Pubmed du 13/04/17

jeudi 13 avril 2017

1. Barber C. Meeting the healthcare needs of adults on the autism spectrum. Br J Nurs ;2017 (Apr 13) ;26(7):420-425.

People with Asperger’s syndrome/high functioning autism (AS/HFA) are just as likely to experience the full range of health conditions and needs as ’neurotypicals’, people who do not have AS/HFA. However, many people with AS/HFA fall between the cracks of health service design and provision as they do not receive support from learning disabilities or mental health services. This article highlights the need for a comprehensive review of healthcare provision, led by people on the autism spectrum.

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2. Barnett JP. Intersectional harassment and deviant embodiment among Autistic adults : (dis)ability, gender and sexuality. Cult Health Sex ;2017 (Apr 12):1-15.

Harassment scholarship increasingly attends to the intersectional nature of harassment and its function within systems of domination. However, little of this work includes disability. In-depth interviews with 24 adults on the autism spectrum in the USA demonstrate the intersections of gender, sexuality and (dis)ability in the construction of deviant embodiments as targets for harassment. These intersections also shape how participants made sense of these experiences of violence. Participants’ disability characteristics were often read as gender or sexual variance, with harassers relying on sexist and heterosexist constructs to frighten, demean or humiliate them for disability characteristics. Participant experiences demonstrate the cisgender basis of ’able-bodied’ identity as well as the ’able-bodied’ basis of cisgender and heterosexual identities and experiences. The interdependency of gender, sexuality and (dis)ability embodiment point to how it is critical for scholars and activists to account for the role of gender and heterosexist harassment in ableist oppression and disability harassment in (hetero)sexist oppression, as well as the limits of current US law enforcement structures in providing redress for harassment.

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3. Barone R, Fichera M, De Grandi M, Battaglia M, Lo Faro V, Mattina T, Rizzo R. Familial 18q12.2 deletion supports the role of RNA-binding protein CELF4 in autism spectrum disorders. Am J Med Genet A ;2017 (Apr 13)

Deletion of 18q12.2 is an increasingly recognized condition with a distinct neuropsychiatric phenotype. Twenty-two patients have been described with overlapping neurobehavioral disturbances including developmental delay, intellectual disability of variable degree, seizures, motor coordination disorder, behavioral/emotional disturbances, and autism spectrum disorders. The CUGBP Elav-like family member 4 (CELF4) gene at 18q12.2 encodes a RNA-binding protein that links to RNA subsets involved in pre- and postsynaptic neurotransmission including almost 30% of potential autism-related genes. Haploinsufficiency of CELF4 was associated with an autism or autistic behavior diagnosis in two adult patients with de novo 18q12.2 deletions. We report on a girl and her mildly affected mother with a 275 kb deletion at 18q12.2 involving CELF4 and KIAA1328 whose disruption is not associated with any known disease. The child was diagnosed with syndromic intellectual disability and autism at 6 years of age. Her mother had minor dysmorphisms, mild intellectual disability, and autistic behavior. The deleted region reported in this family is one of the smallest so far reported at 18q12.2. This is also the first full clinical description of maternally inherited CELF4 haploinsufficiency. The present study refines the molecular and neuropsychiatric phenotype associated with 18q12.2 deletion leading to CELF4 haploinsufficiency and provides evidence for a role for CELF4 in brain development and autism spectrum disorders.

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4. Ben-Itzchak E, Kirzon M, Peled N, Zachor DA. Coherence and content of relating emotions to life events in autism spectrum disorder and typical development : a cross-sectional age study. J Abnorm Child Psychol ;2017 (Apr 12)

