1. Aldersey HM, Turnbull HR, 3rd, Turnbull AP. {{Intellectual and developmental disabilities in kinshasa, democratic republic of the congo: causality and implications for resilience and support}}. {Intellect Dev Disabil};2014 (Jun);52(3):220-233.
Abstract This article reports results of a 7-month qualitative study on intellectual and related developmental disabilities in Kinshasa, Democratic Republic of the Congo, particularly as they relate to the causes and meaning of intellectual and developmental disabilities (IDD). This study raises important questions related to the understanding of resilience of persons affected by IDD and the nature and purpose of support they use or desire.
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2. Auzias G, Viellard M, Takerkart S, Villeneuve N, Poinso F, Fonseca DD, Girard N, Deruelle C. {{Atypical sulcal anatomy in young children with autism spectrum disorder}}. {Neuroimage Clin};2014;4:593-603.
Autism spectrum disorder is associated with an altered early brain development. However, the specific cortical structure abnormalities underlying this disorder remain largely unknown. Nonetheless, atypical cortical folding provides lingering evidence of early disruptions in neurodevelopmental processes and identifying changes in the geometry of cortical sulci is of primary interest for characterizing these structural abnormalities in autism and their evolution over the first stages of brain development. Here, we applied state-of-the-art sulcus-based morphometry methods to a large highly-selective cohort of 73 young male children of age spanning from 18 to 108 months. Moreover, such large cohort was selected through extensive behavioral assessments and stringent inclusion criteria for the group of 59 children with autism. After manual labeling of 59 different sulci in each hemisphere, we computed multiple shape descriptors for each single sulcus element, hereby separating the folding measurement into distinct factors such as the length and depth of the sulcus. We demonstrated that the central, intraparietal and frontal medial sulci showed a significant and consistent pattern of abnormalities across our different geometrical indices. We also found that autistic and control children exhibited strikingly different relationships between age and structural changes in brain morphology. Lastly, the different measures of sulcus shapes were correlated with the CARS and ADOS scores that are specific to the autistic pathology and indices of symptom severity. Inherently, these structural abnormalities are confined to regions that are functionally relevant with respect to cognitive disorders in ASD. In contrast to those previously reported in adults, it is very unlikely that these abnormalities originate from general compensatory mechanisms unrelated to the primary pathology. Rather, they most probably reflect an early disruption on developmental trajectory that could be part of the primary pathology.
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3. Bos DJ, van Raalten TR, Oranje B, Smits AR, Kobussen NA, Belle J, Rombouts SA, Durston S. {{Developmental differences in higher-order resting-state networks in Autism Spectrum Disorder}}. {Neuroimage Clin};2014;4:820-827.
OBJECTIVE: Autism Spectrum Disorder (ASD) has been associated with a complex pattern of increases and decreases in resting-state functional connectivity. The developmental disconnection hypothesis of ASD poses that shorter connections become overly well established with development in this disorder, at the cost of long-range connections. Here, we investigated resting-state connectivity in relatively young boys with ASD and typically developing children. We hypothesized that ASD would be associated with reduced connectivity between networks, and increased connectivity within networks, reflecting poorer integration and segregation of functional networks in ASD. METHODS: We acquired resting-state fMRI from 27 boys with ASD and 29 age- and IQ-matched typically developing boys between 6 and 16 years of age. Functional connectivity networks were identified using Independent Component Analysis (ICA). Group comparisons were conducted using permutation testing, with and without voxel-wise correction for grey matter density. RESULTS: We found no between-group differences in within-network connectivity. However, we did find reduced functional connectivity between two higher-order cognitive networks in ASD. Furthermore, we found an interaction effect with age in the DMN: insula connectivity increased with age in ASD, whereas it decreased in typically developing children. CONCLUSIONS: These results show subtle changes in between network connectivity in relatively young boys with ASD. However, the global architecture of resting-state networks appeared to be intact. This argues against recent suggestions that changes in connectivity in ASD may be the most prominent during development.
