure on vocabulary and morphological skills in school-aged children with ASD who did not have intellectual disability. Forty-seven typically developing children and 30 children with ASD with varying exposure to French participated in the study. We investigated the impact of amount of language exposure, nonverbal IQ, age, and working memory on language abilities via regression analyses. Current amount of language exposure was the strongest predictor of both vocabulary skills (accounting for 62% of the variance) and morphological skills (accounting for 49% of the variance), for both typically-developing children and children with ASD. These findings highlight the central role amount of language exposure plays in vocabulary and morphological development for children with ASD, as it does for typically-developing children. In addition, they provide further evidence that, when provided with adequate language exposure, many children with ASD are capable of acquiring two languages. LAY SUMMARY: We studied typically developing children and children with ASD living in a bilingual society who had varying exposure to French (ranging from bilinguals to monolinguals). We investigated the impact of amount of language exposure, nonverbal IQ, age, and working memory on their vocabulary and morphological skills. Current amount of language exposure was the strongest predictor of language skills in both groups of children. Findings indicate that when provided with adequate language exposure, many children with ASD are capable of acquiring two languages. Autism Research 2018. (c) 2018 International Society for Autism Research, Wiley Periodicals, Inc.
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9. Hagerman R, Jacquemont S, Berry-Kravis E, Des Portes V, Stanfield A, Koumaras B, Rosenkranz G, Murgia A, Wolf C, Apostol G, von Raison F. {{Mavoglurant in Fragile X Syndrome: Results of two open-label, extension trials in adults and adolescents}}. {Scientific reports}. 2018; 8(1): 16970.
Fragile X syndrome (FXS) is the most common monogenic cause of inherited intellectual and developmental disabilities. Mavoglurant, a selective metabotropic glutamate receptor subtype-5 antagonist, has shown positive neuronal and behavioral effects in preclinical studies, but failed to demonstrate any behavioral benefits in two 12-week, randomized, placebo-controlled, double-blind, phase IIb studies in adults and adolescents with FXS. Here we report the long-term safety (primary endpoint) and efficacy (secondary endpoint) results of the open-label extensions. Adolescent (n = 119, aged 12-19 years) and adult (n = 148, aged 18-45 years) participants received up to 100 mg bid mavoglurant for up to 34 months. Both extension studies were terminated prematurely due to lack of proven efficacy in the core studies. Mavoglurant was well tolerated with no new safety signal. Five percent of adults and 16.9 percent of adolescents discontinued treatment due to adverse events. Gradual and consistent behavioral improvements as measured by the ABC-CFX scale were observed, which were numerically superior to those seen in the placebo arm of the core studies. These two extension studies confirm the long-term safety of mavoglurant in FXS, but further investigations are required to determine whether and under which conditions the significant preclinical results obtained with mGluR5 inhibition can translate to humans.
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10. Howell BW, Smith KM. {{Synaptic Structural Protein Dysfunction Leads to Altered Excitation Inhibition Ratios in Models of Autism Spectrum Disorder}}. {Pharmacological research}. 2018.
Genetics is believed to play a key role in the development of Autism Spectrum Disorder (ASD) and a plethora of potential candidate genes have been identified by genetic characterization of patients, their family members and controls. To make sense of this information investigators have searched for common pathways and downstream properties of neural networks that are regulated by these genes. For instance, several candidate genes encode synaptic proteins, and one hypothesis that has emerged is that disruption of the synaptic excitation and inhibition (E/I) balance would destabilize neural processing and lead to ASD phenotypes. Some compelling evidence for this has come from the analyses of mouse and culture models with defects in synaptic structural proteins, which influence several aspects of synapse biology and is the subject of this review. Remaining challenges include identifying the specifics that distinguish ASD from other psychiatric diseases and designing more direct tests of the E/I balance hypothesis.
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11. Molosh AI, Shekhar A. {{Neurofibromatosis type 1 as a model system to study molecular mechanisms of autism spectrum disorder symptoms}}. {Progress in brain research}. 2018; 241: 37-62.
