Pubmed du 09/10/15

Pubmed du jour

2015-10-09 12:03:50

1. {{‘It is easy to find yourself working outside your comfort zone when working with autistic children’}}. {Br Dent J};2015 (Oct 9);219(7):315-316.

Wendy Bellis is Assistant Clinical Director and Specialist Paediatric Senior Dental Officer for Camden and Islington Community Dental Service (Whittington Health). She is considered a world renowned voice on autism and paediatric dentistry, and news editor David Westgarth sat down with her to discuss some of the challenges presented by autistic patients.

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2. Aller MI, Pecoraro V, Paternain AV, Canals S, Lerma J. {{Increased Dosage of High-Affinity Kainate Receptor Gene grik4 Alters Synaptic Transmission and Reproduces Autism Spectrum Disorders Features}}. {J Neurosci};2015 (Oct 7);35(40):13619-13628.

The understanding of brain diseases requires the identification of the molecular, synaptic, and cellular disruptions underpinning the behavioral features that define the disease. The importance of genes related to synaptic function in brain disease has been implied in studies describing de novo germline mutations and copy number variants. Indeed, de novo copy number variations (deletion or duplication of a chromosomal region) of synaptic genes have been recently implicated as risk factors for mental retardation or autism. Among these genes is GRIK4, a gene coding for a glutamate receptor subunit of the kainate type. Here we show that mice overexpressing grik4 in the forebrain displayed social impairment, enhanced anxiety, and depressive states, accompanied by altered synaptic transmission, showing more efficient information transfer through the hippocampal trisynaptic circuit. Together, these data indicate that a single gene variation in the glutamatergic system results in behavioral symptomatology consistent with autism spectrum disorders as well as in alterations in synaptic function in regions involved in social activity. Autistic features of these mice represent powerful tools for improving diagnosis and testing of specific treatments targeting abnormalities in glutamatergic signaling related to autism spectrum disorders. SIGNIFICANCE STATEMENT: A genetic overlap exists between autism spectrum disorders (ASD), currently thought to represent a continuum of the same disorder with varying degrees of severity, and other neurodevelopmental and neuropsychiatric endophenotypes. We show that the duplication of a single gene coding for a high-affinity kainate receptor subunit (i.e., grik4) in a limited area of the brain recapitulates behavioral endophenotypes seen in humans diagnosed with autism (anhedonia, depression, anxiety, and altered social interaction), including some humans with GRIK4 duplications. Therefore, it should be possible to use mice overexpressing grik4 to directly address circuit dysfunctions associated with ASDs and test specific treatments of autism-related behaviors.

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3. Ammanuel S, Chan WC, Adler DA, Lakshamanan BM, Gupta SS, Ewen JB, Johnston MV, Marcus CL, Naidu S, Kadam SD. {{Heightened Delta Power during Slow-Wave-Sleep in Patients with Rett Syndrome Associated with Poor Sleep Efficiency}}. {PLoS One};2015;10(10):e0138113.

Sleep problems are commonly reported in Rett syndrome (RTT); however the electroencephalographic (EEG) biomarkers underlying sleep dysfunction are poorly understood. The aim of this study was to analyze the temporal evolution of quantitative EEG (qEEG) biomarkers in overnight EEGs recorded from girls (2-9 yrs. old) diagnosed with RTT using a non-traditional automated protocol. In this study, EEG spectral analysis identified high delta power cycles representing slow wave sleep (SWS) in 8-9h overnight sleep EEGs from the frontal, central and occipital leads (AP axis), comparing age-matched girls with and without RTT. Automated algorithms quantitated the area under the curve (AUC) within identified SWS cycles for each spectral frequency wave form. Both age-matched RTT and control EEGs showed similar increasing trends for recorded delta wave power in the EEG leads along the antero-posterior (AP). RTT EEGs had significantly fewer numbers of SWS sleep cycles; therefore, the overall time spent in SWS was also significantly lower in RTT. In contrast, the AUC for delta power within each SWS cycle was significantly heightened in RTT and remained heightened over consecutive cycles unlike control EEGs that showed an overnight decrement of delta power in consecutive cycles. Gamma wave power associated with these SWS cycles was similar to controls. However, the negative correlation of gamma power with age (r = -.59; p<0.01) detected in controls (2-5 yrs. vs. 6-9 yrs.) was lost in RTT. Poor % SWS (i.e., time spent in SWS overnight) in RTT was also driven by the younger age-group. Incidence of seizures in RTT was associated with significantly lower number of SWS cycles. Therefore, qEEG biomarkers of SWS in RTT evolved temporally and correlated significantly with clinical severity.