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4. Careaga M, Schwartzer J, Ashwood P. {{Inflammatory profiles in the BTBR mouse: How relevant are they to Autism Spectrum Disorders?}}. {Brain Behav Immun};2014 (Jun 14)
Autism spectrum disorders (ASD) are a group of disorders characterized by core behavioral features including stereotyped interests, repetitive behaviors and impairments in communication and social interaction. In addition, widespread changes in the immune systems of individuals with ASD have been identified, in particular increased evidence of inflammation in the periphery and central nervous system. While the etiology of these disorders remains unclear, it appears that multiple gene and environmental factors are involved. The need for animal models paralleling the behavioral and immunological features of ASD is paramount to better understand the link between immune system dysregulation and behavioral deficits observed in these disorders. As such, the asocial BTBR mouse strain displays both ASD relevant behaviors and persistent immune dysregulation, providing a model system that has and continues to be instructive in understanding the complex nature of ASD.
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5. Chi DL, Masterson EE, Wong JJ. {{U.s. Emergency department admissions for nontraumatic dental conditions for individuals with intellectual and developmental disabilities}}. {Intellect Dev Disabil};2014 (Jun);52(3):193-204.
Abstract The authors hypothesized that individuals with intellectual and developmental disabilities (IDDs) are more likely to have an emergency department (ED) admission for nontraumatic dental conditions (NTDCs). The authors analyzed 2009 U.S. National Emergency Department Sample data and ran logistic regression models for children ages 3-17 years and adults age 18 years or older. The prevalence of NTDC-related ED admissions was 0.8% for children and 2.0% for adults. Children with IDDs were at increased odds of NTDC-related ED admission, but this difference was not statistically significant (odds ratio [OR] = 1.06; 95% confidence interval [CI] = 0.91, 1.23). Adults with IDDs had significantly lower odds of an ED admission for NTDCs (OR = 0.49; 95% CI = 0.44, 0.54). Children with IDDs are not at increased odds of NTDC-related ED admissions, whereas adults with IDDs are at significantly reduced odds.
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6. Edgar JC, Lanza MR, Daina AB, Monroe JF, Khan SY, Blaskey L, Cannon KM, Jenkins J, 3rd, Qasmieh S, Levy SE, Roberts TP. {{Missing and delayed auditory responses in young and older children with autism spectrum disorders}}. {Front Hum Neurosci};2014;8:417.
Background: The development of left and right superior temporal gyrus (STG) 50 ms (M50) and 100 ms (M100) auditory responses in typically developing (TD) children and in children with autism spectrum disorder (ASD) was examined. Reflecting differential development of primary/secondary auditory areas and supporting previous studies, it was hypothesized that whereas left and right M50 STG responses would be observed equally often in younger and older children, left and right M100 STG responses would more often be absent in younger than older children. In ASD, delayed neurodevelopment would be indicated via the observation of a greater proportion of ASD than TD subjects showing missing M100 but not M50 responses in both age groups. Missing M100 responses would be observed primarily in children with ASD with language impairment (ASD + LI) (and perhaps concomitantly lower general cognitive abilities). Methods: Thirty-five TD controls, 63 ASD without language impairment (ASD – LI), and 38 ASD + LI were recruited. Binaural tones were presented. The presence or absence of a STG M50 and M100 was scored. Subjects were grouped into younger (6-10 years old) and older groups (11-15 years old). Results: Although M50 responses were observed equally often in older and younger subjects and equally often in TD and ASD, left and right M50 responses were delayed in ASD – LI and ASD + LI. Group comparisons showed that in younger subjects M100 responses were observed more often in TD than ASD + LI (90 versus 66%, p = 0.04), with no differences between TD and ASD – LI (90 versus 76%, p = 0.14) or between ASD – LI and ASD + LI (76 versus 66%, p = 0.53). In older subjects, whereas no differences were observed between TD and ASD + LI, responses were observed more often in ASD – LI than ASD + LI. Findings were similar when splitting the ASD group into lower- and higher-cognitive functioning groups. Conclusion: Although present in all groups, M50 responses were delayed in ASD. Examining the TD data, findings indicated that by 11 years, a right M100 should be observed in 100% of subjects and a left M100 in 80% of subjects. Thus, by 11 years, lack of a left and especially right M100 offers neurobiological insight into sensory processing that may underlie language or cognitive impairment.
