1. {{Circumcision and autism}}. {Arch Dis Child}. 2015.
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2. A DEM, Eigsti IM. {{The art of common ground: emergence of a complex pragmatic language skill in adolescents with autism spectrum disorders}}. {J Child Lang}. 2015: 1-38.
ABSTRACT Deficits in pragmatic language are central to autism spectrum disorder (ASD). Here we investigate common ground, a pragmatic language skill in which speakers adjust the contents of their speech based on their interlocutor’s perceived knowledge, in adolescents with ASD and typical development (TD), using an experimental narrative paradigm. Consistent with prior research, TD participants produced shorter narrations when they shared knowledge with an interlocutor, an effect not observed at the group level in ASD. This effect was unrelated to general skills such as IQ or receptive vocabulary. In ASD, the effect was correlated with age and symptom severity: older and less severely affected participants did shorten their narratives. Several metrics (including explicit references to common ground, speech disfluencies, and communicative quality ratings) suggested that, although adolescents with ASD did not show implicit reductions in their narrative length, they were aware of common ground, and communicated differently in its presence.
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3. Al-Mamari W, Al-Saegh A, Al-Kindy A, Bruwer Z, Al-Murshedi F, Al-Thihli K. {{Diagnostic Yield of Chromosomal Microarray Analysis in a Cohort of Patients with Autism Spectrum Disorders from a Highly Consanguineous Population}}. {J Autism Dev Disord}. 2015.
Autism Spectrum Disorders are a complicated group of disorders characterized with heterogeneous genetic etiologies. The genetic investigations for this group of disorders have expanded considerably over the past decade. In our study we designed a tired approach and studied the diagnostic yield of chromosomal microarray analysis on patients referred to the Genetic and Developmental Medicine clinic in Sultan Qaboos University in Oman for autism spectrum disorders in a highly consanguineous population. Copy number variants were seen in 27 % of our studied cohort of patients and it was strongly associated with dysmorphic features and congenital anomalies.
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4. Bemben MA, Nguyen QA, Wang T, Li Y, Nicoll RA, Roche KW. {{Autism-associated mutation inhibits protein kinase C-mediated neuroligin-4X enhancement of excitatory synapses}}. {Proc Natl Acad Sci U S A}. 2015; 112(8): 2551-6.
Autism spectrum disorders (ASDs) comprise a highly heritable, multifarious group of neurodevelopmental disorders, which are characterized by repetitive behaviors and impairments in social interactions. Point mutations have been identified in X-linked Neuroligin (NLGN) 3 and 4X genes in patients with ASDs and all of these reside in their extracellular domains except for a single point mutation in the cytoplasmic domain of NLGN4X in which an arginine is mutated to a cysteine (R704C). Here we show that endogenous NLGN4X is robustly phosphorylated by protein kinase C (PKC) at T707, and R704C completely eliminates T707 phosphorylation. Endogenous NLGN4X is intensely phosphorylated on T707 upon PKC stimulation in human neurons. Furthermore, a phospho-mimetic mutation at T707 has a profound effect on NLGN4X-mediated excitatory potentiation. Our results now establish an important interplay between a genetic mutation, a key posttranslational modification, and robust synaptic changes, which can provide insights into the synaptic dysfunction of ASDs.
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5. Chen E, Joseph S. {{Fragile X mental retardation protein: A paradigm for translational control by RNA-binding proteins}}. {Biochimie}. 2015.
Translational control is a common mechanism used to regulate gene expression and occur in bacteria to mammals. Typically in translational control, an RNA-binding protein binds to a unique sequence in the mRNA to regulate protein synthesis by the ribosomes. Alternatively, a protein may bind to or modify a translation factor to globally regulate protein synthesis by the cell. Here, we review translational control by the fragile X mental retardation protein (FMRP), the absence of which causes the neurological disease, fragile X syndrome (FXS).
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6. Duerden EG, Taylor MJ, Lee M, McGrath PA, Davis KD, Roberts W. {{Decreased sensitivity to thermal stimuli in adolescents with autism spectrum disorder: Relation to symptomatology and cognitive ability}}. {J Pain}. 2015.
Social communication deficits and repetitive behaviours are established characteristics of autism spectrum disorder (ASD) and the focus of considerable study. Alterations in pain sensitivity have been widely noted clinically, but remain understudied and poorly understood. The ASD population may be at greater risk for having their pain undermanaged, especially in children with impaired cognitive ability and limited language skills, which may affect their ability to express pain. Given that sensitivity to noxious stimuli in adolescents with ASD has not been systematically assessed, here we measured warm and cool detection thresholds (WDT and CDT) and heat and cold pain threshold (HPT and CPT) levels in 20 high-functioning adolescents with ASD and 55 typically-developing individuals using a method-of-limits quantitative sensory testing protocol. Adolescents with ASD had a loss of sensory function for thermal detection (p<0.001, both WDT and CDT), but not pain threshold (p>0.05, both HPT and CPT) in comparison to controls, with no evidence for significant age or sex effects (p>0.05). Intelligence quotients (IQ) and symptomatology were significantly correlated with a loss of some types of thermal perception in the ASD population (p<0.05, WDT, CDT, HPT). Decreased thermal sensitivity in adolescents with ASD may be associated with cognitive impairments relating to attentional deficits. In conclusion, our findings are consistent with previous literature indicating an association between thermal perception and cortical thickness in brain regions involved in somatosensation, cognition and salience detection. Further brain-imaging research is needed to determine the neural mechanisms underlying thermal perceptual deficits in adolescents with ASD. PERSPECTIVE: We report quantitative evidence for altered thermal thresholds in adolescents with autism spectrum disorder. Reduced sensitivity to warm, cool and heat pain were related to impaired cognitive ability. Caregivers and clinicians should consider cognitive ability when assessing and managing pain in adolescents with autism spectrum disorder.