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4. Baldwin PR, Curtis KN, Patriquin MA, Wolf V, Viswanath H, Shaw C, Sakai Y, Salas R. {{Identifying diagnostically-relevant resting state brain functional connectivity in the ventral posterior complex via genetic data mining in autism spectrum disorder}}. {Autism Res};2015 (Oct 9)
Exome sequencing and copy number variation analyses continue to provide novel insight to the biological bases of autism spectrum disorder (ASD). The growing speed at which massive genetic data are produced causes serious lags in analysis and interpretation of the data. Thus, there is a need to develop systematic genetic data mining processes that facilitate efficient analysis of large datasets. We report a new genetic data mining system, ProcessGeneLists and integrated a list of ASD-related genes with currently available resources in gene expression and functional connectivity of the human brain. Our data-mining program successfully identified three primary regions of interest (ROIs) in the mouse brain: inferior colliculus, ventral posterior complex of the thalamus (VPC), and parafascicular nucleus (PFn). To understand its pathogenic relevance in ASD, we examined the resting state functional connectivity (RSFC) of the homologous ROIs in human brain with other brain regions that were previously implicated in the neuro-psychiatric features of ASD. Among them, the RSFC of the VPC with the medial frontal gyrus (MFG) was significantly more anticorrelated, whereas the RSFC of the PN with the globus pallidus was significantly increased in children with ASD compared with healthy children. Moreover, greater values of RSFC between VPC and MFG were correlated with severity index and repetitive behaviors in children with ASD. No significant RSFC differences were detected in adults with ASD. Together, these data demonstrate the utility of our data-mining program through identifying the aberrant connectivity of thalamo-cortical circuits in children with ASD. Autism Res 2015. (c) 2015 International Society for Autism Research, Wiley Periodicals, Inc.

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5. Bauer NS, Carroll AE, Saha C, Downs SM. {{Computer Decision Support Changes Physician Practice But Not Knowledge Regarding Autism Spectrum Disorders}}. {Appl Clin Inform};2015;6(3):454-465.

OBJECTIVE: To examine whether adding an autism module promoting adherence to clinical guidelines to an existing computer decision support system (CDSS) changed physician knowledge and self-reported clinical practice. METHODS: The CHICA (Child Health Improvement through Computer Automation) system, a CDSS, was enhanced with a module to improve management of autism in 2 of the 4 community pediatric clinics using the system. We examined the knowledge and beliefs of pediatric users using cross-sectional surveys administered at 3 time points (baseline, 12 months and 24 months post-implementation) between November 2010 and January 2013. Surveys measured knowledge, beliefs and self-reported practice patterns related to autism. RESULTS: A total of 45, 39, and 42 pediatricians responded at each time point, respectively, a 95-100% response rate. Respondents’ knowledge of autism and perception of role for diagnosis did not vary between control and intervention groups either at baseline or any of the two post-intervention time points. At baseline, there was no difference between these groups in rates in the routine use of parent-rated screening instruments for autism. However, by 12 and 24 months post-implementation there was a significant difference between intervention and control clinics in terms of the intervention clinics consistently screening eligible patients with a validated autism tool. Physicians at all clinics reported ongoing challenges to community resources for further work-up and treatment related to autism. CONCLUSIONS: A CDSS module to improve primary care management of ASD in pediatric practice led to significant improvements in physician-reported use of validated screening tools to screen for ASDs. However it did not lead to corresponding changes in physician knowledge or attitudes.