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7. Eldridge J, Lane AE, Belkin M, Dennis S. {{Robust features for the automatic identification of autism spectrum disorder in children}}. {J Neurodev Disord};2014;6(1):12.
BACKGROUND: It is commonly reported that children with autism spectrum disorder (ASD) exhibit hyper-reactivity or hypo-reactivity to sensory stimuli. Electroencephalography (EEG) is commonly used to study neural sensory reactivity, suggesting that statistical analysis of EEG recordings is a potential means of automatic classification of the disorder. EEG recordings taken from children, however, are frequently contaminated with large amounts of noise, making analysis difficult. In this paper, we present a method for the automatic extraction of noise-robust EEG features, which serve to quantify neural sensory reactivity. We show the efficacy of a system for the classification of ASD using these features. METHODS: An oddball paradigm was used to elicit event-related potentials from a group of 19 ASD children and 30 typically developing children. EEG recordings were taken and robust features were extracted. A support vector machine, logistic regression, and a naive Bayes classifier were used to classify the children as having ASD or being typically developing. RESULTS: A classification accuracy of 79% was achieved, making our method competitive with other automatic diagnosis methods based on EEG. Additionally, we found that classification performance is reduced if eye blink artifacts are removed during preprocessing. CONCLUSIONS: This study shows that robust EEG features that quantify neural sensory reactivity are useful for the classification of ASD. We showed that noise-robust features are crucial for our analysis, and observe that traditional preprocessing methods may lead to poor classification performance in the face of a large amount of noise. Further exploration of alternative preprocessing methods is warranted.
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8. Geretsegger M, Elefant C, Mossler KA, Gold C. {{Music therapy for people with autism spectrum disorder}}. {Cochrane Database Syst Rev};2014 (Jun 17);6:CD004381.
BACKGROUND: The central impairments of people with autism spectrum disorder (ASD) affect social interaction and communication. Music therapy uses musical experiences and the relationships that develop through them to enable communication and expression, thus attempting to address some of the core problems of people with ASD. The present version of this review on music therapy for ASD is an update of the original Cochrane review published in 2006. OBJECTIVES: To assess the effects of music therapy for individuals with ASD. SEARCH METHODS: We searched the following databases in July 2013: CENTRAL, Ovid MEDLINE, EMBASE, LILACS, PsycINFO, CINAHL, ERIC, ASSIA, Sociological Abstracts, and Dissertation Abstracts International. We also checked the reference lists of relevant studies and contacted investigators in person. SELECTION CRITERIA: All randomised controlled trials (RCTs) or controlled clinical trials comparing music therapy or music therapy added to standard care to ‘placebo’ therapy, no treatment, or standard care for individuals with ASD were considered for inclusion. DATA COLLECTION AND ANALYSIS: Two authors independently selected studies, assessed risk of bias, and extracted data from all included studies. We calculated the pooled standardised mean difference (SMD) and corresponding 95% confidence interval (CI) for continuous outcomes to allow the combination data from different scales and to facilitate the interpretation of effect sizes. Heterogeneity was assessed using the I(2) statistic. In cases of statistical heterogeneity within outcome subgroups, we examined clients’ age, intensity of therapy (number and frequency of therapy sessions), and treatment approach as possible sources of heterogeneity. MAIN RESULTS: We included 10 studies (165 participants) that examined the short- and medium-term effect of music therapy interventions (one week to seven months) for children with ASD. Music was superior to ‘placebo’ therapy or standard care with respect to the primary outcomes social interaction within the therapy context (SMD 1.06, 95% CI 0.02 to 2.10, 1 RCT, n = 10); generalised social interaction outside of the therapy context (SMD 0.71, 95% CI 0.18 to 1.25, 3 RCTs, n = 57, moderate quality evidence), non-verbal communicative skills within the therapy context (SMD 0.57, 95% CI 0.29 to 0.85, 3 RCTs, n = 30), verbal communicative skills (SMD 0.33, 95% CI 0.16 to 0.49, 6 RCTs, n = 139), initiating behaviour (SMD 0.73, 95% CI 0.36 to 1.11, 3 RCTs, n = 22, moderate