1. Adams D, Simpson K, Keen D. {{Exploring Anxiety at Home, School, and in the Community Through Self-Report From Children on the Autism Spectrum}}. {Autism Res};2019 (Dec 2)
Research investigating anxiety in children on the autism spectrum usually reports caregiver rather than self-report perspectives. This study aimed to document children’s own descriptions of their anxiety symptomatology by combining profiles on a standardized autism-specific self-report measure of anxiety (ASC-ASD-C) with the answers from closed- and open-answer questions about anxiety across home, school, and community settings. Across the sample of 113 children on the spectrum aged 6-14 years, the two most frequently endorsed items on the ASC-ASD-C were from the Uncertainty and Performance Anxiety subscales, and the least endorsed were both from the Anxious Arousal subscale. Almost all (96.5%) of the children on the spectrum reported experiencing anxiety in at least one setting, with 40.7% reporting anxiety in all three contexts (home, school, and community). Approximately half of the sample felt their anxiety goes unrecognized by others at school and almost 60% felt it was unrecognized by others when out in the community. The proportion of children reporting having someone to help reduce their anxiety differed across home (86%), school (76%), and community (45%) settings. This highlights the importance of understanding anxiety and its impact, not only within the context of autism but also for each particular child. Autism Res 2019. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: There has been a lot of research focusing on anxiety and autism, but most of it has used parent reports, rather than asking the child themselves. This study summarizes data from 113 children on the autism spectrum, aged 6-14 years. It reports the symptoms of anxiety that these children most and least commonly experience. The results suggest only 40-50% of children feel that others are able to recognize their anxiety at school and when out in the community, suggesting that more training is needed to help adults in these settings to recognize and support anxiety.
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2. Ahmad SF, Ansari MA, Nadeem A, Bakheet SA, Alsanea S, Al-Hosaini KA, Mahmood HM, Alzahrani MZ, Attia SM. {{Inhibition of tyrosine kinase signaling by tyrphostin AG126 downregulates the IL-21/IL-21R and JAK/STAT pathway in the BTBR mouse model of autism}}. {Neurotoxicology};2019 (Dec 4)
Autism spectrum disorder (ASD) comprises a broad range of neurodevelopmental disorders that are associated with deficits in social interaction and communication. The tyrosine kinase inhibitor tyrphostin AG126 represents a promising therapeutic agent for several neuroinflammatory disorders. There are currently no treatments available that can improve ASD and we previously showed that AG126 treatment exerts beneficial effects on BTBR T(+) Itpr3(tf)/J (BTBR) mice, a model for autism that shows the core features of ASD; however, the immunological mechanisms and molecular targets associated with this effect were previously unclear. This study was undertaken to delineate the neuroprotective effect of AG126 on BTBR mice. Here, using this mouse model, we investigated the effects of AG126 administration on IL-21R, IL-21, IL-22, TNF-alpha, NOS2, STAT3, IL-27, and Foxp3 production by CD8(+) T cells in the spleen by flow cytometry. We further explored the mRNA and protein expression of IL-21, IL-22, IL-1beta, TNF-alpha, NOS2, JAK1, STAT3, IL-27, and Foxp3 in brain tissue by RT-PCR, and western blotting. We found that BTBR mice treated with AG126 exhibited significant decreases in IL-21R-, IL-21-, IL-22-, TNF-alpha-, NOS2-, STAT3-producing, and increases in IL-27- and Foxp3-producing, CD8(+) T cells. Our results further demonstrated that AG126 treatment effectively decreased IL-21, IL-22, IL-1beta, TNF-alpha, NOS2, JAK1, and STAT3, and increased IL-27 and Foxp3 mRNA and protein expression in brain tissues. Our findings suggest that AG126 elicits a neuroprotective response through downregulation of the IL-21/IL-21R and JAK/STAT pathway in BTBR mice, which could represent a promising novel therapeutic target for ASD treatment.
