1. Akinsolu FT, Balczar E, Kovacs N, Gall T, Harangi M, Varga O. {{Developing a database for Rett syndrome research performed in the European Union: A resource for researchers and stakeholders}}. {Child Care Health Dev}. 2018.
BACKGROUND: For most rare diseases, which are often significantly under-resourced, sufficient information on funding landscape is missing, which may prevent effective use of research resources and be an obstacle to making effective decisions on research. The objective of this research was to create a database of Rett syndrome research projects carried out in the European Union (EU) and to provide a research landscape analysis. METHOD: Websites of organizations funding research projects were identified and systematically checked. Projects were analysed by date, place, funder types, and research topics. RESULTS: The analysis revealed that the total expenditure on Rett syndrome research was almost euro70 million, allocated among 247 projects mostly performed in Italy and the United Kingdom. The main research sponsor was the European Commission. Highlighting research trends and gaps, this work facilitates changes in rare disease research data management. CONCLUSION: This work demonstrates the feasibility of creating an EU-based research database on Rett syndrome projects. It provides a source of information on research development which is useful for individuals, organizations and key players in the private and public sector to make progressive decisions on Rett syndrome research.
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2. Amos GA, Byrne G, Chouinard PA, Godber T. {{Autism Traits, Sensory Over-Responsivity, Anxiety, and Stress: A Test of Explanatory Models}}. {J Autism Dev Disord}. 2018.
The relationship between autistic traits, stress, and anxiety experienced by the general population was investigated using an adult sample that evaluated the suitability of three theoretical models proposed by Green and Ben-Sasson. Participants completed online questionnaires that were analysed using structural equation modelling and partial correlation analyses. Of the models tested, the model that proposed SOR and stress as mediators of the relationship between autistic traits and anxiety was able to explain the variance in the data better than the other models. Based on these findings, we suggest that sensory neutral environments should be considered for the prevention and management of anxiety and stress symptoms for people in the general population with higher levels of autistic traits.
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3. Avery JA, Ingeholm JE, Wohltjen S, Collins M, Riddell CD, Gotts SJ, Kenworthy L, Wallace GL, Simmons WK, Martin A. {{Neural correlates of taste reactivity in autism spectrum disorder}}. {Neuroimage Clin}. 2018; 19: 38-46.
Selective or ‘picky’ eating habits are common among those with autism spectrum disorder (ASD). These behaviors are often related to aberrant sensory experience in individuals with ASD, including heightened reactivity to food taste and texture. However, very little is known about the neural mechanisms that underlie taste reactivity in ASD. In the present study, food-related neural responses were evaluated in 21 young adult and adolescent males diagnosed with ASD without intellectual disability, and 21 typically-developing (TD) controls. Taste reactivity was assessed using the Adolescent/Adult Sensory Profile, a clinical self-report measure. Functional magnetic resonance imaging was used to evaluate hemodynamic responses to sweet (vs. neutral) tastants and food pictures. Subjects also underwent resting-state functional connectivity scans.The ASD and TD individuals did not differ in their hemodynamic response to gustatory stimuli. However, the ASD subjects, but not the controls, exhibited a positive association between self-reported taste reactivity and the response to sweet tastants within the insular cortex and multiple brain regions associated with gustatory perception and reward. There was a strong interaction between diagnostic group and taste reactivity on tastant response in brain regions associated with ASD pathophysiology, including the bilateral anterior superior temporal sulcus (STS). This interaction of diagnosis and taste reactivity was also observed in the resting state functional connectivity between the anterior STS and dorsal mid-insula (i.e., gustatory cortex).These results suggest that self-reported heightened taste reactivity in ASD is associated with heightened brain responses to food-related stimuli and atypical functional connectivity of primary gustatory cortex, which may predispose these individuals to maladaptive and unhealthy patterns of selective eating behavior. Trial registration: (clinicaltrials.gov identifier) NCT01031407. Registered: December 14, 2009.