quality evidence), and social-emotional reciprocity (SMD 2.28, 95% CI 0.73 to 3.83, 1 RCT, n = 10, low quality evidence). There was no statistically significant difference in non-verbal communicative skills outside of the therapy context (SMD 0.48, 95% CI -0.02 to 0.98, 3 RCTs, n = 57, low quality evidence). Music therapy was also superior to ‘placebo’ therapy or standard care in secondary outcome areas, including social adaptation (SMD 0.41, 95% CI 0.21 to 0.60, 4 RCTs, n = 26), joy (SMD 0.96, 95% CI 0.04 to 1.88, 1 RCT, n = 10), and quality of parent-child relationships (SMD 0.82, 95% CI 0.13 to 1.52, 2 RCTs, n = 33, moderate quality evidence). None of the included studies reported any adverse effects. The small sample sizes of the studies limit the methodological strength of these findings. AUTHORS’ CONCLUSIONS: The findings of this updated review provide evidence that music therapy may help children with ASD to improve their skills in primary outcome areas that constitute the core of the condition including social interaction, verbal communication, initiating behaviour, and social-emotional reciprocity. Music therapy may also help to enhance non-verbal communication skills within the therapy context. Furthermore, in secondary outcome areas, music therapy may contribute to increasing social adaptation skills in children with ASD and to promoting the quality of parent-child relationships. In contrast to the studies included in an earlier version of this review published in 2006, the new studies included in this update enhanced the applicability of findings to clinical practice. More research using larger samples and generalised outcome measures is needed to corroborate these findings and to examine whether the effects of music therapy are enduring. When applying the results of this review to practice, it is important to note that the application of music therapy requires specialised academic and clinical training.
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9. Hoffmann TJ, Windham GC, Anderson M, Croen LA, Grether JK, Risch N. {{Evidence of Reproductive Stoppage in Families With Autism Spectrum Disorder: A Large, Population-Based Cohort Study}}. {JAMA Psychiatry};2014 (Jun 18)
Importance: Few studies have examined the curtailment of reproduction (ie, stoppage) after the diagnosis of a child with autism spectrum disorder (ASD). Objective: To examine stoppage in a large, population-based cohort of families in which a child has received a diagnosis of ASD. Design, Setting, and Participants: Individuals with ASD born from January 1, 1990, through December 31, 2003, were identified in the California Department of Developmental Services records, which were then linked to state birth certificates to identify full sibs and half-sibs and to obtain information on birth order and demographics. A total of 19 710 case families in which the first birth occurred within the study period was identified. These families included 39 361 individuals (sibs and half-sibs). Control individuals were randomly sampled from birth certificates and matched 2:1 to cases by sex, birth year, and maternal age, self-reported race/ethnicity, and county of birth after removal of children receiving services from the California Department of Developmental Services. Using similar linkage methods as for case families, 36 215 pure control families (including 75 724 total individuals) were identified that had no individuals with an ASD diagnosis. Exposures: History of affected children. Main Outcomes and Measures: Stoppage was investigated by comparing the reproductive behaviors of parents after the birth of a child with ASD vs an unaffected child using a survival analysis framework for time to next birth and adjusting for demographic variables. Results: For the first few years after the birth of a child with ASD, the parents’ reproductive behavior was similar to that of control parents. However, birth rates differed in subsequent years; overall, families whose first child had ASD had a second child at a rate of 0.668 (95% CI, 0.635-0.701) that of control families, adjusted for birth year, birth weight, maternal age, and self-reported maternal race/ethnicity. Results were similar when a later-born child was the first affected child in the family. Reproductive curtailment was slightly stronger among women who changed partners (relative rate for second-born children, 0.553 [95% CI, 0.498-0.614]). Conclusions and Relevance: These results provide the first quantitative assessment and convincing statistical evidence of reproductive stoppage related to ASD. These findings have implications for recurrence risk estimation and genetic counseling.
