1. Bittner MD, Rigby BR, Silliman-French L, Nichols DL, Dillon SR. {{Use of technology to facilitate physical activity in children with autism spectrum disorders: A pilot study}}. {Physiol Behav};2017 (May 11);177:242-246.
Deficits in social behavior and communication skills are correlated with reduced gross motor skills in children with autism spectrum disorders (ASD). The ExerciseBuddy application (EB app) was designed to communicate these motor skills to those with ASD and integrates evidence-based practices such as visual support and video modeling supported by The National Professional Development Center on Autism Spectrum Disorders. The purpose of this study was to determine the effectiveness of the EB app in facilitating increased physiologic responses to physical activity via a continuous measurement of energy expenditure and heart rate versus practice-style teaching methods in children with ASD. Six children, ages 5 to 10years, diagnosed with ASD were recruited. Each participant performed a variety of locomotor or object control skills as defined by the Test of Gross Motor Development-2 once per week for 4weeks. Motor skills were communicated and demonstrated using either practice-style teaching methods or the instructional section of the EB app. Energy expenditure and heart rate were measured continuously during each 12-minute session. A Wilcoxon signed-rank test was performed to assess any differences between the use of the app and practice-style teaching methods. The use of the EB app elicited greater values for peak energy expenditure (p=0.043) and peak heart rate response (p=0.028) while performing locomotor skills but no differences were observed while performing object control skills. Similarities were observed with average physiologic responses between the use of the EB app and practice-style teaching methods. The use of the EB app may allow for a greater peak physiologic response during more dynamic movements and a similar average cardiovascular and metabolic response when compared to practice-style teaching methods in children with ASD.
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2. Bralten J, van Hulzen KJ, Martens MB, Galesloot TE, Arias Vasquez A, Kiemeney LA, Buitelaar JK, Muntjewerff JW, Franke B, Poelmans G. {{Autism spectrum disorders and autistic traits share genetics and biology}}. {Mol Psychiatry};2017 (May 16)
Autism spectrum disorders (ASDs) and autistic traits in the general population may share genetic susceptibility factors. In this study, we investigated such potential overlap based on common genetic variants. We developed and validated a self-report questionnaire of autistic traits in adults. We then conducted genome-wide association studies (GWASs) of six trait scores derived from the questionnaire through exploratory factor analysis in 1981 adults from the general population. Using the results from the Psychiatric Genomics Consortium GWAS of ASDs, we observed genetic sharing between ASDs and the autistic traits ‘childhood behavior’, ‘rigidity’ and ‘attention to detail’. Gene-set analysis subsequently identified ‘rigidity’ to be significantly associated with a network of ASD gene-encoded proteins that regulates neurite outgrowth. Gene-wide association with the well-established ASD gene MET reached significance. Taken together, our findings provide evidence for an overlapping genetic and biological etiology underlying ASDs and autistic population traits, which suggests that genetic studies in the general population may yield novel ASD genes.Molecular Psychiatry advance online publication, 16 May 2017; doi:10.1038/mp.2017.98.
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3. Brewer R, Biotti F, Bird G, Cook R. {{Typical integration of emotion cues from bodies and faces in Autism Spectrum Disorder}}. {Cognition};2017 (May 16);165:82-87.
Contextual cues derived from body postures bias how typical observers categorize facial emotion; the same facial expression may be perceived as anger or disgust when aligned with angry and disgusted body postures. Individuals with Autism Spectrum Disorder (ASD) are thought to have difficulties integrating information from disparate visual regions to form unitary percepts, and may be less susceptible to visual illusions induced by context. The current study investigated whether individuals with ASD exhibit diminished integration of emotion cues extracted from faces and bodies. Individuals with and without ASD completed a binary expression classification task, categorizing facial emotion as ‘Disgust’ or ‘Anger’. Facial stimuli were drawn from a morph continuum blending facial disgust and anger, and presented in isolation, or accompanied by an angry or disgusted body posture. Participants were explicitly instructed to disregard the body context. Contextual modulation was inferred from a shift in the resulting psychometric functions.Contrary to prediction, observers with ASD showed typical integration of emotion cues from the face and body. Correlation analyses suggested a relationship between the ability to categorize emotion from isolated faces, and susceptibility to contextual influence within the ASD sample; individuals with imprecise facial emotion classification were influenced more by body posture cues.