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4. de Giambattista C, Ventura P, Trerotoli P, Margari M, Palumbi R, Margari L. {{Subtyping the Autism Spectrum Disorder: Comparison of Children with High Functioning Autism and Asperger Syndrome}}. {J Autism Dev Disord}. 2018.
Since Hans Asperger’s first description (Arch Psych Nervenkrankh 117:76-136, 1944), through Lorna Wing’s translation and definition (Psychol Med 11:115-129, 1981), to its introduction in the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM, 1994), Asperger Syndrome has always aroused huge interest and debate, until vanishing in the DSM fifth edition (2013). The debate regarded its diagnostic validity and its differentiation from high functioning autism (HFA). The present study aimed to examine whether AS differed from HFA in clinical profiles and to analyze the impact of DSM-5’s innovation. Differences in cognitive, language, school functioning and comorbidities, were revealed when 80 AS and 70 HFA patients (3-18 years) were compared. Results suggested that an AS empirical distinction within autism spectrum disorder should be clinically useful.
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5. Doenyas C. {{Dietary interventions for autism spectrum disorder: New perspectives from the gut-brain axis}}. {Physiol Behav}. 2018; 194: 577-82.
There is still controversy surrounding the effectiveness of dietary interventions for autism spectrum disorder (ASD), namely the gluten-free/casein free diet and the ketogenic diet. Additionally, as studies mainly investigated their impact on ASD symptoms and behaviors, much remains unknown about their mechanisms of action and physiological effects. Given the recent surge of global interest in the gut-brain axis and its involvement in ASD, we underline the importance of understanding the physiological effects of such restrictive diets that remove certain nutritional items from one’s diet. Some evidence has emerged with findings of the gut-microbial, inflammatory, and neuronal effects of these diets. We propose probiotics as a potential alternative that can serve similar biological purposes as these elimination diets and outline different physiological routes whereby probiotics can lead to improvements for individuals with ASD. We hope that future research can delineate the complete physiological effects of these diets. Such knowledge can guide the creation of more informed interventions, which conserve the components resulting in positive behavioral change while being less restrictive and devoid of the harmful effects of limiting certain nutrients.
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6. Feldman JI, Kuang W, Conrad JG, Tu A, Santapuram P, Simon DM, Foss-Feig JH, Kwakye LD, Stevenson RA, Wallace MT, Woynaroski TG. {{Brief Report: Differences in Multisensory Integration Covary with Sensory Responsiveness in Children with and without Autism Spectrum Disorder}}. {J Autism Dev Disord}. 2018.
Research shows that children with autism spectrum disorder (ASD) differ in their behavioral patterns of responding to sensory stimuli (i.e., sensory responsiveness) and in various other aspects of sensory functioning relative to typical peers. This study explored relations between measures of sensory responsiveness and multisensory speech perception and integration in children with and without ASD. Participants were 8-17 year old children, 18 with ASD and 18 matched typically developing controls. Participants completed a psychophysical speech perception task, and parents reported on children’s sensory responsiveness. Psychophysical measures (e.g., audiovisual accuracy, temporal binding window) were associated with patterns of sensory responsiveness (e.g., hyporesponsiveness, sensory seeking). Results indicate that differences in multisensory speech perception and integration covary with atypical patterns of sensory responsiveness.
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7. Garcia-Pastor T, Salinero JJ, Theirs CI, Ruiz-Vicente D. {{Obesity Status and Physical Activity Level in Children and Adults with Autism Spectrum Disorders: A Pilot Study}}. {J Autism Dev Disord}. 2018.