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6. Bitsika V, Sharpley CF, Agnew LL, Andronicos NM. {{Age-related differences in the association between stereotypic behaviour and salivary cortisol in young males with an Autism Spectrum Disorder}}. {Physiol Behav};2015 (Oct 9);152(Pt A):238-243.

To identify if age influenced the relationship between one of the central symptoms of Autism Spectrum Disorder (ASD) and physiological stress, the association between stereotypic behaviour (SB) and stress-related cortisol concentrations was examined in a sample of 150 young males with an ASD. Parent-rated SB was significantly correlated with cortisol concentrations for boys aged 6years to 12years but not for adolescents aged 13years to 18years. This age-related difference in this association was not a function of cortisol concentrations but was related to differences in SB across these two age groups. IQ did not have a significant effect on this relationship, suggesting that age-related learning may have been a possible pathway for reduced SB during adolescence. The aspect of SB that was most powerfully related to cortisol was general repetitive behaviour rather than movements of specific body parts. Explanations of these findings are raised for further investigation.

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7. Conti E, Pannek K, Calderoni S, Gaglianese A, Fiori S, Brovedani P, Scelfo D, Rose S, Tosetti M, Cioni G, Guzzetta A. {{High angular resolution diffusion imaging in a child with autism spectrum disorder and comparison with his unaffected identical twin}}. {Funct Neurol};2015 (Oct 5):1-6.

In recent years, the use of brain diffusion MRI has led to the hypothesis that children with autism spectrum disorder (ASD) show abnormally connected brains. We used the model of disease-discordant identical twins to test the hypothesis that higher-order diffusion MRI protocols are able to detect abnormal connectivity in a single subject. We studied the structural connectivity of the brain of a child with ASD, and of that of his unaffected identical twin, using high angular resolution diffusion imaging (HARDI) probabilistic tractography. Cortical regions were automatically parcellated from high-resolution structural images, and HARDI-based connection matrices were produced for statistical comparison. Differences in diffusion indexes between subjects were tested by Wilcoxon signed rank test. Tracts were defined as discordant when they showed a between-subject difference of 10 percent or more. Around 11 percent of the discordant intra-hemispheric tracts showed lower fractional anisotropy (FA) values in the ASD twin, while only 1 percent showed higher values. This difference was significant. Our findings in a disease-discordant identical twin pair confirm previous literature consistently reporting lower FA values in children with ASD.

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8. Doumas M, McKenna R, Murphy B. {{Postural Control Deficits in Autism Spectrum Disorder: The Role of Sensory Integration}}. {J Autism Dev Disord};2015 (Oct 7)
We investigated the nature of sensory integration deficits in postural control of young adults with ASD. Postural control was assessed in a fixed environment, and in three environments in which sensory information about body sway from visual, proprioceptive or both channels was inaccurate. Furthermore, two levels of inaccurate information were used within each channel (gain 1 and 1.6). ASD participants showed greater postural sway when information from both channels was inaccurate. In addition, control participants’ ellipse area at gain 1.6 was identical to ASD participants’ at gain 1, reflecting hyper-reactivity in ASD. Our results provide evidence for hyper-reactivity in posture-related sensory information, which reflects a general, rather than channel-specific sensory integration impairment in ASD.

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9. Izadi-Najafabadi S, Mirzakhani-Araghi N, Miri-Lavasani N, Nejati V, Pashazadeh-Azari Z. {{Implicit and explicit motor learning: Application to children with Autism Spectrum Disorder (ASD)}}. {Res Dev Disabil};2015 (Oct 9);47:284-296.

AIMS AND OBJECTIVES: This study aims to determine whether children with Autism Spectrum Disorder (ASD) are capable of learning a motor skill both implicitly and explicitly. METHODS: In the present study, 30 boys with ASD, aged 7-11 with IQ average of 81.2, were compared with 32 typical IQ- and age-matched boys on their performance on a serial reaction time task (SRTT). Children were grouped by ASD and typical children and by implicit and explicit learning groups for the SRTT. RESULTS: Implicit motor learning occurred in both children with ASD (p=.02) and typical children (p=.01). There were no significant differences between groups (p=.39). However, explicit motor learning was only observed in typical children (p=.01) not children with ASD (p=.40). There was a significant difference between groups for explicit learning (p=.01). DISCUSSION: The results of our study showed that implicit motor learning is not affected in children with ASD. Implications for implicit and explicit learning are applied to the CO-OP approach of motor learning with children with ASD.

