1. Adihe Lokanga R, Zhao XN, Entezam A, Usdin K. {{X inactivation plays a major role in the gender bias in somatic expansion in a mouse model of the fragile X-related disorders: implications for the mechanism of repeat expansion}}. {Hum Mol Genet};2014 (May 8)
The Fragile X-related disorders are X-linked disorders resulting from the inheritance of FMR1 alleles with >54 CGG/CCG repeats in their 5′ UTR. The repeats expand both somatically and on intergenerational transmission and increased repeat numbers are associated with increased risk of disease and increased risk of further expansion. The mechanism responsible for expansion is unknown. Here, we show in a knockin mouse model of these disorders that somatic expansion is much less common in females than in males. We show that this is due in large part to the fact that expansions occur only when the repeat is on the active X chromosome. However, even when this is taken into account, expansions in females are still less common than expected. This additional gender effect is not due to a protective effect of estrogen, a deleterious effect of testosterone or to differences in the expression of the Fmr1 gene or a variety of X-linked and autosomal DNA repair genes. However, our data do suggest that a higher level of expression of genes that protect against oxidative damage in females may contribute to their lower levels of expansion. Whatever the basis, our data suggest that the risk for somatic expansion may be lower in women than it is in men. This could help explain the reduced penetrance of some aspects of disease pathology in women. The fact that expansion only occurs when the Fmr1 allele is on the active X chromosome has important implications for the mechanism of repeat expansion.
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2. Carter EJ, Williams DL, Hodgins JK, Lehman JF. {{Are Children with Autism More Responsive to Animated Characters? A Study of Interactions with Humans and Human-Controlled Avatars}}. {J Autism Dev Disord};2014 (May 25)
Few direct comparisons have been made between the responsiveness of children with autism to computer-generated or animated characters and their responsiveness to humans. Twelve 4- to 8-year-old children with autism interacted with a human therapist; a human-controlled, interactive avatar in a theme park; a human actor speaking like the avatar; and cartoon characters who sought social responses. We found superior gestural and verbal responses to the therapist; intermediate response levels to the avatar and the actor; and poorest responses to the cartoon characters, although attention was equivalent across conditions. These results suggest that even avatars that provide live, responsive interactions are not superior to human therapists in eliciting verbal and non-verbal communication from children with autism in this age range.
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3. Eom S, Fisher B, Dezort C, Berg AT. {{Routine developmental, autism, behavioral, and psychological screening in epilepsy care settings}}. {Dev Med Child Neurol};2014 (May 27)
AIM: Screening for cognitive impairment, developmental delay, and neuropsychiatric problems is not always performed in children with epilepsy. The aim of this study was to assess the value of this screening and its validity for determining previously unidentified (‘actionable’) problems in children with epilepsy. METHOD: New and existing patients with epilepsy were recruited from a hospital-based epilepsy center. The parent of the child completed screening evaluations for development (Ages and Stages Questionnaire [ASQ], 0-66mo), autism (Modified Checklist for Autism in Toddlers [mCHAT], 16-30mo), social communication (Social Communication Questionnaire [SCQ], >/=4y), and psychiatric concerns (Strengths and Difficulties Questionnaire [SDQ], 4-17y). RESULTS: We screened 236 children overall (136 males [58%], 100 females [42%]; mean age [SD] 6y 7mo [4y 6mo]). Of these, 176 children (75%) had established epilepsy diagnoses and 60 (25%) were patients with new-onset epilepsy. Of those with new-onset disease, 22 (37%) were determined not to have epilepsy. Positive findings by test were 82% (ASQ), 54% (mCHAT), 15%, (SCQ), and 58% (SDQ). Findings were actionable in 46 children (20%): 18% of findings in children with established epilepsy and 23% of findings in patients with new-onset epilepsy. Of the 46 children for whom further referrals were made, the parents of 28 (61%) have pursued further evaluations. INTERPRETATION: In this study, children with existing and new-onset diagnoses of epilepsy had actionable screening findings. These findings support the development of systematic screening of comorbidities for children with epilepsy.