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3. Arnold S, Foley KR, Hwang YIJ, Richdale AL, Uljarevic M, Lawson LP, Cai RY, Falkmer T, Falkmer M, Lennox NG, Urbanowicz A, Trollor J. {{Cohort profile: the Australian Longitudinal Study of Adults with Autism (ALSAA)}}. {BMJ Open};2019 (Dec 4);9(12):e030798.
PURPOSE: There is a significant knowledge gap regarding the lives of adults on the autism spectrum. Some literature suggests significant health and mental health inequalities for autistic adults, yet there is a lack of comprehensive longitudinal studies exploring risk factors. Further, most research does not include the perspective of autistic adults in its conduct or design. Here, we describe the baseline characteristics and inclusive research approach of a nationwide longitudinal study. PARTICIPANTS: The Autism Cooperative Research Centre for Living with Autism’s Australian Longitudinal Study of Adults with Autism (ALSAA) is a questionnaire-based longitudinal study of autistic adults (25+ years old) with follow-up at 2-year intervals. Autistic advisors were involved in each stage of research apart from data analysis. Three questionnaires were developed: self-report, informant report (ie, proxy report) and carers (ie, carer experiences and characteristics). FINDINGS TO DATE: An inclusive research protocol was developed and agreed with autistic advisors. Baseline data were collected from 295 autistic adults (M=41.8 years, SD=12.0) including 42 informant responses, 146 comparison participants and 102 carers. The majority of autistic participants (90%) had been diagnosed in adulthood (M=35.3 years, SD=15.1). When compared with controls, autistic adults scored higher on self-report measures of current depression and anxiety. Participant comments informed ongoing data gathering. Participants commented on questionnaire length, difficulty with literal interpretation of forced response items and expressed gratitude for research in this area. FUTURE PLANS: A large comprehensive dataset relating to autistic adults and their carers has been gathered, creating a good platform for longitudinal follow-up repeat surveys and collaborative research. Several outputs are in development, with focus on health service barriers and usage, caregivers, impact of diagnosis in adulthood, further scale validations, longitudinal analyses of loneliness, suicidal ideation, mental illness risk factors and other areas. Baseline data confirm poorer mental health of autistic adults. The ALSAA demonstrates a working approach to inclusive research.
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4. Bickford CD, Oberlander TF, Lanphear NE, Weikum WM, Janssen PA, Ouellette-Kuntz H, Hanley GE. {{Identification of Pediatric Autism Spectrum Disorder Cases Using Health Administrative Data}}. {Autism Res};2019 (Dec 4)
Administrative data are frequently used to identify Autism Spectrum Disorder (ASD) cases in epidemiological studies. However, validation studies on this mode of case ascertainment have lacked access to high-quality clinical diagnostic data and have not followed published reporting guidelines. We report on the diagnostic accuracy of using readily available health administrative data for pediatric ASD case ascertainment. The validation cohort included almost all the ASD-positive children born in British Columbia, Canada from April 1, 2000 to December 31, 2009 and consisted of 8,670 children in total. 4,079 ASD-positive and 2,787 ASD-negative children were identified using Autism Diagnostic Observation Schedule (ADOS) and Autism Diagnostic Interview-Revised (ADI-R) assessments done through the British Columbia Autism Assessment Network (BCAAN). An additional 1,804 ADOS/ADI-R assessed ASD-positive children were identified using Ministry of Education records. This prospectively collected clinical data (the diagnostic gold standard) was then linked to each child’s physician billing and hospital discharge data. The diagnostic accuracy of 11 algorithms that used the administrative data to assign ASD case status was assessed. For all algorithms, high positive predictive values (PPVs) were observed alongside low values for other measures of diagnostic accuracy illustrating that PPVs alone are not an adequate measure of diagnostic accuracy. We show that British Columbia’s health administrative data cannot reliably be used to discriminate between children with ASD and children with other developmental disorders. Utilizing these data may result in misclassification bias. Methodologically sound, region-specific validation studies are needed to support the use of administrative data for ASD case ascertainment. Autism Res 2019. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Health administrative data are frequently used to identify Autism Spectrum Disorder (ASD) cases for research purposes. However, previous validation studies on this sort of case identification have lacked access to high-quality clinical diagnostic data and have not followed published reporting guidelines. We show that British Columbia’s health administrative data cannot reliably be used to discriminate between children with ASD and children with other developmental disorders.
