1. Ahmad SF, Ansari MA, Nadeem A, Bakheet SA, Al-Ayadhi LY, Attia SM. {{Upregulation of peripheral CXC and CC chemokine receptor expression on CD4+ T cells is associated with immune dysregulation in children with autism}}. {Prog Neuropsychopharmacol Biol Psychiatry}. 2017.
Autism spectrum disorders (ASD) are characterized by disturbances in social interactions and communication, restricted repetitive interests, and stereotyped behavior. Cumulative evidence recommends that there are immune alterations in ASD. Chemokine receptors are known to play an important role in the central nervous system (CNS) and in many neuro inflammatory disorders. The main objective of this study was to explore the role of CXC and CC chemokine receptors signaling in children with autism. We examined chemokine receptor production of CXCR2, CXCR3, CXCR5, and CXCR7 in all peripheral blood mononuclear cells (PBMCs) and in CD4+ T cells of typically developing control children (TD) and autistic children (AU). We also examined chemokine receptor production of CCR3, CCR5, CCR7, and CCR9 in all PBMCs and in CD4+ T cells of AU and TD samples using flow cytometric analysis. In addition, we measured mRNA expression levels of CXC and CC chemokine receptors using quantitative RT-PCR analysis. Our results showed the increased production of CXCR2+, CXCR3+, CXCR5+, and CXCR7+ and CCR3+, CCR5+, CCR7+, and CCR9+ in all PBMCs and in CD4+ T cells of children with AU as compared to TD controls. Our results show that chemokine receptor signaling components might provide unique therapeutic targets for children with AU and other neurological disorders.
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2. Ahmad SF, Nadeem A, Ansari MA, Bakheet SA, Al-Ayadhi LY, Attia SM. {{Upregulation of IL-9 and JAK-STAT signaling pathway in children with autism}}. {Prog Neuropsychopharmacol Biol Psychiatry}. 2017; 79(Pt B): 472-80.
Autism spectrum disorder (ASD) gradually develops predominantly neurodevelopmental disorders, which are socially diagnosed in early childhood. Though the etiopathology of ASD is not clear, immune alteration has been suggested as autism’s pathophysiological mechanism. Previous studies found that several cytokines and transcription factor activation pathways were significantly increased in ASD. IL-9 has been confirmed to play a significant role in the central nervous system (CNS). The aim of the present study was to investigate the understudied role of pro- and anti-inflammatory cytokines and the JAK-STAT signaling pathway in ASD. We examined the IL-1beta, IL-4, IFN-gamma, and IL-9 positive immunostaining in all cells, and CD4+ T cells, in ASD and normally developing control children (TD), on peripheral blood mononuclear cells (PBMCs), using flow cytometry. We explored PBMC mRNA expression levels for IL-1beta, IL-4, IFN-gamma, IL-9, JAK1, and STAT5, by using real-time PCR (RT-PCR). We also explored PBMC protein expression levels for IL-1beta, IL-4, IL-9, pJAK1, and pSTAT5 by using western blotting. We found that the children with ASD had increased IL-1beta, IL-4, IFN-gamma, and IL-9 positive immunostaining in all cells, and in CD4+ cells, relative to the TD controls. The mRNA and protein expression for IL-1beta, IL-4, IFN-gamma, IL-9, JAK1, pJAK1, STAT5, and pSTAT5 were also significantly elevated in ASD relative to TD controls. These results suggested that cytokines and JAK-STAT activation signaling have an essential role in immune dysfunction in ASD.
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3. Chadman KK. {{Animal models for autism in 2017 and the consequential implications to drug discovery}}. {Expert Opin Drug Discov}. 2017: 1-8.