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4. Dou Y, Yang X, Li Z, Wang S, Zhang Z, Ye AY, Yan L, Yang C, Wu Q, Li J, Zhao B, Huang AY, Wei L. {{Post-zygotic single-nucleotide mosaicisms contribute to the etiology of autism spectrum disorder and autistic traits and the origin of mutations}}. {Hum Mutat};2017 (May 14)
The roles and characteristics of post-zygotic single-nucleotide mosaicisms (pSNMs) in autism spectrum disorders (ASD) remain unclear. In this study of the whole-exomes of 2,321 families in the Simons Simplex Collection (SSC), we identified 1,248 putative pSNMs in children and 285 de novo SNPs in children with detectable parental mosaicism. Ultra-deep amplicon resequencing suggested a validation rate of 51%. Analyses of validated pSNMs revealed that missense/loss-of-function (LoF) pSNMs with a high mutant allele fraction (MAF> = 0.2) contributed to ASD diagnoses (P = 0.022, OR = 5.25), whereas missense/LoF pSNMs with a low MAF (MAF<0.2) contributed to autistic traits in male non-ASD siblings (P = 0.033). LoF pSNMs in parents were less likely to be transmitted to offspring than neutral pSNMs (P = 0.037), and missense/LoF pSNMs in parents with a low MAF were transmitted more to probands than to siblings (P = 0.016, OR = 1.45). We estimated that pSNMs in probands or de novo mutations inherited from parental pSNMs increased the risk of ASD by approximately 6%. Adding pSNMs into the Transmission and De novo Association test (TADA) model revealed 13 new ASD risk genes. These results expand the existing repertoire of genes involved in ASD and shed new light on the contribution of genomic mosaicisms to ASD diagnoses and autistic traits. This article is protected by copyright. All rights reserved. Lien vers le texte intégral (Open Access ou abonnement)
5. Duda M, Haber N, Daniels J, Wall DP. {{Crowdsourced validation of a machine-learning classification system for autism and ADHD}}. {Transl Psychiatry};2017 (May 16);7(5):e1133.
Autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) together affect >10% of the children in the United States, but considerable behavioral overlaps between the two disorders can often complicate differential diagnosis. Currently, there is no screening test designed to differentiate between the two disorders, and with waiting times from initial suspicion to diagnosis upwards of a year, methods to quickly and accurately assess risk for these and other developmental disorders are desperately needed. In a previous study, we found that four machine-learning algorithms were able to accurately (area under the curve (AUC)>0.96) distinguish ASD from ADHD using only a small subset of items from the Social Responsiveness Scale (SRS). Here, we expand upon our prior work by including a novel crowdsourced data set of responses to our predefined top 15 SRS-derived questions from parents of children with ASD (n=248) or ADHD (n=174) to improve our model’s capability to generalize to new, ‘real-world’ data. By mixing these novel survey data with our initial archival sample (n=3417) and performing repeated cross-validation with subsampling, we created a classification algorithm that performs with AUC=0.89+/-0.01 using only 15 questions.
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6. Esnafoglu E, Cirrik S, Ayyildiz SN, Erdil A, Erturk EY, Dagli A, Noyan T. {{Increased Serum Zonulin Levels as an Intestinal Permeability Marker in Autistic Subjects}}. {J Pediatr};2017 (May 11)
OBJECTIVE: To evaluate the serum levels of zonulin, which regulates tight junctions between enterocytes and is a physiological modulator controlling intestinal permeability, in patients with autism spectrum disorders (ASDs). STUDY DESIGN: Serum zonulin levels were determined in 32 patients with ASD and 33 healthy controls using an enzyme-linked immunosorbent assay. The severity of ASD symptoms was assessed with the Childhood Autism Rating Scale. RESULTS: Serum zonulin levels were significantly higher in the patients with ASD (122.3 +/- 98.46 ng/mL) compared with the healthy controls (41.89 +/- 45.83 ng/mL). There was a positive correlation between zonulin levels and Childhood Autism Rating Scale score when all subjects were assessed (r = 0.523; P < .001). CONCLUSIONS: This study suggests that zonulin, which regulates intestinal permeability, plays a role in the development of symptoms of ASD. Lien vers le texte intégral (Open Access ou abonnement)
7. Fairthorne J, de Klerk N, Leonard HM, Schieve LA, Yeargin-Allsopp M. {{Maternal Race-Ethnicity, Immigrant Status, Country of Birth, and the Odds of a Child With Autism}}. {Child Neurol Open};2017 (Jan-Dec);4:2329048×16688125.
