1. Delgado MS, Camprubi C, Tumer Z, Martinez F, Mila M, Monk D. {{Screening individuals with intellectual disability, autism and Tourette’s syndrome for KCNK9 mutations and aberrant DNA methylation within the 8q24 imprinted cluster}}. {Am J Med Genet B Neuropsychiatr Genet};2014 (Jul 1)
The phenotype overlap between autism spectrum disorders (ASD) & intellectual disabilities (ID) is mirrored at the genetic level, with common genes being reported mutated in variety of developmental disabilities. However despite widespread genetic screening for mutations, in approximately 40-60% of childhood developmental disorders the genetic cause remains unknown. Several genome-wide linkage screens in ASD have identified a locus mapping to distal 8q. We have recently identified a novel brain-specific imprinted cluster at this location, which contains the reciprocally expressed maternal KCNK9 and paternally expressed non-coding PEG13 transcripts, the latter located within an intron of TRAPPC9. Interestingly, mutations of KCNK9 and TRAPPC9 have been reported in Birk-Barel mental retardation and non-syndromic familial forms of ID, respectively. Here, we report a genetic screen for KCNK9 coding mutations and potential epigenetic aberrations that could result in deregulated imprinting in a cohort of 120 ID, 86 ASD and 86 Tourette syndrome patients. Fifteen of the ID patients had clinical characteristics overlapping with Birk-Barel syndrome. Sequencing of the two coding exons of KCNK9 failed to identify pathologic mutations, with only one variant, rs2615374, being present with allele frequencies similar to those described in dbSNP database. DNA methylation profiling of the KCNK9 and TRAPPC9 promoters, the maternally methylated PEG13 DMR and a long-range enhancer region were normal in all patients. Our findings suggest that mutations of KCNK9 or epigenetic disturbances within the PEG13 imprinted cluster do not significantly contribute to the cause of the developmental disabilities tested in this study. (c) 2014 Wiley Periodicals, Inc.
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2. Diolordi L, Del Balzo V, Bernabei P, Vitiello V, Donini LM. {{Eating habits and dietary patterns in children with autism}}. {Eat Weight Disord};2014 (Jul 1)
The children with autism have feeding problems such as chewing, preference for the same food that often are responsible for the nutrient imbalance. In this study, we have analyzed the differences in food consumption (food frequency) and eating behavior (CEBI test) between children with autism and their typically developing peers. A statistically significant difference was observed between the two groups for the consumption of milk, yogurt, pulses, rice, and fruit juices (p </= 0,005). We observed a significant difference in the analysis of CEBI results when considering the 6- to 9.5-year-aged subgroup with autism vs control subgroup (103.50 and 110.14, respectively). The advices given by nutritionists have proved crucial to improve eating habits in children with autism, in the follow-up.
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3. Fujiwara T, Kawachi I. {{Are maternal social networks and perceptions of trust associated with suspected autism spectrum disorder in offspring? A population-based study in Japan}}. {PLoS One};2014;9(7):e101359.
OBJECTIVE: To investigate the associations of maternal social networks and perceptions of trust with the prevalence of suspected autism spectrum disorders in 18-month-old offspring in Japan. METHODS: Questionnaires included measurements of maternal social networks (number of relatives or friends they could call upon for assistance), maternal perceptions of trust, mutual assistance (i.e. individual measures of « cognitive social capital »), and social participation (i.e. individual measures of « structural social capital ») as well as the Modified Checklist for Autism in Toddlers to detect suspected autism spectrum disorder (ASD). These tools were mailed to all families with 18-month-old toddlers in Chiba, a city near Tokyo (N = 6061; response rate: 64%). The association between social capital or social network indicators and suspected ASD were analyzed, adjusted for covariates by logistic regression analysis. RESULTS: Low maternal social trust was found to be significantly positively associated with suspected ASD in toddlers compared with high maternal social trust (adjusted odds ratio [OR]: 1.82, 95% confidence interval [CI]: 1.38 to 2.40); mutual aid was also significantly positively related (low vs. high: OR, 1.82, 95% CI: 1.38 to 2.40). However, maternal community participation showed U-shape association with suspected ASD of offspring. Maternal social network showed consistent inverse associations with suspected ASD of offspring, regardless of the type of social connection (e.g., relatives, neighbors, or friends living outside of their neighborhood). CONCLUSIONS: Mothers’ cognitive social capital and social networks, but not structural social capital, might be associated with suspected ASD in offspring.
