1. Bonnet-Brilhault F, Alirol S, Blanc R, Bazaud S, Marouillat S, Thepault RA, Andres CR, Lemonnier E, Barthelemy C, Raynaud M, Toutain A, Gomot M, Laumonnier F. {{GABA/Glutamate synaptic pathways targeted by integrative genomic and electrophysiological explorations distinguish autism from intellectual disability}}. {Mol Psychiatry};2015 (Jun 9)
Phenotypic and genetic heterogeneity is predominant in autism spectrum disorders (ASD), for which the molecular and pathophysiological bases are still unclear. Significant comorbidity and genetic overlap between ASD and other neurodevelopmental disorders are also well established. However, little is understood regarding the frequent observation of a wide phenotypic spectrum associated with deleterious mutations affecting a single gene even within multiplex families. We performed a clinical, neurophysiological (in vivo electroencephalography-auditory-evoked related potentials) and genetic (whole-exome sequencing) follow-up analysis of two families with known deleterious NLGN4X gene mutations (either truncating or overexpressing) present in individuals with ASD and/or with intellectual disability (ID). Complete phenotypic evaluation of the pedigrees in the ASD individuals showed common specific autistic behavioural features and neurophysiological patterns (abnormal MisMatch Negativity in response to auditory change) that were absent in healthy parents as well as in family members with isolated ID. Whole-exome sequencing in ASD patients from each family identified a second rare inherited genetic variant, affecting either the GLRB or the ANK3 genes encoding NLGN4X interacting proteins expressed in inhibitory or in excitatory synapses, respectively. The GRLB and ANK3 mutations were absent in relatives with ID as well as in control databases. In summary, our findings provide evidence of a double-hit genetic model focused on excitatory/inhibitory synapses in ASD, that is not found in isolated ID, associated with an atypical in vivo neurophysiological pattern linked to predictive coding.Molecular Psychiatry advance online publication, 9 June 2015; doi:10.1038/mp.2015.75.
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2. Burkett K, Morris E, Manning-Courtney P, Anthony J, Shambley-Ebron D. {{African American Families on Autism Diagnosis and Treatment: The Influence of Culture}}. {J Autism Dev Disord};2015 (Jun 9)
Cultural factors such as health care access and autism spectrum disorder (ASD) symptom interpretations have been proposed as impacting delayed diagnosis and treatment for African American children with ASD. A qualitative study of urban African American families caring for their child with autism was conducted with 24 family members and 28 ASD professionals. Cultural caring meant families protected their child from harm including potential or actual distrustful encounters, and took action for their child and community to optimize their child’s health and address the knowledge deficits of ASD within their community. Families and professionals believed cultural influences delayed families’ receiving and seeking appropriate health care for the African American child with ASD affecting timely autism diagnosis and treatment.
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3. Cerliani L, Mennes M, Thomas RM, Di Martino A, Thioux M, Keysers C. {{Increased Functional Connectivity Between Subcortical and Cortical Resting-State Networks in Autism Spectrum Disorder}}. {JAMA Psychiatry};2015 (Jun 10)
Importance: Individuals with autism spectrum disorder (ASD) exhibit severe difficulties in social interaction, motor coordination, behavioral flexibility, and atypical sensory processing, with considerable interindividual variability. This heterogeneous set of symptoms recently led to investigating the presence of abnormalities in the interaction across large-scale brain networks. To date, studies have focused either on constrained sets of brain regions or whole-brain analysis, rather than focusing on the interaction between brain networks. Objectives: To compare the intrinsic functional connectivity between brain networks in a large sample of individuals with ASD and typically developing control subjects and to estimate to what extent group differences would predict autistic traits and reflect different developmental trajectories. Design, Setting, and Participants: We studied 166 male individuals (mean age, 17.6 years; age range, 7-50 years) diagnosed as having DSM-IV-TR autism or Asperger syndrome and 193 typical developing male individuals (mean age, 16.9 years; age range, 6.5-39.4 years) using resting-state functional magnetic resonance imaging (MRI). Participants were matched for age, IQ, head motion, and eye status (open or closed) in the MRI scanner. We analyzed data from the Autism Brain Imaging Data Exchange (ABIDE), an aggregated MRI data set from 17 centers, made public in August 2012. Main Outcomes and Measures: We estimated correlations between time courses of brain networks extracted using a data-driven method (independent component analysis). Subsequently, we associated estimates of interaction strength between networks with age and autistic traits indexed by the Social Responsiveness Scale. Results: Relative to typically developing control participants, individuals with ASD showed increased functional connectivity between primary sensory networks and subcortical networks (thalamus and basal ganglia) (all t >/= 3.13, P < .001 corrected). The strength of such connections was associated with the severity of autistic traits in the ASD group (all r >/= 0.21, P < .0067 corrected). In addition, subcortico-cortical interaction decreased with age in the entire sample (all r </= -0.09, P < .012 corrected), although this association was significant only in typically developing participants (all r </= -0.13, P < .009 corrected). Conclusions and Relevance: Our results showing ASD-related impairment in the interaction between primary sensory cortices and subcortical regions suggest that the sensory processes they subserve abnormally influence brain information processing in individuals with ASD. This might contribute to the occurrence of hyposensitivity or hypersensitivity and of difficulties in top-down regulation of behavior.
