1. Al-Jabery K, Obafemi-Ajayi T, Olbricht GR, Takahashi TN, Kanne S, Wunsch D. {{Ensemble statistical and subspace clustering model for analysis of autism spectrum disorder phenotypes}}. {Conf Proc IEEE Eng Med Biol Soc}. 2016; 2016: 3329-33.
Heterogeneity in Autism Spectrum Disorder (ASD) is complex including variability in behavioral phenotype as well as clinical, physiologic, and pathologic parameters. The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) now diagnoses ASD using a 2-dimensional model based social communication deficits and fixated interests and repetitive behaviors. Sorting out heterogeneity is crucial for study of etiology, diagnosis, treatment and prognosis. In this paper, we present an ensemble model for analyzing ASD phenotypes using several machine learning techniques and a k-dimensional subspace clustering algorithm. Our ensemble also incorporates statistical methods at several stages of analysis. We apply this model to a sample of 208 probands drawn from the Simon Simplex Collection Missouri Site patients. The results provide useful evidence that is helpful in elucidating the phenotype complexity within ASD. Our model can be extended to other disorders that exhibit a diverse range of heterogeneity.
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2. Ariza J, Rogers H, Hartvigsen A, Snell M, Dill M, Judd D, Hagerman P, Martinez-Cerdeno V. {{Iron accumulation and dysregulation in the putamen in fragile X-associated tremor/ataxia syndrome}}. {Mov Disord}. 2017.
BACKGROUND: Fragile X-associated tremor/ataxia syndrome is an adult-onset disorder associated with premutation alleles of the FMR1 gene. This disorder is characterized by progressive action tremor, gait ataxia, and cognitive decline. Fragile X-associated tremor/ataxia syndrome pathology includes dystrophic white matter and intranuclear inclusions in neurons and astrocytes. We previously demonstrated that the transport of iron into the brain is altered in fragile X-associated tremor/ataxia syndrome; therefore, we also expect an alteration of iron metabolism in brain areas related to motor control. Iron is essential for cell metabolism, but uncomplexed iron leads to oxidative stress and contributes to the development of neurodegenerative diseases. We investigated a potential iron modification in the putamen – a structure that participates in motor learning and performance – in fragile X-associated tremor/ataxia syndrome. METHODS: We used samples of putamen obtained from 9 fragile X-associated tremor/ataxia syndrome and 9 control cases to study iron localization using Perl’s method, and iron-binding proteins using immunostaining. RESULTS: We found increased iron deposition in neuronal and glial cells in the putamen in fragile X-associated tremor/ataxia syndrome. We also found a generalized decrease in the amount of the iron-binding proteins transferrin and ceruloplasmin, and decreased number of neurons and glial cells that contained ceruloplasmin. However, we found increased levels of iron, transferrin, and ceruloplasmin in microglial cells, indicating an attempt by the immune system to remove the excess iron. CONCLUSIONS: Overall, found a deficit in proteins that eliminate extra iron from the cells with a concomitant increase in the deposit of cellular iron in the putamen in Fragile X-associated tremor/ataxia syndrome. (c) 2017 International Parkinson and Movement Disorder Society.
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3. Bhandary S, Hari N. {{Salivary biomarker levels and oral health status of children with autistic spectrum disorders: a comparative study}}. {Eur Arch Paediatr Dent}. 2017.
AIM: To evaluate the oral health status, salivary flow rate, pH and buffering capacity in children with autistic spectrum disorders (ASD) in comparison to their healthy siblings. METHODS: A total of 30 subjects with ASD and 30 normal healthy siblings between the ages of 6-12 years of both genders attending various special schools and hospitals of Mangalore, India were recruited. Estimation of salivary pH, flow rate and buffering capacity were performed and oral health status was assessed using the WHO oral assessment form for children (World Health Organization in Oral health surveys: basic methods, World Health Organization, Geneva, 2013). The oral hygiene of the subjects was assessed using the oral hygiene index-simplified. Dental erosive lesions, presence of mucosal lesions and dental trauma were recorded for both the study and the control groups. RESULTS: It was observed that salivary pH and buffering capacity were lower in children with ASD than their healthy siblings, the dental caries incidence was higher in ASD children when compared to their healthy siblings and oral hygiene was fair with gingival bleeding in children with ASD. CONCLUSIONS: This study clearly indicates a need for better home care measures, parent, caregiver and institutional education on the importance of oral well-being among children with ASD.