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4. Gabis LV, Pomeroy J. {{An etiologic classification of autism spectrum disorders}}. {Isr Med Assoc J};2014 (May);16(5):295-298.
BACKGROUND: Autism spectrum disorders (ASD) represent a common phenotype related to multiple etiologies, such as genetic, brain injury (e.g., prematurity), environmental (e.g., viral, toxic), multiple or unknown causes. OBJECTIVES: To devise a clinical classification of children diagnosed with ASD according to etiologic workup. METHODS: Children diagnosed with ASD (n = 436) from two databases were divided into groups of symptomatic cryptogenic or idiopathic, and variables within each database and diagnostic category were compared. RESULTS: By analyzing the two separate databases, 5.4% of the children were classified as symptomatic, 27% as cryptogenic and 67.75% as idiopathic. Among other findings, the entire symptomatic group demonstrated language delays, but almost none showed evidence for regression. Our results indicate similarities between the idiopathic and cryptogenic subgroups in most of the examined variables, and mutual differences from the symptomatic subgroup. The similarities between the first two subgroups support prior evidence that most perinatal factors and minor physical anomalies do not contribute to the development of core symptoms of autism. CONCLUSIONS: Differences in gender and clinical and diagnostic features were found when etiology was used to create subtypes of ASD. This classification could have heuristic importance in the search for an autism gene(s).
5. Gentile I, Zappulo E, Bonavolta R, Maresca R, Messana T, Buonomo AR, Portella G, Sorrentino R, Settimi A, Pascotto A, Borgia G, Bravaccio C. {{Prevalence and Titre of Antibodies to Cytomegalovirus and Epstein-Barr Virus in Patients with Autism Spectrum Disorder}}. {In Vivo};2014 (07-08);28(4):621-626.
Background/Aim: The etiology of autism spectrum disorders (ASD) is currently unknown. Few studies have explored the role of Cytomegalovirus (CMV) and Epstein Barr Virus (EBV) as potential etiological factors of ASD. The aim of the present study was to evaluate the seropositivity rate and antibody titre to CMV and EBV in children with ASD compared to same-aged healthy controls. Patients and Methods: We compared the seropositivity rate and titre of antibodies to CMV and EBV in 54 children with ASD (19 with autistic disorder and 35 with non-autistic disorder ASD) and in 46 controls. Results: Seropositivity rate and titre of the two antibodies were not dissimilar between cases and controls. However, considering only patients with ASD, those seropositive for CMV tended to test worse to the major severity scales than the seronegative ones. Conclusion: Titre and seropositivity rate of antibodies to CMV and EBV are similar between children with ASD and healthy controls.
6. Gentile I, Zappulo E, Bonavolta R, Maresca R, Riccio MP, Buonomo AR, Portella G, Settimi A, Pascotto A, Borgia G, Bravaccio C. {{Exposure to Varicella Zoster Virus Is Higher in Children with Autism Spectrum Disorder than in Healthy Controls. Results from a Case-control Study}}. {In Vivo};2014 (07-08);28(4):627-631.
Background/Aim: Autism spectrum disorder (ASD) is a group of central nervous system disorders lacking a definite etiology. The aim of the present study was to compare the exposure rate and titer of antibodies to Varicella Zoster Virus (VZV) in children with ASD and in healthy controls. Patients and Methods: We enrolled 54 children with ASD and 46 control individuals. Results: The exposure rate and titer of anti-VZV antibodies were significantly higher in children with ASD compared to controls (59% vs. 39% and 694 mIU/ml vs. 94 mIU/ml, respectively). Conclusion: In the present case-control study, exposure to VZV was found to be independently associated with ASD.