The purpose of the present study was to compare body composition and physical activity level between children and adults with Autism Spectrum Disorders (ASD). A sample of 78 children, adolescents and adults participated in the study. Anthropometrics and physical activity, using GT1M accelerometer, were assessed. Overweight and obesity prevalence was higher in men vs. male children (p < 0.001) and in men vs. women (p = 0.035). Children recorded more moderate to vigorous physical activity (p = 0.040) than adults. Normal-weight children and adolescents combined as one age group, accomplished more moderate to vigorous physical activity, steps and less sedentary time compared to their overweight and obese counterparts during the weekend. Obesity status may negatively affect physical activity level in ASD individuals. Lien vers le texte intégral (Open Access ou abonnement)
8. Griesi-Oliveira K, Suzuki AM, Alves AY, Mafra A, Yamamoto GL, Ezquina S, Magalhaes YT, Forti FL, Sertie AL, Zachi EC, Vadasz E, Passos-Bueno MR. {{Actin cytoskeleton dynamics in stem cells from autistic individuals}}. {Sci Rep}. 2018; 8(1): 11138.
Several lines of indirect evidence, such as mutations or dysregulated expression of genes related to cytoskeleton, have suggested that cytoskeletal dynamics, a process essential for axons and dendrites development, is compromised in autism spectrum disorders (ASD). However, no study has yet examined whether cytoskeleton dynamics is functionally altered in cells from ASD patients. Here we investigated the regulation of actin cytoskeleton dynamics in stem cells from human exfoliated deciduous teeth (SHEDs) of 13 ASD patients and 8 control individuals by inducing actin filament depolymerization and then measuing their reconstruction upon activation of the RhoGTPases Rac, Cdc42 or RhoA. We observed that stem cells from seven ASD individuals (53%) presented altered dymanics of filament reconstruction, including a patient recently studied by our group whose iPSC-derived neuronal cells show shorten and less arborized neurites. We also report potentially pathogenic genetic variants that might be related to the alterations in actin repolymerization dynamics observed in some patient-derived cells. Our results suggest that, at least for a subgroup of ASD patients, the dynamics of actin polymerization is impaired, which might be ultimately leading to neuronal abnormalities.
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9. Kolta B, Rossi G. {{Paraphilic Disorder in a Male Patient with Autism Spectrum Disorder: Incidence or Coincidence}}. {Cureus}. 2018; 10(5): e2639.
Paraphilic disorder in patients with autism spectrum disorder (ASD) can be extremely disturbing to both the patient and caretakers. It can interfere with these patient’s ability to develop social skills, which are essential for adaptation, and function within society. This case report details the history of an 18-year-old male patient previously diagnosed with Asperger’s syndrome, who also exhibited symptoms consistent with paraphilic disorder. A review of the literature was then conducted to determine if there is any documented association of paraphilic disorder, or abnormal sexual behavior in patients with ASD. Several case reports involving patients with ASD, and co-morbid paraphilic disorder have been described in the literature. ASD appears to be associated with paraphilic disorder.
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10. Mazurek MO, Curran A, Burnette C, Sohl K. {{ECHO Autism STAT: Accelerating Early Access to Autism Diagnosis}}. {J Autism Dev Disord}. 2018.
Although early diagnosis of autism is critical for promoting access to early intervention, many children experience significant diagnostic delays. Shortages of healthcare providers, limited capacity at autism centers, and geographic and socioeconomic challenges contribute to these delays. The current pilot study examined the feasibility of a new model for training community-based primary care providers (PCPs) in underserved areas in screening and diagnosis of young children at highest risk for autism. By combining hands-on training in standardized techniques with ongoing virtual mentorship and practice, the program emphasized both timely diagnosis and appropriate referral for more comprehensive assessment when necessary. Results indicated improvements in PCP practice and self-efficacy, and feasibility of the model for enhancing local access to care.
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11. Morrison-Levy N, Go C, Ochi A, Otsubo H, Drake J, Rutka J, Weiss SK. {{Children with autism spectrum disorders and drug-resistant epilepsy can benefit from epilepsy surgery}}. {Epilepsy Behav}. 2018; 85: 200-4.