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4. Carlson C, Suliman A, Prakash P, Thompson D, Wang S, Natarajan B, Warren S, Shangxian W. {{Bed-based instrumentation for unobtrusive sleep quality assessment in severely disabled autistic children}}. {Conf Proc IEEE Eng Med Biol Soc}. 2016; 2016: 4909-12.
The relationship between sleep quality and daytime wellness and performance in severely disabled, autistic children is not well understood. While polysomnography and, more recently, actigraphy serve as means to obtain sleep assessment data from neurotypical children and adults, these techniques are not well-suited to severely autistic children. This paper presents recent progress on a bed sensor suite that can unobtrusively track physiological and behavioral parameters used to assess sleep quality. Electromechanical films and load cells provide data that yield heart rate, respiration rate, center of position, in-and-out-of-bed activity, and general movement, while thermocouples are used to detect bed-wetting events.
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5. Cowan RJ, Abel L, Candel L. {{A Meta-Analysis of Single-Subject Research on Behavioral Momentum to Enhance Success in Students with Autism}}. {J Autism Dev Disord}. 2017.
We conducted a meta-analysis of single-subject research studies investigating the effectiveness of antecedent strategies grounded in behavioral momentum for improving compliance and on-task performance for students with autism. First, we assessed the research rigor of those studies meeting our inclusionary criteria. Next, in order to apply a universal metric to help determine the effectiveness of this category of antecedent strategies investigated via single-subject research methods, we calculated effect sizes via omnibus improvement rate differences (IRDs). Outcomes provide additional support for behavioral momentum, especially interventions incorporating the high-probability command sequence. Implications for research and practice are discussed, including the consideration of how single-subject research is systematically reviewed to assess the rigor of studies and assist in determining overall intervention effectiveness .
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6. Curie A, Lesca G, Bussy G, Manificat S, Arnaud V, Gonzalez S, Revol O, Calender A, Gerard D, des Portes V. {{Asperger syndrome and early-onset schizophrenia associated with a novel MECP2 deleterious missense variant}}. {Psychiatr Genet}. 2017.
Methyl-CpG-binding protein 2 (MECP2) deleterious variants, which are responsible for Rett syndrome in girls, are involved in a wide spectrum of developmental disabilities in males. A neuropsychiatric phenotype without intellectual disability is uncommon in patients with MECP2 deleterious variants. We report on two dizygotic twins with an MECP2-related psychiatric disorder without intellectual disability. Neuropsychological and psychiatric phenotype assessments were performed, and a genetic analysis was carried out. Both patients fulfilled the Pervasive Developmental Disorder criteria on Autism Diagnostic Observation Schedule and Asperger syndrome criteria on Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV). One patient developed early-onset schizophrenia (DSM-IV criteria) with two acute psychotic episodes, the latest one following corticosteroids and sodium valproate intake, with major hyperammonemia. A novel MECP2 gene transversion c.491 G>T [p.(Ser164Ile)] was found in both twins. Pathogenicity of this variant was considered on the basis of strong clinical and molecular data. The underlying molecular basis of neuropsychiatric disorders may have important consequences on genetic counseling and therapeutic strategies.
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7. Gelsomini M, Garzotto F, Montesano D, Occhiuto D. {{Wildcard: A wearable virtual reality storytelling tool for children with intellectual developmental disability}}. {Conf Proc IEEE Eng Med Biol Soc}. 2016; 2016: 5188-91.
Our research aims at supporting existing therapies for children with intellectual and developmental disorders (IDD). The personal and social autonomy is the desired end state to be achieved to enable a smooth integration in the real world. We developed and tested a framework for storytelling and learning activities that exploits an immersive virtual reality viewer to interact with target users. We co-designed our system with experts from the medical sector, identifying features that allow patients to stay focused on exercises to perform. Our approach triggers a learning process for a seamless assimilation of common behavioral skills useful in every day’s life. This paper highlights the technologic challenges in healthcare and discusses cutting-edge interaction paradigms.
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8. Getz KD. {{Response to Letter Re: Maternal Pre-Pregnancy Body Mass Index and Autism Spectrum Disorder in the Offspring}}. {Paediatr Perinat Epidemiol}. 2017; 31(2): 166.
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9. Ghanouni P, Memari AH, Gharibzadeh S, Eghlidi J, Moshayedi P. {{Effect of Social Stimuli on Postural Responses in Individuals with Autism Spectrum Disorder}}. {J Autism Dev Disord}. 2017.