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4. Chevallier C, Parish-Morris J, McVey A, Rump KM, Sasson NJ, Herrington JD, Schultz RT. {{Measuring social attention and motivation in autism spectrum disorder using eye-tracking: Stimulus type matters}}. {Autism Res};2015 (Jun 10)
Autism Spectrum Disorder (ASD) is characterized by social impairments that have been related to deficits in social attention, including diminished gaze to faces. Eye-tracking studies are commonly used to examine social attention and social motivation in ASD, but they vary in sensitivity. In this study, we hypothesized that the ecological nature of the social stimuli would affect participants’ social attention, with gaze behavior during more naturalistic scenes being most predictive of ASD vs. typical development. Eighty-one children with and without ASD participated in three eye-tracking tasks that differed in the ecological relevance of the social stimuli. In the « Static Visual Exploration » task, static images of objects and people were presented; in the « Dynamic Visual Exploration » task, video clips of individual faces and objects were presented side-by-side; in the « Interactive Visual Exploration » task, video clips of children playing with objects in a naturalistic context were presented. Our analyses uncovered a three-way interaction between Task, Social vs. Object Stimuli, and Diagnosis. This interaction was driven by group differences on one task only-the Interactive task. Bayesian analyses confirmed that the other two tasks were insensitive to group membership. In addition, receiver operating characteristic analyses demonstrated that, unlike the other two tasks, the Interactive task had significant classification power. The ecological relevance of social stimuli is an important factor to consider for eye-tracking studies aiming to measure social attention and motivation in ASD. Autism Res 2015. (c) 2015 International Society for Autism Research, Wiley Periodicals, Inc.
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5. Currais A, Farrokhi C, Dargusch R, Goujon-Svrzic M, Maher P. {{Dietary glycemic index modulates the behavioral and biochemical abnormalities associated with autism spectrum disorder}}. {Mol Psychiatry};2015 (Jun 9)
Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder of unknown etiology, but very likely resulting from both genetic and environmental factors. There is good evidence for immune system dysregulation in individuals with ASD. However, the contribution of insults such as dietary factors that can also activate the immune system have not been explored in the context of ASD. In this paper, we show that the dietary glycemic index has a significant impact on the ASD phenotype. By using BTBR mice, an inbred strain that displays behavioral traits that reflect the diagnostic symptoms of human ASD, we found that the diet modulates plasma metabolites, neuroinflammation and brain markers of neurogenesis in a manner that is highly reflective of ASD in humans. Overall, the manuscript supports the idea that ASD results from gene-environment interactions and that in the presence of a genetic predisposition to ASD, diet can make a large difference in the expression of the condition.Molecular Psychiatry advance online publication, 9 June 2015; doi:10.1038/mp.2015.64.