OBJECTIVE: The objective of this research was to evaluate a cohort of children with both autism spectrum disorder (ASD) and drug-resistant epilepsy (DRE) after epilepsy surgery to determine predictors of best outcome. METHODS: Retrospective chart review was done for 29 children ages 2 to 18years with ASD and DRE who had neurosurgical intervention for seizure management over 15years at one institution. All subjects had at least 1year of follow-up. Data abstraction included demographic information, seizure diagnosis, treatment, investigations, surgical intervention, neuropsychological assessment, and outcome. Statistical analysis software (SAS) was used for statistical analysis. Engel classification was used to assess seizure outcome. RESULTS: Fifteen subjects had resective surgery. Fourteen had palliative surgery with vagal nerve stimulator (VNS) insertion (13) and corpus callosotomy (1). Of the 29 subjects, 35% had class I outcome (all in the resective group). When combining all subjects (resective and palliative), 66% of subjects benefited with class I-III outcomes. In the total cohort, age at time of surgery was significant, with class I outcome more frequently seen in the younger age group when compared with classes II-IV (p=0.01). CONCLUSION: A subset of children with ASD can benefit from resective surgery, and for those who are not candidates, a VNS can offer significant improvements in seizure control.
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12. Okamoto Y, Kitada R, Miyahara M, Kochiyama T, Naruse H, Sadato N, Okazawa H, Kosaka H. {{Altered perspective-dependent brain activation while viewing hands and associated imitation difficulties in individuals with autism spectrum disorder}}. {Neuroimage Clin}. 2018; 19: 384-95.
Background: Individuals with autism spectrum disorder (ASD) appear to have a unique awareness of their own body, which may be associated with difficulties of gestural interaction. In typically developing (TD) individuals, the perception of body parts is processed in various brain regions. For instance, activation of the lateral occipito-temporal cortex (LOTC) is known to depend on perspective (i.e., first- or third-person perspective) and identity (i.e., own vs. another person’s body). In the present study, we examined how perspective and identity affect brain activation in individuals with ASD, and how perspective- and identity-dependent brain activation is associated with gestural imitation abilities. Methods: Eighteen young adults with ASD and 18 TD individuals participated in an fMRI study in which the participants observed their own or another person’s hands from the first- and third-person perspectives. We examined whether the brain activation associated with perspective and identity was altered in individuals with ASD. Furthermore, we identified the brain regions the activity of which correlated with gestural imitation difficulties in individuals with ASD. Results: In the TD group, the left LOTC was more strongly activated by viewing a hand from the third-person perspective compared with the first-person perspective. This perspective effect in the left LOTC was significantly attenuated in the ASD group. We also observed significant group differences in the perspective effect in the medial prefrontal cortex (mPFC). Correlation analysis revealed that the perspective effect in the inferior parietal lobule (IPL) and cerebellum was associated with the gestural imitation ability in individuals with ASD. Conclusions: Our study suggests that atypical visual self-body recognition in individuals with ASD is associated with an altered perspective effect in the LOTC and mPFC, which are thought to be involved in the physical and core selves, respectively. Furthermore, the gestural imitation difficulty in individuals with ASD might be associated with the altered activation in the IPL and cerebellum, but not in the LOTC. These findings shed light on common and divergent neural mechanisms underlying atypical visual self-body awareness and gestural interaction in ASD.
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13. Ormstad H, Bryn V, Verkerk R, Skjeldal OH, Halvorsen B, Saugstad OD, Isaksen J, Maes M. {{Serum tryptophan, tryptophan catabolites and brain-derived neurotrophic factor in subgroups of youngsters with autism spectrum disorders}}. {CNS & neurological disorders drug targets}. 2018.