Neurofibromatosis type 1 (NF1) is monogenic neurodevelopmental disorder caused by mutation of NF1 gene, which leads to increased susceptibility to various tumors formations. Additionally, majority of patients with NF1 are experience high incidence of cognitive deficits. Particularly, we review the growing number of reports demonstrated a higher incidence of autism spectrum disorder (ASD) in individuals with NF1. In this review we also discuss face validity of preclinical Nf1 mouse models. Then we describe discoveries from these animal models that have uncovered the deficiencies in the regulation of Ras and other intracellular pathways as critical mechanisms underlying the Nf1 cognitive problems. We also summarize and interpret recent preclinical and clinical studies that point toward potential pharmacological therapies for NF1 patients.
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12. Nadig A, Flanagan T, White K, Bhatnagar S. {{Results of a RCT on a Transition Support Program for Adults with ASD: Effects on Self-Determination and Quality of Life}}. {Autism research : official journal of the International Society for Autism Research}. 2018.
Few evidence-based services exist for people with Autism Spectrum Disorder (ASD) as they transition into adulthood, particularly those that foster appreciation of one’s own goals and strengths. We developed a transition service for adults with ASD (without Intellectual Disability), and conducted a randomized controlled trial (RCT) focusing on self-report of Quality of Life and Self-Determination outcomes. Thirty participants aged 18-29 were randomized to immediate or delayed intervention, with 26 participants analyzed after 4 were lost to follow-up. Curriculum was tailored to participants’ self-expressed needs in three areas: social communication, self-determination, and working with others. Groups of four-to-six participants with ASD and two facilitators met weekly for 10 weeks. Positive intervention effects were observed on self-report of Quality of Life; the intervention group scored on average 2 points higher than the control group, 95% CI [-0.2, 3.9]. Positive effects were also observed on the Self Determination Scale (Interpersonal Cognitive Problem-Solving subdomain), where the intervention group scored 2 points higher than control group 95% CI [0.082, 3.4]. In addition, participants rated skills targeted by the curriculum 6 points higher after versus before intervention, 95% CI [3.7, 8.6]. This was echoed by a subset of parents rating their child’s skills as seven points higher after versus before intervention, 95% CI [1, 14]. Autism Research 2018. (c) 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: These findings indicate that it is possible to increase Self-Determination and subjective Quality of Life in adults with ASD through a brief group-format service, and provide a model for doing so. Self-Determination abilities are linked to improved adult outcomes in individuals with other disabilities. These often overlooked factors should be incorporated in programming for adults with ASD as they transition to adulthood.
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13. Ogawa R, Kagitani-Shimono K, Matsuzaki J, Tanigawa J, Hanaie R, Yamamoto T, Tominaga K, Hirata M, Mohri I, Taniike M. {{Abnormal cortical activation during silent reading in adolescents with autism spectrum disorder}}. {Brain & development}. 2018.
OBJECTIVE: Autism spectrum disorder (ASD) is a developmental disorder characterized by communication deficits and social difficulties, and individuals with ASD frequently exhibit varied levels of language abilities. However, the neurophysiological mechanisms underlying their language deficits remain unclear. To gain insight into the neurophysiological mechanisms of receptive language deficits, we assessed cortical activation patterns in adolescents with ASD during silent word-reading. METHODS: We used magnetoencephalography to measure cortical activation during a silent word-reading task in 14 adolescent boys with high-functioning ASD and 17 adolescent boys with typical development (TD). RESULTS: Compared with participants with TD, those with ASD exhibited significantly decreased cortical activation in the left middle temporal gyrus, left temporoparietal junction, bilateral superior temporal gyrus, left posterior insula, and right occipitotemporal gyrus, and increased activation in the right anterior insula. Participants with ASD also exhibited a lack of left-lateralization in the central sulcus and abnormal right-lateralization in the anterior insula area. Furthermore, in participants with ASD, we found that abnormal activation of the right central sulcus correlated significantly with lower visual word comprehension scores, and that decreased activation of the right anterior insula correlated significantly with the severity of social interaction difficulties. CONCLUSION: Our findings suggest that atypical cortical activation and lateralization in the temporal-frontal area, which is associated with higher-order language processing functions, such as semantic analysis, may play a crucial role in visual word comprehension and social interaction difficulties in adolescents with ASD.