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7. Jaber M. {{Autism is (Also) a movement disorder}}. {Mov Disord}. 2015.
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8. Jameel L, Vyas K, Bellesi G, Cassell D, Channon S. {{Great Expectations: The Role of Rules in Guiding Pro-social Behaviour in Groups with High Versus Low Autistic Traits}}. {J Autism Dev Disord}. 2015.
Measuring autistic traits in the general population has proven sensitive for examining cognition. The present study extended this to pro-social behaviour, investigating the influence of expectations to help others. A novel task describing characters in need of help was administered to students scoring high versus low on the Autism-Spectrum Quotient. Scenarios had two variants, describing either a ‘clear-cut’ or ‘ambiguous’ social rule. Participants with high versus low autistic traits were less pro-social and sympathetic overall towards the characters. The groups’ ratings of characters’ expectations were comparable, but those with high autistic traits provided more rule-based rationales in the clear-cut condition. This pattern of relatively intact knowledge in the context of reduced pro-social behaviour has implications for social skill training programmes.
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9. Jo H, Schieve LA, Rice CE, Yeargin-Allsopp M, Tian LH, Blumberg SJ, Kogan MD, Boyle CA. {{Age at Autism Spectrum Disorder (ASD) Diagnosis by Race, Ethnicity, and Primary Household Language Among Children with Special Health Care Needs, United States, 2009-2010}}. {Matern Child Health J}. 2015.
We examined prevalence of diagnosed autism spectrum disorder (ASD) and age at diagnosis according to child’s race/ethnicity and primary household language. From the 2009-2010 National Survey of Children with Special Health Care Needs, we identified 2729 3-17-year-old US children whose parent reported a current ASD diagnosis. We compared ASD prevalence, mean diagnosis age, and percentage with later diagnoses (>/=5 years) across racial/ethnic/primary household language groups: non-Hispanic-white, any language (NHW); non-Hispanic-black, any language (NHB); Hispanic-any-race, English (Hispanic-English); and Hispanic-any-race, other language (Hispanic-Other). We assessed findings by parent-reported ASD severity level and adjusted for family sociodemographics. ASD prevalence estimates were 15.3 (NHW), 10.4 (NHB), 14.1 (Hispanic-English), and 5.2 (Hispanic-Other) per 1000 children. Mean diagnosis age was comparable across racial/ethnic/language groups for 3-4-year-olds. For 5-17-year-olds, diagnosis age varied by race/ethnicity/language and also by ASD severity. In this group, NHW children with mild/moderate ASD had a significantly higher proportion (50.8 %) of later diagnoses than NHB (33.5 %) or Hispanic-Other children (18.0 %). However, NHW children with severe ASD had a comparable or lower (albeit non-significant) proportion (16.4 %) of later diagnoses than NHB (37.8 %), Hispanic-English (30.8 %), and Hispanic-Other children (12.0 %). While NHW children have comparable ASD prevalence and diagnosis age distributions as Hispanic-English children, they have both higher prevalence and proportion of later diagnoses than NHB and Hispanic-Other children. The diagnosis age findings were limited to mild/moderate cases only. Thus, the prevalence disparity might be primarily driven by under-representation (potentially under-identification) of older children with mild/moderate ASD in the two minority groups.
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10. Johnston SB, Raines RT. {{Conformational Stability and Catalytic Activity of PTEN Variants Linked to Cancers and Autism Spectrum Disorders}}. {Biochemistry}. 2015; 54(7): 1576-82.
Phosphoinositides are membrane components that play critical regulatory roles in mammalian cells. The enzyme PTEN, which catalyzes the dephosphorylation of the phosphoinositide PIP3, is damaged in most sporadic tumors. Mutations in the PTEN gene have also been linked to autism spectrum disorders and other forms of delayed development. Here, human PTEN is shown to be on the cusp of unfolding under physiological conditions. Variants of human PTEN linked to somatic cancers and disorders on the autism spectrum are shown to be impaired in their conformational stability, catalytic activity, or both. Those variants linked only to autism have activity higher than the activity of those linked to cancers. PTEN-L, which is a secreted trans-active isoform, has conformational stability greater than that of the wild-type enzyme. These data indicate that PTEN is a fragile enzyme cast in a crucial role in cellular metabolism and suggest that PTEN-L is a repository for a critical catalytic activity.