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10. Jacob A, Scott M, Falkmer M, Falkmer T. {{The Costs and Benefits of Employing an Adult with Autism Spectrum Disorder: A Systematic Review}}. {PLoS One};2015;10(10):e0139896.

BACKGROUND: Despite an ambition from adults with Autism Spectrum Disorder (ASD) to be employed, there are limited opportunities for competitive employment for this group. Employment is not only an entitlement enjoyed by others in society, but employing adults with ASD also has economic benefits by decreasing lost productivity and resource costs for this group. Few studies have explored the cost-benefit ratio for employing adults with ASD and even fewer have taken the viewpoint of the employer, particularly applying this situation to ASD. Until such study occurs, employers may continue to be reluctant to employ adults from this group. OBJECTIVE: This review aimed to examine the costs, benefits and the cost-benefit ratio of employing adults with ASD, from a societal perspective and from the perspective of employers. METHODS: Eight databases were searched for scientific studies within defined inclusion criteria. These databases included CINAHL Plus, Cochrane Library, Emerald, Ovid Medline, ProQuest, PsycINFO, Scopus and Web of Science. RESULTS AND CONCLUSION: Enhancing the opportunities for adults with ASD to join the workforce is beneficial from a societal perspective, not only from an inclusiveness viewpoint, but also from a strict economic standpoint. Providing supported employment services for adults with ASD does not only cut the cost compared with providing standard care, it also results in better outcomes for adults with ASD. Despite the fact that ASD was the most expensive group to provide vocational rehabilitation services for, adults with ASD have a strong chance of becoming employed once appropriate measures are in place. Hence, rehabilitation services could be considered as a worthwhile investment. The current systematic review uncovered the fact that very few studies have examined the benefits, the costs and the cost-benefit ratio of employing an adult with ASD from the perspective of employers indicating a need for this topic to be further explored.

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11. Jann K, Hernandez LM, Beck-Pancer D, McCarron R, Smith RX, Dapretto M, Wang DJ. {{Altered resting perfusion and functional connectivity of default mode network in youth with autism spectrum disorder}}. {Brain Behav};2015 (Sep);5(9):e00358.

BACKGROUND: Neuroimaging studies can shed light on the neurobiological underpinnings of autism spectrum disorders (ASD). Studies of the resting brain have shown both altered baseline metabolism from PET/SPECT and altered functional connectivity (FC) of intrinsic brain networks based on resting-state fMRI. To date, however, no study has investigated these two physiological parameters of resting brain function jointly, or explored the relationship between these measures and ASD symptom severity. METHODS: Here, we used pseudo-continuous arterial spin labeling with 3D background-suppressed GRASE to assess resting cerebral blood flow (CBF) and FC in 17 youth with ASD and 22 matched typically developing (TD) children. RESULTS: A pattern of altered resting perfusion was found in ASD versus TD children including frontotemporal hyperperfusion and hypoperfusion in the dorsal anterior cingulate cortex. We found increased local FC in the anterior module of the default mode network (DMN) accompanied by decreased CBF in the same area. In our cohort, both alterations were associated with greater social impairments as assessed with the Social Responsiveness Scale (SRS-total T scores). While FC was correlated with CBF in TD children, this association between FC and baseline perfusion was disrupted in children with ASD. Furthermore, there was reduced long-range FC between anterior and posterior modules of the DMN in children with ASD. CONCLUSION: Taken together, the findings of this study – the first to jointly assess resting CBF and FC in ASD – highlight new avenues for identifying novel imaging markers of ASD symptomatology.

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12. Lee SB, Song SH, Ham JH, Song DH, Cheon KA. {{Idiom Comprehension Deficits in High-Functioning Autism Spectrum Disorder Using a Korean Autism Social Language Task}}. {Yonsei Med J};2015 (Nov);56(6):1613-1618.