7. Gentile I, Zappulo E, Bonavolta R, Maresca R, Riccio MP, Buonomo AR, Portella G, Vallefuoco L, Settimi A, Pascotto A, Borgia G, Bravaccio C. {{Prevalence of Herpes Simplex Virus 1 and 2 Antibodies in Patients with Autism Spectrum Disorders}}. {In Vivo};2014 (07-08);28(4):667-671.
Background/Aim: The etiology of autism spectrum disorder (ASD) is unknown, even though it is hypothesized that a viral infection could trigger this disorder. The aim of this study was to evaluate the seropositivity rate and antibody level of Herpes Simplex Virus 1 (HSV1) and Herpes Simplex Virus 2 (HSV2) in children with ASD compared to same-aged healthy controls. Patients and Methods: We compared seropositivity rate and levels of antibodies to HSV1/2 in 54 children with ASD (19 with autistic disorder and 35 with non-autistic ASD) and in 46 controls. Results: Seropositivity rate and levels of anti-HSV1/2 were not dissimilar between cases and controls. Exposure to HSV2 was minimal. Conclusion: Rate of contact with HSV1 and HSV2 assessed by the mean of detection of specific antibodies was similar between children with ASD and healthy controls.
8. Hauser CT, Kover ST, Abbeduto L. {{Maternal well-being and child behavior in families with fragile X syndrome}}. {Res Dev Disabil};2014 (Jun 28);35(10):2477-2486.
The purpose of this study was to examine the bidirectional relationships relationship between maternal mental health status, maternal stress, family environment and behavioral functioning of children with fragile X syndrome (FXS), the leading cause of inherited intellectual disability. Children with FXS commonly demonstrate challenging behavior related to anxiety, attention, and aggression, whereas mothers of children with FXS have been identified as susceptible to mental health challenges due to their status as genetic carriers of the FXS premutation, as well as the environmental stressors of raising children with special needs. The longitudinal design of this study builds upon prior work that established a concurrent relationship among these factors in families of children with other intellectual disorders. Findings indicated that maternal mental health status was not significantly related to changes in levels of child challenging behavior, heightened child challenging behavior was related to improvements in maternal depression over time, and heightened levels of child challenging behavior was related to increased feelings of maternal closeness toward the child over time. The unexpected nature of the results regarding maternal depression and closeness provides new and more complex hypotheses about how mothers of special needs children demonstrate adaptation and resilience. The findings have implications for maternal and familial mental health treatment as well as future research.
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9. Ingalhalikar M, Parker WA, Bloy L, Roberts TP, Verma R. {{Creating multimodal predictors using missing data: classifying and subtyping Autism Spectrum Disorder}}. {J Neurosci Methods};2014 (Jun 28)
BACKGROUND: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by wide range of symptoms and severity including domains such as language impairment (LI). This study aims to create a quantifiable marker of ASD and a stratification marker for LI using multimodality imaging data that can handle missing data by including subjects that fail to complete all the aspects of a multimodality imaging study, obviating the need to remove subjects with incomplete data, as is done by conventional methods. METHODS: An ensemble of classifiers with several subsets of complete data is employed. The outputs from such subset classifiers are fused using a weighted aggregation giving an aggregate probabilistic score for each subject. Such fusion classifiers are created to obtain a marker for ASD and to stratify LI using three categories of features, two extracted from separate auditory tasks using magnetoencephalography (MEG) and the third extracted from diffusion tensor imaging (DTI). RESULTS: A clear distinction between ASD and neurotypical controls (5-fold accuracy of 83.3% and testing accuracy of 87%) and between ASD/+LI and ASD/-LI (5-fold accuracy of 70.1% and testing accuracy of 61.1%) was obtained. One of the MEG features, mismatch field (MMF) latency contributed the most to group discrimination, followed by DTI features from superior temporal white matter and superior longitudinal fasciculus as determined by feature ranking. Comparison with existing methods- Higher classification accuracy was achieved in comparison with single modality classifiers. CONCLUSION: This methodology can be readily applied in large studies where high percentage of missing data is expected.