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5. Clark BC, Kopp A, Morey W, Djukic A. {{Serial follow-up of corrected QT interval in Rett syndrome}}. {Dev Med Child Neurol};2019 (Dec 4)
AIM: To identify factors associated with baseline prolonged corrected QT (QTc) and higher risk of QTc prolongation during follow-up in patients with Rett syndrome (RTT). METHOD: A retrospective review of patients receiving an electrocardiogram (ECG) between June 2012 and June 2018 was performed. Age, methyl-CpG binding protein 2 gene (MECP2) mutation, RTT Severity Scale (RSSS) score, breathing abnormalities, seizure frequency, medications, and ECG parameters were collected. Prolonged QTc was defined as greater than or equal to 460ms. Comparisons at baseline and during follow-up were made. RESULTS: In total, 129 unique patients (all female) had 349 ECGs. At baseline, 12 (9.3%) had a prolonged QTc (median 474ms, interquartile range 470-486ms) and were more likely to have moderate/severe breathing abnormalities (66.7% vs 24.8%; p=0.005) and take selective serotonin reuptake inhibitors (SSRIs) (41.7% vs 15.4%; p=0.04). There was no difference in age, RSSS score, seizures, or mutation. Twenty-six developed prolonged QTc during a median follow-up of 1 year 7 months (interquartile range 0-3y 6mo). QTc prolongation was associated with p.(Thr158Met) mutation versus the remaining six common mutations (hazard ratio 4.1, 95% confidence interval 1.4-12.0; p=0.01) but not with age, RSSS score, seizures, breathing abnormalities, or SSRIs. INTERPRETATION: Breathing abnormalities and SSRIs were associated with baseline QTc prolongation and those with p.(Thr158Met) mutation were more likely to develop prolonged QTc over time. Identification of patients with prolonged QTc warrants increased clinical monitoring.
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6. Dekker LP, Visser K, van der Vegt EJM, Maras A, van der Ende J, Tick NT, Verhulst FC, Greaves-Lord K. {{Insight into Informant Discrepancies Regarding Psychosexual Functioning of Adolescents with and without Autism Spectrum Disorder}}. {J Res Adolesc};2019 (Dec 4)
The private nature of psychosexual functioning leads adolescents and their parents to have different perspectives, which highlights studying parent-child informant discrepancies in this domain. We investigated informant discrepancy in psychosexual functioning, using the self-report and parent report versions of the Teen Transition Inventory (TTI), of adolescents with autism spectrum disorder (ASD; 136 parent-child dyads) compared to adolescents from the general population (GP; 70 parent-child dyads). Significantly larger informant discrepancies exist in ASD dyads than GP dyads in most domains of psychosexual functioning, except for Body image, Sexual behavior, and Confidence in the future. It is important to use and pay attention to both informants, as discrepancies are relevant for both research and clinical practice regarding psychosexual functioning.
