1. Clawson A, South M, Baldwin SA, Larson MJ. {{Electrophysiological Endophenotypes and the Error-Related Negativity (ERN) in Autism Spectrum Disorder: A Family Study}}. {J Autism Dev Disord}. 2017.
We examined the error-related negativity (ERN) as an endophenotype of ASD by comparing the ERN in families of ASD probands to control families. We hypothesized that ASD probands and families would display reduced-amplitude ERN relative to controls. Participants included 148 individuals within 39 families consisting of a mother, father, sibling, and proband. Robust ANOVAs revealed non-significant differences in ERN amplitude and behavioral performance among ASD probands relative to control youth. In subsequent multiple regression analyses group and kinship (proband, sibling, mother, father) did not significantly predict DeltaERN (error minus correct ERN) or behavioral performance. Results do not provide evidence for the ERN as an endophenotype of ASD. Future research is needed to examine state- or trait-related factors influencing ERN amplitudes in ASD.
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2. Linke AC, Jao Keehn RJ, Pueschel EB, Fishman I, Muller RA. {{Children with ASD show links between aberrant sound processing, social symptoms, and atypical auditory interhemispheric and thalamocortical functional connectivity}}. {Dev Cogn Neurosci}. 2017.
Autism spectrum disorder (ASD) is a complex and prevalent neurodevelopmental disorder characterized by social and communicative deficits, as well as repetitive behaviors and atypical sensitivity to sensory stimulation. Alterations in network connectivity are widely recognized, but their interplay with social and sensory symptoms remains largely unclear. Here, functional magnetic resonance imaging and diagnostic and behavioral assessments were used in a cohort of children and adolescents with ASD (n=40) and matched typically developing (TD, n=38) controls to examine the relation between auditory processing, interhemispheric and thalamocortical network connectivity, and social-behavioral symptom severity. We found that atypical processing of sounds was related to social, cognitive, and communicative impairments. Additionally, severity of sensory processing deficits and lower verbal IQ were related to reduced interhemispheric connectivity of auditory cortices in ASD. Increased connectivity between the thalamus and auditory cortex in ASD, however, was associated with reduced cognitive and behavioral symptomatology, suggesting that thalamocortical overconnectivity might reflect a compensatory mechanism in ASD. These findings provide novel evidence for links between auditory sensory deficits and impairments in social interaction and communication.
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3. Liu J, Yao L, Zhang W, Xiao Y, Liu L, Gao X, Shah C, Li S, Tao B, Gong Q, Lui S. {{Gray matter abnormalities in pediatric autism spectrum disorder: a meta-analysis with signed differential mapping}}. {Eur Child Adolesc Psychiatry}. 2017.
The gray matter abnormalities revealed by magnetic resonance imaging are inconsistent, especially in pediatric individuals with autism spectrum disorder (ASD) (age < 18 years old), a phenomenon possibly related to the core pathophysiology of ASD. The purpose of our meta-analysis was to identify and map the specific gray matter abnormalities in pediatric ASD individuals thereby exploring the potential effects of clinical and demographic characteristics of these gray matter changes. A systematic search was conducted to identify voxel-based morphometry studies in pediatric individuals with ASD. The effect-size signed differential mapping method was used to quantitatively estimate the regional gray matter abnormalities in pediatric ASD individuals. Meta-regression was used to examine the associations among age, gender, intelligence quotient, symptom severity and gray matter changes. Fifteen studies including 364 pediatric individuals with ASD (male = 282, age = 10.3 +/- 4.4 years) and 377 healthy controls (male = 289, age = 10.5 +/- 4.2 years) were included. Pediatric ASD individuals showed significant gray matter increases in the right angular gyrus, left superior and middle frontal gyrus, left precuneus, left inferior occipital gyrus and right inferior temporal gyrus, most of which involving the default mode network, and decreases in the left cerebellum and left postcentral gyrus. The meta-regression analysis showed that the repetitive behavior scores of the Autism Diagnostic Interview-Revised were positively associated with increased gray matter volumes in the right angular gyrus. Increased rather than decreased gray matter volume, especially involving the angular gyrus and prefrontal cortex may be the core pathophysiology in the early course of ASD. Lien vers le texte intégral (Open Access ou abonnement)
4. O’Connor RM, Stone EF, Wayne CR, Marcinkevicius EV, Ulgherait M, Delventhal R, Pantalia MM, Hill VM, Zhou CG, McAllister S, Chen A, Ziegenfuss JS, Grueber WB, Canman JC, Shirasu-Hiza MM. {{A Drosophila model of Fragile X syndrome exhibits defects in phagocytosis by innate immune cells}}. {J Cell Biol}. 2017.