Understanding one’s own emotions is an important part of social-emotional development in early childhood. Few studies have looked at the ability of children with autism spectrum disorder (ASD) to relate their own emotions to previous life events. Our previous study showed that the description of events that elicited specific emotions is qualitatively and quantitatively different in ASD in comparison to typically developing (TD) pre-adolescents. The current study evaluated differences in coherence and content of responses to questions on emotions in ASD and TD in two age groups. The evaluation was based on the section on Emotions of the Autism Diagnostic Observation Schedule Module 3 test. The study included 96 boys, 48 diagnosed with ASD (IQ>/=85) and 48 TD children, divided into younger (6:0-8:0y) and older (8:2-11:0y) groups. Young TD children were able to give coherent responses to questions on experiences that evoked basic emotions. Children with ASD gave fewer coherent responses and more ’no response’ and ’odd’ responses across the examined age range. Only in the TD group was the level of vocabulary associated with the number of coherent statements. TD children gave more responses with content related to interpersonal relationships, self-awareness and social events than children with ASD. Deficits in coherence and content of responses to questions on emotions related to previous life events derive from the core deficits of ASD. The significant quantitative and qualitative gap that exists between ASD and TD may be useful during the diagnostic process of ASD in childhood.

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5. Duy PQ, Budimirovic DB. Fragile X Syndrome : Lessons Learned from the Most Translated Neurodevelopmental Disorder in Clinical Trials. Transl Neurosci ;2017 (Jan) ;8:7-8.

Fragile X syndrome (FXS) is the leading genetic cause of autism spectrum disorder (ASD) and inherited intellectual disability (ID) worldwide. Preclinical successes in understanding the biology of FXS have led to numerous translational attempts in human clinical trials of therapeutics that target the excitatory/inhibitory neural signaling imbalances thought to underlie FXS. Despite the preclinical success story, the negative results of the human clinical trials have been deemed to be at least in part disappointing by the field. In this commentary, we contend that such negative studies results in clinical trials may actually propel the FXS field forward by serving as important lessons for designing and implementing improved future clinical trials such that can objectively assess the full range of responses to new therapeutics.

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6. Gillberg C, Fernell E, Kocovska E, Minnis H, Bourgeron T, Thompson L, Allely CS. The role of cholesterol metabolism and various steroid abnormalities in autism spectrum disorders : A hypothesis paper. Autism Res ;2017 (Apr 12)

Based on evidence from the relevant research literature, we present a hypothesis that there may be a link between cholesterol, vitamin D, and steroid hormones which subsequently impacts on the development of at least some of the "autisms" [Coleman & Gillberg]. Our hypothesis, driven by the peer reviewed literature, posits that there may be links between cholesterol metabolism, which we will refer to as "steroid metabolism" and findings of steroid abnormalities of various kinds (cortisol, testosterone, estrogens, progesterone, vitamin D) in autism spectrum disorder (ASD). Further research investigating these potential links is warranted to further our understanding of the biological mechanisms underlying ASD. Autism Res 2017. (c) 2017 The Authors Autism Research published by Wiley Periodicals, Inc. on behalf of International Society for Autism Research.

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7. Gillespie-Lynch K, Kapp SK, Brooks PJ, Pickens J, Schwartzman B. Whose Expertise Is It ? Evidence for Autistic Adults as Critical Autism Experts. Front Psychol ;2017 ;8:438.

Autistic and non-autistic adults’ agreement with scientific knowledge about autism, how they define autism, and their endorsement of stigmatizing conceptions of autism has not previously been examined. Using an online survey, we assessed autism knowledge and stigma among 636 adults with varied relationships to autism, including autistic people and nuclear family members. Autistic participants exhibited more scientifically based knowledge than others. They were more likely to describe autism experientially or as a neutral difference, and more often opposed the medical model. Autistic participants and family members reported lower stigma. Greater endorsement of the importance of normalizing autistic people was associated with heightened stigma. Findings suggest that autistic adults should be considered autism experts and involved as partners in autism research.

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8. Janke V, Perovic A. Contrasting Complement Control, Temporal Adjunct Control and Controlled Verbal Gerund Subjects in ASD : The Role of Contextual Cues in Reference Assignment. Front Psychol ;2017 ;8:448.