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7. Du RY, Yiu CKY, King NM. {{Health- and oral health-related quality of life among preschool children with autism spectrum disorders}}. {Eur Arch Paediatr Dent};2019 (Dec 4)
PURPOSE: To assess the health-related quality of life (HrQoL) and oral health-related quality of life (OHrQoL) of preschool children with autism spectrum disorders (ASD) and to determine the associated factors. METHODS: A case-control study of preschool children with and without ASD was undertaken. H&OHrQoL were assessed employing Pediatric Quality-of-Life Inventory Version 4.0 (PedsQL 4.0) and Early Childhood Oral Health Impact Scale (ECOHIS). Differences in PedsQL and ECOHIS scores were determined between groups and correlation between PedsQL and ECOHIS was explored. Regression analyses were conducted to determine key factors associated with H&OHrQoL. RESULTS: Parents of 510 children (253 cases and 257 controls) completed the H&OHrQoL questionnaire assessments. Significant difference in PedsQL (p < 0.001) and ECOHIS (p < 0.001) scores was apparent between children with and without ASD. There was a positive and weak correlation between PedsQL and ECOHIS scores (r = - 0.45, p < 0.01). In regression analyses, the presence of ASD was associated with an increased likelihood of having lower PedsQL (OR 0.10, 95% CI 0.06-0.15, p < 0.001) and higher ECOHIS scores (OR 2.34, 95% CI 1.60-3.42, p < 0.001). CONCLUSIONS: Differences in H&OHrQoL exist among preschool children with and without ASD. There was a significant but weak correlation between children's H&OHrQoL. Both H&OHrQoL were associated with autism spectrum disorders. Lien vers le texte intégral (Open Access ou abonnement)
8. Durkin MS, Wolfe BL. {{Trends in Autism Prevalence in the U.S.: A Lagging Economic Indicator?}}. {J Autism Dev Disord};2019 (Dec 4)
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9. Goris J, Brass M, Cambier C, Delplanque J, Wiersema JR, Braem S. {{The relation between preference for predictability and autistic traits}}. {Autism Res};2019 (Dec 4)
A common idea about individuals with autism spectrum disorder (ASD) is that they have an above-average preference for predictability and sameness. However, surprisingly little research has gone toward this core symptom, and some studies suggest the preference for predictability in ASD might be less general than commonly assumed. Here, we investigated this important symptom of ASD using three different paradigms, which allowed us to measure preference for predictability under well-controlled experimental conditions. Specifically, we used a dimensional approach by investigating correlations between autistic traits (as measured with the Autism-Spectrum Quotient and Social Responsiveness Scale in a neurotypical population) and the scores on three different tasks. The « music preference » task assessed preferences for tone sequences that varied in predictability. The « perceptual fluency » task required participants to evaluate stimuli that were preceded by a similar versus dissimilar subliminally presented prime. The « gambling » task presented four decks of cards that had equal outcome probabilities but varied in predictability. We observed positive correlations between autistic traits and a preference for predictability in both the music preference and perceptual fluency task. We did not find our hypothesized correlation with gambling behavior but did observe a post hoc correlation showing that participants with more autistic traits were faster to choose the predictable deck. Together, these findings show that a relation between autistic traits and preference for predictability can be observed in a standardized lab environment, and should be considered an important first step toward a better, more mechanistic understanding of insistence on sameness in ASD. Autism Res 2019. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: A core symptom of autism spectrum disorder (ASD) is a strong preference for predictability, but little research has gone toward it. We show that neurotypical adults with more autistic traits have stronger preferences for predictable tunes, evaluate images that can be predicted as more beautiful, and are faster in choosing a gambling option resulting in predictable reward. These results offer the first important evidence that insistence on sameness in ASD can be studied in controlled lab settings.
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10. Haggarty CJ, Malinowski P, McGlone FP, Walker SC. {{Autistic traits modulate cortical responses to affective but not discriminative touch}}. {Eur J Neurosci};2019 (Dec 2)
The sense of touch is primarily considered a discriminative and exteroceptive sense, facilitating the detection, manipulation and exploration of objects, via an array of low threshold mechanoreceptors and fast conducting Abeta afferents. However, a class of unmyelinated, low threshold mechanoreceptors identified in the hairy skin of mammals have been proposed to constitute a second, anatomically distinct system coding the affective qualities of touch. Unlike Abetas, which increase their firing rate linearly with the velocity of a stimulus moving across their receptive field, the response of these C-tactile afferents (CTs) is described by an inverted ‘U’ curve fit, responding optimally to a skin temperature stimulus moving at between 1-10cm/s. Given the distinct velocity tuning of these fast and slow touch fibres, here we used ERPs to compare the time course of neural responses to 1st (fast) and 2nd (slow) touch systems. We identified a higher amplitude P300 in response to fast, Abeta targeted, versus slow CT-targeted, stroking touch. In contrast, we identified a previously described, C-fibre specific, ultra-late-potential (ULP) associated with CT-targeted input. Of special note as regards the function of CTs is that the amplitude of the ULP was negatively correlated with self-reported levels of autistic traits, which is consistent with the hypothesised affective and social significance of this response. Taken together these findings provide further support for distinct discriminative and affective touch systems and suggests the temporal resolution of EEG provides an as yet underutilised tool for exploring individual differences in response sensitivity to CT targeted touch.