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10. Holwerda A, Brouwer S, de Boer MR, Groothoff JW, van der Klink JJ. {{Expectations from Different Perspectives on Future Work Outcome of Young Adults with Intellectual and Developmental Disabilities}}. {J Occup Rehabil};2014 (Jun 17)
Purpose Expectations strongly influence future employment outcomes and social networks seem to mediate employment success of young adults with intellectual and developmental disabilities. The aim of this study is to examine the expectations of young adults with intellectual and developmental disabilities from special needs education, their parents and their school teachers regarding future work and the extent to which these expectations predict work outcome. Methods Data on 341 young adults with intellectual or developmental disabilities, coming from special needs education, aged 17-20 years, and with an ability to work according to the Social Security Institute were examined. Results The school teacher’s expectation was the only perspective that significantly predicted entering competitive employment, with a complementary effect of the expectation of parents and a small additional effect of the expectation of the young adult. Conclusions Expectations of school teachers and parents are valuable in predicting work outcome. Therefore, it is important for professionals working with the young adult in the transition from school to work to incorporate the knowledge of school teachers and parents regarding the abilities of the young adult to enter competitive employment as a valuable source of information.
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11. Malkki H. {{Neurodevelopmental disorders: Elevated fetal sex steroids might confer risk for autism}}. {Nat Rev Neurol};2014 (Jun 17)
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12. Masi A, Quintana DS, Glozier N, Lloyd AR, Hickie IB, Guastella AJ. {{Cytokine aberrations in autism spectrum disorder: a systematic review and meta-analysis}}. {Mol Psychiatry};2014 (Jun 17)
The role of non-diagnostic features in the pathophysiology of autism spectrum disorders (ASDs) is unclear. Increasing evidence suggests immune system alterations in ASD may be implicated in the severity of behavioral impairment and other developmental outcomes. The primary objective of this meta-analysis was to investigate if there is a characteristic abnormal cytokine profile in ASD compared with healthy controls (HCs). We identified relevant studies following a search of MEDLINE, EMBASE, PsycINFO, Web of Knowledge and Scopus. A meta-analysis was performed on studies comparing plasma and serum concentrations of cytokines in unmedicated participants with ASD and HCs. Results were reported according to PRISMA statement. Seventeen studies with a total sample size of 743 participants with ASD and 592 HC were included in the analysis. Nineteen cytokines were assessed. Concentrations of interleukin (IL)-1beta (P<0.001), IL-6 (P=0.03), IL-8 (P=0.04), interferon-gamma (P=0.02), eotaxin (P=0.01) and monocyte chemotactic protein-1 (P<0.05) were significantly higher in the participants with ASD compared with the HC group, while concentrations of transforming growth factor-beta1 were significantly lower (P<0.001). There were no significant differences between ASD participants and controls for the other 12 cytokines analyzed. The findings of our meta-analysis identified significantly altered concentrations of cytokines in ASD compared to HCs, strengthening evidence of an abnormal cytokine profile in ASD where inflammatory signals dominate.Molecular Psychiatry advance online publication, 17 June 2014; doi:10.1038/mp.2014.59.
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13. Meguid NA, Ismail MF, El-Mahdy RS, Barakat MA, El-Awady MK. {{Simple molecular diagnostic method for Fragile X syndrome in Egyptian patients: Pilot study}}. {Acta Biochim Pol};2014 (Jun 16)
Background: Poor knowledge about Fragile X syndrome (FXS) may be a major barrier to early diagnosis that could improve quality of life and prognosis especially in the developing countries. Aim: The aim of this study was to evaluate simple and reproducible method for premutation detection in females of fragile X families for the first time in Egypt. Subjects and Methods: We have developed a rapid modified polymerase chain reaction (PCR)-based screening tool for expanded Fragile X mental retardation 1 (FMR1) alleles. This method utilizes betaine as additive to facilitate FMR 1 gene amplification. We screened fifty three males, thirty two first-degree females; twenty normal healthy controls in addition to six reference samples. Results: Simple PCR method showed 16 males with abnormal CGG repeats, where 10 of their mothers and four sisters had FMR 1 premutation. Consanguineous marriage was present in 66.6% percent of the studied families. Studying the correlation between genotype and clinical manifestations showed premature ovarian failure in 40% and learning disability in 50% of the studied female carriers. Conclusion: FXS has to be ruled out in families with consanguineous parents, before assuming that familial mental retardation is due to autosomal recessive gene defects. Early carrier detection may reduce the number of affected children. In conclusion, more studies are still needed of much larger sample size with known allele sizes in order to guarantee the accuracy of the method used.