INTRODUCTION: Autism spectrum disorder (ASD) is characterized by deficits in social communication and restricted interests/repetitive behaviors, for which there are currently no approved drug treatments. The core symptoms of ASD vary widely in severity and are often accompanied by other neuropsychiatric disorders. Drug discovery has been challenging because of the lack of understanding of the underlying pathophysiology of ASD as well as the heterogeneity of symptoms and symptom severity. Areas covered: In this review, the author discusses animal models of ASD used as targets for drug discovery, focusing primarily on non-syndromic models, primarily rodents. They highlight the wide range of drug targets examined in animal models. While very little of this work has resulted in drug therapy for the behavioral symptoms of ASD yet, it has increased our knowledge of the biology of ASD that is critical for driving drug discovery and has already provided many new drug targets for investigation. Expert opinion: The information gathered from the animal models of ASD is increasing our understanding of the underlying pathophysiology for ASD and is leading to better therapeutic targets. However, the issue of small sample size, heterogeneity within clinical samples, and a lack of replicable outcome measures must be addressed to move forward.
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4. Curran EA, O’Keeffe GW, Looney AM, Moloney G, Hegarty SV, Murray DM, Khashan AS, Kenny LC. {{Exposure to Hypertensive Disorders of Pregnancy Increases the Risk of Autism Spectrum Disorder in Affected Offspring}}. {Mol Neurobiol}. 2017.
There is growing awareness that prenatal adversity may increase the risk of autism spectrum disorder (ASD). Here, we examined the association between hypertensive disorders of pregnancy (HDP) and ASD risk at 7 years of age using the Millennium Cohort Study (MCS), a representative cohort of 13,192 children born in the UK from 2000 to 2001. We also sought to examine cytokine expression in the serum of women with pre-eclampsia, which is the most common HDP, and whether exposure of foetal neurons to this serum could change patterns of neuronal growth. HDP were reported by mothers 9 months post-delivery. ASD was parent reported at age seven, based on a doctor or health care professional’s diagnosis. Weighted logistic regression was used for data analysis, adjusting for several potential confounders including maternal alcohol consumption, education, depression, age, and poverty status. Sensitivity analyses were performed excluding pre-term births, small for gestational age (SGA), and pre-pregnancy hypertension and depression. There was a significant association between HDP and a twofold increased risk of ASD (AOR = 2.10 [95% CI 1.20-3.70]). Excluding preterm births, SGA births, and offspring of women who had pre-pregnancy hypertension or over the age of 40 did not change the results materially. At the cellular level, exposure of foetal cortical neurons to 3% serum isolated from women with an established HDP increased neuronal growth and branching in vitro. These findings indicate that HDP exposure may increase the risk of ASD in the offspring.
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5. D’Alli RE, Valcante G. {{Mental Health Crisis Management for Youths With Autism Spectrum Disorder Requires a Paradigm Shift}}. {Psychiatr Serv}. 2017; 68(10): 985.
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6. Duan X, Chen H, He C, Long Z, Guo X, Zhou Y, Uddin LQ. {{Resting-state functional under-connectivity within and between large-scale cortical networks across three low-frequency bands in adolescents with autism}}. {Prog Neuropsychopharmacol Biol Psychiatry}. 2017; 79(Pt B): 434-41.
Although evidence is accumulating that autism spectrum disorder (ASD) is associated with disruption of functional connections between and within brain networks, it remains largely unknown whether these abnormalities are related to specific frequency bands. To address this question, network contingency analysis was performed on brain functional connectomes obtained from 213 adolescent participants across nine sites in the Autism Brain Imaging Data Exchange (ABIDE) multisite sample, to determine the disrupted connections between and within seven major cortical networks in adolescents with ASD at Slow-5, Slow-4 and Slow-3 frequency bands and further assess whether the aberrant intra- and inter-network connectivity varied as a function of ASD symptoms. Overall under-connectivity within and between large-scale intrinsic networks in ASD was revealed across the three frequency bands. Specifically, decreased connectivity strength within the default mode network (DMN), between DMN and visual network (VN), ventral attention network (VAN), and between dorsal attention network (DAN) and VAN was observed in the lower frequency band (slow-5, slow-4), while decreased connectivity between limbic network (LN) and frontal-parietal network (FPN) was observed in the higher frequency band (slow-3). Furthermore, weaker connectivity within and between specific networks correlated with poorer communication and social interaction skills in the slow-5 band, uniquely. These results demonstrate intrinsic under-connectivity within and between multiple brain networks within predefined frequency bands in ASD, suggesting that frequency-related properties underlie abnormal brain network organization in the disorder.