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11. Harrop C, Jones DR, Sasson NJ, Zheng S, Nowell SW, Parish-Morris J. {{Social and Object Attention Is Influenced by Biological Sex and Toy Gender-Congruence in Children With and Without Autism}}. {Autism Res};2019 (Dec 4)
Emerging research suggests social attention in autism spectrum disorder (ASD) girls is enhanced relative to ASD boys but may also be affected by the type of social and nonsocial content presented. This study examined how biological sex and gender norms interact to influence visual attention in 79 school-aged children observing scenes that included gender-associated toys and actors of both sexes. Attention to social (faces) and object activity (hands with toys) stimuli was measured. Previously described distinctions between social attention in ASD boys and girls were replicated, with ASD girls looking more at faces than ASD boys. Irrespective of diagnosis, males and females attended more to actors that shared their same sex, and attended more to toys with gender-associations that were consistent with their own sex, suggesting that social and object salience increases for children under sex-consistent conditions. Importantly, ASD and typically developing (TD) children increased their gaze to faces when male actors were shown playing with female-associated toys, suggesting that both groups of children are sensitive to societal messages about the acceptability of males playing with female-associated toys. Our findings provide further evidence of heightened attention to faces in ASD girls relative to ASD boys, and indicate that social attention in ASD and TD children is influenced by who (male or female actor) and what (male- or female-associated toy) is being observed. Collectively, these results present a nuanced profile of attention in ASD that adds to a growing body of research indicating subtle phenotypic differences in ASD girls that may impact identification, assessment, and intervention. Autism Res 2019. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Sex differences observed in typical development may also be present in individuals with autism. In this study, we developed an eye-tracking paradigm featuring videos of boys and girls playing with toys that varied in their gender associations. Attention to faces differed between autistic and non-autistic children but was also influenced by the sex of the actor and gender-association of toys. Autistic females demonstrated subtle attention differences that distinguished them from autistic males and may influence referral, diagnosis, and intervention.
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12. Holloway CA, Munro N, Jackson J, Phillips S, Ropar D. {{Exploring the autistic and police perspectives of the custody process through a participative walkthrough}}. {Res Dev Disabil};2019 (Dec 4);97:103545.
BACKGROUND: Research suggests that autistic individuals may be more likely to come into contact with police and have more negative experiences in police custody. However, limited information about the difficulties they experience during the custody process is available. AIMS: This study explores the experiences of autistic individuals and officers during a walkthrough of the custody process to identify specific difficulties in these encounters and what support is needed to overcome these. METHODS AND PROCEDURES: A participative walkthrough method was developed to provide autistic individuals and officers an interactive opportunity to identify areas where further support in the custody process was needed. Two autistic participants and three officers took part in the study. OUTCOMES AND RESULTS: Autistic participants reported negative experiences due to: i) the emotional impact of the physical setting and custody process ii) communication barriers leading to increased anxiety and iii) exposure to sensory demands. Officers highlighted three factors which limit their ability to support autistic individuals effectively: i) the custody context ii) barriers to communication and iii) knowledge and understanding of autism. CONCLUSIONS AND IMPLICATIONS: Adjustments are needed to the custody process and environment to support interactions between autistic individuals and officers and improve the overall wellbeing of autistic individuals.