The risk of autism spectrum disorder varies by maternal race-ethnicity, immigration status, and birth region. In this retrospective cohort study, Western Australian state registries and a study population of 134 204 mothers enabled us to examine the odds of autism spectrum disorder with intellectual disability in children born from 1994 to 2005 by the aforementioned characteristics. We adjusted for maternal age, parity, socioeconomic status, and birth year. Indigenous women were 50% less likely to have a child with autism spectrum disorder with intellectual disability than Caucasian, nonimmigrant women. Overall, immigrant women were 40% less likely to have a child with autism spectrum disorder with intellectual disability than nonimmigrant women. However, Black women from East Africa had more than 3.5 times the odds of autism spectrum disorder with intellectual disability in their children than Caucasian nonimmigrant women. Research is implicated on risk and protective factors for autism spectrum disorder with intellectual disability in the children of immigrant women.
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8. Gantois I, Khoutorsky A, Popic J, Aguilar-Valles A, Freemantle E, Cao R, Sharma V, Pooters T, Nagpal A, Skalecka A, Truong VT, Wiebe S, Groves IA, Jafarnejad SM, Chapat C, McCullagh EA, Gamache K, Nader K, Lacaille JC, Gkogkas CG, Sonenberg N. {{Metformin ameliorates core deficits in a mouse model of fragile X syndrome}}. {Nat Med};2017 (May 15)
Fragile X syndrome (FXS) is the leading monogenic cause of autism spectrum disorders (ASD). Trinucleotide repeat expansions in FMR1 abolish FMRP expression, leading to hyperactivation of ERK and mTOR signaling upstream of mRNA translation. Here we show that metformin, the most widely used drug for type 2 diabetes, rescues core phenotypes in Fmr1-/y mice and selectively normalizes ERK signaling, eIF4E phosphorylation and the expression of MMP-9. Thus, metformin is a potential FXS therapeutic.
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9. Henry LA, Crane L, Nash G, Hobson Z, Kirke-Smith M, Wilcock R. {{Verbal, Visual, and Intermediary Support for Child Witnesses with Autism During Investigative Interviews}}. {J Autism Dev Disord};2017 (May 13)
Three promising investigative interview interventions were assessed in 270 children (age 6-11 years): 71 with autism spectrum disorder (ASD) and 199 who were typically developing (TD). Children received ‘Verbal Labels’, ‘Sketch Reinstatement of Context’ or ‘Registered Intermediary’ interviews designed to improve interview performance without decreasing accuracy. Children with ASD showed no increases in the number of correct details recalled for any of the three interview types (compared to a Best-Practice police interview), whereas TD children showed significant improvements in the Registered Intermediary and Verbal Labels interviews. Findings suggested that children with ASD can perform as well as TD children in certain types of investigative interviews, but some expected benefits (e.g., of Registered Intermediaries) were not apparent in this study.
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10. Kirsten TB, Bernardi MM. {{Prenatal lipopolysaccharide induces hypothalamic dopaminergic hypoactivity and autistic-like behaviors: repetitive self-grooming and stereotypies}}. {Behav Brain Res};2017 (May 16)
Previous investigations by our group have shown that prenatal exposure to lipopolysaccharide (LPS), which mimics infection by gram-negative bacteria, induces social, cognitive, and communication deficits. For a complete screening of autistic-like behaviors, the objective of this study was to evaluate if our rat model also induces restricted and repetitive stereotyped behaviors. Thus, we studied the self-grooming microstructure. We also studied the neurochemistry of hypothalamus and frontal cortex, which are brain areas related to autism to better understand central mechanisms involved in our model. Prenatal LPS exposure on gestational day 9.5 increased the head washing episodes (frequency and time), as well as the total self-grooming. However, body grooming, paw/leg licking, tail/genital grooming, and circling behavior/tail chasing did not vary significantly among the groups. Moreover, prenatal LPS induced dopaminergic hypoactivity (HVA metabolite and turnover) in the hypothalamus. Therefore, our rat model induced restricted and repetitive stereotyped behaviors and the other main symptoms of autism experimentally studied in rodent models and also found in patients. The hypothalamic dopaminergic impairments seem to be associated with the autistic-like behaviors.