PURPOSE: High-functioning autism spectrum disorder (ASD) involves pragmatic impairment of language skills. Among numerous tasks for assessing pragmatic linguistic skills, idioms are important to evaluating high-functioning ASD. Nevertheless, no assessment tool has been developed with specific consideration of Korean culture. Therefore, we designed the Korean Autism Social Language Task (KASLAT) to test idiom comprehension in ASD. The aim of the current study was to introduce this novel psychological tool and evaluate idiom comprehension deficits in high-functioning ASD. MATERIALS AND METHODS: The participants included 42 children, ages 6-11 years, who visited our child psychiatric clinic between April 2014 and May 2015. The ASD group comprised 16 children; the attention deficit hyperactivity disorder (ADHD) group consisted of 16 children. An additional 10 normal control children who had not been diagnosed with either disorder participated in this study. Idiom comprehension ability was assessed in these three groups using the KASLAT. RESULTS: Both ASD and ADHD groups had significantly lower scores on the matched and mismatched tasks, compared to the normal control children (matched tasks mean score: ASD 11.56, ADHD 11.56, normal control 14.30; mismatched tasks mean score: ASD 6.50, ADHD 4.31, normal control 11.30). However, no significant differences were found in scores of KASLAT between the ADHD and ASD groups. CONCLUSION: These findings suggest that children with ASD exhibit greater impairment in idiom comprehension, compared to normal control children. The KASLAT may be useful in evaluating idiom comprehension ability.

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13. Maiano C, Normand CL, Salvas MC, Moullec G, Aime A. {{Prevalence of School Bullying Among Youth with Autism Spectrum Disorders: A Systematic Review and Meta-Analysis}}. {Autism Res};2015 (Oct 9)
The true extent of school bullying among youth with autism spectrum disorders (ASD) remains an underexplored area. The purpose of this meta-analysis is to: (a) assess the proportion of school-aged youth with ASD involved in school bullying as perpetrators, victims or both; (b) examine whether the observed prevalence estimates vary when different sources of heterogeneity related to the participants’ characteristics and to the assessment methods are considered; and (c) compare the risk of school bullying between youth with ASD and their typically developing (TD) peers. A systematic literature search was performed and 17 studies met the inclusion criteria. The resulting pooled prevalence estimate for general school bullying perpetration, victimization and both was 10%, 44%, and 16%, respectively. Pooled prevalence was also estimated for physical, verbal, and relational school victimization and was 33%, 50%, and 31%, respectively. Moreover, subgroup analyses showed significant variations in the pooled prevalence by geographic location, school setting, information source, type of measures, assessment time frame, and bullying frequency criterion. Finally, school-aged youth with ASD were found to be at greater risk of school victimization in general, as well as verbal bullying, than their TD peers. Autism Res 2015. (c) 2015 International Society for Autism Research, Wiley Periodicals, Inc.

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14. Miller M, Iosif AM, Young GS, Hill M, Phelps Hanzel E, Hutman T, Johnson S, Ozonoff S. {{School-age outcomes of infants at risk for autism spectrum disorder}}. {Autism Res};2015 (Oct 9)
Studies of infants at risk for autism spectrum disorder (ASD) have proliferated, but few of these samples have been followed longer-term. We conducted a follow-up study, at age 5.5-9 years, of younger siblings of children with ASD (high-risk group, n = 79) or typical development (low-risk group, n = 60), originally recruited as infants. Children with ASD were excluded because of the focus on understanding the range of non-ASD outcomes among high-risk siblings. Using examiner ratings, parent ratings, and standardized assessments, we evaluated differences in clinical outcomes, psychopathology symptoms, autism symptoms, language skills, and nonverbal cognitive abilities. After adjusting for covariates, the high-risk group had increased odds of any clinically elevated/impaired score across measures relative to the low-risk group (43% vs. 12%, respectively). The high-risk group also had increased odds of examiner-rated Clinical Concerns (CC) outcomes (e.g., ADHD concerns, broader autism phenotype, speech-language difficulties, anxiety/mood problems, learning problems) relative to the low-risk group (38% vs. 13%, respectively). The high-risk group with CC outcomes had higher parent-reported psychopathology and autism symptoms, and lower directly-assessed language skills, than the Low-Risk Typically Developing (TD) and High-Risk TD groups, which did not differ. There were no differences in nonverbal cognitive skills. For some in the high-risk group, clinical concerns persisted from early childhood, whereas for others clinical concerns were first evident at school-age. Results suggest continued vulnerability in at least a subgroup of school-age children with a family history of ASD and suggest that this population may benefit from continued screening and monitoring into the school-age years. Autism Res 2015. (c) 2015 International Society for Autism Research, Wiley Periodicals, Inc.