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14. Osorio AAC, Russowsky Brunoni A. {{Transcranial direct current stimulation in children with autism spectrum disorder: a systematic scoping review}}. {Developmental medicine and child neurology}. 2018.
AIM: Our aim was to review available studies which test transcranial direct current stimulation (tDCS) to reduce symptom severity in children with autism spectrum disorder (ASD). METHOD: We performed a systematic scoping review in PubMed and PsychINFO databases for studies employing tDCS in children and adolescents with ASD. RESULTS: We found five studies (two small randomized controlled studies, one experimental study, one quasi-experimental study, and one case study) reporting positive effects of tDCS in ASD symptom reduction. Study design varied greatly and sample size ranged from 1 to 20 patients. INTERPRETATION: Preliminary evidence is encouraging of the potential usefulness of tDCS for treatment of ASD in children and adolescents. It suggests tentative support for reductions in symptom severity and, according to parental reports and clinical observations, improvements in some aspects of language. However, the evidence is sparse and of low quality, so the true effect of tDCS is likely to be substantially different from the estimate of effect in this review. Therefore, future randomized controlled trials are needed to draw conclusions regarding tDCS efficacy in paediatric samples with ASD. WHAT THIS PAPER ADDS: There is low confidence in the estimate of effect, but tentatively encouraging results warrant further investigation.
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15. Pagalan L, Bickford C, Weikum W, Lanphear B, Brauer M, Lanphear N, Hanley GE, Oberlander TF, Winters M. {{Association of Prenatal Exposure to Air Pollution With Autism Spectrum Disorder}}. {JAMA pediatrics}. 2018.
Importance: The etiology of autism spectrum disorder (ASD) is poorly understood, but prior studies suggest associations with airborne pollutants. Objective: To evaluate the association between prenatal exposures to airborne pollutants and ASD in a large population-based cohort. Design, Setting, and Participants: This population-based cohort encompassed nearly all births in Metro Vancouver, British Columbia, Canada, from 2004 through 2009, with follow-up through 2014. Children were diagnosed with ASD using a standardized assessment with the Autism Diagnostic Interview-Revised and Autism Diagnostic Observation Schedule. Monthly mean exposures to particulate matter with a diameter less than 2.5 microm (PM2.5), nitric oxide (NO), and nitrogen dioxide (NO2) at the maternal residence during pregnancy were estimated with temporally adjusted, high-resolution land use regression models. The association between prenatal air pollution exposures and the odds of developing ASD was evaluated using logistic regression adjusted for child sex, birth month, birth year, maternal age, maternal birthplace, and neighborhood-level urbanicity and income band. Data analysis occurred from June 2016 to May 2018. Exposures: Mean monthly concentrations of ambient PM2.5, NO, and NO2 at the maternal residence during pregnancy, calculated retrospectively using temporally adjusted, high-resolution land use regression models. Main Outcomes and Measures: Autism spectrum disorder diagnoses based on standardized assessment of the Autism Diagnostic Interview-Revised and Autism Diagnostic Observation Schedule. The hypothesis being tested was formulated during data collection. Results: In a cohort of 132256 births, 1307 children (1.0%) were diagnosed with ASD by the age of 5 years. The final sample size for the PM2.5-adjusted model was 129439 children, and for NO and NO2, it was 129436 children; of these, 1276 (1.0%) were diagnosed with ASD. Adjusted odds ratios for ASD per interquartile range (IQR) were not significant for exposure to PM2.5 during pregnancy (1.04 [95% CI, 0.98-1.10] per 1.5 mug/m3 increase [IQR] in PM2.5) or NO2 (1.06 [95% CI, 0.99-1.12] per 4.8 ppb [IQR] increase in NO2) but the odds ratio was significant for NO (1.07 [95% CI, 1.01-1.13] per 10.7 ppb [IQR] increase in NO). Odds ratios for male children were 1.04 (95% CI, 0.98-1.10) for PM2.5; 1.09 (95% CI, 1.02-1.15) for NO; and 1.07 (95% CI, 1.00-1.13) for NO2. For female children, they were for 1.03 (95% CI, 0.90-1.18) for PM2.5; 0.98 (95% CI, 0.83-1.13) for NO; and 1.00 (95% CI, 0.86-1.16) for NO2. Conclusions and Relevance: In a population-based birth cohort, we detected an association between exposure to NO and ASD but no significant association with PM2.5 and NO2.