14. Mohn JL, Alexander J, Pirone A, Palka CD, Lee SY, Mebane L, Haydon PG, Jacob MH. {{Adenomatous polyposis coli protein deletion leads to cognitive and autism-like disabilities}}. {Mol Psychiatry};2014 (Jun 17)
Intellectual disabilities (IDs) and autism spectrum disorders link to human APC inactivating gene mutations. However, little is known about adenomatous polyposis coli’s (APC’s) role in the mammalian brain. This study is the first direct test of the impact of APC loss on central synapses, cognition and behavior. Using our newly generated APC conditional knock-out (cKO) mouse, we show that deletion of this single gene in forebrain neurons leads to a multisyndromic neurodevelopmental disorder. APC cKO mice, compared with wild-type littermates, exhibit learning and memory impairments, and autistic-like behaviors (increased repetitive behaviors, reduced social interest). To begin to elucidate neuronal changes caused by APC loss, we focused on the hippocampus, a key brain region for cognitive function. APC cKO mice display increased synaptic spine density, and altered synaptic function (increased frequency of miniature excitatory synaptic currents, modestly enhanced long-term potentiation). In addition, we found excessive beta-catenin levels and associated changes in canonical Wnt target gene expression and N-cadherin synaptic adhesion complexes, including reduced levels of presenilin1. Our findings identify some novel functional and molecular changes not observed previously in other genetic mutant mouse models of co-morbid cognitive and autistic-like disabilities. This work thereby has important implications for potential therapeutic targets and the impact of their modulation. We provide new insights into molecular perturbations and cell types that are relevant to human ID and autism. In addition, our data elucidate a novel role for APC in the mammalian brain as a hub that links to and regulates synaptic adhesion and signal transduction pathways critical for normal cognition and behavior.Molecular Psychiatry advance online publication, 17 June 2014; doi:10.1038/mp.2014.61.
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15. Mouti A, Reddihough D, Marraffa C, Hazell P, Wray J, Lee K, Kohn M. {{Fluoxetine for Autistic Behaviors (FAB trial): study protocol for a randomized controlled trial in children and adolescents with autism}}. {Trials};2014 (Jun 16);15(1):230.
BACKGROUND: Serotonin reuptake inhibitors (SSRIs) are commonly prescribed off-label for children with autism. To date, clinical trials examining the use of SSRIs in autism have been limited by small sample sizes and inconclusive results. The efficacy and safety of SSRIs for moderating autistic behaviors is yet to be adequately examined to provide evidence to support current clinical practice. The aim of the Fluoxetine for Autistic Behaviors (FAB) study is to determine the efficacy and safety of low dose fluoxetine compared with placebo, for reducing the frequency and severity of repetitive stereotypic behaviors in children and adolescents with an autism spectrum disorder (ASD). The relationship between the effectiveness of fluoxetine treatment and serotonin transporter genotype will also be explored. METHODS: The FAB study is a multicenter, double-blinded, randomized controlled trial, funded by the Australian Government’s National Health and Medical Research Council (NHMRC) grant. Participants will be aged between 7.5 and 17 years with a confirmed diagnosis of ASD. Eligible participants will be randomized to either placebo or fluoxetine for a 16-week period. Medication will be titrated over the first four weeks. Reponses to medication will be monitored fortnightly using the Clinical Global Impressions Scale (CGI). The primary outcome measure is the Children’s Yale-Brown Obsessive Compulsive Scale-Modified for Pervasive Developmental Disorders (CYBOCS-PDD), administered at baseline and 16 weeks. Secondary outcome measures include the Aberrant Behaviour Scale (ABC), the Spence Children’s Anxiety Scale Parent Report (SCAS-P), and the Repetitive Behaviors Scale (RBS-R), measured at baseline and 16 weeks. Participants will be invited to undergo genetic testing for SLC6A4 allele variants using a cheek swab. Continuous outcomes, including the primary outcome will be compared between the active and placebo groups using unadjusted linear regression. Binary outcomes will be compared using unadjusted logistic regression. DISCUSSION: The FAB study is a large clinical trial to specifically investigate the efficacy of low dose fluoxetine for restricted, repetitive, and stereotyped behaviors in ASD. The outcomes of this study will contribute to evidence-based interventions used in clinical practice to assist children with ASD.Trial registration: Australian and New Zealand Clinical Trials Registry ACTRN12608000173392; registered on 9 April, 2008.