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13. Kaneko S, Kato TA, Makinodan M, Komori T, Ishida R, Kishimoto N, Takahashi M, Yasuda Y, Hashimoto R, Iwasaka H, Tanaka A, Uchida Y, Kanba S, Kishimoto T. {{The Self-Construal Scale: A Potential Tool for Predicting Subjective Well-Being of Individuals With Autism Spectrum Disorder}}. {Autism Res};2019 (Dec 2)
Despite accumulating evidence that culture shapes the symptoms of autism spectrum disorder (ASD), no studies have yet applied the Self-Construal Scale to individuals with ASD. We compared the self-construals (measured using the Self-Construal Scale) of 31 high-functioning Japanese individuals with ASD with those of 60 typically developing (TD) individuals. We also examined how the self-construals of individuals with ASD related to their intelligence quotient, adverse childhood experiences, attention deficit hyperactivity disorder, ASD symptoms during adulthood and preschool years, and subjective well-being. Individuals with ASD were more likely to display independent self-construals than were TD individuals; unexpectedly, however, a substantial proportion of individuals with ASD (43.8%) displayed relatively interdependent self-construals. Among individuals with ASD, self-construals were significantly associated with ASD symptoms during preschool years, and with satisfaction of the need for autonomy and frustration of the need for relatedness. Evaluating self-construals can help predict the subjective well-being of high-functioning individuals with ASD. Moreover, the Self-Construal Scale may be useful for understanding the heterogeneous phenotypes of ASD, based on its association with autistic symptoms during preschool years, suggesting that the scale is a potential tool to develop efficient interventions for high-functioning individuals with ASD. Autism Res 2019. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Autism Spectrum Disorders (ASD) are a group of disorders presenting a variety of symptoms and biological origins that can complicate choosing an intervention best suited for improving well-being. Results indicate that a self-construal scale could help understand individuals with high-functioning ASD by independent and interdependent self-construals that are associated with ASD symptoms during preschool years and adult subjective well-being. Our findings suggest that this scale can help understand ASD and select appropriate interventions.
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14. Kim SH, Buzzell G, Faja S, Choi YB, Thomas HR, Brito NH, Shuffrey LC, Fifer WP, Morrison FD, Lord C, Fox N. {{Neural dynamics of executive function in cognitively able kindergarteners with autism spectrum disorders as predictors of concurrent academic achievement}}. {Autism};2019 (Dec 3):1362361319874920.
Although electrophysiological (electroencephalography) measures of executive functions (e.g. error monitoring) have been used to predict academic achievement in typically developing children, work investigating a link between error monitoring and academic skills in children with autism spectrum disorder is limited. In this study, we employed traditional electrophysiological and advanced time-frequency methods, combined with principal component analyses, to extract neural activity related to error monitoring and tested their relations to academic achievement in cognitively able kindergarteners with autism spectrum disorder. In total, 35 cognitively able kindergarteners with autism spectrum disorder completed academic assessments and the child-friendly « Zoo Game » Go/No-go task at school entry. The Go/No-go task successfully elicited an error-related negativity and error positivity in children with autism spectrum disorder as young as 5 years at fronto-central and posterior electrode sites, respectively. We also observed increased response-related theta power during errors relative to correct trials at fronto-central sites. Both larger error positivity and theta power significantly predicted concurrent academic achievement after controlling for behavioral performance on the Zoo Game and intelligence quotient. These results suggest that the use of time-frequency electroencephalography analyses, combined with traditional event-related potential measures, may provide new opportunities to investigate neurobiological mechanisms of executive function and academic achievement in young children with autism spectrum disorder.
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15. Loi E, Moi L, Blois S, Bacchelli E, Vega Benedetti AF, Cameli C, Fadda R, Maestrini E, Carta M, Doneddu G, Zavattari P. {{ELMOD3-SH2D6 gene fusion as a possible co-star actor in autism spectrum disorder scenario}}. {J Cell Mol Med};2019 (Dec 4)
Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders characterized by high heritability. It is known that genetic factors contribute to ASD pathogenesis. In particular, copy number variants (CNVs) are involved in ASD susceptibility and can affect gene expression regulation. 2p11.2 microdeletions encompassing ELMOD3, CAPG and SH2D6 genes have been described in four unrelated ASD families. The present study revealed that this microdeletion is responsible for the production of a chimeric transcript generated from the fusion between ELMOD3 and SH2D6. The identified transcript showed significantly higher expression levels in subjects carrying the deletion compared to control subjects, suggesting that it is not subjected to nonsense-mediated decay and might encode for a chimeric protein. In conclusion, this study suggests the possible involvement of this gene fusion, together with the other previously identified variants, in ASD.