This study examines two complex syntactic dependencies (complement control and sentence-final temporal adjunct control) and one pragmatic dependency (controlled verbal gerund subjects) in children with ASD. Sixteen high-functioning (HFA) children (aged 6-16) with a diagnosis of autism and no language impairment, matched on age, gender and non-verbal MA to one TD control group, and on age, gender and verbal MA to another TD control group, undertook three picture-selection tasks. Task 1 measured their base-line interpretations of the empty categories (ec). Task 2 preceded these sentence sets with a weakly established topic cueing an alternative referent and Task 3 with a strongly established topic cueing an alternative referent. In complement control (Ron persuaded Hermione ec to kick the ball) and sentence-final temporal adjunct control (Harry tapped Luna while ec feeding the owl), the reference of the ec is argued to be related obligatorily to the object and subject respectively. In controlled verbal-gerund subjects (VGS) (ec Rowing the boat clumsily made Luna seasick), the ec’s reference is resolved pragmatically. Referent choices across the three tasks were compared. TD children chose the object uniformly in complement control across all tasks but in adjunct control, preferences shifted toward the object in Task 3. In controlled VGSs, they exhibited a strong preference for an internal-referent interpretation in Task 1, which shifted in the direction of the cues in Tasks 2 and 3. HFA children gave a mixed performance. They patterned with their TD counterparts on complement control and controlled VGSs but performed marginally differently on adjunct control : no TD groups were influenced by the weakly established topic in Task 2 but all groups were influenced by the strongly established topic in Task 3. HFA children were less influenced than the TD children, resulting in their making fewer object choices overall but revealing parallel patterns of performance. In this first study of three sub-types of control in ASD, we demonstrate that HFA children consult the same pragmatic cues to the same degree as TD children, in spite of the diverse pragmatic deficits reported for this population.

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9. Jitlina K, Zumbo B, Mirenda P, Ford L, Bennett T, Georgiades S, Waddell C, Smith IM, Volden J, Duku E, Zwaigenbaum L, Szatmari P, Vaillancourt T, Elsabbagh M. Psychometric Properties of the Spence Children’s Anxiety Scale : Parent Report in Children with Autism Spectrum Disorder. J Autism Dev Disord ;2017 (Apr 13)

Although anxiety is frequently reported in children with autism spectrum disorder (ASD), existing anxiety scales are often psychometrically inappropriate for this population. This study examined the internal structure, reliability, convergent and discriminant validity of the Spence Children’s Anxiety Scale-Parent Report (SCAS-P ; Spence 1999) in 238 school-aged children with ASD. While confirmatory factor analysis did not support the original six-correlated-factor structure, structural support as well as acceptable internal consistency and convergent validity was found for Generalized Anxiety, Separation Anxiety, Panic, and Agoraphobia subscales. Use of the SCAS-P in its original form for assessment in children with ASD was not supported. However, four subscales showed viability, and may benefit re-analyses of existing SCAS-P data and future scale adaptations for research and clinical purposes.

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10. Jones RM, Carberry C, Hamo A, Lord C. Placebo-like response in absence of treatment in children with Autism. Autism Res ;2017 (Apr 12)

Caregiver report is the most common measure of change in pediatric psychiatry. Yet, placebo response rates pose significant challenges to reliably detect a treatment response. The present study simulated an eight-week clinical trial protocol for Autism Spectrum Disorder (ASD) for the purpose of testing the feasibility and validity of several outcome measures. Twenty caregivers answered questions about their child’s behavior on their smartphone each week and completed a battery of paper questionnaires during weeks one and eight. No treatment was administered. Caregivers reported a significant decrease in problem behaviors on the Aberrant Behavior Checklist (ABC) (29% decrease) and general ASD behaviors on the Social Responsiveness Scale (SRS) (7% decrease). There was also a trend of behavior improvement from smartphone questions but no significant changes in clinical ratings of core diagnostic features of ASD. Participation in a comprehensive protocol in the absence of a particular treatment significantly influenced how caregivers perceived the severity of their children’s problem behaviors. These placebo-like effects represent substantial challenges for randomized controlled trials (RCTs) that use treatment as usual and have implications for future behavioral and pharmacological treatment trial designs. Autism Res 2017. (c) 2017 International Society for Autism Research, Wiley Periodicals, Inc.