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6. English MC, Maybery MT, Visser TA. {{Individuals with Autistic-Like Traits Show Reduced Lateralization on a Greyscales Task}}. {J Autism Dev Disord};2015 (Jun 10)
Individuals with autism spectrum conditions attend less to the left side of centrally presented face stimuli compared to neurotypical individuals, suggesting a reduction in right hemisphere activation. We examined whether a similar bias exists for non-facial stimuli in a large sample of neurotypical adults rated above- or below-average on the autism spectrum quotient (AQ). Using the « greyscales » task, we found the typical leftward bias in the below-average group was significantly reduced in the above-average group. Moreover, a negative correlation between leftward bias and the social skills factor of the AQ suggested a link between atypical hemispheric activation and social difficulties in high-AQ trait individuals that extends to non-facial stimuli.
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7. Ginevra MC, Nota L, Stokes MA. {{The differential effects of Autism and Down’s syndrome on sexual behavior}}. {Autism Res};2015 (Jun 7)
Although sexuality plays a major role in the socialization of people, few studies have examined the sexual behaviors of individuals with developmental disabilities. Because of this, we decided to investigate sexuality in adolescents with autism spectrum disorder (ASD) and Down’s syndrome (Ds) and to compare them with typically developing adolescents, by surveying their parents. Specifically, it was hypothesized that young people with ASD would display lower levels over five domains: social behavior, privacy, sex education, sexual behavior, and parental concerns, than peers with Ds and typically developing young people. In addition, we sought to verify developmental trends in five domains with age for each group. Overall, 269 parents participated; 94 parents of typically developing adolescents, 93 parents of adolescents diagnosed with Ds, and 82 parents of adolescents diagnosed with ASD. Participants were surveyed with a Sexual Behavior Scale developed by Stokes and Kaur [] that assesses parents’ reports of their child’s: social behavior, privacy awareness, sex education, sexual behavior and parental concerns about the child’s behaviors. It was found that three groups were significantly different on all five domains, adolescents with ASD reportedly displaying lower levels than other groups. Moreover, there was a significant improvement in knowledge of privacy and parental concerns with age for adolescents with ASD and a decline in sex education for adolescents with Ds. The results obtained emphasize the need to train adolescents with developmental disability, and especially for adolescents with ASD through sex education programs. Autism Res 2015. (c) 2015 International Society for Autism Research, Wiley Periodicals, Inc.
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8. Green SA, Hernandez L, Tottenham N, Krasileva K, Bookheimer SY, Dapretto M. {{Neurobiology of Sensory Overresponsivity in Youth With Autism Spectrum Disorders}}. {JAMA Psychiatry};2015 (Jun 10)
Importance: More than half of youth with autism spectrum disorders (ASDs) have sensory overresponsivity (SOR), an extreme negative reaction to sensory stimuli. However, little is known about the neurobiological basis of SOR, and there are few effective treatments. Understanding whether SOR is due to an initial heightened sensory response or to deficits in regulating emotional reactions to stimuli has important implications for intervention. Objective: To determine differences in brain responses, habituation, and connectivity during exposure to mildly aversive sensory stimuli in youth with ASDs and SOR compared with youth with ASDs without SOR and compared with typically developing control subjects. Design, Setting, and Participants: Functional magnetic resonance imaging was used to examine brain responses and habituation to mildly aversive auditory and tactile stimuli in 19 high-functioning youths with ASDs and 19 age- and IQ-matched, typically developing youths (age range, 9-17 years). Brain activity was related to parents’ ratings of children’s SOR symptoms. Functional connectivity between the amygdala and orbitofrontal cortex was compared between ASDs subgroups with and without SOR and typically developing controls without SOR. The study dates were March 2012 through February 2014. Main Outcomes and Measures: Relative increases in blood oxygen level-dependent signal response across the whole brain and within the amygdala during exposure to sensory stimuli compared with fixation, as well as correlation between blood oxygen level-dependent signal change in the amygdala and orbitofrontal cortex. Results: The mean age in both groups was 14 years and the majority in both groups (16 of 19 each) were male. Compared with neurotypical control participants, participants with ASDs displayed stronger activation in primary sensory cortices and the amygdala (P < .05, corrected). This activity was positively correlated with SOR symptoms after controlling for anxiety. The ASDs with SOR subgroup had decreased neural habituation to stimuli in sensory cortices and the amygdala compared with groups without SOR. Youth with ASDs without SOR showed a pattern of amygdala downregulation, with negative connectivity between the amygdala and orbitofrontal cortex (thresholded at z > 1.70, P < .05). Conclusions and Relevance: Results demonstrate that youth with ASDs and SOR show sensorilimbic hyperresponsivity to mildly aversive tactile and auditory stimuli, particularly to multiple modalities presented simultaneously, and show that this hyperresponsivity is due to failure to habituate. In addition, findings suggest that a subset of youth with ASDs can regulate their responses through prefrontal downregulation of amygdala activity. Implications for intervention include minimizing exposure to multiple sensory modalities and building coping strategies for regulating emotional response to stimuli.