This study was aimed to investigate the effects of social versus non-social stimuli on postural responses in 21 boys with autism spectrum disorder (ASD) (mean age of 11.6 +/- 1.5) compared with 30 typically developing (TD) boys (mean age of 11.7 +/- 1.8). Postural control of children was examined while they were standing on a force plate and viewing images of an object, male face, or female face in sequence. Each image was shown in two trials and each trial lasted for 20 s. Results indicated a significant interaction between group and task (p < 0.05), meaning that children with ASD but not TD children showed an increased postural sway during face tasks than during object task. Furthermore children with higher autism severity compared to those with lower severity showed an increased change in response to social stimuli (p < 0.01). It seems that the postural control of children with ASD was more affected by the social stimuli than TD children. Lien vers le texte intégral (Open Access ou abonnement)
10. Griffiths DL, Farrell LJ, Waters AM, White SW. {{ASD Traits Among Youth with Obsessive-Compulsive Disorder}}. {Child Psychiatry Hum Dev}. 2017.
Research has shown high rates of comorbid psychiatric disorders among samples of youth with obsessive-compulsive disorder (OCD) (Farrell et al., Psychiatry Res 199(2):115-123, 2012; Lewin et al., Psychiatry Res 178(2):317-322, 2010; POTS Team, J Am Med Assoc 292(16):1969-1976, 2004). Autism and autistic traits co-occur at high rates within clinical samples of youth with OCD (Ivarsson and Melin in J Anxiety Disord 22(6):969-978, 2008; Stewart et al. in Child Psychiatry Hum Dev 1-9, 2016). This study extends the literature by examining the relationship between ASD traits, family accommodation, and functional impairment in a sample of youth with OCD across a wide age range (n = 80; aged 7-17 years). Results indicated that autistic traits, as measured by the social responsiveness scale (SRS), were elevated in 32.5% of youth (based on a T-score of 66T and above) relative to typically developing youth, as well as youth with non-autism-related psychiatric disorders (Constantino and Gruber in Social responsiveness scale, Western Psychogical Services, Torrance, 2012). Furthermore, 27.5% of youth scored within a moderate range (66T-75T) and 5% of youth scored within a severe range (76T or higher) on the SRS, typical of children with ASD (Constantino and Gruber in Social responsiveness scale, Western Psychogical Services, Torrance, 2012). Additionally, ASD traits were associated with greater functional impairment above OCD severity. Furthermore, family accommodation mediated the relationship between ASD traits and functional impairment. Implications of these findings are discussed in the context of clinical assessment and direction for further research.
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11. Karp EA, Ibanez LV, Warren Z, Stone WL. {{Brief Report: What Drives Parental Concerns About Their 18-Month-Olds at Familial Risk for Autism Spectrum Disorder?}}. {J Autism Dev Disord}. 2017.
Parent-reported developmental concerns can be a first step toward further screening and intervention for children at risk for ASD. However, little is known about the extent to which parental well-being and child behavior contribute to parental concerns, especially in families who already have one child with ASD. This study included 54 parents and their 18-month-old high-risk toddlers to examine the extent to which parents’ well-being (i.e., parenting stress and self-efficacy), and children’s behavior (i.e., expressive language and social communication) contribute to parents’ concerns regarding their toddler’s development. Results revealed that parental concerns were predicted by their own well-being as well as their toddler’s expressive language, highlighting the importance of addressing the needs of both parent and child in intervention settings.
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12. Linstead E, Burns R, Nguyen D, Tyler D, Duy N. {{AMP: A platform for managing and mining data in the treatment of Autism Spectrum Disorder}}. {Conf Proc IEEE Eng Med Biol Soc}. 2016; 2016: 2545-9.
We introduce AMP (Autism Management Platform), an integrated health care information system for capturing, analyzing, and managing data associated with the diagnosis and treatment of Autism Spectrum Disorder in children. AMP’s mobile application simplifies the means by which parents, guardians, and clinicians can collect and share multimedia data with one another, facilitating communication and reducing data redundancy, while simplifying retrieval. Additionally, AMP provides an intelligent web interface and analytics platform which allow physicians and specialists to aggregate and mine patient data in real-time, as well as give relevant feedback to automatically learn data filtering preferences over time. Together AMP’s mobile app, web client, and analytics engine implement a rich set of features that streamline the data collection and analysis process in the context of a secure and easy-to-use system so that data may be more effectively leveraged to guide treatment.