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15. Odriozola P, Uddin LQ, Lynch CJ, Kochalka J, Chen T, Menon V. {{Insula response and connectivity during social and non-social attention in children with autism}}. {Soc Cogn Affect Neurosci};2015 (Oct 9)
Autism spectrum disorder (ASD) is characterized by reduced attention to salient social stimuli. Here we use two visual oddball tasks to investigate brain systems engaged during attention to social (face) and non-social (scene) stimuli. We focused on the dorsal and ventral subdivisions of the anterior insula (dAI and vAI, respectively), anatomically distinct regions contributing to a ‘salience network’ that is known to regulate attention to behaviorally meaningful stimuli. Children with ASD performed comparably to their typically developing (TD) peers, but they engaged the right dAI and vAI differently in response to deviant faces compared with deviant scenes. Multivariate activation patterns in the dAI reliably discriminated between children with ASD and TD children with 85% classification accuracy, and children with ASD activated the vAI more than their TD peers. Children with ASD and their TD peers also differed in dAI connectivity patterns to deviant faces, with stronger within-salience network interactions in the ASD group and stronger cross-network interactions in the TD group. Our findings point to atypical patterns of right anterior insula activation and connectivity in ASD and suggest that multiple functions subserved by the insula, including attention and affective processing of salient social stimuli, are aberrant in children with the disorder.

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16. Payakachat N, Tilford JM, Ungar WJ. {{National Database for Autism Research (NDAR): Big Data Opportunities for Health Services Research and Health Technology Assessment}}. {Pharmacoeconomics};2015 (Oct 7)
The National Database for Autism Research (NDAR) is a US National Institutes of Health (NIH)-funded research data repository created by integrating heterogeneous datasets through data sharing agreements between autism researchers and the NIH. To date, NDAR is considered the largest neuroscience and genomic data repository for autism research. In addition to biomedical data, NDAR contains a large collection of clinical and behavioral assessments and health outcomes from novel interventions. Importantly, NDAR has a global unique patient identifier that can be linked to aggregated individual-level data for hypothesis generation and testing, and for replicating research findings. As such, NDAR promotes collaboration and maximizes public investment in the original data collection. As screening and diagnostic technologies as well as interventions for children with autism are expensive, health services research (HSR) and health technology assessment (HTA) are needed to generate more evidence to facilitate implementation when warranted. This article describes NDAR and explains its value to health services researchers and decision scientists interested in autism and other mental health conditions. We provide a description of the scope and structure of NDAR and illustrate how data are likely to grow over time and become available for HSR and HTA.

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17. Rommelse N, Langerak I, van der Meer J, de Bruijn Y, Staal W, Oerlemans A, Buitelaar J. {{Intelligence May Moderate the Cognitive Profile of Patients with ASD}}. {PLoS One};2015;10(10):e0138698.