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9. Hu VW, Sarachana T, Sherrard RM, Kocher KM. {{Investigation of sex differences in the expression of RORA and its transcriptional targets in the brain as a potential contributor to the sex bias in autism}}. {Mol Autism};2015;6:7.
BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by significant impairment in reciprocal social interactions and communication coupled with stereotyped, repetitive behaviors and restricted interests. Although genomic and functional studies are beginning to reveal some of the genetic complexity and underlying pathobiology of ASD, the consistently reported male bias of ASD remains an enigma. We have recently proposed that retinoic acid-related orphan receptor alpha (RORA), which is reduced in the brain and lymphoblastoid cell lines of multiple cohorts of individuals with ASD and oppositely regulated by male and female hormones, might contribute to the sex bias in autism by differentially regulating target genes, including CYP19A1 (aromatase), in a sex-dependent manner that can also lead to elevated testosterone levels, a proposed risk factor for autism. METHODS: In this study, we examine sex differences in RORA and aromatase protein levels in cortical tissues of unaffected and affected males and females by re-analyzing pre-existing confocal immunofluorescence data from our laboratory. We further investigated the expression of RORA and its correlation with several of its validated transcriptional targets in the orbital frontal cortex and cerebellum as a function of development using RNAseq data from the BrainSpan Atlas of the Developing Human Brain. In a pilot study, we also analyzed the expression of Rora and the same transcriptional targets in the cortex and cerebellum of adult wild-type male and female C57BL/6 mice. RESULTS: Our findings suggest that Rora/RORA and several of its transcriptional targets may exhibit sexually dimorphic expression in certain regions of the brain of both mice and humans. Interestingly, the correlation coefficients between Rora expression and that of its targets are much higher in the cortex of male mice relative to that of female mice. A strong positive correlation between the levels of RORA and aromatase proteins is also seen in the cortex of control human males and females as well as ASD males, but not ASD females. CONCLUSIONS: Based on these studies, we suggest that disruption of Rora/RORA expression may have a greater impact on males, since sex differences in the correlation of RORA and target gene expression indicate that RORA-deficient males may experience greater dysregulation of genes relevant to ASD in certain brain regions during development.
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10. Huang F, Long Z, Chen Z, Li J, Hu Z, Qiu R, Zhuang W, Tang B, Xia K, Jiang H. {{Investigation of Gene Regulatory Networks Associated with Autism Spectrum Disorder Based on MiRNA Expression in China}}. {PLoS One};2015;10(6):e0129052.
Autism spectrum disorder (ASD) comprise a group of neurodevelopmental disorders characterized by deficits in social and communication capacities and repetitive behaviors. Increasing neuroscientific evidence indicates that the neuropathology of ASD is widespread and involves epigenetic regulation in the brain. Differentially expressed miRNAs in the peripheral blood from autism patients were identified by high-throughput miRNA microarray analyses. Five of these miRNAs were confirmed through quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis. A search for candidate target genes of the five confirmed miRNAs was performed through a Kyoto encyclopedia of genes and genomes (KEGG) biological pathways and Gene Ontology enrichment analysis of gene function to identify gene regulatory networks. To the best of our knowledge, this study provides the first global miRNA expression profile of ASD in China. The differentially expressed miR-34b may potentially explain the higher percentage of male ASD patients, and the aberrantly expressed miR-103a-3p may contribute to the abnormal ubiquitin-mediated proteolysis observed in ASD.