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11. Li Q, Han Y, Dy ABC, Hagerman RJ. {{The Gut Microbiota and Autism Spectrum Disorders}}. {Front Cell Neurosci};2017;11:120.
Gastrointestinal (GI) symptoms are a common comorbidity in patients with autism spectrum disorder (ASD), but the underlying mechanisms are unknown. Many studies have shown alterations in the composition of the fecal flora and metabolic products of the gut microbiome in patients with ASD. The gut microbiota influences brain development and behaviors through the neuroendocrine, neuroimmune and autonomic nervous systems. In addition, an abnormal gut microbiota is associated with several diseases, such as inflammatory bowel disease (IBD), ASD and mood disorders. Here, we review the bidirectional interactions between the central nervous system and the gastrointestinal tract (brain-gut axis) and the role of the gut microbiota in the central nervous system (CNS) and ASD. Microbiome-mediated therapies might be a safe and effective treatment for ASD.
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12. Luo M, Fan J, Wenger TL, Harr MH, Racobaldo M, Mulchandani S, Dubbs H, Zackai EH, Spinner NB, Conlin LK. {{CMIP haploinsufficiency in two patients with autism spectrum disorder and co-occurring gastrointestinal issues}}. {Am J Med Genet A};2017 (May 15)
Autism spectrum disorder (ASD) is a genetically heterogeneous group of disorders characterized by impairments in social communication and restricted interests. Though some patients with ASD have an identifiable genetic cause, the cause of most ASD remains elusive. Many ASD susceptibility loci have been identified through clinical studies. We report two patients with syndromic ASD and persistent gastrointestinal issues who carry de novo deletions involving the CMIP gene detected by genome-wide SNP microarray and fluorescence in situ hybridization (FISH) analysis. Patient 1 has a 517 kb deletion within 16q23.2q23.3 including the entire CMIP gene. Patient 2 has a 1.59 Mb deletion within 16q23.2q23.3 that includes partial deletion of CMIP in addition to 12 other genes, none of which have a known connection to ASD or other clinical phenotypes. The deletion of CMIP is rare in general population and was not found among a reference cohort of approximately 12,000 patients studied in our laboratory who underwent SNP array analysis for various indications. A 280 kb de novo deletion containing the first 3 exons of CMIP was reported in one patient who also demonstrated ASD and developmental delay. CMIP has previously been identified as a susceptibility locus for specific language impairment (SLI). It is notable that both patients in this study had significant gastrointestinal issues requiring enteral feedings, which is unusual for patients with ASD, in addition to unusually elevated birth length, further supporting a shared causative gene. These findings suggest that CMIP haploinsufficiency is the likely cause of syndromic ASD in our patients.
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13. Milen MT, Nicholas DB. {{Examining transitions from youth to adult services for young persons with autism}}. {Soc Work Health Care};2017 (May 16):1-13.
Autism Spectrum Disorder (ASD) presents pervasive challenges for individuals throughout their lifetime. Although some financial, community, and individual supports are available for children, there are fewer resources available for adults with ASD, their families, and/or caregivers. It is important to understand the multidimensional shifts associated with the transition from adolescence to adulthood for individuals with ASD. METHODS: To better understand the transitional process, a qualitative study comprised 11 semi-structured interviews with individuals with ASD and their families. Interviews elicited the experiences of individuals and families impacted by ASD as they transition to adulthood and adult systems of care. FINDINGS: This study found that individuals with ASD and their family are exposed to a « lifetime of difficult transitions » due to a limited number of service providers and resources including stringent and restrictive program and funding criteria. As a result, individuals with ASD and their families were concerned about the ability of some individuals with ASD to establish meaningful lives in adulthood. These findings challenge existing barriers and broader societal values and stigma that impede emerging adults with developmental disabilities.
