1. Batebi N, Moghaddam HS, Hasanzadeh A, Fakour Y, Mohammadi MR, Akhondzadeh S. {{Folinic Acid as Adjunctive Therapy in Treatment of Inappropriate Speech in Children with Autism: A Double-Blind and Placebo-Controlled Randomized Trial}}. {Child Psychiatry Hum Dev}. 2020.
This is a double-blind, placebo-controlled randomized trial to investigate the potential therapeutic effects of folinic acid/placebo as an adjuvant to risperidone on inappropriate speech and other behavioral symptoms of autism spectrum disorder (ASD). Fifty-five ASD children (age (mean ± standard deviation) = 13.40 ± 2.00; male/female: 35/20) were evaluated for behavioral symptoms at baseline, week 5, and week 10 using the aberrant behavior checklist-community (ABC-C). Folinic acid dosage was 2 mg/kg up to 50 mg per day for the entire course of the study. The repeated measures analysis showed significant effect for time × treatment interaction on inappropriate speech (F = 3.51; df = 1.61; P = 0.044), stereotypic behavior (F = 4.02; df = 1.37; P = 0.036), and hyperactivity/noncompliance (F = 6.79; df = 1.66; P = 0.003) subscale scores. In contrast, no significant effect for time × treatment interaction was found on lethargy/social withdrawal (F = 1.06; df = 1.57; P = 0.336) and irritability (F = 2.86; df = 1.91; P = 0.064) subscale scores. Our study provided preliminary evidence suggesting that folinic acid could be recommended as a beneficial complementary supplement for alleviating speech and behavioral symptoms in children with ASD.Clinical trial registeration: This trial was registered in the Iranian Registry of Clinical Trials ( www.irct.ir ; No. IRCT20090117001556N114).
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2. Cantin-Garside KD, Srinivasan D, Ranganathan S, White SW, Nussbaum MA. {{Multi-level modeling with nonlinear movement metrics to classify self-injurious behaviors in autism spectrum disorder}}. {Sci Rep}. 2020; 10(1): 16699.
Self-injurious behavior (SIB) is among the most dangerous concerns in autism spectrum disorder (ASD), often requiring detailed and tedious management methods. Sensor-based behavioral monitoring could address the limitations of these methods, though the complex problem of classifying variable behavior should be addressed first. We aimed to address this need by developing a group-level model accounting for individual variability and potential nonlinear trends in SIB, as a secondary analysis of existing data. Ten participants with ASD and SIB engaged in free play while wearing accelerometers. Movement data were collected from > 200 episodes and 18 different types of SIB. Frequency domain and linear movement variability measures of acceleration signals were extracted to capture differences in behaviors, and metrics of nonlinear movement variability were used to quantify the complexity of SIB. The multi-level logistic regression model, comprising of 12 principal components, explained > 65% of the variance, and classified SIB with > 75% accuracy. Our findings imply that frequency-domain and movement variability metrics can effectively predict SIB. Our modeling approach yielded superior accuracy than commonly used classifiers (~ 75 vs. ~ 64% accuracy) and had superior performance compared to prior reports (~ 75 vs. ~ 69% accuracy) This work provides an approach to generating an accurate and interpretable group-level model for SIB identification, and further supports the feasibility of developing a real-time SIB monitoring system.
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3. Ceylan MF, Tural Hesapcioglu S, Yavas CP, Senat A, Erel O. {{Serum Is-Modified Albumin Levels, Myeloperoxidase Activity and Peripheral Blood Mononuclear Chemia cells in Autism Spectrum Disorder (ASD)}}. {J Autism Dev Disord}. 2020.
Genetic, neurobiological, neurochemical, environmental factors and their interactions contribute to autism phenotypes. Blood from 48 (age range: 4-17) autism spectrum disorder diagnosed patients (ASD) and 38 age- and gender-matched healthy control subjects was analyzed for numbers of neutrophils, lymphocytes, monocytes, albumin, serum Ischemia-Modified Albumin (IMA) levels and myeloperoxidase activity. The serum IMA levels, myeloperoxidase activity and peripheral blood mononuclear cells count were significantly higher in ASD cases than in the control subjects. There were no significant differences in albumin levels between the patient and control groups. These results suggest that the immune system, oxidative stress and myeloperoxidase activity may be activated in ASD. There is a clinical benefit from the early detection of ASD using myeloperoxidase activity, IMA levels and monocyte counts.