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11. Kharrat M, Kamoun Y, Kamoun F, Ellouze E, Maalej M, Fendri-Kriaa N, Ammar-Keskes L, Belghith N, Gargouri A, Triki C, Fakhfakh F. Clinical, Molecular, and Computational Analysis in Patients With a Novel Double Mutation and a New Synonymous Variant in MeCP2 : Report of the First Missense Mutation Within the AT-hook1 Cluster in Rett Syndrome. J Child Neurol ;2017 (Jan 01):883073817701622.

Rett syndrome is an X-linked neurodevelopmental disorder, primarily caused by MECP2 mutations. In this study, clinical, molecular and bioinformatics analyses were performed in Rett patients to understand the relationship between MECP2 mutation type and the clinical severity. Two double MeCP2 mutations were detected : a novel one (p.G185 V in cis with p.R255X) in P1 and a known one (p.P179 S in cis with p.R255X) in P2. Besides, a novel synonymous mutation (c.807C>T ; p.G269G), which could affect mRNA splicing, was identified in P3. The results from clinical severity analysis have shown that P1 was more severely affected than P2 with CSS being 35 and 14, respectively. Therefore, the phenotypic variability in P1 and P2 could be explained by the potential pathogenic effect of the RTT-causing missense mutation p.G185 V in the AT-hook1. In conclusion, clinical, molecular, and in silico investigations in the studied patients have been proven to be substantial for the genotype-phenotype correlation.

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12. Khetrapal N, Thornton R. C-Command in the Grammars of Children with High Functioning Autism. Front Psychol ;2017 ;8:402.

A recent study questioned the adherence of children with Autism Spectrum Disorders (ASD) to a linguistic constraint on the use of reflexive pronouns (Principle A) in sentences like Bart’s dad is touching himself. This led researchers to question whether children with ASD are able to compute the hierarchical structural relationship of c-command, and raised the possibility that the children rely on a linear strategy for reference assignment. The current study investigates the status of c-command in children with ASD by testing their interpretation of sentences like (1) and (2) that tease apart use of c-command and a linear strategy for reference assignment. The girl who stayed up late will not get a dime or a jewel (C-command)The girl who didn’t go to sleep will get a dime or a jewel (Non C-command) These examples both contain negation (not or didn’t) and disjunction (or). In (1), negation c-commands the disjunction phrase, yielding a conjunctive entailment. This gives rise to the meaning that the girl who stayed up late won’t get a dime and she won’t get a jewel. In (2), negation is positioned inside a relative clause and it does not c-command disjunction. Therefore, no conjunctive entailment follows. Thus, (2) is true if the girl just gets a dime or just a jewel, or possibly both. If children with ASD lack c-command, then (1) will not give rise to a conjunctive entailment. In this case, children might rely on a linear strategy for reference assignment. Since negation precedes disjunction in both (1) and (2), they might be interpreted in a similar manner. Likewise, children who show knowledge of c-command should perform well on sentences governed by Principle A. These hypotheses were tested in experiments with 12 Australian children with HFA, aged 5 ;4 to 12 ;7, and 12 typically-developing controls, matched on non-verbal IQ. There was no significant difference in the pattern of responses by children with HFA and the control children on either (1) and (2) or the Principle A sentences. The findings provide preliminary support for the proposal that knowledge of c-command and Principle A is intact in HFA children.