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16. Patel J, Lukkes JL, Shekhar A. {{Overview of genetic models of autism spectrum disorders}}. {Progress in brain research}. 2018; 241: 1-36.
Autism spectrum disorders (ASDs) are a group of neurodevelopment disorders that are characterized by heterogenous cognitive deficits and genetic factors. As more ASD risk genes are identified, genetic animal models have been developed to parse out the underlying neurobiological mechanisms of ASD. In this review, we discuss a subset of genetic models of ASD, focusing on those that have been widely studied and strongly linked to ASD. We focus our discussion of these models in the context of the theories and potential mechanisms of ASD, including disruptions in cell growth and proliferation, spine dynamics, synaptic transmission, excitation/inhibition balance, intracellular signaling, neuroinflammation, and behavior. In addition to ASD pathophysiology, we examine the limitations and challenges that genetic models pose for the study of ASD biology. We end with a review of innovative techniques and concepts of ASD pathology that can be further applied to and studied using genetic ASD models.
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17. Renthal W, Boxer LD, Hrvatin S, Li E, Silberfeld A, Nagy MA, Griffith EC, Vierbuchen T, Greenberg ME. {{Characterization of human mosaic Rett syndrome brain tissue by single-nucleus RNA sequencing}}. {Nature neuroscience}. 2018.
In females with X-linked genetic disorders, wild-type and mutant cells coexist within brain tissue because of X-chromosome inactivation, posing challenges for interpreting the effects of X-linked mutant alleles on gene expression. We present a single-nucleus RNA sequencing approach that resolves mosaicism by using single-nucleotide polymorphisms in genes expressed in cis with the X-linked mutation to determine which nuclei express the mutant allele even when the mutant gene is not detected. This approach enables gene expression comparisons between mutant and wild-type cells within the same individual, eliminating variability introduced by comparisons to controls with different genetic backgrounds. We apply this approach to mosaic female mouse models and humans with Rett syndrome, an X-linked neurodevelopmental disorder caused by mutations in the gene encoding the methyl-DNA-binding protein MECP2, and observe that cell-type-specific DNA methylation predicts the degree of gene upregulation in MECP2-mutant neurons. This approach can be broadly applied to study gene expression in mosaic X-linked disorders.
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18. Roux S, Bailly Y, Bossu JL. {{Regional and sex-dependent alterations in Purkinje cell density in the valproate mouse model of autism}}. {Neuroreport}. 2018.
Neuropathological and neuroimaging studies indicate a decrease in Purkinje cell (PC) density in the cerebellum of autistic patients and rodent models of autism. Autism is far more prevalent in males than females, and sex-specific properties of PCs have been reported recently. We investigated the differential sensitivity of PCs in the valproate acid (VPA) mouse model of autism by estimating the linear density of PCs immununolabelled with calbindin in the cerebellum of males and females. Whereas prenatal VPA treatment surprisingly increased PC linear density in both sexes 13 days after birth (P13), it significantly reduced the linear density of PCs in the cerebellum of 40-day-old (P40) males, but not females. In males, PC loss was more pronounced in the posterior part of the cerebellum and was significant in the VIth, VIIth, IXth and paramedian lobules. In females, PC loss was restricted to the paramedian lobule. These results suggest that this sex-specific sensitivity of PCs to VPA may contribute towards the motor disturbances and behavioural abnormalities observed in autism.