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7. Genc-Tosun D, Kurt O. {{Teaching multi-step requesting to children with autism spectrum disorder using systematic instruction and a speech-generating device}}. {Augment Altern Commun}. 2017: 1-11.
The purpose of this study was to examine the effectiveness of an iPad-based speech-generating device (SGD) and an intervention package in teaching multi-step requesting to children with autism spectrum disorder (ASD). The intervention package comprised discrete trial teaching, time delay, graduated guidance, and reinforcement. Social validity data were also collected from parents and teachers. Three male participants with ASD, aged 4-5 years, participated in the study, which was conducted using a multiple-probe-across-participants design. Findings of the study showed that the SGD and the intervention package were effective in teaching multi-step requesting to all participants. Furthermore, the target skill was maintained and generalized to different materials and individuals. Social validity findings indicated that opinions of the mothers and teachers were positive. On the other hand, the father of one participant stated that he was concerned with possible negative effects of using tablet computers. The findings are discussed with regard to the parents’ opinions, and implications for practice and research.
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8. Golubeva AV, Joyce SA, Moloney G, Burokas A, Sherwin E, Arboleya S, Flynn I, Khochanskiy D, Moya-Perez A, Peterson V, Rea K, Murphy K, Makarova O, Buravkov S, Hyland NP, Stanton C, Clarke G, Gahan CGM, Dinan TG, Cryan JF. {{Microbiota-related Changes in Bile Acid & Tryptophan Metabolism are Associated with Gastrointestinal Dysfunction in a Mouse Model of Autism}}. {EBioMedicine}. 2017.
Autism spectrum disorder (ASD) is one of the most prevalent neurodevelopmental conditions worldwide. There is growing awareness that ASD is highly comorbid with gastrointestinal distress and altered intestinal microbiome, and that host-microbiome interactions may contribute to the disease symptoms. However, the paucity of knowledge on gut-brain axis signaling in autism constitutes an obstacle to the development of precision microbiota-based therapeutics in ASD. To this end, we explored the interactions between intestinal microbiota, gut physiology and social behavior in a BTBR T+Itpr3tf/J mouse model of ASD. Here we show that a reduction in the relative abundance of very particular bacterial taxa in the BTBR gut – namely, bile-metabolizing Bifidobacterium and Blautia species, – is associated with deficient bile acid and tryptophan metabolism in the intestine, marked gastrointestinal dysfunction, as well as impaired social interactions in BTBR mice. Together these data support the concept of targeted manipulation of the gut microbiota for reversing gastrointestinal and behavioral symptomatology in ASD, and offer specific plausible targets in this endeavor.
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9. Hampton T. {{Early Brain Imaging in Infants May Help Predict Autism}}. {JAMA}. 2017; 318(13): 1211-2.
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10. Hong SJ, Valk SL, Di Martino A, Milham MP, Bernhardt BC. {{Multidimensional Neuroanatomical Subtyping of Autism Spectrum Disorder}}. {Cereb Cortex}. 2017: 1-11.
Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders with multiple biological etiologies and highly variable symptoms. Using a novel analytical framework that integrates cortex-wide MRI markers of vertical (i.e., thickness, tissue contrast) and horizontal (i.e., surface area, geodesic distance) cortical organization, we could show that a large multi-centric cohort of individuals with ASD falls into 3 distinctive anatomical subtypes (ASD-I: cortical thickening, increased surface area, tissue blurring; ASD-II: cortical thinning, decreased distance; ASD-III: increased distance). Bootstrap analysis indicated a high consistency of these biotypes across thousands of simulations, while analysis of behavioral phenotypes and resting-state fMRI showed differential symptom load (i.e., Autism Diagnostic Observation Schedule; ADOS) and instrinsic connectivity anomalies in communication and social-cognition networks. Notably, subtyping improved supervised learning approaches predicting ADOS score in single subjects, with significantly increased performance compared to a subtype-blind approach. The existence of different subtypes may reconcile previous results so far not converging on a consistent pattern of anatomical anomalies in autism, and possibly relate the presence of diverging corticogenic and maturational anomalies. The high accuracy for symptom severity prediction indicates benefits of MRI biotyping for personalized diagnostics and may guide the development of targeted therapeutic strategies.
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11. Jafari T, Rostampour N, Fallah AA, Hesami A. {{The association between mercury levels and autism spectrum disorders: A systematic review and meta-analysis}}. {J Trace Elem Med Biol}. 2017; 44: 289-97.
BACKGROUND & AIMS: The relationship between mercury and autism spectrum disorders (ASD) has always been a topic of controversy among researchers. This study aimed to assess the relationship between ASD and mercury levels in hair, urine, blood, red blood cells (RBC), and brain through a meta-analysis. METHODS: A systematic search was performed in several databases including PubMed, ISI Web of Science, Cochrane register of controlled trials, Google Scholar, Scopus, and MagIran until June 2017. Case-control studies evaluating concentration of total mercury in different tissues of ASD patients and comparing them to the healthy subjects (control group) were identified. Necessary data were extracted and random effects model was used to calculate overall effect and its 95% corresponding confidence interval (CI) from the effect sizes. RESULTS: A total of 44 studies were identified that met the necessary criteria for meta-analysis. The mercury level in whole blood (Hedges=0.43, 95% CI: 0.12, 0.74, P=0.007), RBC (Hedges=1.61, 95% CI: 0.83, 2.38, P<0.001), and brain (0.61ng/g, 95% CI, 0.02, 1.19, P=0.043) was significantly higher in ASD patients than healthy subjects, whereas mercury level in hair (-0.14mg/g, 95% CI: -0.28, -0.01, P=0.039) was significantly lower in ASD patients than healthy subjects. The mercury level in urine was not significantly different between ASD patients and healthy subjects (0.51mg/g creatinine, 95% CI: -0.14, 1.16, P=0.121). CONCLUSIONS: Results of the current meta-analysis revealed that mercury is an important causal factor in the etiology of ASD. It seems that the detoxification and excretory mechanisms are impaired in ASD patients which lead to accumulation of mercury in the body. Future additional studies on mercury levels in different tissues of ASD patients should be undertaken. Lien vers le texte intégral (Open Access ou abonnement)
12. Kaushik G, Xia Y, Pfau JC, Thomas MA. {{Dysregulation of autism-associated synaptic proteins by psychoactive pharmaceuticals at environmental concentrations}}. {Neurosci Lett}. 2017.
Autism Spectrum Disorders (ASD) are complex neurological disorders for which the prevalence in the U.S. is currently estimated to be 1 in 50 children. A majority of cases of idiopathic autism in children likely result from unknown environmental triggers in genetically susceptible individuals. These triggers may include maternal exposure of a developing embryo to environmentally relevant minute concentrations of psychoactive pharmaceuticals through ineffectively purified drinking water. Previous studies in our lab examined the extent to which gene sets associated with neuronal development were up- and down-regulated (enriched) in the brains of fathead minnows treated with psychoactive pharmaceuticals at environmental concentrations. The aim of this study was to determine whether similar treatments would alter in vitro expression of ASD-associated synaptic proteins on differentiated human neuronal cells. Human SK-N-SH neuroblastoma cells were differentiated for two weeks with 10muM retinoic acid (RA) and treated with environmentally relevant concentrations of fluoxetine, carbamazepine or venlafaxine, and flow cytometry technique was used to analyze expression of ASD-associated synaptic proteins. Data showed that carbamazepine individually, venlafaxine individually and mixture treatment at environmental concentrations significantly altered the expression of key synaptic proteins (NMDAR1, PSD95, SV2A, HTR1B, HTR2C and OXTR). Data indicated that psychoactive pharmaceuticals at extremely low concentrations altered the in vitro expression of key synaptic proteins that may potentially contribute to neurological disorders like ASD by disrupting neuronal development.