Fragile X syndrome, the most common known monogenic cause of autism, results from the loss of FMR1, a conserved, ubiquitously expressed RNA-binding protein. Recent evidence suggests that Fragile X syndrome and other types of autism are associated with immune system defects. We found that Drosophila melanogaster Fmr1 mutants exhibit increased sensitivity to bacterial infection and decreased phagocytosis of bacteria by systemic immune cells. Using tissue-specific RNAi-mediated knockdown, we showed that Fmr1 plays a cell-autonomous role in the phagocytosis of bacteria. Fmr1 mutants also exhibit delays in two processes that require phagocytosis by glial cells, the immune cells in the brain: neuronal clearance after injury in adults and the development of the mushroom body, a brain structure required for learning and memory. Delayed neuronal clearance is associated with reduced recruitment of activated glia to the site of injury. These results suggest a previously unrecognized role for Fmr1 in regulating the activation of phagocytic immune cells both in the body and the brain.
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5. Perera H, Jeewandara KC, Seneviratne S, Guruge C. {{Culturally adapted pictorial screening tool for autism spectrum disorder: A new approach}}. {World J Clin Pediatr}. 2017; 6(1): 45-51.
AIM: To assess the performance of a newly designed, culturally adapted screening tool for autism spectrum disorder (ASD). METHODS: Items for the screening tool were modeled from already documented checklists and diagnostic criteria for ASD. Each item in text was paired with a photograph that illustrated the written content, which was in the 2 main local languages. The final product had 21 items and was named the pictorial autism assessment schedule (PAAS). Performance of PAAS was tested on a clinical sample of 18-48 mo old children, diagnosis naive, presenting with developmental deficits. Mothers completed PAAS checklist. Based on clinical diagnosis, which was taken as the gold standard, children were later grouped into ASD (Group 1) and non-ASD developmental disorders (Group 2). Mothers of a control sample of typically developing children also completed PAAS (Group 3). RESULTS: A total of 105 children (Group 1-45, Group 2-30, Group 3-30) participated in the study. Mean age of Group 1 and Group 2 were 36 and 40 mo respectively. Majority were male in all 3 groups. Performance of PAAS in discriminating between ASD and non-ASD developmental disorders was sensitivity 88.8%, specificity 60.7%, positive predictive value (PPV) 78.4%, negative predictive value (NPV) 77.2%, likelihood ratio (LR+) 2.26, and LR- 0.18. Performance of PAAS in discriminating between ASD and typical development was sensitivity 88.0%, specificity 93.3%, PPV 95.2%, NPV 84.0%, LR+ 13.3 and LR- 0.12. The results indicated that that a positive result from PAAS was 2.26 times more likely to be found in a child with ASD than in a child with non-ASD developmental disorder. A positive result from PAAS was 13.3 times more likely to be found in a child with ASD than in a child with typical development. CONCLUSION: PAAS is an effective tool in screening for ASD. Further study is indicated to evaluate the feasibility of using this instrument for community screening for ASD.
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6. Sacrey LR, Zwaigenbaum L, Szatmari P, Bryson S, Georgiades S, Brian J, Smith IM, Vaillancourt T, Garon N, Roncadin C, Elsabbagh M. {{Brief Report: Characteristics of preschool children with ASD vary by ascertainment}}. {J Autism Dev Disord}. 2017.
Prospective studies of infant siblings of children diagnosed with autism spectrum disorder (ASD) provide a unique opportunity to characterize ASD as it unfolds. A critical question that remains unanswered is whether and how these children with ASD resemble other children identified from the community, including those with no family history. The purpose of this study was to compare clinical characteristics of children with ASD identified by each method (n = 86 per group), drawn from two Canadian longitudinal research cohorts. Children ascertained from a prospective cohort were less severely affected and included a larger proportion of girls, compared to the clinically referred sample. These results may have important implications for conclusions drawn from studies of high-risk and clinically referred cohorts.