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13. Li J, Wang L, Yu P, Shi L, Zhang K, Sun ZS, Xia K. Vitamin D-related genes are subjected to significant de novo mutation burdens in autism spectrum disorder. Am J Med Genet B Neuropsychiatr Genet ;2017 (Apr 13)

Vitamin D deficiency is a putative environmental risk factor for autism spectrum disorder (ASD). Besides, de novo mutations (DNMs) play essential roles in ASD. However, it remains unclear whether vitamin D-related genes (VDRGs) carry a strong DNM burden. For the 943 reported VDRGs, we analyzed publicly-available DNMs from 4,327 ASD probands and 3,191 controls. We identified 126 and 44 loss-of-function or deleterious missense mutations in the probands and the controls, respectively, representing a significantly higher DNM burden (p = 1.06 x 10-5 ; odds ratio = 2.11). Specifically, 18 of the VDRGs were found to harbor recurrent functional DNMs in the probands, compared with only one in the controls. In addition, we found that 108 VDRGs with functional DNMs in the probands were significantly more likely to exhibit haploinsufficiency and genic intolerance (p < 0.0078). These VDRGs were also significantly interconnected and co-expressed, and also with other known ASD-risk genes (p < 0.0014), thereby forming a functional network enriched in chromatin modification, transcriptional regulation, and neuronal function. We provide straightforward genetic evidences for the first time that VDRGs with a strong degree of DNM burden in ASD and DNMs of VDRGs could be involved in the mechanism underlying in ASD pathogenesis.

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14. Modyanova N, Perovic A, Wexler K. Grammar Is Differentially Impaired in Subgroups of Autism Spectrum Disorders : Evidence from an Investigation of Tense Marking and Morphosyntax. Front Psychol ;2017 ;8:320.

Deficits in the production of verbal inflection (tense marking, or finiteness) are part of the Optional Infinitive (OI) stage of typical grammatical development. They are also a hallmark of language impairment : they have been used as biomarkers in guiding genetic studies of Specific Language Impairment (SLI), and have also been observed in autism spectrum disorders (ASD). To determine the detailed nature of finiteness abilities in subgroups of ASD [autism with impaired language (ALI) vs. autism with normal language (ALN)], we compared tense marking abilities in 46 children with ALI and 37 children with ALN with that of two groups of nonverbal mental age (MA) and verbal MA-matched typically developing (TD) controls, the first such study described in the literature. Our participants’ performance on two elicited production tasks, probing third-person-singular -s and past tense -ed, from the Rice/Wexler Test of Early Grammatical Impairment (TEGI, Rice and Wexler, 2001), revealed extensive deficits in the ALI group : their ability to correctly mark tense was significantly worse than their much younger TD controls’, and significantly worse than that of the ALN group. In contrast, the ALN group performed similarly to their TD controls. We found good knowledge of the meaning of tense, and of case and agreement, in both ASD groups. Similarly, both ASD groups showed distributions of null or overt subjects with nonfinite and finite verbs in line with those found in young TD children. A key difference, however, was that the ALI group used (rather than simply omitted) the wrong tense in some sentences, a feature not reported in the OI stage for TD or SLI children. Our results confirm a clear distinction in the morphosyntactic abilities of the two subgroups of children with ASD : the language system responsible for finiteness in the ALN group seems to be functioning comparably to that of the TD children, whereas the ALI group, despite showing knowledge of case and agreement, seems to experience an extensive grammatical deficit with respect to finiteness which does not seem to improve with age. Crucially, our ALI group seems to have worse grammatical abilities even than those reported for SLI.

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15. Nickel K, Tebartz van Elst L, Perlov E, Endres D, Muller GT, Riedel A, Fangmeier T, Maier S. Altered white matter integrity in adults with autism spectrum disorder and an IQ >100 : a diffusion tensor imaging study. Acta Psychiatr Scand ;2017 (Apr 13)