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13. Klusek J, Ruber A, Roberts JE. {{Impaired eye contact in the FMR1 premutation is not associated with social anxiety or the broad autism phenotype}}. {Clin Neuropsychol}. 2017: 1-16.
OBJECTIVE: The Fragile X Mental Retardation-1 (FMR1) premutation is a common genetic abnormality, affecting ~1:150 women in the United States. Clinical neuropsychologists are becoming increasingly aware of their role in the clinical management of the FMR1 premutation, which is associated with risk for a range of cognitive, executive, neuromotor, and psychological impairments, including neurodegenerative disease. This study investigated atypical eye contact as a critical neuropsychological phenotype associated with the FMR1 premutation. METHODS: Thirty-eight women with the FMR1 premutation and 27 control women engaged in a 20-min conversational sample with an examiner. Eye contact quality was coded from the videotaped samples by blinded coders. Mixed models tested group differences in eye contact during the beginning and the end of the conversation. Social anxiety and broad autism phenotype (BAP) traits were tested as predictors of eye contact quality across the groups. RESULTS: Women with the FMR1 premutation exhibited significantly reduced eye contact during both the beginning and the end of the social interaction, despite a ‘warm-up’ effect where eye contact improved by the end of the interaction. Eye contact quality was not associated with social anxiety or BAP traits. CONCLUSIONS: This study supports reduced eye contact as a phenotypic feature of the FMR1 premutation, which presents independent of social anxiety and the BAP. These findings contribute to a growing understanding of the neuropsychological phenotype of the FMR1 premutation, which has public health implications given that >1 million individuals in the United States carry this genetic abnormality.
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14. Kostrubiec V, Huys R, Jas B, Kruck J. {{Age-dependent Relationship Between Socio-adaptability and Motor Coordination in High Functioning Children with Autism Spectrum Disorder}}. {J Autism Dev Disord}. 2017.
Abnormal perceptual-motor coordination is hypothesized here to be involved in social deficits of autism spectrum disorder (ASD). To test this hypothesis, high functioning children with ASD and typical controls, similar in age as well as verbal and perceptive performance, performed perceptual-motor coordination tasks and several social competence tests. Spontaneous coordination, and intentionally required in-phase and anti-phase were examined. The oscillation kinematics, as well as the accuracy and stability of spontaneous coordination were similar in both groups. In intentional coordination, ASD children produced less accurate, less stable and less complex relative phases than the control group, and in-phase and anti-phase performances that were similar in accuracy, stability, and complexity. An age-dependent relationship between socio-adaptability and coordination skills suggested these skills develop together.
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15. Liu T, Liu X, Li Y, Zhu C, Markey PS, Pelowski M. {{Assessing autism at its social and developmental roots: A review of Autism Spectrum Disorder studies using functional near-infrared spectroscopy}}. {Neuroimage}. 2017.
We review a relatively new method for studying the developing brain in children and infants with Autism Spectrum Disorder (ASD). Despite advances in behavioral screening and brain imaging, due to paradigms that do not easily allow for testing of awake, very young, and socially-engaged children-i.e., the social and the baby brain-the biological underpinnings of this disorder remain a mystery. We introduce an approach based on functional near-infrared spectroscopy (fNIRS), which offers a noninvasive imaging technique for studying functional activations by measuring changes in the brain’s hemodynamic properties. This further enables measurement of brain activation in upright, interactive settings, while maintaining general equivalence to fMRI findings. We review the existing studies that have used fNIRS for ASD, discussing their promise, limitations, and their technical aspects, gearing this study to the researcher who may be new to this technique and highlighting potential targets for future research.