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4. Holroyd TA, Sauer MA, Limaye RJ. {{Vaccine decision-making among parents of children on Medicaid with and without autism spectrum disorder}}. {Vaccine}. 2020; 38(43): 6777-84.
BACKGROUND: The belief that there is a link between the MMR vaccine and autism has led to a decline in childhood-immunization uptake and a resurgence of preventable infectious diseases. This study aimed to understand how the vaccine decision-making process differed between parents with a child diagnosed with autism and parents with a child that did not have autism. METHODS: Interviews were conducted in September-December 2018 with 24 racially and demographically diverse parents of children on Medicaid at two Baltimore clinics serving Medicaid patients, one of which only serves families of children with autism. We conducted a semi-structured, qualitative, in-person in-depth interview study to explore parental perceptions of vaccine-decision making. Interviews with participants were transcribed from audio recordings. We then extracted and analyzed the types of barriers each participant experienced. RESULTS: Parent descriptions of their vaccine decision-making process focused on three primary factors: concerns about vaccines, the relationship between the child’s provider and the parent, and risk perception. These findings are in line with existing literature that has articulated key factors in the vaccine decision-making process generally. Parents of a child with autism were more likely to consider the idea that vaccines were linked to autism in their decision-making process, and were less likely to be influenced by personalized recommendations from the child’s health care provider. CONCLUSION: Parental concerns about vaccines, the parent-provider relationship, and vaccine risk perception all contribute to vaccine decision-making among parents of children with and without ASD. However, providers may find it especially difficult to manage parental misconceptions about vaccines and developmental disabilities. Future studies can identify alternative communication techniques and determine what mechanisms may be more effective in encouraging vaccine acceptance among parents of children with ASD.
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5. Jain S, Thiagarajan B, Shi Z, Clabaugh C, Matarić MJ. {{Modeling engagement in long-term, in-home socially assistive robot interventions for children with autism spectrum disorders}}. {Science robotics}. 2020; 5(39).
Socially assistive robotics (SAR) has great potential to provide accessible, affordable, and personalized therapeutic interventions for children with autism spectrum disorders (ASD). However, human-robot interaction (HRI) methods are still limited in their ability to autonomously recognize and respond to behavioral cues, especially in atypical users and everyday settings. This work applies supervised machine-learning algorithms to model user engagement in the context of long-term, in-home SAR interventions for children with ASD. Specifically, we present two types of engagement models for each user: (i) generalized models trained on data from different users and (ii) individualized models trained on an early subset of the user’s data. The models achieved about 90% accuracy (AUROC) for post hoc binary classification of engagement, despite the high variance in data observed across users, sessions, and engagement states. Moreover, temporal patterns in model predictions could be used to reliably initiate reengagement actions at appropriate times. These results validate the feasibility and challenges of recognition and response to user disengagement in long-term, real-world HRI settings. The contributions of this work also inform the design of engaging and personalized HRI, especially for the ASD community.
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6. Jiang M, Francis SM, Tseng A, Srishyla D, DuBois M, Beard K, Conelea C, Zhao Q, Jacob S. {{Predicting Core Characteristics of ASD Through Facial Emotion Recognition and Eye Tracking in Youth}}. {Annual International Conference of the IEEE Engineering in Medicine and Biology Society IEEE Engineering in Medicine and Biology Society Annual International Conference}. 2020; 2020: 871-5.
Autism Spectrum Disorder (ASD) is a heterogeneous neurodevelopmental disorder (NDD) with a high rate of comorbidity. The implementation of eye-tracking methodologies has informed behavioral and neurophysiological patterns of visual processing across ASD and comorbid NDDs. In this study, we propose a machine learning method to predict measures of two core ASD characteristics: impaired social interactions and communication, and restricted, repetitive, and stereotyped behaviors and interests. Our method extracts behavioral features from task performance and eye-tracking data collected during a facial emotion recognition paradigm. We achieved high regression accuracy using a Random Forest regressor trained to predict scores on the SRS-2 and RBS-R assessments; this approach may serve as a classifier for ASD diagnosis.