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14. Newell C, Johnsen VL, Yee NC, Xu WJ, Klein MS, Khan A, Rho JM, Shearer J. {{Ketogenic diet leads to O-GlcNAc modification in the BTBRT+tf/j mouse model of autism}}. {Biochim Biophys Acta};2017 (May 11)
BACKGROUND: Protein O-linked-beta-N-acetyl glucosamine (O-GlcNAc) is a post-translational modification to Ser/Thr residues that integrates energy supply with demand. Abnormal O-GlcNAc patterning is evident in several neurological disease states including epilepsy, Alzheimer’s disease and autism spectrum disorder (ASD). A potential treatment option for these disorders includes the high-fat, low-carbohydrate, ketogenic diet (KD). The goal of this study was to determine whether the KD induces changes in O-GlcNAc in the BTBRT+tf/j (BTBR) mouse model of ASD. METHODS: Juvenile male (5weeks), age-matched C57 or BTBR mice consumed a chow diet (13% kcal fat) or KD (75% kcal fat) for 10-14days. Following these diets, brain (prefrontal cortex) and liver were examined for gene expression levels of key O-GlcNAc mediators, global and protein specific O-GlcNAc as well as indicators of energy status. RESULTS: The KD reduced global O-GlcNAc in the livers of all animals (p<0.05). Reductions were likely mediated by lower protein levels of O-GlcNAc transferase (OGT) and increased O-GlcNAcase (OGA) (p<0.05). In contrast, no differences in global O-GlcNAc were noted in the brain (p>0.05), yet OGT and OGA expression (mRNA) were elevated in both C57 and BTBR animals (p<0.05). CONCLUSIONS: The KD has tissue specific impacts on O-GlcNAc. Although levels of O-GlcNAc play an important role in neurodevelopment, levels of this modification in the juvenile mouse brain were stable with the KD despite large fluctuations in energy status. This suggests that it is unlikely that the KD exerts it therapeutic benefit in the BTBR model of ASD by O-GlcNAc related pathways. Lien vers le texte intégral (Open Access ou abonnement)
15. Solders SK, Carper RA, Muller RA. {{White matter compromise in autism? Differentiating motion confounds from true differences in diffusion tensor imaging}}. {Autism Res};2017 (May 15)
Common findings from diffusion tensor imaging (DTI) in autism spectrum disorder (ASD) include reduced fractional anisotropy (FA), and increased mean and radial diffusivity (MD, RD) of white matter tracts. However, findings may be confounded by head motion. We examined how group-level motion matching affects DTI comparisons between ASD and typically developing (TD) groups. We included 57 ASD and 50 TD participants, comparing three subsets at increasing levels of motion-matching stringency: full sample (FS); quality-controlled (QC); and quantitatively-matched (QM). Groups were compared on diffusivity measures using Tract-Based Spatial Statistics (TBSS) and probabilistic tractography. Two methods for estimating diffusivity were compared: dti-fit and restore. TBSS: In set FS, FA was reduced in the ASD compared to the TD group throughout the right hemisphere. This effect was less extensive in set QC and absent in set QM. However, effect sizes remained stable or increased with better quality-control in some regions. Tractography: In set QM, MD was significantly higher in ASD overall and RD was higher in bilateral ILF. Effects were more robust in QM than in FS or QC sets. Effect sizes in several tracts increased with stringent quality matching. Restore improved tensor estimates, with some increases in effect sizes, but did not fully compensate for reduced quality. Findings suggest that some previously reported DTI findings for ASD may have been confounded by motion. However, effects in the tightly matched subset indicate that tract-specific anomalies probably do exist in ASD. Our results highlight the need for careful quality-control and motion-matching. Autism Res 2017. (c) 2017 International Society for Autism Research, Wiley Periodicals, Inc.
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16. Souders MC, Zavodny S, Eriksen W, Sinko R, Connell J, Kerns C, Schaaf R, Pinto-Martin J. {{Sleep in Children with Autism Spectrum Disorder}}. {Curr Psychiatry Rep};2017 (Jun);19(6):34.
The purposes of this paper are to provide an overview of the state of the science of sleep in children with autism spectrum disorder (ASD), present hypotheses for the high prevalence of insomnia in children with ASD, and present a practice pathway for promoting optimal sleep. Approximately two thirds of children with ASD have chronic insomnia, and to date, the strongest evidence on promoting sleep is for sleep education, environmental changes, behavioral interventions, and exogenous melatonin. The Sleep Committee of the Autism Treatment Network (ATN) developed a practice pathway, based on expert consensus, to capture best practices for screening, identification, and treatment for sleep problems in ASD in 2012. An exemplar case is presented to integrate key constructs of the practice pathway and address arousal and sensory dysregulation in a child with ASD and anxiety disorder. This paper concludes with next steps for dissemination of the practice pathway and future directions for research of sleep problems in ASD.