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16. Naviaux JC, Schuchbauer MA, Li K, Wang L, Risbrough VB, Powell SB, Naviaux RK. {{Reversal of autism-like behaviors and metabolism in adult mice with single-dose antipurinergic therapy}}. {Transl Psychiatry};2014;4:e400.
Autism spectrum disorders (ASDs) now affect 1-2% of the children born in the United States. Hundreds of genetic, metabolic and environmental factors are known to increase the risk of ASD. Similar factors are known to influence the risk of schizophrenia and bipolar disorder; however, a unifying mechanistic explanation has remained elusive. Here we used the maternal immune activation (MIA) mouse model of neurodevelopmental and neuropsychiatric disorders to study the effects of a single dose of the antipurinergic drug suramin on the behavior and metabolism of adult animals. We found that disturbances in social behavior, novelty preference and metabolism are not permanent but are treatable with antipurinergic therapy (APT) in this model of ASD and schizophrenia. A single dose of suramin (20 mg kg(-1) intraperitoneally (i.p.)) given to 6-month-old adults restored normal social behavior, novelty preference and metabolism. Comprehensive metabolomic analysis identified purine metabolism as the key regulatory pathway. Correction of purine metabolism normalized 17 of 18 metabolic pathways that were disturbed in the MIA model. Two days after treatment, the suramin concentration in the plasma and brainstem was 7.64 muM pmol mul(-1) (+/-0.50) and 5.15 pmol mg(-1) (+/-0.49), respectively. These data show good uptake of suramin into the central nervous system at the level of the brainstem. Most of the improvements associated with APT were lost after 5 weeks of drug washout, consistent with the 1-week plasma half-life of suramin in mice. Our results show that purine metabolism is a master regulator of behavior and metabolism in the MIA model, and that single-dose APT with suramin acutely reverses these abnormalities, even in adults.
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17. Reichow B, Gelbar NW, Mouradjian K, Shefcyk A, Smith IC. {{Characteristics of international websites with information on developmental disabilities}}. {Res Dev Disabil};2014 (Jun 18);35(10):2293-2298.
The Internet often serves as a primary resource for individuals seeking health-related information, and a large and growing number of websites contain information related to developmental disabilities. This paper presents the results of an international evaluation of the characteristics and content of the top 10 ranked results (i.e., not including sponsored results – pay-per-click) returned when one of five terms related to developmental disabilities (i.e., ADHD, autism, down syndrome, learning disability, intellectual disability) was entered into one of six country specific Google online search engines (i.e., Australia (https://www.google.com.au), Canada (https://www.google.ca), Ireland (https://www.google.ie), New Zealand (https://www.google.co.nz), the United Kingdom (https://www.google.co.uk), and the United States (https://www.google.com)) on October 22, 2013. Collectively, we found that international consumers of websites related to developmental disabilities will encounter different websites with differing content and terminology, and should be critical consumers to ensure they locate the information they are seeking.