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11. Kiykim E, Zeybek CA, Zubarioglu T, Cansever S, Yalcinkaya C, Soyucen E, Aydin A. {{Inherited metabolic disorders in Turkish patients with autism spectrum disorders}}. {Autism Res};2015 (Jun 7)
Autism spectrum disorders (ASDs) are a major health problem because of their high prevalence in the general population. The pathophysiology of ASD remains unclear, although genetic defects may be detected in 10-20% of affected patients. Among these cases, the prevalence of inherited metabolic disorders (IMD) has not been extensively evaluated. IMDs responsible for ASDs are usually identified via clinical manifestations such as microcephaly, dysmorphic features, convulsions, and hepatosplenomegaly. Infrequently, patients with no additional clinical symptoms suggestive of an IMD may be diagnosed as having an idiopathic ASD. High consanguinity rates have resulted in an increased prevalence of IMDs in the Turkish population. The aim of this study was to explore the benefits of systematic screening for IMD among Turkish patients with ASDs. In our study, data were retrospectively collected for 778 children with ASDs. In all cases, the metabolic investigations included an arterial blood gas analysis, serum ammonia and lactate levels, a quantitative plasma amino acid analysis, a whole blood acylcarnitine profile via tandem mass spectrometry and a urine organic acid profile. Urinary glycosaminoglycan levels and homocysteine levels were screened in selected cases; 300 of the 778 patients with ASDs whose physical and metabolic investigations were complete and met this study’s criteria were enrolled. Among the 300 children with autism, IMD were diagnosed in nine patients as follows: two patients were diagnosed with phenylketonuria, and one patient was diagnosed with partial biotinidase deficiency; one patient was diagnosed with mucopolysaccharidosis type III, and one patient was diagnosed with classical homocystinuria; one patient was diagnosed with glutaric acidemia type 1, and one patient was diagnosed with short chain acyl-CoA dehydrogenase deficiency; one patient was diagnosed with argininemia, and one patient was diagnosed with L-2-hydroxyglutaric aciduria. Autism Res 2015. (c) 2015 International Society for Autism Research, Wiley Periodicals, Inc.
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12. Mandy W, Tchanturia K. {{Do women with eating disorders who have social and flexibility difficulties really have autism? A case series}}. {Mol Autism};2015;6:6.
BACKGROUND: Many women with eating disorders (EDs) have social impairments and difficulties with flexibility. It is unclear to what extent these are manifestations of an underlying autism spectrum disorder (ASD); or whether they are instead the consequence of starvation, anxiety, low mood or obsessive compulsive disorder, all of which are highly prevalent in EDs. The resolution of this clinically and theoretically important uncertainty will require the use of gold-standard ASD assessment measures. To date these have not been employed in ED research. This case series is the first report of a well-validated, direct-observational measure of ASD, the Autism Diagnostic Observation Schedule (ADOS), being administered to women with EDs. We aimed to learn about the feasibility of the ADOS in this population, and to contribute to debates about whether a sub-group with EDs really have ASD. METHODS: Ten women (mean age = 26.4 years, range = 19 to 38 years) who had a suspected ASD due to social and flexibility difficulties and were receiving treatment for ED (seven anorexia, two ED not otherwise specified, one bulimia) at a specialist service (four inpatient, six outpatient) received an ADOS Module 4 assessment. RESULTS: All 10 participants completed all activities of the ADOS Module 4. Five scored in the ASD range on the ADOS diagnostic algorithm. An additional two were judged likely to have ASD, even though they scored below the ADOS’s diagnostic threshold. This was on the basis of clinical observation, participant self-report and parent report. The seven women who we estimated to have ASD all reported autistic difficulties prior to the onset of their ED. They commonly described longstanding non-autistic neurodevelopmental problems, including dyslexia, dyspraxia and epilepsy. Only one had a childhood diagnosis of ASD. CONCLUSIONS: A substantial proportion of women with EDs who present with social and flexibility difficulties may have an unrecognised ASD, indicated by a constellation of autistic difficulties that appears to predate the onset of their eating problems. The ADOS is a useful component of an ASD assessment for adult women with ED.