OBJECTIVE : White matter (WM) alterations have been reported in children and adults with autism spectrum disorder (ASD). In particular, impaired connectivity of limbic structures may be related to social deficits. Heterogeneous findings could be explained in terms of differences in sample characteristics and methodology. In this context, non-syndromic forms might differ substantially in WM structure from secondary ASD forms. METHOD : In an attempt to recruit a homogeneous study sample, we included adults with high-functioning ASD and an IQ > 100 to decrease the influence of syndromic forms being often associated with cognitive deficits. Diffusion tensor imaging (DTI) was performed in 30 participants with ASD and 30 pairwise-matched controls. Fractional anisotropy (FA) and mean diffusivity (MD) as surrogate imaging markers for WM integrity were calculated. RESULTS : We found a significant FA decrease in the ASD group in the genu and body of the corpus callosum (CC). Increased MD was detected in the subgenual anterior cingulate cortex (sACC). CONCLUSION : The finding of decreased WM integrity in the genu of the CC is in line with earlier studies reporting a decreased number of interhemispheric fibers in the frontal lobe of ASD. Alterations in the sACC might be associated with ’Theory of mind’ deficits.

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16. Sagar A, Pinto D, Najjar F, Guter SJ, Macmillan C, Cook EH. De novo unbalanced translocation (4p duplication/8p deletion) in a patient with autism, OCD, and overgrowth syndrome. Am J Med Genet A ;2017 (Apr 13)

Chromosomal abnormalities, such as unbalanced translocations and copy number variants (CNVs), are found in autism spectrum disorders (ASDs) [Sanders et al. () Neuron 70 : 863-885]. Many chromosomal abnormalities, including sub microscopic genomic deletions and duplications, are missed by G-banded karyotyping or Fragile X screening alone and are picked up by chromosomal microarrays [Shen et al. () Pediatrics 125 : e727-735]. Translocations involving chromosomes 4 and 8 are possibly the second most frequent translocation in humans and are often undetected in routine cytogenetics [Giglio et al. () Circulation 102 : 432-437]. Deletions of 4p16 have been associated with Wolf-Hirschhorn syndrome while 4p16 duplications have been associated with an overgrowth syndrome and mild to moderate mental retardation [Partington et al. () Journal of Medical Genetics 34 : 719-728]. The 8p23.3 region contains the autism candidate gene DLGAP2, which can contribute to autism when disrupted [Marshall et al. () The American Journal of Human Genetics 82 : 477-488] . There has been a case report of a family with autism spectrum disorder (ASD), prominent obsessional behavior, and overgrowth in patients with der (8) t (4 ;8) p (16 ;23) [Partington et al. ()]. This is an independent report of a male patient with autism, obsessive compulsive disorder (OCD), attention-deficit hyperactivity disorder (ADHD), and an overgrowth syndrome, whose de novo unbalanced translocation der (8) t (4 ;8) p (16.1—>ter ; 23.1—>ter) was initially missed by routine cytogenetics but detected with SNP microarray, allowing higher resolution of translocation breakpoints.

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17. Shuffrey LC, Guter SJ, Delaney S, Jacob S, Anderson GM, Sutcliffe JS, Cook EH, Veenstra-VanderWeele J. Is there sexual dimorphism of hyperserotonemia in autism spectrum disorder ?. Autism Res ;2017 (Apr 12)

Approximately 30% of individuals with autism spectrum disorder (ASD) have elevated whole blood serotonin (5-HT) levels. Genetic linkage and association studies of ASD and of whole blood 5-HT levels as a quantitative trait have revealed sexual dimorphism. Few studies have examined the presence of a sex difference on hyperserotonemia within ASD. To assess whether the rate of hyperserotonemia is different in males than in females with ASD, we measured whole blood 5-HT levels in 292 children and adolescents with ASD, the largest sample in which this biomarker has been assessed. Based upon previous work suggesting that hyperserotonemia is more common prior to puberty, we focused our analysis on the 182 pre-pubertal children with ASD. 42% of pre-pubertal participants were within the hyperserotonemia range. In this population, we found that males were significantly more likely to manifest hyperserotonemia than females (P = 0.03). As expected, no significant difference was found in the post-pubertal population. Additional work will be needed to replicate this intriguing finding and to understand whether it could potentially explain differences in patterns of ASD risk between males and females. Autism Res 2017. (c) 2017 International Society for Autism Research, Wiley Periodicals, Inc.

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