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19. Sorcinelli A, Ference J, Curtin S, Vouloumanos A. {{Preference for speech in infancy differentially predicts language skills and autism-like behaviors}}. {Journal of experimental child psychology}. 2018; 178: 295-316.
Early emerging biases for conspecific vocalizations are a hallmark of early development. Typically developing neonates listen to speech more than many other sounds, including non-biological non-speech sounds, but listen equally to speech and monkey calls. By 3months of age, however, infants prefer speech over both non-biological non-speech sounds and monkey calls. We examined whether different listening preferences continue to develop along different developmental trajectories and whether listening preferences are related to developmental outcomes. Given the static preference for speech over non-biological non-speech sounds and the dynamic preference for speech over monkey calls between birth and 3months, we examined whether 9-month-olds prefer speech over non-biological non-speech sounds (Experiment 1) and prefer speech over monkey calls (Experiment 2). We compared preferences for sounds in infants at low risk (SIBS-TD) and infants at high risk (SIBS-A) of autism spectrum disorder (ASD), a heterogeneous population who differ from typically developing infants in their preferences for speech, and examined whether listening preferences predict vocabulary and autism-like behaviors at 12months for both groups. At 9months, SIBS-TD listened longer to speech than to non-speech sounds and listened longer to monkey calls than to speech, whereas SIBS-A listened longer to speech than to non-speech sounds but listened equally to speech and monkey calls. SIBS-TD’s preferences did not predict immediate developmental outcomes. In contrast, SIBS-A who preferred speech over non-speech or monkey calls had larger vocabularies and fewer markers of autism-like behaviors at 12months, which could have positive developmental implications.
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20. Sotoodeh MS, Taheri-Torbati H, Sohrabi M, Ghoshuni M. {{Perception of biological motions is preserved in people with autism spectrum disorder: electrophysiological and behavioural evidences}}. {Journal of intellectual disability research : JIDR}. 2018.
BACKGROUND: There have been some controversies over the ability of individuals with autism spectrum disorder (ASD) to perceive biological motion. In this study, we used electroencephalography and behavioural measures (recognition test) to examine whether or not children with ASD can correctly identify biological motion. METHOD: Twenty participants with ASD (mean = 11.3, SD = 2.1 years) and 20 typically developed (TD) participants (mean = 11.4, SD = 2.8 years) participated in the study. They watched videos and point light displays of actions, and their EEG was recorded. Then they answered action recognition test, and their accuracy and response times were recorded. RESULTS: Our findings showed that children with ASD had the same mu suppression as a TD age-matched control group in both point light display and video presentations. Furthermore, the results showed that while TD and ASD groups did not differ in accuracy, ASD participants had a slower reaction time. CONCLUSION: Taken together, our results indicate that the perception of non-emotional BMs is preserved in children with ASD.
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21. Vithayathil J, Pucilowska J, Landreth GE. {{ERK/MAPK signaling and autism spectrum disorders}}. {Progress in brain research}. 2018; 241: 63-112.
The MAPK pathway is a prominent intracellular signaling pathway regulating various intracellular functions. Components of this pathway are mutated in a related collection of congenital syndromes collectively referred to as neuro-cardio-facio-cutaneous syndromes (NCFC) or Rasopathies. Recently, it has been appreciated that these disorders are associated with autism spectrum disorders (ASD). In addition, idiopathic ASD has also implicated the MAPK signaling cascade as a common pathway that is affected by many of the genetic variants that have been found to be linked to ASDs. This chapter describes the components of the MAPK pathway and how it is regulated. Furthermore, this chapter will highlight the various functions of the MAPK pathway during both embryonic development of the central nervous system (CNS) and its roles in neuronal physiology and ultimately, behavior. Finally, we will summarize the perturbations to MAPK signaling in various models of autism spectrum disorders and Rasopathies to highlight how dysregulation of this pivotal pathway may contribute to the pathogenesis of autism.