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13. Pisula E, Ziegart-Sadowska K. {{Broader Autism Phenotype in Siblings of Children with ASD-A Review}}. {Int J Mol Sci};2015;16(6):13217-13258.
Although less pronounced, social, cognitive, and personality characteristics associated with autism spectrum disorders (ASD) may be present in people who do not meet ASD diagnostic criteria, especially in first-degree relatives of individuals with ASD. Research on these characteristics, referred to as broader autism phenotype (BAP), provides valuable data on potential expressions of autism-specific deficits in the context of family relations. This paper offers a review of research on BAP in siblings of individuals with ASD, focusing on reports regarding social, communication, and cognitive deficits, published from 1993 to 2014. The studies are divided into two groups based on participants’ age: papers on preschool and older siblings of individuals with ASD; and publications on infants at risk for ASD. On the basis of this review, suggestions are offered for further research and its significance for our understanding of the genetic determinants of autism.
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14. Sandin S, Schendel D, Magnusson P, Hultman C, Suren P, Susser E, Gronborg T, Gissler M, Gunnes N, Gross R, Henning M, Bresnahan M, Sourander A, Hornig M, Carter K, Francis R, Parner E, Leonard H, Rosanoff M, Stoltenberg C, Reichenberg A. {{Autism risk associated with parental age and with increasing difference in age between the parents}}. {Mol Psychiatry};2015 (Jun 9)
Advancing paternal and maternal age have both been associated with risk for autism spectrum disorders (ASD). However, the shape of the association remains unclear, and results on the joint associations is lacking. This study tests if advancing paternal and maternal ages are independently associated with ASD risk and estimates the functional form of the associations. In a population-based cohort study from five countries (Denmark, Israel, Norway, Sweden and Western Australia) comprising 5 766 794 children born 1985-2004 and followed up to the end of 2004-2009, the relative risk (RR) of ASD was estimated by using logistic regression and splines. Our analyses included 30 902 cases of ASD. Advancing paternal and maternal age were each associated with increased RR of ASD after adjusting for confounding and the other parent’s age (mothers 40-49 years vs 20-29 years, RR=1.15 (95% confidence interval (CI): 1.06-1.24), P-value<0.001; fathers50 years vs 20-29 years, RR=1.66 (95% CI: 1.49-1.85), P-value<0.001). Younger maternal age was also associated with increased risk for ASD (mothers <20 years vs 20-29 years, RR=1.18 (95% CI: 1.08-1.29), P-value<0.001). There was a joint effect of maternal and paternal age with increasing risk of ASD for couples with increasing differences in parental ages. We did not find any support for a modifying effect by the sex of the offspring. In conclusion, as shown in multiple geographic regions, increases in ASD was not only limited to advancing paternal or maternal age alone but also to differences parental age including younger or older similarly aged parents as well as disparately aged parents.Molecular Psychiatry advance online publication, 9 June 2015; doi:10.1038/mp.2015.70.
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15. Schwichtenberg AJ, Malow BA. {{Melatonin Treatment in Children with Developmental Disabilities}}. {Sleep Med Clin};2015 (Jun);10(2):181-187.
Melatonin is commonly recommended to treat sleep problems in children with developmental disabilities. However, few studies document the efficacy and safety of melatonin in these populations. This article reviews recent studies of melatonin efficacy in developmental disabilities. Overall, short treatment trials were associated with a significant decrease in sleep onset latency time for each of the disorders reviewed, with 1 notable exception-tuberous sclerosis. Reported side effects were uncommon and mild. Across disorders, additional research is needed to draw disability-specific conclusions. However, studies to date provide positive support for future trials that include larger groups of children with specific disabilities/syndromes.
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16. Shah P, Sowden S. {{Insights into Social Perception in Autism}}. {J Neurosci};2015 (Jun 10);35(23):8689-8690.