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7. Sangu N, Shimojima K, Takahashi Y, Ohashi T, Tohyama J, Yamamoto T. {{A 7q31.33q32.1 microdeletion including LRRC4 and GRM8 is associated with severe intellectual disability and characteristics of autism}}. {Hum Genome Var}. 2017; 4: 17001.
A 4-year-old boy with severe intellectual disability (ID) and characteristics of autism was found to have a de novo 1.9-Mb microdeletion in 7q31.33q32.1, in which LRRC4, GRM8, and 11 other genes were included. GRM8 is associated with attention deficit hyperactivity disorder. LRRC4 is related to synaptic cell adhesion molecules, some of which are associated with autism. The deletion of LRRC4 may be responsible for the severe ID and characteristics of autism observed in the present patient.
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8. Shaw W. {{Elevated Urinary Glyphosate and Clostridia Metabolites With Altered Dopamine Metabolism in Triplets With Autistic Spectrum Disorder or Suspected Seizure Disorder: A Case Study}}. {Integr Med (Encinitas)}. 2017; 16(1): 50-7.
CONTEXT: Autism is a neurodevelopmental disorder for which a number of genetic, environmental, and nutritional causes have been proposed. Glyphosate is used widely as a crop desiccant and as an herbicide in fields of genetically modified foods that are glyphosate resistant. Several researchers have proposed that it may be a cause of autism, based on epidemiological data that correlates increased usage of glyphosate with an increased autism rate. OBJECTIVE: The current study was intended to determine if excessive glyphosate was present in the triplets and their parents and to evaluate biochemical findings for the family to determine the potential effects of its presence. DESIGN: The author performed a case study with the cooperation of the parents and the attending physician. SETTING: The study took place at The Great Plains Laboratory, Inc (Lenexa, KS, USA). PARTICIPANTS: Participants were triplets, 2 male children and 1 female, and their parents. The 2 male children had autism, whereas the female had a possible seizure disorder. All 3 had elevated urinary glyphosate, and all of the triplets and their mother had elevated values of succinic acid or tiglylglycine, which are indicators of mitochondrial dysfunction. INTERVENTION: The participants received a diet of organic food only. OUTCOME MEASURES: The study performed organic acids, glyphosate, toxic chemicals and tiglylglycine, and creatinine testing of the participants’ urine. RESULTS: The 2 male triplets with autism had abnormalities on at least 1 organic acids test, including elevated phenolic compounds such as 4-cresol, 3-[3-hydroxyphenyl]-3-hydroxypropionic acid and 4-hydroxyphenylacetic acid, which have been previously associated with Clostridia bacteria and autism. The female, who was suspected of having a seizure disorder but not autism, did not have elevated phenolic compounds but did have a significantly elevated value of the metabolite tiglylglycine, a marker for mitochondrial dysfunction and/or mutations. One male triplet was retested postintervention and was found to have a markedly lower amount of glyphosate in his urine. CONCLUSIONS: The pattern of metabolites in the urine samples of the males with autism are consistent with a recent theory of autism that connects widespread glyphosate use with alteration of animal and human gastrointestinal flora. That theory is that the normally beneficial bacteria species that are sensitive to glyphosate are diminished and harmful bacteria species, such as Clostridia, that are insensitive to glyphosate, are increased following exposure to glyphosate. Excessive dopamine, caused by inhibition of dopamine-beta-hydroxylase by Clostridia metabolites, in turn, produces oxidative species that damage neuronal Krebs cycle enzymes, neuronal mitochondria, and neuronal structural elements such as the neurofibrils.
9. Strati F, Cavalieri D, Albanese D, De Felice C, Donati C, Hayek J, Jousson O, Leoncini S, Renzi D, Calabro A, De Filippo C. {{New evidences on the altered gut microbiota in autism spectrum disorders}}. {Microbiome}. 2017; 5(1): 24.