BACKGROUND: The intelligence of individuals with Autism Spectrum Disorder (ASD) varies considerably. The pattern of cognitive deficits associated with ASD may differ depending on intelligence. We aimed to study the absolute and relative severity of cognitive deficits in participants with ASD in relation to IQ. METHODS: A total of 274 children (M age = 12.1, 68.6% boys) participated: 30 ASD and 22 controls in the below average Intelligence Quotient (IQ) group (IQ<85), 57 ASD and 54 controls in the average IQ group (85<IQ<115) and 41 ASD and 70 controls in the above average IQ group (IQ>115). Matching for age, sex, Full Scale IQ (FSIQ), Verbal IQ (VIQ), Performance IQ (PIQ) and VIQ-PIQ difference was performed. Speed and accuracy of social cognition, executive functioning, visual pattern recognition and basic processing speed were examined per domain and as a composite score. RESULTS: The composite score revealed a trend significant IQ by ASD interaction (significant when excluding the average IQ group). In absolute terms, participants with below average IQs performed poorest (regardless of diagnosis). However, in relative terms, above average intelligent participants with ASD showed the most substantial cognitive problems (particularly for social cognition, visual pattern recognition and verbal working memory) since this group differed significantly from the IQ-matched control group (p < .001), whereas this was not the case for below-average intelligence participants with ASD (p = .57). CONCLUSIONS: In relative terms, cognitive deficits appear somewhat more severe in individuals with ASD and above average IQs compared to the below average IQ patients with ASD. Even though high IQ ASD individuals enjoy a certain protection from their higher IQ, they clearly demonstrate cognitive impairments that may be targeted in clinical assessment and treatment. Conversely, even though in absolute terms ASD patients with below average IQs were clearly more impaired than ASD patients with average to above average IQs, the differences in cognitive functioning between participants with and without ASD on the lower end of the IQ spectrum were less pronounced. Clinically this may imply that cognitive assessment and training of cognitive skills in below average intelligent children with ASD may be a less fruitful endeavour. These findings tentatively suggest that intelligence may act as a moderator in the cognitive presentation of ASD, with qualitatively different cognitive processes affected in patients at the high and low end of the IQ spectrum.

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18. Talbott EO, Marshall LP, Rager JR, Arena VC, Sharma RK, Stacy SL. {{Air toxics and the risk of autism spectrum disorder: the results of a population based case-control study in southwestern Pennsylvania}}. {Environ Health};2015;14:80.

BACKGROUND: Autism spectrum disorders (ASD) constitute a major public health problem affecting one in 68 children. There is little understanding of the causes of ASD despite its serious social impact. Air pollution contains many toxicants known to have adverse effects on the fetus. We conducted a population based case-control study in southwestern Pennsylvania to estimate the association between ASD and 2005 US EPA modeled NATA (National Air Toxics Assessment) levels for 30 neurotoxicants. METHODS: A total of 217 ASD cases born between 2005 and 2009 were recruited from local ASD diagnostic and treatment centers. There were two different control groups: 1) interviewed controls (N = 224) frequency matched by child’s year of birth, sex and race with complete residential histories from prior to pregnancy through the child’s second birthday, and 2) 5,007 controls generated from a random sample of birth certificates (BC controls) using residence at birth. We used logistic regression analysis comparing higher to first quartile of exposure to estimate odds ratios (ORs) and 95% confidence intervals (CI), adjusting for mother’s age, education, race, smoking status, child’s year of birth and sex. RESULTS: Comparing fourth to first quartile exposures for all births, the adjusted OR for styrene was 2.04 (95% CI = 1.17-3.58, p = 0.013) for the interviewed case-control analysis and 1.61 (95% CI = 1.08-2.40, p = 0.018) for the BC analysis. In the BC comparison, chromium also exhibited an elevated OR of 1.60 (95% CI = 1.08-2.38, p = 0.020), which was similarly elevated in the interviewed analysis (OR = 1.52, 95% CI = 0.87-2.66). There were borderline significant ORs for the BC comparison for methylene chloride (OR = 1.41, 95% CI = 0.96-2.07, p = 0.082) and PAHs (OR = 1.44, 95% CI = 0.98-2.11, p = 0.064). CONCLUSIONS: Living in areas with higher levels of styrene and chromium during pregnancy was associated with increased risk of ASD, with borderline effects for PAHs and methylene chloride. These results are consistent with other studies. It is unclear, however, whether these chemicals are risk factors themselves or if they reflect the effect of a mixture of pollutants. Future work should include improved spatiotemporal estimates of exposure to air toxics, taking into account the dynamic movement of individuals during daily life.

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