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4. Gupta AR, Pirruccello M, Cheng F, Kang HJ, Fernandez TV, Baskin JM, Choi M, Liu L, Ercan-Sencicek AG, Murdoch JD, Klei L, Neale BM, Franjic D, Daly MJ, Lifton RP, De Camilli P, Zhao H, Sestan N, State MW. {{Rare deleterious mutations of the gene EFR3A in autism spectrum disorders}}. {Mol Autism};2014;5:31.
BACKGROUND: Whole-exome sequencing studies in autism spectrum disorder (ASD) have identified de novo mutations in novel candidate genes, including the synaptic gene Eighty-five Requiring 3A (EFR3A). EFR3A is a critical component of a protein complex required for the synthesis of the phosphoinositide PtdIns4P, which has a variety of functions at the neural synapse. We hypothesized that deleterious mutations in EFR3A would be significantly associated with ASD. METHODS: We conducted a large case/control association study by deep resequencing and analysis of whole-exome data for coding and splice site variants in EFR3A. We determined the potential impact of these variants on protein structure and function by a variety of conservation measures and analysis of the Saccharomyces cerevisiae Efr3 crystal structure. We also analyzed the expression pattern of EFR3A in human brain tissue. RESULTS: Rare nonsynonymous mutations in EFR3A were more common among cases (16 / 2,196 = 0.73%) than matched controls (12 / 3,389 = 0.35%) and were statistically more common at conserved nucleotides based on an experiment-wide significance threshold (P = 0.0077, permutation test). Crystal structure analysis revealed that mutations likely to be deleterious were also statistically more common in cases than controls (P = 0.017, Fisher exact test). Furthermore, EFR3A is expressed in cortical neurons, including pyramidal neurons, during human fetal brain development in a pattern consistent with ASD-related genes, and it is strongly co-expressed (P < 2.2 x 10(-16), Wilcoxon test) with a module of genes significantly associated with ASD. CONCLUSIONS: Rare deleterious mutations in EFR3A were found to be associated with ASD using an experiment-wide significance threshold. Synaptic phosphoinositide metabolism has been strongly implicated in syndromic forms of ASD. These data for EFR3A strengthen the evidence for the involvement of this pathway in idiopathic autism.
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5. Hamidpour M, Hamidpour R, Hamidpour S, Shahlari M. {{Chemistry, Pharmacology, and Medicinal Property of Sage () to Prevent and Cure Illnesses such as Obesity, Diabetes, Depression, Dementia, Lupus, Autism, Heart Disease, and Cancer}}. {J Tradit Complement Med};2014 (Apr);4(2):82-88.
For a long time, sage (Salvia) species have been used in traditional medicine for the relief of pain, protecting the body against oxidative stress, free radical damages, angiogenesis, inflammation, bacterial and virus infection, etc., Several studies suggest that sage species can be considered for drug development because of their reported pharmacology and therapeutic activities in many countries of Asia and Middle East, especially China and India. These studies suggest that Salvia species, in addition to treating minor common illnesses, might potentially provide novel natural treatments for the relief or cure of many serious and life-threatening diseases such as depression, dementia, obesity, diabetes, lupus, heart disease, and cancer. This article presents a comprehensive analysis of the botanical, chemical, and pharmacological aspects of sage (Saliva).
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6. Joosten A, Girdler S, Albrecht MA, Horlin C, Falkmer M, Leung D, Ordqvist A, Fleischer H, Falkmer T. {{Gaze and visual search strategies of children with Asperger syndrome/high functioning autism viewing a magic trick}}. {Dev Neurorehabil};2014 (May 27):1-8.
Abstract Objective: To examine visual search patterns and strategies used by children with and without Asperger syndrome/high functioning autism (AS/HFA) while watching a magic trick. Limited responsivity to gaze cues is hypothesised to contribute to social deficits in children with AS/HFA. Methods: Twenty-one children with AS/HFA and 31 matched peers viewed a video of a gaze-cued magic trick twice. Between the viewings, they were informed about how the trick was performed. Participants’ eye movements were recorded using a head-mounted eye-tracker. Results: Children with AS/HFA looked less frequently and had shorter fixation on the magician’s direct and averted gazes during both viewings and more frequently at not gaze-cued objects and on areas outside the magician’s face. After being informed of how the trick was conducted, both groups made fewer fixations on gaze-cued objects and direct gaze. Conclusions: Information may enhance effective visual strategies in children with and without AS/HFA.