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22. Walsh KS, Rau S. {{Measurement considerations in pediatric research on autism spectrum disorders}}. {Progress in brain research}. 2018; 241: 193-220.
Studying Autism Spectrum Disorders (ASD) in genetic syndromes has gained interest in the scientific community as a way to elucidate mechanisms and symptom profiles to understand ASD more broadly. Appropriate and adequate measurement of constructs, symptomatology, and outcomes in clinical research is of vital importance in establishing the prevalence of such symptoms and measuring change in symptoms in the context of clinical trials. As such, we provide an overview of the prevalence of ASD, present current diagnostic guidelines, discuss important comorbidities to consider, describe current assessment strategies in assessing ASD, and discuss these within the context of a specific genetic condition to highlight how ASD can be best evaluated.
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23. Xixis KI, Ham A, Farmer A, Allman A, Augustyn M. {{Focal Electrographic Seizures in a Patient With Autism Spectrum Disorder and Speech Delay}}. {Journal of developmental and behavioral pediatrics : JDBP}. 2018.
CASE: A 6-year-old boy with a diagnosis of autism spectrum disorder (ASD) presented to primary care for a new-patient, transfer-of-care evaluation. At the initial encounter, the patient used a maximum of 60 words and was receiving speech and language therapy (SLT) through school. Family history was positive for seizures in the father and paternal grandfather as well as ASD in an older brother. Referrals to genetics, private SLT, and an autism specialist were offered, although the latter was declined by family. The subsequent genetics evaluation resulted in discovery of a small gain on chromosome 1q42.2 and associated partial duplication of the DISC1 gene. The assay could not determine the exact clinical significance of the abnormality, but similarly sized and located abnormalities involving the DISC1 gene are reported in some patients with ASD and developmental delay. During a follow-up pediatrics appointment, the father expressed his wish for further evaluation of causes of autism spectrum disorder (ASD) and requested an electroencephalography (EEG) evaluation. The family concomitantly reported slow improvement in speech with therapy, the use of up to 200 words, and the ability to count to 10. The primary care physician reiterated that EEG and imaging studies are not indicated for an isolated ASD diagnosis with no supporting history or physical examination indications. The clinician discussed ASD-recommended therapies with the family. Neurology referral was made per parental request. The patient subsequently presented to neurology at the age of 7 years. The parents reiterated during the initial neurologic developmental history that the patient had shown some improvement with speech and language therapy in the past 18 months, knew as many as 200 to 300 words, and could put some words together into simple sentences. Gross and fine motor development were felt to be within the normal range for age. The parents also reported some scripting, and mild echolalia was noted on examination. Notably, there was no history of language regression. Apart from language delay, the neurologic examination was otherwise normal at initial evaluation. Given this clinical picture, ASD treatment options were again discussed. Despite education, parents continued to request for EEG evaluation as a workup for the etiology of the patient’s ASD. Electroencephalography was ultimately ordered owing to the strong and repeated paternal request despite denial of any seizure-like episodes in the patient. EEG unexpectedly showed extremely frequent, almost constant focal electrographic seizures arising from the T3/T5 electrodes in the speech area of the left temporal lobe, prompting the initiation of oxcarbazepine maintenance therapy. Because of the noted abnormalities on EEG, magnetic resonance imaging (MRI) was obtained. Mild abnormalities were noted on MRI study including possible minimal inferior cerebellar vermian hypoplasia, mildly prominent bodies of the lateral ventricles, and nonspecific, nonenhancing punctate T2 hyperintensities in the subcortical white matter. These findings were not felt to be clinically relevant to the patient’s presentation or seizure evaluation. No repeat imaging was ordered. Hindsight is always 20/20. As a clinician evaluating the patient initially, would you have pursued further workup sooner?