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17. Sung C, Sanchez J, Kuo HJ, Wang CC, Leahy MJ. {{Gender Differences in Vocational Rehabilitation Service Predictors of Successful Competitive Employment for Transition-Aged Individuals with Autism}}. {J Autism Dev Disord};2015 (Jun 10)
As males and females with autism spectrum disorder (ASD) experience different symptomology, their needs for vocational rehabilitation (VR) are unique as they transition into adulthood. This study examined the effects of gender differences in VR service predictors on employment outcomes for transition-aged individuals with ASD. A total of 1696 individuals (857 males and 839 females) were analyzed from a sample of RSA-911 data of FY 2011. Hierarchical logistic regression analyses were conducted. Results revealed both gender-independent VR service predictors (with job placement and on-the-job supports more beneficial for both genders) and gender-specific predictors of employment (with counseling and guidance, job search assistance, and other services more beneficial for the male group). This study provides support for individualized gender-specific VR services for people with ASD.
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18. Turi M, Burr DC, Igliozzi R, Aagten-Murphy D, Muratori F, Pellicano E. {{Children with autism spectrum disorder show reduced adaptation to number}}. {Proc Natl Acad Sci U S A};2015 (Jun 8)
Autism is known to be associated with major perceptual atypicalities. We have recently proposed a general model to account for these atypicalities in Bayesian terms, suggesting that autistic individuals underuse predictive information or priors. We tested this idea by measuring adaptation to numerosity stimuli in children diagnosed with autism spectrum disorder (ASD). After exposure to large numbers of items, stimuli with fewer items appear to be less numerous (and vice versa). We found that children with ASD adapted much less to numerosity than typically developing children, although their precision for numerosity discrimination was similar to that of the typical group. This result reinforces recent findings showing reduced adaptation to facial identity in ASD and goes on to show that reduced adaptation is not unique to faces (social stimuli with special significance in autism), but occurs more generally, for both parietal and temporal functions, probably reflecting inefficiencies in the adaptive interpretation of sensory signals. These results provide strong support for the Bayesian theories of autism.
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19. Viel JF, Warembourg C, Le Maner-Idrissi G, Lacroix A, Limon G, Rouget F, Monfort C, Durand G, Cordier S, Chevrier C. {{Pyrethroid insecticide exposure and cognitive developmental disabilities in children: The PELAGIE mother-child cohort}}. {Environ Int};2015 (Sep);82:69-75.
Pyrethroid insecticides are widely used in agriculture and in homes. Despite the neurotoxicity of these insecticides at high doses, few studies have examined whether lower-level exposures could adversely affect children’s neurodevelopment. The PELAGIE cohort included 3421 pregnant women from Brittany, France between 2002 and 2006. When their children reached their sixth birthday, 428 mothers from the cohort were randomly selected, successfully contacted and found eligible. A total of 287 (67%) mothers agreed to participate with their children in the neuropsychological follow-up. Two cognitive domains were assessed by the Wechsler Intelligence Scale for Children: verbal comprehension and working memory. Five pyrethroid and two organophosphate insecticide metabolites were measured in maternal and child first-void urine samples collected between 6 and 19 gestational weeks and at 6years of age, respectively. Linear regression models were used to estimate associations between cognitive scores and urinary pyrethroid metabolite concentrations, adjusting for organophosphate metabolite concentrations and potential confounders. Maternal prenatal pyrethroid metabolite concentrations were not consistently associated with any children’s cognitive scores. By contrast, childhood 3-PBA and cis-DBCA concentrations were both negatively associated with verbal comprehension scores (P-trend=0.04 and P-trend<0.01, respectively) and with working memory scores (P-trend=0.05 and P-trend<0.01, respectively). No associations were observed for the three other childhood pyrethroid metabolite concentrations (4-F-3-PBA, cis-DCCA, and trans-DCCA). Low-level childhood exposures to deltamethrin (as cis-DBCA is its principal and selective metabolite), in particular, and to pyrethroid insecticides, in general (as reflected in levels of the 3-PBA metabolite) may negatively affect neurocognitive development by 6years of age. Whatever their etiology, these cognitive deficits may be of importance educationally, because cognitive impairments in children interfere with learning and social development. Potential causes that can be prevented are of paramount public health importance.