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10. Jamal W, Das S, Oprescu IA, Maharatna K, Apicella F, Sicca F. {{Classification of autism spectrum disorder using supervised learning of brain connectivity measures extracted from synchrostates}}. {J Neural Eng};2014 (Jul 1);11(4):046019.
Objective. The paper investigates the presence of autism using the functional brain connectivity measures derived from electro-encephalogram (EEG) of children during face perception tasks. Approach. Phase synchronized patterns from 128-channel EEG signals are obtained for typical children and children with autism spectrum disorder (ASD). The phase synchronized states or synchrostates temporally switch amongst themselves as an underlying process for the completion of a particular cognitive task. We used 12 subjects in each group (ASD and typical) for analyzing their EEG while processing fearful, happy and neutral faces. The minimal and maximally occurring synchrostates for each subject are chosen for extraction of brain connectivity features, which are used for classification between these two groups of subjects. Among different supervised learning techniques, we here explored the discriminant analysis and support vector machine both with polynomial kernels for the classification task. Main results. The leave one out cross-validation of the classification algorithm gives 94.7% accuracy as the best performance with corresponding sensitivity and specificity values as 85.7% and 100% respectively. Significance. The proposed method gives high classification accuracies and outperforms other contemporary research results. The effectiveness of the proposed method for classification of autistic and typical children suggests the possibility of using it on a larger population to validate it for clinical practice.
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11. King D, Dockrell J, Stuart M. {{Constructing fictional stories: A study of story narratives by children with autistic spectrum disorder}}. {Res Dev Disabil};2014 (Jun 27);35(10):2438-2449.
Children with autistic spectrum disorder (ASD) are reported to have difficulties with narrative language but little is known about how this affects their production of fictional stories. In this study, we aimed to establish whether fictional narratives of children with ASD differed from those of typically developing children and if performance was commensurate with levels of oral language. Fictional stories produced by 27 high functioning children with ASD, aged 11-14 yrs, were compared with those of language and age matched groups of typically developing children. Differences were found between the children with ASD and comparison groups in structural, evaluative and global features of their stories indicating specific difficulties with this form of narrative. Stories of the ASD group were shorter and contained fewer causal statements than those of both comparison groups and sentences were less grammatically complex than those of the age match but not the language match group. In global measures, the stories of the ASD group were impoverished relative to both comparison groups. The results are discussed in relation to cognitive theories of autism and language development.
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12. Nuske HJ, Vivanti G, Dissanayake C. {{Reactivity to fearful expressions of familiar and unfamiliar people in children with autism: an eye-tracking pupillometry study}}. {J Neurodev Disord};2014;6(1):14.
BACKGROUND: Individuals with autism are often reported to have difficulty with emotion processing. However, clinical and experimental data show that they are sensitive to familiarity; for example, they show normative attachment to familiar people, and have normative brain activity in response to familiar faces. To date, no study has measured their reactivity to the emotions of familiar vs. unfamiliar people. Thus, our aim was to determine whether individuals with autism would show normative reactivity to emotion in familiar people. METHODS: Participants were 21 children with autism and 21 children with typical development, aged two to five years, matched on age and gender. The children observed videos of familiar people (their child-care teachers) and unfamiliar people expressing fear, whilst their visual attention and pupillary reactions were recorded (the latter as an index of emotional reactivity), using eye tracking technology. RESULTS: The children with autism showed normative pupillary reactions (peak magnitude) to fear expressed by familiar people, but a reduced response to fear expressed by unfamiliar people. However, across familiarity conditions, the children with autism had longer latency peak responses than the typically developing children. This pattern of findings was independent of cognitive factors or visual attention as visual attention by group was not related to familiarity condition. The children with autism had reduced visual attention to neutral faces; however, on fearful faces there were no group differences. Abnormalities in pupillary reactivity in the autism group were related to less prosocial behaviour and more severe play and communication deficits. CONCLUSIONS: Children with autism were less atypical in their responses to fearful expressions of people they know, arguing against a pervasive emotional impairment in autism, but rather one that may be mediated by familiarity.