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13. Mamun KA, Bardhan S, Ullah MA, Anagnostou E, Brian J, Akhter S, Rabbani MG, Al Mamun KA. {{Smart autism – a mobile, interactive and integrated framework for screening and confirmation of autism}}. {Conf Proc IEEE Eng Med Biol Soc}. 2016; 2016: 5989-92.
Smart Autism is a cloud based, automated framework for autism screening and confirmation. In developing countries, due to lack of resources and expertise, autism is detected later than early ages which consequently delays timely intervention. Therefore a mobile, interactive and integrated framework is proposed to screen and confirm autism in different age group (0 to 17 years) with 3 layers of assessment process. Firstly, it screens by evaluating the responses of pictorial based screening questionnaire through mobile application. If autism is suspected, then in virtual assessment process, the child watches a video, its reaction is recorded and uploaded to the cloud for remote expert assessment. If autism is still suspected, then the child is referred to the nearest Autism Resource Center (ARC) for actual assessment. Analyzing these results, the integrated framework confirms autism automatically and reduce user’s ARC visit. It is expected that the proposed framework will bring changes in autism diagnosis process and create awareness.
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14. Mundy P, Novotny S, Swain-Lerro L, McIntyre N, Zajic M, Oswald T. {{Joint-Attention and the Social Phenotype of School-Aged Children with ASD}}. {J Autism Dev Disord}. 2017.
The validity of joint attention assessment in school-aged children with ASD is unclear (Lord, Jones, Journal of Child Psychology and Psychiatry 53(5):490-509, 2012). This study examined the feasibility and validity of a parent-report measure of joint attention related behaviors in verbal children and adolescents with ASD. Fifty-two children with ASD and 34 controls were assessed with the Childhood Joint Attention Rating Scale (C-JARS). The C-JARS exhibited internally consistency, alpha = 0.88, and one factor explained 49% of the scale variance. Factor scores correctly identified between 88 and 94% of the children with ASD and 62-82% of controls. These scores were correlated with the ADOS-2, but not other parent-report symptom measures. The C-JARS appears to assess a unique dimension of the social-phenotype of children with ASD.
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15. Qin YL, Tang SY. {{Maternal Pre-pregnancy Body Mass Index and Autism Spectrum Disorder among Offspring}}. {Paediatr Perinat Epidemiol}. 2017; 31(2): 165.
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16. Reiff M, Bugos E, Giarelli E, Bernhardt BA, Spinner NB, Sankar PL, Mulchandani S. {{« Set in Stone » or « Ray of Hope »: Parents’ Beliefs About Cause and Prognosis After Genomic Testing of Children Diagnosed with ASD}}. {J Autism Dev Disord}. 2017.
Despite increasing utilization of chromosomal microarray analysis (CMA) for autism spectrum disorders (ASD), limited information exists about how results influence parents’ beliefs about etiology and prognosis. We conducted in-depth interviews and surveys with 57 parents of children with ASD who received CMA results categorized as pathogenic, negative or variant of uncertain significance. Parents tended to incorporate their child’s CMA results within their existing beliefs about the etiology of ASD, regardless of CMA result. However, parents’ expectations for the future tended to differ depending on results; those who received genetic confirmation for their children’s ASD expressed a sense of concreteness, acceptance and permanence of the condition. Some parents expressed hope for future biomedical treatments as a result of genetic research.
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17. Warren S, Prakash P, Thompson D, Natarajan B, Carlson C, Fowler K, Brokesh E, Xin J, Piersel W, Kesterson J, Stoffregen S. {{Design projects motivated and informed by the needs of severely disabled autistic children}}. {Conf Proc IEEE Eng Med Biol Soc}. 2016; 2016: 3015-8.
Technology can positively impact the lives of severely disabled autistic children if used to (a) gather situational awareness data regarding their health, development, and behavior and (b) assist them with learning and day-to-day activities. This paper summarizes student design projects in the Kansas State University (KSU) College of Engineering that are motivated and informed by the needs of severely disabled children at Heartspring, Wichita, KS. These efforts are supported through the National Science Foundation’s General and Age-Related Disabilities Engineering (GARDE) program. Projects relate thematically to (1) facets of a bed sensor system that unobtrusively tracks nighttime health parameters and child activity and (2) miscellaneous resources geared toward paraeducator (« para ») and child well-being and development.