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16. Pacheva I, Ivanov I. {{Targeted biomedical treatment for Autism Spectrum Disorder}}. {Curr Pharm Des};2019 (Dec 4)
BACKGROUND: A diagnosis of autism spectrum disorders (ASD) represents presentations with impairment in communication and behaviour that vary considerably in their clinical manifestations, and etiology as well as in their likely pathophysiology. A growing body of data indicates that deleterious effect of oxidative stress, mitochondrial dysfunction, immune dysregulation and neuroinflammation, as well as their interconnections are important aspects of the pathophysiology of ASD. Glutathione deficiency decreases the mitochondrial protection against oxidants and tumor necrosis factor (TNF)-alpha; immune dysregulation and inflammation inhibit mitochondrial function through TNF-alpha; autoantibodies against the folate receptors underpin cerebral folate deficiency, resulting in disturbed methylation, and mitochondrial dysfunction. Such pathophysiological processes can arise environmental and epigenetic factors as well as their combined interactions, such as environmental toxicant exposures in individuals with (epi)genetically impaired detoxification. The emerging evidence on biochemical alterations in ASD is forming the basis for treatments aimed to target its biological underpinnings, which is of some importance, given the uncertain and slow effects of the various educational interventions most commonly used. METHODS: Literature-based review of the biomedical treatment options for ASD that are derived from established pathophysiological processes. RESULTS: Most proposed biomedical treatments show significant clinical utility only in ASD subgroups, with specified pre-treatment biomarkers that are ameliorated by the specified treatment. For example, folinic acid supplementation has positive effects in ASD patients with identified folate receptor autoantibodies, whilst the clinical utility of methylcobalamine is apparent in ASD patients with impaired methylation capacity. Mitochondrial modulating cofactors should be considered when mitochondrial dysfunction is evident, although further research is required to identify the most appropriate single or combined treatment. Multivitamins/multiminerals formulas, as well as biotin seem appropriate following the identification of metabolic abnormalities, with doses tapered to individual requirements. A promising area, requiring further investigations, is the utilization of antipurinergic therapies, such as low dose suramin. CONCLUSION: The assessment and identification of relevant physiological alterations and targeted intervention is more likely to produce positive treatment outcomes. As such, current evidence indicates the utility of an approach based on personalized and evidence-based medicine, rather than treatment targeted to all that may not always be beneficial (primum non nocere).
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17. Royston R, Oliver C, Howlin P, Dosse A, Armitage P, Moss J, Waite J. {{The Profiles and Correlates of Psychopathology in Adolescents and Adults with Williams, Fragile X and Prader-Willi Syndromes}}. {J Autism Dev Disord};2019 (Dec 4)
Psychopathology is prevalent in Williams (WS), fragile X (FXS) and Prader-Willi (PWS) syndromes. However, little is known about the potential correlates of psychopathology in these groups. A questionnaire study was completed by 111 caregivers of individuals with WS (n = 35); FXS (n = 50) and PWS (n = 26). Mean age was 26 years (range 12-57 years); 74 (67%) were male. Multiple regression analyses indicated that higher rates of health problems and sensory impairments predicted higher psychopathology in WS (p < .0001). In PWS, poorer adaptive ability predicted higher overall psychiatric disturbance (p = .001), generalised anxiety (p = .006) and hyperactivity (p = .003). There were no significant predictors in FXS. This study highlights dissociations in the potential risk markers of psychopathology between genetic syndromes. Implications for intervention are discussed. Lien vers le texte intégral (Open Access ou abonnement)
18. Ruggieri V, Gomez JLC, Martinez MM, Arberas C. {{Aging and Autism: Understanding, Intervention, and Proposals to Improve Quality of Life}}. {Curr Pharm Des};2019 (Dec 4)
BACKGROUND: The population of persons with autism spectrum disorder (ASD) has been increasing and is currently estimated to be 1 in 58 births. The increased prevalence of ASD together with the lack of knowledge on the processes of aging in this population, the support needed in this stage of life, and the associated risk factors, have led to an urgent need for further research. METHODS: This study provides a review of the literature on social- and health-related conditions that may appear when persons with ASD grow old. RESULTS: In addition to the autism-related conditions, different neurological, genetic, and environmental factors may be involved in the process of aging. In this complex setting, this study provides proposals that may guide the development of support services that may improve quality of life for aging people with ASD. CONCLUSION: Aging in ASD is emerging as a growing problem, which requires immediate planning and targetted treatment development.