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16. Lundwall RA, Stephenson KG, Neeley-Tass ES, Cox JC, South M, Bigler ED, Anderberg E, Prigge MD, Hansen BD, Lainhart JE, Kellems RO, Petrie JA, Gabrielsen TP. {{Relationship between brain stem volume and aggression in children diagnosed with autism spectrum disorder}}. {Res Autism Spectr Disord}. 2017; 34: 44-51.
BACKGROUND: Aggressive behaviors are common in individuals diagnosed with autism spectrum disorder (ASD) and may be phenotypic indicators of different subtypes within ASD. In current research literature for non-ASD samples, aggression has been linked to several brain structures associated with emotion and behavioral control. However, few if any studies exist investigating brain volume differences in individuals with ASD who have comorbid aggression as indicated by standardized diagnostic and behavioral measures. METHOD: We examined neuroimaging data from individuals rigorously diagnosed with ASD versus typically developing (TD) controls. We began with data from brain volume regions of interest (ROI) taken from previous literature on aggression including the brainstem, amygdala, orbitofrontal cortex, anterior cingulate cortex, and dorsolateral prefrontal cortex. We defined aggression status using the Irritability subscale of the Aberrant Behavior Checklist and used lasso logistic regression to select among these predictor variables. Brainstem volume was the only variable shown to be a predictor of aggression status. RESULTS: We found that smaller brainstem volumes are associated with higher odds of being in the high aggression group. CONCLUSIONS: Understanding brain differences in individuals with ASD who engage in aggressive behavior from those with ASD who do not can inform treatment approaches. Future research should investigate brainstem structure and function in ASD to identify possible mechanisms related to arousal and aggression.
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17. Nakanishi M, Nomura J, Ji X, Tamada K, Arai T, Takahashi E, Bucan M, Takumi T. {{Correction: Functional significance of rare neuroligin 1 variants found in autism}}. {PLoS Genet}. 2017; 13(10): e1007035.
[This corrects the article DOI: 10.1371/journal.pgen.1006940.].
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18. Saghazadeh A, Rezaei N. {{Systematic review and meta-analysis links autism and toxic metals and highlights the impact of country development status: Higher blood and erythrocyte levels for mercury and lead, and higher hair antimony, cadmium, lead, and mercury}}. {Prog Neuropsychopharmacol Biol Psychiatry}. 2017; 79(Pt B): 340-68.
BACKGROUND: Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disorder that affects cognitive and higher cognitive functions. Increasing prevalence of ASD and high rates of related comorbidities has caused serious health loss and placed an onerous burden on the supporting families, caregivers, and health care services. Heavy metals are among environmental factors that may contribute to ASD. However, due to inconsistencies across studies, it is still hard to explain the association between ASD and toxic metals. Therefore the objective of this study was to investigate the difference in heavy metal measures between patients with ASD and control subjects. METHODS: We included observational studies that measured levels of toxic metals (antimony, arsenic, cadmium, lead, manganese, mercury, nickel, silver, and thallium) in different specimens (whole blood, plasma, serum, red cells, hair and urine) for patients with ASD and for controls. The main electronic medical database (PubMed and Scopus) were searched from inception through October 2016. RESULTS: 52 studies were eligible to be included in the present systematic review, of which 48 studies were included in the meta-analyses. The hair concentrations of antimony (standardized mean difference (SMD)=0.24; 95% confidence interval (CI): 0.03 to 0.45) and lead (SMD=0.60; 95% confidence interval (CI): 0.17 to 1.03) in ASD patients were significantly higher than those of control subjects. ASD patients had higher erythrocyte levels of lead (SMD=1.55, CI: 0.2 to 2.89) and mercury (SMD=1.56, CI: 0.42 to 2.70). There were significantly higher blood lead levels in ASD patients (SMD=0.43, CI: 0.02 to 0.85). Sensitivity analyses showed that ASD patients in developed but not in developing countries have lower hair concentrations of cadmium (SMD=-0.29, CI: -0.46 to -0.12). Also, such analyses indicated that ASD patients in developing but not in developed lands have higher hair concentrations of lead (SMD=1.58, CI: 0.80 to 2.36) and mercury (SMD=0.77, CI: 0.31 to 1.23). These findings were confirmed by meta-regression analyses indicating that development status of countries significantly influences the overall effect size of mean difference for hair arsenic, cadmium, lead, and mercury between patients with ASD and controls. CONCLUSION: The findings help highlighting the role of toxic metals as environmental factors in the etiology of ASD, especially in developing lands. While there are environmental factors other than toxic metals that greatly contribute to the etiology of ASD in developed lands. It would be, thus, expected that classification of ASD includes etiological entities of ASD on the basis of implication of industrial pollutants (developed vs. developing ASD).