BACKGROUND: There is evidence that changes in neuro-immune responses coupled with dysfunctions in serotonin metabolism underpin the pathophysiology of autism spectrum disorders (ASD). OBJECTIVE: This study aimed to delineate whether ASD subgroups or characteristics show aberrations in tryptophan and brain-derived neurotrophic factor (BDNF) metabolism. METHODS: 65 individuals with ASD (diagnosed according to ICD criteria) and 30 healthy control patients were included. Measured were serum levels of tryptophan, kynurenine (KYN), kynurenic acid (KA), quinolinic acid (QA), BDNF and PRO-BDNF and total blood 5-HT and 5-OH-tryptophan (5-HTP). RESULTS: Elevated BDNF levels and lower tryptophan and KA levels were characteristics of both childhood autism and intellectual disability disorder, whilst elevated tryptophan and lower 5-HT synthesis were hallmarks of Asperger syndrome. A pathological MRI was associated with elevated tryptophan and lowered KA. Abnormal EEG results and dysmorphology were both associated with an elevated BDNF/ PRO-BDNF ratio. Any brain pathology and gastro-intestinal symptoms were accompanied by lowered KA. CONCLUSIONS: Increased BDNF production and changes in the metabolism of tryptophan are associated with many ASD characteristics, showing particularly strong associations with childhood autism and Intellectual and Developmental Disabilities. Peripheral BDNF and tryptophan metabolism appear to take part in the pathophysiology of autism spectrum disorders and their phenotypes.
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14. Raghavan R, Fallin MD, Hong X, Wang G, Ji Y, Stuart EA, Paige D, Wang X. {{Cord and Early Childhood Plasma Adiponectin Levels and Autism Risk: A Prospective Birth Cohort Study}}. {J Autism Dev Disord}. 2018.
Emerging research suggests that adiponectin, a cytokine produced by adipose tissue, may be implicated in ASD. In this prospective birth cohort study (n = 847), we assessed the association between cord, early childhood plasma adiponectin and the risk of developing ASD. ASD was defined based on ICD codes of physician diagnosis. Cord adiponectin levels were inversely associated with ASD risk (aOR 0.50; 95% CI 0.33, 0.77), independent of preterm birth, early childhood adiponectin and other known ASD risk factors. Early childhood adiponectin, assessed prior to ASD diagnosis, was associated with lower risk of ASD, which attenuated after adjusting for cord adiponectin, indicating the relative importance of cord adiponectin in ASD risk. Further research is warranted to confirm our findings and elucidate biological mechanisms.
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15. Shivers CM, McGregor CM. {{Brief Report: Sibling Feelings Toward their Brother or Sister With or Without Autism or Intellectual Disability}}. {J Autism Dev Disord}. 2018.
The present study examined 97 adolescent siblings of individuals with autism spectrum disorder (ASD), intellectual and developmental disabilities (IDD), or no disabilities. Siblings reported on their feelings toward their brother or sister (anxiety, hostility, and positive affect), and parents reported on general optimism, child behavior problems, and perceptions of how the child impacts the family, including the sibling. There were no differences between siblings of individuals with ASD and siblings of individuals with IDD on any sibling self-reported feelings toward their brother or sister, though parents of individuals with ASD reported significantly less optimism and more negative perception of the child’s impact on the family than did parents of children with IDD or no disability.
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16. Tangsuwansri C, Saeliw T, Thongkorn S, Chonchaiya W, Suphapeetiporn K, Mutirangura A, Tencomnao T, Hu VW, Sarachana T. {{Investigation of epigenetic regulatory networks associated with autism spectrum disorder (ASD) by integrated global LINE-1 methylation and gene expression profiling analyses}}. {PLoS One}. 2018; 13(7): e0201071.