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7. Konkel L. {{Phthalates and Autistic Traits: Exploring the Association between Prenatal Exposures and Child Behavior}}. {Environmental health perspectives}. 2020; 128(10): 104001.
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8. Macoun SJ, Schneider I, Bedir B, Sheehan J, Sung A. {{Pilot Study of an Attention and Executive Function Cognitive Intervention in Children with Autism Spectrum Disorders}}. {J Autism Dev Disord}. 2020.
This pilot study investigated the efficacy of a game-based cognitive training program (Caribbean Quest; CQ) for improving attention and executive function (EF) in school-aged children with Autism Spectrum Disorder (ASD). CQ is a ‘serious game’ that uses a hybrid process-specific/compensatory approach to remediate attention and EF abilities through repetitive, hierarchically graded exercises delivered in an adaptive format. Game-play is accompanied by instruction in metacognitive strategies delivered by an adult trainer. Twenty children diagnosed with ASD (ages 6-12 years) completed 12 h of intervention in schools over 8-10 weeks that was facilitated by a trained Research Assistant. Pre-post testing indicated near transfer gains for visual working memory and selective attention and far transfer effects for math fluency. Exit interviews with parents and school staff indicated anecdotal gains in attention, EF, emotion-regulation, flexibility, communication, and social skills. Overall, this study provides preliminary support for the feasibility and potential efficacy of the CQ when delivered in schools to children with ASD.
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9. Oakley BF, Tillmann J, Ahmad J, Crawley D, San José Cáceres A, Holt R, Charman T, Banaschewski T, Buitelaar J, Simonoff E, Murphy D, Loth E. {{How do core autism traits and associated symptoms relate to quality of life? Findings from the Longitudinal European Autism Project}}. {Autism}. 2020: 1362361320959959.
Previous studies suggest that some autistic individuals report lower satisfaction, or well-being, with different aspects of everyday life than those without autism. It is unclear whether this might be partly explained by symptoms of anxiety and/or depression, which affect at least 20%-50% of autistic people. In this study, we measured individual differences in well-being in 573 six to thirty-year-olds with and without a diagnosis of autism. We investigated whether individual differences in well-being were explained by autism traits (e.g. social-communication difficulties) and/or anxiety and depression symptoms. We showed that, though well-being was lower for some autistic individuals, compared to those without autism, many autistic individuals reported good well-being. Where well-being was reduced, this was particularly explained by depression symptoms, across all ages. For children/adolescents, anxiety and social-communication difficulties were also related to some aspects of well-being. Our study suggests that support and services for improving mental health, especially depression symptoms, may also improve broader outcomes for autistic people.
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10. O’Keeffe C, Dominguez MC, O’Rourke E, Lynch T, Reilly RB. {{Decreased Theta Power Reflects Disruption in Postural Control Networks of Fragile X Premutation Carriers()}}. {Annual International Conference of the IEEE Engineering in Medicine and Biology Society IEEE Engineering in Medicine and Biology Society Annual International Conference}. 2020; 2020: 2845-8.
FRM1 premutation carriers exhibit various subtle deficits in balance and stability, prior to the development of the movement disorder Fragile X Associated Tremor/Ataxia Syndrome (FXTAS). Force plate posturography has increasingly been combined with the temporal sensitive imaging methods such as EEG to offer insight into the neural mechanisms which govern postural control. This study investigated cortical theta power during continuous balance and its relationship to balance performance in Fragile X premutation carriers. Eight premutation carriers and 6 controls stood on a force platform under altered sensory and cognitive conditions while postural sway and high-density EEG data were simultaneously recorded. Carriers exhibited greater sway area when sensory input was reduced (p=0.01) and cognitive load was increased (p=0.01), as well as significantly reduced frontal theta power compared to the Control Group. The relationship between theta power and postural control seen in the control group may indicate an increase in error detection caused by reduced visual input and greater discrepancies between expected and actual balance state. While the lower theta power in frontal regions of carriers may indicate a disruption in neural networks underpinning postural control. Such results provide new insight into the neural correlates of balance control in Fragile X premutation carriers.