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13. Yau VM, Green PG, Alaimo CP, Yoshida CK, Lutsky M, Windham GC, Delorenze G, Kharrazi M, Grether JK, Croen LA. {{Prenatal and neonatal peripheral blood mercury levels and autism spectrum disorders}}. {Environ Res};2014 (Jun 27);133C:294-303.
BACKGROUND: Prenatal and early-life exposures to mercury have been hypothesized to be associated with increased risk of autism spectrum disorders (ASDs). OBJECTIVES: This study investigated the association between ASDs and levels of total mercury measured in maternal serum from mid-pregnancy and infant blood shortly after birth. METHODS: The study sample was drawn from the Early Markers for Autism (EMA) Study. Three groups of children who were born in Orange County, CA in 2000-2001 were identified: children with ASD (n=84), children with intellectual disability or developmental delay (DD) (n=49), and general population controls (GP) (n=159). Maternal serum specimens and newborn bloodspots were retrieved from the California Department of Public Health prenatal and newborn screening specimen archives. Blood mercury levels were measured in maternal serum samples using mass spectrometer and in infant bloodspots with a 213nm laser. RESULTS: Maternal serum and infant blood mercury levels were significantly correlated among all study groups (all correlations >0.38, p<0.01). Adjusted logistic regression models showed no significant associations between ASD and log transformed mercury levels in maternal serum samples (ASD vs. GP: OR [95% CI]=0.96 [0.49-1.90]; ASD vs. DD: OR [95% CI]=2.56 [0.89-7.39]). Results for mercury levels in newborn blood samples were similar (ASD vs. GP: OR [95% CI]=1.18 [0.71-1.95]; ASD vs. DD: OR [95% CI]=1.96 [0.75-5.14]). CONCLUSIONS: Results indicate that levels of total mercury in serum collected from mothers during mid-pregnancy and from newborn bloodspots were not significantly associated with risk of ASD, though additional studies with greater sample size and covariate measurement are needed.
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14. Zhang QB, Jiang LF, Kong LY, Lu YJ. {{Serum Brain-derived neurotrophic factor levels in Chinese children with autism spectrum disorders: A pilot study}}. {Int J Dev Neurosci};2014 (Jun 28)
Brain-derived neurotrophic factor (BDNF) plays a critical role in the pathogenesis of Autism spectrum disorders (ASD). The purpose of this study was to investigate the potential role of BDNF in Chinese children with ASD. Sixty patients (48 male, 12 female) diagnosed with ASD and 60 healthy sex and age control subjects were assessed for serum BDNF content at admission. BDNF were assayed with enzyme-linked immunosorbent assay methods, and severity of ASD was evaluated with the Childhood Autism Rating Scale (CARS) Score. The results indicated that the median serum BDNF levels were significantly (P<0.0001) higher in children with ASD as compared to normal cases [17.6(IQR: 13.7-21.4) ng/ml and 11.5(9.6-13.8) ng/ml, respectively]. Based on the Receiver operating characteristic (ROC) curve, the optimal cut-off value of serum BDNF levels as an indicator for auxiliary diagnosis of autism was projected to be 15.0ng/ml. Further, we found that an increased risk of ASD was associated with BDNF levels >15.0ng/ml (adjusted OR 10.4, 95% CI: 4.39-29.32) after adjusting for above possible confounders. Our study demonstrated that serum BDNF levels were associated with ASD, and higher levels could be considered as an independent risk factor of ASD.