BACKGROUND: The exact cause and mechanisms underlying the pathobiology of autism spectrum disorder (ASD) remain unclear. Dysregulation of long interspersed element-1 (LINE-1) has been reported in the brains of ASD-like mutant mice and ASD brain tissues. However, the role and methylation of LINE-1 in individuals with ASD remain unclear. In this study, we aimed to investigate whether LINE-1 insertion is associated with differentially expressed genes (DEGs) and to assess LINE-1 methylation in ASD. METHODS: To identify DEGs associated with LINE-1 in ASD, we reanalyzed previously published transcriptome profiles and overlapped them with the list of LINE-1-containing genes from the TranspoGene database. An Ingenuity Pathway Analysis (IPA) of DEGs associated with LINE-1 insertion was conducted. DNA methylation of LINE-1 was assessed via combined bisulfite restriction analysis (COBRA) of lymphoblastoid cell lines from ASD individuals and unaffected individuals, and the methylation levels were correlated with the expression levels of LINE-1 and two LINE-1-inserted DEGs, C1orf27 and ARMC8. RESULTS: We found that LINE-1 insertion was significantly associated with DEGs in ASD. The IPA showed that LINE-1-inserted DEGs were associated with ASD-related mechanisms, including sex hormone receptor signaling and axon guidance signaling. Moreover, we observed that the LINE-1 methylation level was significantly reduced in lymphoblastoid cell lines from ASD individuals with severe language impairment and was inversely correlated with the transcript level. The methylation level of LINE-1 was also correlated with the expression of the LINE-1-inserted DEG C1orf27 but not ARMC8. CONCLUSIONS: In ASD individuals with severe language impairment, LINE-1 methylation was reduced and correlated with the expression levels of LINE-1 and the LINE-1-inserted DEG C1orf27. Our findings highlight the association of LINE-1 with DEGs in ASD blood samples and warrant further investigation. The molecular mechanisms of LINE-1 and the effects of its methylation in ASD pathobiology deserve further study.
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17. Thabtah F, Kamalov F, Rajab K. {{A new computational intelligence approach to detect autistic features for autism screening}}. {International journal of medical informatics}. 2018; 117: 112-24.
Autism Spectrum Disorder (ASD) is one of the fastest growing developmental disability diagnosis. General practitioners (GPs) and family physicians are typically the first point of contact for patients or family members concerned with ASD traits observed in themselves or their family member. Unfortunately, some families and adult patients are unaware of ASD traits that may be exhibited and as a result do not seek out necessary diagnostic services or contact their GP. Therefore, providing a quick, accessible, and simple tool utilizing items related to ASD to these families may increase the likelihood they will seek professional assessment and is vital to the early detection and treatment of ASD. This study aims at identifying fewer, albeit influential, features in common ASD screening methods in order to achieve efficient screening as demands on evaluating the items’ influences on ASD within existing tools is urgent. To achieve this aim, a computational intelligence method called Variable Analysis (Va) is proposed that considers feature-to-class correlations and reduces feature-to-feature correlations. The results of the Va have been verified using two machine learning algorithms by deriving automated classification systems with respect to specificity, sensitivity, positive predictive values (PPVs), negative predictive values (NPVs), and predictive accuracy. Experimental results using cases and controls related to items in three common screening methods, along with features related to individuals, have been analysed and compared with results obtained from other common filtering methods. The results exhibited that Va was able to derive fewer numbers of features from adult, adolescent, and child screening methods yet maintained competitive predictive accuracy, sensitivity, and specificity rates.
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18. Zhao Y, Pan Q, Du C. {{Logistic Regression Augmented Community Detection for Network Data with Application in Identifying Autism-Related Gene Pathways}}. {Biometrics}. 2018.
When searching for gene pathways leading to specific disease outcomes, additional information on gene characteristics is often available that may facilitate to differentiate genes related to the disease from irrelevant background when connections involving both types of genes are observed and their relationships to the disease are unknown. We propose method to single out irrelevant background genes with the help of auxiliary information through a logistic regression, and cluster relevant genes into cohesive groups using the adjacency matrix. Expectation-maximization algorithm is modified to maximize a joint pseudolikelihood assuming latent indicators for relevance to the disease and latent group memberships as well as Poisson or multinomial distributed link numbers within and between groups. A robust version allowing arbitrary linkage patterns within the background is further derived. Asymptotic consistency of label assignments under the stochastic blockmodel is proven. Superior performance and robustness in finite samples are observed in simulation studies. The proposed robust method identifies previously missed gene sets underlying autism related neurological diseases using diverse data sources including de novo mutations, gene expressions and protein-protein interactions. This article is protected by copyright. All rights reserved.