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17. Spain D, Sin J, Paliokosta E, Furuta M, Prunty JE, Chalder T, Murphy DG, Happe FG. {{Family therapy for autism spectrum disorders}}. {Cochrane Database Syst Rev};2017 (May 16);5:Cd011894.
BACKGROUND: Autism spectrum disorders (ASDs) are characterised by impairments in communication and reciprocal social interaction. These impairments can impact on relationships with family members, augment stress and frustration, and contribute to behaviours that can be described as challenging. Family members of individuals with ASD can experience high rates of carer stress and burden, and poor parental efficacy. While there is evidence to suggest that individuals with ASD and family members derive benefit from psychological interventions designed to reduce stress and mental health morbidity, and enhance coping, most studies to date have targeted the needs of either individuals with ASD, or family members. We wanted to examine whether family (systemic) therapy, aimed at enhancing communication, relationships or coping, is effective for individuals with ASD and their wider family network. OBJECTIVES: To evaluate the clinical effectiveness and acceptability of family therapy as a treatment to enhance communication or coping for individuals with ASD and their family members. If possible, we will also seek to establish the economic costs associated with family therapy for this clinical population. SEARCH METHODS: On 16 January 2017 we searched CENTRAL, MEDLINE, Embase, 10 other databases and three trials registers. We also handsearched reference lists of existing systematic reviews and contacted study authors in the field. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs investigating the effectiveness of family therapy for young people or adults with ASD or family members, or both, delivered via any modality and for an unspecified duration, compared with either standard care, a wait-list control, or an active intervention such as an alternative type of psychological therapy. DATA COLLECTION AND ANALYSIS: Two authors independently screened each title and abstract and all full-text reports retrieved. To enhance rigour, 25% of these were independently screened by a third author. MAIN RESULTS: The search yielded 4809 records. Of these, we retrieved 37 full-text reports for further scrutiny, which we subsequently excluded as they did not meet the review inclusion criteria, and identified one study awaiting classification. AUTHORS’ CONCLUSIONS: Few studies have examined the effectiveness of family therapy for ASD, and none of these are RCTs. Further research studies employing methodologically robust trial designs are needed to establish whether family therapy interventions are clinically beneficial for enhancing communication, strengthening relationships, augmenting coping and reducing mental health morbidity for individuals with ASD and family members.
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18. Stuger J. {{Kafka and Autism : The Undisclosed Logic Behind Kafka’s Work}}. {J Autism Dev Disord};2017 (May 16)
In this paper the hypothesis is presented that Franz Kafka was a person with autism. This is done by analyzing and discussing his biography, letters, diaries and major works. Kafka’s autism is an integral diagnosis which encompasses both his personal life and his work. This interpretation is contrary to other interpretations from the past which in all cases were only partially applicable to explain Kafka’s life and work. In Kafka research the big secret of Kafka was how he was able to write he did, like no one before him had done. The function and use of parables are also discussed to support this autism hypothesis concerning Franz Kafka which ultimately makes his life and work more understandable and accessible.
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19. Szoko N, McShane AJ, Natowicz MR. {{Proteomic explorations of autism spectrum disorder}}. {Autism Res};2017 (May 16)
Proteomics, the large-scale study of protein expression in cells and tissues, is a powerful tool to study the biology of clinical conditions and has provided significant insights in many experimental systems. Herein, we review the basics of proteomic methodology and discuss challenges in using proteomic approaches to study autism. Unlike other experimental approaches, such as genomic approaches, there have been few large-scale studies of proteins in tissues from persons with autism. Most of the proteomic studies on autism used blood or other peripheral tissues; few studies used brain tissue. Some studies found dysregulation of aspects of the immune system or of aspects of lipid metabolism, but no consistent findings were noted. Based on the challenges in using proteomics to study autism, we discuss considerations for future studies. Apart from the complex technical considerations implicit in any proteomic analysis, key nontechnical matters include attention to subject and specimen inclusion/exclusion criteria, having adequate sample size to ensure appropriate powering of the study, attention to the state of specimens prior to proteomic analysis, and the use of a replicate set of specimens, when possible. We conclude by discussing some potentially productive uses of proteomics, potentially coupled with other approaches, for future autism research including: (1) proteomic analysis of banked human brain specimens; (2) proteomic analysis of tissues from animal models of autism; and (3) proteomic analysis of induced pluripotent stem cells that are differentiated into various types of brain cells and neural organoids. Autism Res 2017. (c) 2017 International Society for Autism Research, Wiley Periodicals, Inc.