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18. Xin JF, Sheppard ME, Brown M. {{Brief Report: Using iPads for Self-Monitoring of Students with Autism}}. {J Autism Dev Disord}. 2017.
This study examined the effect of using an iPad for students with autism spectrum disorder (ASD) on self-monitoring their behaviors in class. Four students with ASD were taught on-task behaviors by watching self-modeled video saved in the application « Choiceworks » on their iPads, and collected data on their own behaviors. A single subject research design with ABAB phases was used. Student behaviors were observed using interval recording and behavioral occurrences were compared across phases. Results showed that the participating students’ on-task behaviors (e.g., facing forward, looking at teacher, i.e. eye contact, and working on the assignment) were increased when an iPad was used for their self-monitoring.
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19. Zhou H, Zhang L, Zou X, Luo X, Xia K, Wu L, Wang Y, Xu X, Ge X, Jiang YH, Fombonne E, Yan W. {{Chinese Norms for the Autism Spectrum Rating Scale}}. {Neurosci Bull}. 2017.
This study aimed to establish norms for the modified Chinese version of the Autism Spectrum Rating Scale (ASRS). Participants were recruited from Shanghai, Harbin, Guangzhou, and Changsha, China, and their parents and teachers were invited to complete the Chinese Parent version and the Teacher version of the ASRS. In both versions, boys had significantly higher sub-scale scores and total score (T-score) by 1-3 and 4-5 points respectively, than girls (both P < 0.001). Age had weak correlations with some sub-scores and the T-score (r ranged from -0.1859 to 0.0738), and some reached significance (P < 0.03). The correlations appeared stronger and were more common in females. The T-score based on Chinese norms ideally correlated with the score based on the United States norms in boys and girls for both versions. Norms for the Chinese version of the ASRS for children aged 6-12 years are proposed and may be helpful for screening individuals with autism spectrum disorders from the general population of children. Lien vers le texte intégral (Open Access ou abonnement)
20. Zhubi A, Chen Y, Guidotti A, Grayson DR. {{Epigenetic regulation of RELN and GAD1 in the frontal cortex (FC) of autism spectrum disorder (ASD) subjects}}. {Int J Dev Neurosci}. 2017.
Both Reelin (RELN) and glutamate decarboxylase 67 (GAD1) have been implicated in the pathophysiology of Autism Spectrum Disorders (ASD). We have previously shown that both mRNAs are reduced in the cerebella (CB) of ASD subjects through a mechanism that involves increases in the amounts of MECP2 binding to the corresponding promoters. In the current study, we examined the expression of RELN, GAD1, GAD2, and several other mRNAs implicated in this disorder in the frontal cortices (FC) of ASD and CON subjects. We also focused on the role that epigenetic processes play in the regulation of these genes in ASD brain. Our goal is to better understand the molecular basis for the down-regulation of genes expressed in GABAergic neurons in ASD brains. We measured mRNA levels corresponding to selected GABAergic genes using qRT-PCR in RNA isolated from both ASD and CON groups. We determined the extent of binding of MECP2 and DNMT1 repressor proteins by chromatin immunoprecipitation (ChIP) assays. The amount of 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) present in the promoters of the target genes was quantified by methyl DNA immunoprecipitation (MeDIP) and hydroxyl MeDIP (hMeDIP). We detected significant reductions in the mRNAs associated with RELN and GAD1 and significant increases in mRNAs encoding the Ten-eleven Translocation (TET) enzymes 1, 2, and 3. We also detected increased MECP2 and DNMT1 binding to the corresponding promoter regions of GAD1, RELN, and GAD2. Interestingly, there was decreased amounts of 5mC at both promoters and little change in 5hmC content in these same DNA fragments. Our data demonstrate that RELN, GAD1, and several other genes selectively expressed in GABAergic neurons, are down-regulated in post-mortem ASD FC. In addition, we observed increased DNMT1 and MECP2 binding at the corresponding promoters of these genes. The finding of increased MECP2 binding to the RELN, GAD1 and GAD2 promoters, with reduced amounts of 5mC and unchanged amounts of 5hmC present in these regions, suggests the possibility that DNMT1 interacts with and alters MECP2 binding properties to selected promoters. Comparisons between data obtained from the FC with CB studies showed some common themes between brain regions which are discussed.