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7. Knoth IS, Vannasing P, Major P, Michaud JL, Lippe S. {{Alterations of visual and auditory evoked potentials in fragile X syndrome}}. {Int J Dev Neurosci};2014 (May 27)
BACKGROUND: Fragile X Syndrome (FXS) is the most common monogenic form of intellectual disability and one of the few known monogenic causes of autism. It is caused by a trinucleotide repeat expansion in the FMR1 (‘Fragile X Mental Retardation 1’) gene, which prevents expression of the ‘Fragile X Mental Retardation Protein’ (FMRP). In FXS, the absence of FMRP leads to altered structural and functional development of the synapse, while preventing activity-based synapse maturation and synaptic pruning, which are essential for normal brain development and cognitive development. Possible impairments in information processing can be non-invasively investigated using electrophysiology. METHODS: We compared auditory (AEP) and visual (VEP) evoked potentials in twelve adolescents and young adults (10-22 years) affected by FXS to healthy controls matched by chronological age (N=12) and developmental age of cognitive functioning (N=9; 5-7 years), using analysis of variance. RESULTS: In the visual modality, the N70 and N2 amplitude have been found increased in FXS in comparison to the chronological, but not the developmental control group at occipital sites, whereas in the auditory modality N1, P2 and N2 amplitude as well as N2 latency have been found increased in FXS, relative to both chronological and developmental control groups at mid-central sites. CONCLUSIONS: The AEP/VEP profile suggests disruptions in sensory processing specific to FXS that exceed immaturity of physiological activity. In addition, the auditory modality seems to be more affected than the visual modality. Results are discussed in light of possible underlying neuronal mechanisms, including deficits in synaptic pruning and neuronal inhibition that might account for a hyperreactive nervous system in FXS.
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8. Lawson RP, Rees G, Friston KJ. {{An aberrant precision account of autism}}. {Front Hum Neurosci};2014;8:302.
Autism is a neurodevelopmental disorder characterized by problems with social-communication, restricted interests and repetitive behavior. A recent and thought-provoking article presented a normative explanation for the perceptual symptoms of autism in terms of a failure of Bayesian inference (Pellicano and Burr, 2012). In response, we suggested that when Bayesian inference is grounded in its neural instantiation-namely, predictive coding-many features of autistic perception can be attributed to aberrant precision (or beliefs about precision) within the context of hierarchical message passing in the brain (Friston et al., 2013). Here, we unpack the aberrant precision account of autism. Specifically, we consider how empirical findings-that speak directly or indirectly to neurobiological mechanisms-are consistent with the aberrant encoding of precision in autism; in particular, an imbalance of the precision ascribed to sensory evidence relative to prior beliefs.
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9. Leung RC, Zakzanis KK. {{Brief Report: Cognitive Flexibility in Autism Spectrum Disorders: A Quantitative Review}}. {J Autism Dev Disord};2014 (May 27)
Impairments in cognitive flexibility have been used to characterize the neuropsychological presentation of persons with autism spectrum disorders (ASDs). Previous studies have yielded mixed results. Our objective was to systematically review the sensitivity of cognitive flexibility measures in ASD using quantitative methods employed by meta-analytic statistical techniques. Seventy-two studies met inclusion criteria for analysis and included a total of 2,137 individuals with ASD and 2,185 healthy controls. Our findings demonstrate that while the shift sub-scale of the self-report version of the Behavioral Rating Inventory of Executive Function (BRIEF) showed approximate absolute discriminability, of all the performance measures that were systematically reviewed and evaluated, none could reliably differentiate between individuals with ASD and controls; this is not surprising given that cognitive flexibility is not a core deficit of ASD. Our findings suggest that while the shift sub-scale of the self-report version of the BRIEF is a promising clinical marker, clinical performance measures of cognitive flexibility may lack ecological validity and lastly, reinforces that impairments in cognitive flexibility do not uniformly characterize all persons with ASD.