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19. Sorensen T, Zane E, Feng T, Narayanan S, Grossman R. {{Cross-Modal Coordination of Face-Directed Gaze and Emotional Speech Production in School-Aged Children and Adolescents with ASD}}. {Sci Rep};2019 (Dec 4);9(1):18301.
Autism spectrum disorder involves persistent difficulties in social communication. Although these difficulties affect both verbal and nonverbal communication, there are no quantitative behavioral studies to date investigating the cross-modal coordination of verbal and nonverbal communication in autism. The objective of the present study was to characterize the dynamic relation between speech production and facial expression in children with autism and to establish how face-directed gaze modulates this cross-modal coordination. In a dynamic mimicry task, experiment participants watched and repeated neutral and emotional spoken sentences with accompanying facial expressions. Analysis of audio and motion capture data quantified cross-modal coordination between simultaneous speech production and facial expression. Whereas neurotypical children produced emotional sentences with strong cross-modal coordination and produced neutral sentences with weak cross-modal coordination, autistic children produced similar levels of cross-modal coordination for both neutral and emotional sentences. An eyetracking analysis revealed that cross-modal coordination of speech production and facial expression was greater when the neurotypical child spent more time looking at the face, but weaker when the autistic child spent more time looking at the face. In sum, social communication difficulties in autism spectrum disorder may involve deficits in cross-modal coordination. This finding may inform how autistic individuals are perceived in their daily conversations.
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20. Xu L, Liu Y, Yu J, Li X, Yu X, Cheng H, Li J. {{Characterizing autism spectrum disorder by deep learning spontaneous brain activity from functional near-infrared spectroscopy}}. {J Neurosci Methods};2019 (Nov 30):108538.
BACKGROUND: Functional near-infrared spectroscopy (fNIRS) was used to investigate spontaneous hemodynamic fluctuations in the bilateral temporal cortices for typically developing (TD) children and children with autism spectrum disorder (ASD). NEW METHOD: This paper proposed an approach to estimate the global time-varying behavior of brain activity through the measurement on change in first-order statistical properties directly from fNIRS time series. Then, a deep learning model combining the long-short term memory (LSTM) and convolutional neural network (CNN) was constructed based on the integration strategy with improved bagging algorithm, with the purpose to explore the potential patterns of temporal variation for ASD identification. RESULTS: Based on the theory of stationarity, analysis on the global time-varying behavior of hemodynamic fluctuations in oxy-hemoglobin (HbO2) and deoxy-hemoglobin (Hb) demonstrated that children with ASD showed weaker internal logic, but stronger memory and persistence to random shocks than TD children. Differentiating between ASD and TD with the proposed deep learning approach resulted in high accurate classification with sensitivity of 97.1% and specificity of 94.3%. COMPARISON WITH EXISTING METHODS: Using fNIRS time series of Hb from single optical channel, we achieved a better classification accuracy of 95.7% that was about 8% higher than previous methods with similar data. CONCLUSIONS: The characterization on time-varying behavior of brain activity holds promise for better understanding the underlying causes to ASD. And the deployed deep learning framework with an integration manner has the potential for screening children with risk of ASD.