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18. Rieffe C, De Bruin M, De Rooij M, Stockmann L. {{Approach and avoidant emotion regulation prevent depressive symptoms in children with an Autism Spectrum Disorder}}. {Int J Dev Neurosci};2014 (Jun 18)
The prevalence of depression is high in children with Autism Spectrum Disorders (ASD), but its etiology has not yet been studied in this group. Emotion dysregulation is a well-known contributor to the development of depression in typically developing (TD) children, which might also apply to children with ASD. In this study, we examined the longitudinal relationship between three different ways of emotion regulation (approach, avoidance and worry/rumination) and depressive symptoms in children with ASD and a group of TD children which were compatible with the ASD group (age 9-15 years old). Children filled out self-report questionnaires at 3 time points (with a 9 month break between each session). To account for missing data multiple imputations were used. A regression model with clustered bootstrapping was used to establish which factors contributed to depression and to identify possible differences between the ASD and TD group. Approach and avoidant strategies prevented the development of depressive symptoms in both respective groups, whereas elevated levels of worry/rumination in turn increased children’s depressive symptoms. Besides differences in absolute levels (children with ASD scored higher on symptoms of depression and lower on approach strategies than the TD group), no other differences between the groups emerged.
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19. Segovia F, Holt R, Spencer M, Gorriz JM, Ramirez J, Puntonet CG, Phillips C, Chura L, Baron-Cohen S, Suckling J. {{Identifying endophenotypes of autism: a multivariate approach}}. {Front Comput Neurosci};2014;8:60.
The existence of an endophenotype of autism spectrum condition (ASC) has been recently suggested by several commentators. It can be estimated by finding differences between controls and people with ASC that are also present when comparing controls and the unaffected siblings of ASC individuals. In this work, we used a multivariate methodology applied on magnetic resonance images to look for such differences. The proposed procedure consists of combining a searchlight approach and a support vector machine classifier to identify the differences between three groups of participants in pairwise comparisons: controls, people with ASC and their unaffected siblings. Then we compared those differences selecting spatially collocated as candidate endophenotypes of ASC.
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20. White SW, Mazefsky CA, Dichter GS, Chiu PH, Richey JA, Ollendick TH. {{Social-cognitive, physiological, and neural mechanisms underlying emotion regulation impairments: Understanding anxiety in autism spectrum disorder}}. {Int J Dev Neurosci};2014 (Jun 18)
Anxiety is one of the most common clinical problems among children, adolescents, and adults with autism spectrum disorder (ASD), yet we know little about its etiology in the context of ASD. We posit that emotion regulation (ER) impairments are a risk factor for anxiety in ASD. Specifically, we propose that one reason why anxiety disorders are so frequently comorbid with ASD is because ER impairments are ubiquitous to ASD, stemming from socio-cognitive, physiological, and neurological processes related to impaired cognitive control, regulatory processes, and arousal. In this review, we offer a developmental model of how ER impairments may arise in ASD, and when (moderating influences) and how (meditational mechanisms) they result in anxiety.
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21. Yoshimasu K, Kiyohara C, Takemura S, Nakai K. {{A meta-analysis of the evidence on the impact of prenatal and early infancy exposures to mercury on autism and attention deficit/hyperactivity disorder in the childhood}}. {Neurotoxicology};2014 (Jun 18)
Although a measurable number of epidemiological studies have been conducted to clarify the associations between mercury exposure during embryo or early infancy and later incidences of autism spectrum disorders (ASD) or attention-deficit hyperactivity disorder (ADHD), the conclusion still remains unclear. Meta-analysis was conducted for two major exposure sources; i.e., thimerosal vaccines that contain ethylmercury (clinical exposure), and environmental sources, using relevant literature published before April 2014. While thimerosal exposures did not show any material associations with an increased risk of ASD or ADHD (the summary odds ratio (OR) 0.99, 95% confidence interval (CI) 0.80-1.24 for ASD; OR 0.91, 95% CI 0.70-1.13 for ADHD/ADD), significant associations were observed for environmental exposures in both ASD (OR 1.66, 95% CI 1.14-2.17) and ADHD (OR 1.60, 95% CI 1.10-2.33). The summary ORs were similar after excluding studies not adjusted for confounders. Moderate adverse effects were observed only between environmental inorganic or organic mercury exposures and ASD/ADHD. However, these results should be interpreted with caution since the number of epidemiological studies on this issue was limited and still at an early stage. Further studies focused on subjects with genetic vulnerabilities of developmental disorders are warranted for better understanding of the effects of such environmental exposures.