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19. Turner TN, Coe BP, Dickel DE, Hoekzema K, Nelson BJ, Zody MC, Kronenberg ZN, Hormozdiari F, Raja A, Pennacchio LA, Darnell RB, Eichler EE. {{Genomic Patterns of De Novo Mutation in Simplex Autism}}. {Cell}. 2017.
To further our understanding of the genetic etiology of autism, we generated and analyzed genome sequence data from 516 idiopathic autism families (2,064 individuals). This resource includes >59 million single-nucleotide variants (SNVs) and 9,212 private copy number variants (CNVs), of which 133,992 and 88 are de novo mutations (DNMs), respectively. We estimate a mutation rate of approximately 1.5 x 10-8 SNVs per site per generation with a significantly higher mutation rate in repetitive DNA. Comparing probands and unaffected siblings, we observe several DNM trends. Probands carry more gene-disruptive CNVs and SNVs, resulting in severe missense mutations and mapping to predicted fetal brain promoters and embryonic stem cell enhancers. These differences become more pronounced for autism genes (p = 1.8 x 10-3, OR = 2.2). Patients are more likely to carry multiple coding and noncoding DNMs in different genes, which are enriched for expression in striatal neurons (p = 3 x 10-3), suggesting a path forward for genetically characterizing more complex cases of autism.
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20. Wang X, Kery R, Xiong Q. {{Synaptopathology in autism spectrum disorders: Complex effects of synaptic genes on neural circuits}}. {Prog Neuropsychopharmacol Biol Psychiatry}. 2017.
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21. Zhang L, Wade J, Bian D, Fan J, Swanson A, Weitlauf A, Warren Z, Sarkar N. {{Cognitive Load Measurement in a Virtual Reality-based Driving System for Autism Intervention}}. {IEEE Trans Affect Comput}. 2017; 8(2): 176-89.
Autism Spectrum Disorder (ASD) is a highly prevalent neurodevelopmental disorder with enormous individual and social cost. In this paper, a novel virtual reality (VR)-based driving system was introduced to teach driving skills to adolescents with ASD. This driving system is capable of gathering eye gaze, electroencephalography, and peripheral physiology data in addition to driving performance data. The objective of this paper is to fuse multimodal information to measure cognitive load during driving such that driving tasks can be individualized for optimal skill learning. Individualization of ASD intervention is an important criterion due to the spectrum nature of the disorder. Twenty adolescents with ASD participated in our study and the data collected were used for systematic feature extraction and classification of cognitive loads based on five well-known machine learning methods. Subsequently, three information fusion schemes-feature level fusion, decision level fusion and hybrid level fusion-were explored. Results indicate that multimodal information fusion can be used to measure cognitive load with high accuracy. Such a mechanism is essential since it will allow individualization of driving skill training based on cognitive load, which will facilitate acceptance of this driving system for clinical use and eventual commercialization.