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10. Liang SG, Si-Tu MJ, Huang Y. {{[Research advance in autistic traits in non-affected population of autism spectrum disorder]}}. {Zhongguo Dang Dai Er Ke Za Zhi};2014 (May);16(5):560-565.
Autistic traits including social reciprocal deficits, communication deficits and stereotyped behaviors, are manifested not only in patients with autism spectrum disorders (ASD) and their families, but also in general population. In recent years, there has much research related to autistic traits. This ariticle summarizes research advance of autistic traits in ASD relations and general population.
11. Liao ST, Hwang YS, Chen YJ, Lee P, Chen SJ, Lin LY. {{Home-based DIR/Floortime Intervention Program for Preschool Children with Autism Spectrum Disorders: Preliminary Findings}}. {Phys Occup Ther Pediatr};2014 (May 27)
ABSTRACT Improving parent-child interaction and play are important outcomes for children with autism spectrum disorder (ASD). Play is the primary occupation of children. In this pilot study conducted in Taiwan, we investigated the effects of the developmental, individual difference, and relationship-based (DIR)/Floortime home-based intervention program on social interaction and adaptive functioning of children with ASD. The participants were 11 children with ASD, ages from 45-69 months, and their mothers. Mothers were instructed the principles of the approach by an occupational therapist. All 11 children and their mothers completed the 10-week home-based intervention program, undergoing an average of 109.7 hr of intervention. Children made significant changes in mean scores for emotional functioning, communication, and daily living skills. Moreover, the mothers perceived positive changes in their parent-child interactions. The findings of this pilot study contribute to knowledge regarding the effects of home-based DIR/Floortime intervention program on increasing the social interaction and adaptive behaviors of children with ASD in Taiwan.
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12. Lu S, Sonney J, Kieckhefer GM. {{Asthma Management in Children With Autism Spectrum Disorders: Pearls for a Successful Clinical Encounter}}. {J Pediatr Health Care};2014 (May 21)
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13. Nebel MB, Eloyan A, Barber AD, Mostofsky SH. {{Precentral gyrus functional connectivity signatures of autism}}. {Front Syst Neurosci};2014;8:80.
Motor impairments are prevalent in children with autism spectrum disorders (ASD) and are perhaps the earliest symptoms to develop. In addition, motor skills relate to the communicative/social deficits at the core of ASD diagnosis, and these behavioral deficits may reflect abnormal connectivity within brain networks underlying motor control and learning. Despite the fact that motor abnormalities in ASD are well-characterized, there remains a fundamental disconnect between the complexity of the clinical presentation of ASD and the underlying neurobiological mechanisms. In this study, we examined connectivity within and between functional subregions of a key component of the motor control network, the precentral gyrus, using resting state functional Magnetic Resonance Imaging data collected from a large, heterogeneous sample of individuals with ASD as well as neurotypical controls. We found that the strength of connectivity within and between distinct functional subregions of the precentral gyrus was related to ASD diagnosis and to the severity of ASD traits. In particular, connectivity involving the dorsomedial (lower limb/trunk) subregion was abnormal in ASD individuals as predicted by models using a dichotomous variable coding for the presence of ASD, as well as models using symptom severity ratings. These findings provide further support for a link between motor and social/communicative abilities in ASD.
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14. Peterson C. {{Theory of mind understanding and empathic behavior in children with autism spectrum disorders}}. {Int J Dev Neurosci};2014 (May 27)
This paper begins with a review of past research on theory of mind and empathy in children with ASD. Using varied operational definitions of empathy ranging from physiological heart rate through story vignettes to reports by privileged observers (e.g., teachers) of children’s empathic behavior, results of previous studies are limited and contradictory. Thus new evidence is needed to answer two key questions: Are children with ASD less empathic than typically developing children? Do individual differences in theory of mind (ToM) understanding among children with ASD predict differences in their behavioral empathy? An original empirical study of 76 children aged 3-12 years (37 with ASD; 39 with typical development) addressed these. Results showed that children with ASD were significantly less empathic, according to their teachers, than typically developing children. However, this was not because of their slower ToM development. Findings showed equally clearly that ToM understanding was unrelated to empathy in children with ASD. The same was true for typically developing children once age and verbal maturity were controlled. Indeed, even the subgroup of older children with ASD in the sample who passed false belief tests were significantly less empathic than younger preschoolers who failed them.