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11. Reynolds CD, Nolan SO, Smith GD, Jefferson TS, Hodges SL, Brewster AL, Lugo JN. {{Increased expression of Fragile X mental retardation protein in malformative lesions of patients with focal cortical dysplasia}}. {Neuroreport}. 2020; 31(14): 1036-41.
OBJECTIVE: Focal cortical dysplasia (FCD) accounts for nearly half of all cases of medically refractory epilepsy in the pediatric and adult patient populations. This neurological disorder stems from localized malformations in cortical brain tissue due to impaired neuronal proliferation, differentiation, and migration patterns. Recent studies in animal models have highlighted the potential role of the Fragile X mental retardation protein (FMRP) levels in FCD. The purpose of this study was to investigate the status of FMRP activation in cortical brain tissues surgically resected from patients with FCD. In parallel, this study also investigated protein levels within the PI3K/AKT/mTOR and canonical Wnt signaling pathways. METHODS: Pathologic tissue from malformative lesions of FCD patients with medically refractory epilepsy was compared to relatively normal control non-epileptic tissue from patients with intracranial neoplasms. A series of western blotting assays were performed to assess key proteins in the PI3K/AKT/mTOR, canonical Wnt signaling pathways, and FMRP. RESULTS: There was suppression of S235/236-phosphorylated S6, GSK3α, and GSK3β protein levels in samples derived from FCD patients, compared to non-epileptic controls. FCD samples also had significantly greater levels of total and S499-phosphorylated FMRP. CONCLUSION: These findings support our hypothesis that malformative lesions associated with FCD are characterized by high levels of FMRP activation along with dysregulation of both PI3K/AKT/mTOR and canonical Wnt signaling. These novel clinical findings extend previous work in animal models, further suggesting a potential unforeseen role of GSK3α and GSK3β in the pathophysiology of FCD and refractory epilepsy.
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12. Rosales MK, Wilder DA, Montalvo M, Fagan B. {{Evaluation of the high-probability instructional sequence to increase compliance with multiple low-probability instructions among children with autism}}. {Journal of applied behavior analysis}. 2020.
The high-probability (high-p) instructional sequence typically consists of the delivery of a series of high-p instructions immediately followed by the delivery of a low-probability (low-p) instruction and is a commonly used procedure to increase compliance among children with intellectual disabilities. In the current study, we used withdrawal designs to evaluate the use of the high-p sequence to increase compliance with a series of 2 or 3 low-p instructions among 3 children with autism. The sequence was moderately effective in increasing compliance with all low-p instructions for 2 participants. Compliance exhibited by the 3rd participant, for whom the high-p sequence was ineffective, increased when differential reinforcement was delivered. We discuss the utility of the high-p sequence to increase compliance with multiple instructions and the putative mechanisms responsible for the effects of the sequence.
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13. Sáez-Suanes GP, García-Villamisar D, Del Pozo Armentia A, Dattilo J. {{Emotional dysregulation and uncertainty intolerance as transdiagnostic mediators of anxiety in adults with autism spectrum disorders and intellectual disability}}. {Res Dev Disabil}. 2020; 106: 103784.
BACKGROUND: There is extensive documentation supporting the comorbidity of anxiety and autistic spectrum disorder (ASD). Transdiagnostic factors such as executive functions, emotion regulation, and uncertainty intolerance are associated with anxiety in ASD. AIM: The primary aim of this paper is to study anxiety symptoms in adults with ASD and ID and their relationship with transdiagnostic variables. METHOD: 121 adults (M = 35.46 years, SD = 9.46) with ASD and intellectual disabilities (ID) were evaluated to determine the predictive and mediating role of executive functioning, emotional regulation and intolerance to uncertainty. RESULTS: Hierarchical linear regression showed uncertainty intolerance was a predictor of anxiety. A multiple mediation analysis supported the mediating role of uncertainty intolerance and emotional regulation between ASD and anxiety. CONCLUSIONS AND IMPLICATIONS: These findings suggest that interventions designed to reduce anxiety symptoms in people with ASD and ID should include among their goals emotional regulation and especially intolerance of uncertainty.