BACKGROUND: Autism spectrum disorders (ASDs) are neurodevelopmental conditions characterized by social and behavioural impairments. In addition to neurological symptoms, ASD subjects frequently suffer from gastrointestinal abnormalities, thus implying a role of the gut microbiota in ASD gastrointestinal pathophysiology. RESULTS: Here, we characterized the bacterial and fungal gut microbiota in a cohort of autistic individuals demonstrating the presence of an altered microbial community structure. A fraction of 90% of the autistic subjects were classified as severe ASDs. We found a significant increase in the Firmicutes/Bacteroidetes ratio in autistic subjects due to a reduction of the Bacteroidetes relative abundance. At the genus level, we observed a decrease in the relative abundance of Alistipes, Bilophila, Dialister, Parabacteroides, and Veillonella in the ASD cohort, while Collinsella, Corynebacterium, Dorea, and Lactobacillus were significantly increased. Constipation has been then associated with different bacterial patterns in autistic and neurotypical subjects, with constipated autistic individuals characterized by high levels of bacterial taxa belonging to Escherichia/Shigella and Clostridium cluster XVIII. We also observed that the relative abundance of the fungal genus Candida was more than double in the autistic than neurotypical subjects, yet due to a larger dispersion of values, this difference was only partially significant. CONCLUSIONS: The finding that, besides the bacterial gut microbiota, also the gut mycobiota contributes to the alteration of the intestinal microbial community structure in ASDs opens the possibility for new potential intervention strategies aimed at the relief of gastrointestinal symptoms in ASDs.
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10. Sznajer Y. {{Neurobehavioural vulnerability and autistic traits in RASopathies}}. {Dev Med Child Neurol}. 2017.
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11. Taylor LJ, Eapen V, Maybery M, Midford S, Paynter J, Quarmby L, Smith T, Williams K, Whitehouse AJ. {{Brief Report: An Exploratory Study of the Diagnostic Reliability for Autism Spectrum Disorder}}. {J Autism Dev Disord}. 2017.
Previous research shows inconsistency in clinician-assigned diagnoses of Autism Spectrum Disorder (ASD). We conducted an exploratory study that examined the concordance of diagnoses between a multidisciplinary assessment team and a range of independent clinicians throughout Australia. Nine video-taped Autism Diagnostic Observation Schedule (ADOS) assessments were collected from two Australian sites. Twenty-seven Australian health professionals each observed two video-recordings and rated the degree to which the individual met the DSM-5 criteria for ASD. There was 100% agreement on the diagnostic classification for only 3 of the 9 video clips (33%), with the remaining 6 clips (66%) reaching poor reliability. In addition, only 24% of the participating clinicians achieved ‘good’ or ‘excellent’ levels of agreement (Cohen’s kappa > 0.6) with the original ASD assessment. These findings have implications for clinical guidelines for ASD assessments.
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12. Wang X, Wang S, Fan Y, Huang D, Zhang Y. {{Speech-specific categorical perception deficit in autism: An Event-Related Potential study of lexical tone processing in Mandarin-speaking children}}. {Sci Rep}. 2017; 7: 43254.
Recent studies reveal that tonal language speakers with autism have enhanced neural sensitivity to pitch changes in nonspeech stimuli but not to lexical tone contrasts in their native language. The present ERP study investigated whether the distinct pitch processing pattern for speech and nonspeech stimuli in autism was due to a speech-specific deficit in categorical perception of lexical tones. A passive oddball paradigm was adopted to examine two groups (16 in the autism group and 15 in the control group) of Chinese children’s Mismatch Responses (MMRs) to equivalent pitch deviations representing within-category and between-category differences in speech and nonspeech contexts. To further examine group-level differences in the MMRs to categorical perception of speech/nonspeech stimuli or lack thereof, neural oscillatory activities at the single trial level were further calculated with the inter-trial phase coherence (ITPC) measure for the theta and beta frequency bands. The MMR and ITPC data from the children with autism showed evidence for lack of categorical perception in the lexical tone condition. In view of the important role of lexical tones in acquiring a tonal language, the results point to the necessity of early intervention for the individuals with autism who show such a speech-specific categorical perception deficit.
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13. Westmark CJ. {{Commentary: Depletion of the Fragile X Mental Retardation Protein in Embryonic Stem Cells Alters the Kinetics of Neurogenesis}}. {Front Mol Neurosci}. 2017; 10: 29.