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15. Siniscalco D. {{The searching for autism biomarkers: a commentary on: a new methodology of viewing extra-axial fluid and cortical abnormalities in children with autism via transcranial ultrasonography}}. {Front Hum Neurosci};2014;8:240.
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16. Uddin M, Tammimies K, Pellecchia G, Alipanahi B, Hu P, Wang Z, Pinto D, Lau L, Nalpathamkalam T, Marshall CR, Blencowe BJ, Frey BJ, Merico D, Yuen RK, Scherer SW. {{Brain-expressed exons under purifying selection are enriched for de novo mutations in autism spectrum disorder}}. {Nat Genet};2014 (May 25)
A universal challenge in genetic studies of autism spectrum disorders (ASDs) is determining whether a given DNA sequence alteration will manifest as disease. Among different population controls, we observed, for specific exons, an inverse correlation between exon expression level in brain and burden of rare missense mutations. For genes that harbor de novo mutations predicted to be deleterious, we found that specific critical exons were significantly enriched in individuals with ASD relative to their siblings without ASD (P < 1.13 x 10-38; odds ratio (OR) = 2.40). Furthermore, our analysis of genes with high exonic expression in brain and low burden of rare mutations demonstrated enrichment for known ASD-associated genes (P < 3.40 x 10-11; OR = 6.08) and ASD-relevant fragile-X protein targets (P < 2.91 x 10-157; OR = 9.52). Our results suggest that brain-expressed exons under purifying selection should be prioritized in genotype-phenotype studies for ASD and related neurodevelopmental conditions.
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17. White E. {{Science, pseudoscience, and the frontline practitioner: the vaccination/autism debate}}. {J Evid Based Soc Work};2014 (May 27);11(3):269-274.
This article demonstrates how misinformation concerning autism and vaccinations was created and suggests that social workers may be perfectly poised to challenge pseudoscience interpretations. Utilizing social network theory, this article illustrates how erroneous research, mass media, and public opinion led to a decreased use of vaccinations in the United States and a seven-fold increase in measles outbreaks. It traces the dissemination of spurious research results and demonstrates how information was transmitted via a system of social network nodes and community ties. This article encourages social workers, as frontline knowledge brokers, to counter misinformation, which may lead to significant public health consequences.
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18. Williams AL, DeSesso JM. {{Gestational/Perinatal chlorpyrifos exposure is not associated with autistic-like behaviors in rodents}}. {Crit Rev Toxicol};2014 (May 27):1-12.
Although animal models cannot exactly replicate human psychiatric disorders, they may be useful to investigate whether the behaviors associated with certain exposures in animals parallel those observed in people. According to the most current version of the Diagnostic and Statistical Manual of Mental Disorders, autism is diagnosed based on (1) persistent deficits in social communication and social interaction; and (2) the presence of restricted, repetitive patterns of behavior, interests and activities. To address whether developmental chlorpyrifos (CPF) exposure was associated with the development of autistic behaviors, a literature search was conducted to identify studies in rats and mice involving gestational or early postnatal exposure to CPF or CPF oxon (CPO, the active metabolite of CPF) and subsequent behavioral testing to assess behaviors related to autism. A total of 13 studies conducted in six different laboratories were identified. Analysis of these studies found that perinatal CPF exposure was generally associated with (1) no effect or increased social communications; (2) no effect or increased social encounters; (3) no effect, reduced stereotypies, or conflicting findings on stereotypic behaviors; and (4) no effect or increased preference for novelty and reduced anxiety in novel environments. These behavioral findings are generally inconsistent with the types of behaviors that would be expected in children with clinical autism. Based on the results of this analysis of rodent model studies involving CPF/CPO exposure, it cannot be concluded that gestational and/or perinatal CPF exposure is likely to be associated with the development of autism-like behaviors in humans.