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20. Tsai HJ, Cebula K, Fletcher-Watson S. {{The Role of the Broader Autism Phenotype and Environmental Stressors in the Adjustment of Siblings of Children with Autism Spectrum Disorders in Taiwan and the United Kingdom}}. {J Autism Dev Disord};2017 (May 13)
The influence of the broader autism phenotype (BAP) on the adjustment of siblings of children with autism has previously been researched mainly in Western cultures. The present research evaluated a diathesis-stress model of sibling adjustment using a questionnaire study including 80 and 75 mother-typically developing sibling dyads in Taiwan and the United Kingdom (UK). UK siblings reported elevated adjustment difficulties compared to the Taiwanese sample and to normative data. Whilst higher BAP levels were generally associated with greater adjustment difficulties, differences were found across cultures and respondents. Although significant diathesis-stress interactions were found, these were in the opposite direction from those predicted by the model, and differed across cultural settings. Implications for culturally-sensitive sibling support are considered.
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21. Tumuluru RV, Corbett-Dick P, Aman MG, Smith T, Arnold LE, Pan X, Buchan-Page KA, Brown NV, Ryan MM, Hyman SL, Hellings J, Williams C, Hollway JA, Lecavalier L, Rice RR, Jr., McAuliffe-Bellin S, Handen BL. {{Adverse Events of Atomoxetine in a Double-Blind Placebo-Controlled Study in Children with Autism}}. {J Child Adolesc Psychopharmacol};2017 (May 16)
OBJECTIVE: Attention-deficit/hyperactivity disorder (ADHD) symptoms, including inattention and over activity, occur in approximately one-third of children with autism spectrum disorder (ASD). We describe the rate and duration of adverse events in a randomized controlled trial of atomoxetine (ATX) and parent training (PT) for ADHD symptoms and noncompliance in children with ASD. METHODS: We conducted a 10-week, double-blind, 2 x 2 trial of ATX and PT with 128 children (ages 5-14) randomized to ATX alone, ATX+PT, placebo+PT, or placebo alone. For 6 weeks, ATX (or placebo) doses were clinically adjusted to a maximum of 1.8 mg/(kg.day) and maintained for an additional 4 weeks. An average of seven PT sessions were conducted in the two PT arms. Adverse events (AEs) were assessed through parent ratings of common symptoms on a seven-point Likert severity scale and through direct interviews with study medical staff. RESULTS: ATX was associated with decreased appetite and fatigue, but was otherwise well tolerated. Most reported AEs lasted 4 weeks or less. Unlike reports with typically developing (TD) children, there were no concerns with QTc changes or suicidal ideation. CONCLUSIONS: This study extends the findings of previous studies of ATX in ASD by documenting that the type of AEs was similar to that of TD children, with no significant safety concerns.
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22. Weiner DJ, Wigdor EM, Ripke S, Walters RK, Kosmicki JA, Grove J, Samocha KE, Goldstein JI, Okbay A, Bybjerg-Grauholm J, Werge T, Hougaard DM, Taylor J, Skuse D, Devlin B, Anney R, Sanders SJ, Bishop S, Mortensen PB, Borglum AD, Smith GD, Daly MJ, Robinson EB. {{Polygenic transmission disequilibrium confirms that common and rare variation act additively to create risk for autism spectrum disorders}}. {Nat Genet};2017 (May 15)
Autism spectrum disorder (ASD) risk is influenced by common polygenic and de novo variation. We aimed to clarify the influence of polygenic risk for ASD and to identify subgroups of ASD cases, including those with strongly acting de novo variants, in which polygenic risk is relevant. Using a novel approach called the polygenic transmission disequilibrium test and data from 6,454 families with a child with ASD, we show that polygenic risk for ASD, schizophrenia, and greater educational attainment is over-transmitted to children with ASD. These findings hold independent of proband IQ. We find that polygenic variation contributes additively to risk in ASD cases who carry a strongly acting de novo variant. Lastly, we show that elements of polygenic risk are independent and differ in their relationship with phenotype. These results confirm that the genetic influences on ASD are additive and suggest that they create risk through at least partially distinct etiologic pathways.