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11. Kosmicki JA, Sochat V, Duda M, Wall DP. {{Searching for a minimal set of behaviors for autism detection through feature selection-based machine learning}}. {Transl Psychiatry}. 2015; 5: e514.
Although the prevalence of autism spectrum disorder (ASD) has risen sharply in the last few years reaching 1 in 68, the average age of diagnosis in the United States remains close to 4-well past the developmental window when early intervention has the largest gains. This emphasizes the importance of developing accurate methods to detect risk faster than the current standards of care. In the present study, we used machine learning to evaluate one of the best and most widely used instruments for clinical assessment of ASD, the Autism Diagnostic Observation Schedule (ADOS) to test whether only a subset of behaviors can differentiate between children on and off the autism spectrum. ADOS relies on behavioral observation in a clinical setting and consists of four modules, with module 2 reserved for individuals with some vocabulary and module 3 for higher levels of cognitive functioning. We ran eight machine learning algorithms using stepwise backward feature selection on score sheets from modules 2 and 3 from 4540 individuals. We found that 9 of the 28 behaviors captured by items from module 2, and 12 of the 28 behaviors captured by module 3 are sufficient to detect ASD risk with 98.27% and 97.66% accuracy, respectively. A greater than 55% reduction in the number of behaviorals with negligible loss of accuracy across both modules suggests a role for computational and statistical methods to streamline ASD risk detection and screening. These results may help enable development of mobile and parent-directed methods for preliminary risk evaluation and/or clinical triage that reach a larger percentage of the population and help to lower the average age of detection and diagnosis.
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12. McEvilly M, Wicks S, Dalman C. {{Sick Leave and Work Participation Among Parents of Children with Autism Spectrum Disorder in the Stockholm Youth Cohort: A Register Linkage Study in Stockholm, Sweden}}. {J Autism Dev Disord}. 2015.
This population-based register study explored the association between having a child with/without autism spectrum disorder (ASD) and parental sick leave and work participation. Parents of children with ASD living in Stockholm, Sweden in 2006 were more likely to be on sick leave, not in the labor force, or earning low income when compared to parents who did not have a child with ASD and these results remained after adjusting for familial socioeconomic factors and parental psychiatric care. Sick leave among parents was associated with having a child with ASD without intellectual disability (ID) but not ASD with ID. Although Sweden has policies helping families with children with ASD this study suggests that there exist unmet needs among these parents.
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13. Mohd Roffeei SH, Abdullah N, Basar SK. {{Seeking social support on Facebook for children with Autism Spectrum Disorders (ASDs)}}. {Int J Med Inform}. 2015.
PURPOSE: This study examined the types of social support messages exchanged between parents and/or caregivers of children with Autism Spectrum Disorders (ASDs) who communicate via Facebook (FB); it studies two autism support groups: Autism Malaysia (AM) and Autism Children Club (ACA). METHOD: A total of 3637 messages including both postings (381) and comments (3256) were gathered from August to November 2013. The study employed a deductive content-analysis approach. The qualitative data were analyzed for social support themes adapted from the Social Support Behavior Code (SSBC). Before collecting the data, email was sent to the FB groups’ moderators to gain formal consent from the members. RESULT: The finding indicated that the highest percentage of messages offered dealt with Informational support (30.7%) followed by Emotional support (27.8%). Network and Esteem support messages were responsible for 20.97% and 20.2%, respectively. Tangible Assistance was the least frequent category (0.4%). A majority of these messages discussed and addressed challenges and difficulties associated with caring and raising ASD children, as well as issues such as children’s social lives and self-care routines. CONCLUSION: Understandings of how FB is used to seek social support could impact supporting and maintaining effective communication among parents and/or caregivers of children with ASDs. This information could also improve approaches used by health professionals in developing, improving and evaluating social support systems for parents/caregivers.
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14. Naviaux JC, Wang L, Li K, Bright AT, Alaynick WA, Williams KR, Powell SB, Naviaux RK. {{Antipurinergic therapy corrects the autism-like features in the Fragile X (Fmr1 knockout) mouse model}}. {Mol Autism}. 2015; 6: 1.
BACKGROUND: This study was designed to test a new approach to drug treatment of autism spectrum disorders (ASDs) in the Fragile X (Fmr1) knockout mouse model. METHODS: We used behavioral analysis, mass spectrometry, metabolomics, electron microscopy, and western analysis to test the hypothesis that the disturbances in social behavior, novelty preference, metabolism, and synapse structure are treatable with antipurinergic therapy (APT). RESULTS: Weekly treatment with the purinergic antagonist suramin (20 mg/kg intraperitoneally), started at 9 weeks of age, restored normal social behavior, and improved metabolism, and brain synaptosomal structure. Abnormalities in synaptosomal glutamate, endocannabinoid, purinergic, and IP3 receptor expression, complement C1q, TDP43, and amyloid beta precursor protein (APP) were corrected. Comprehensive metabolomic analysis identified 20 biochemical pathways associated with symptom improvements. Seventeen pathways were shared with human ASD, and 11 were shared with the maternal immune activation (MIA) model of ASD. These metabolic pathways were previously identified as functionally related mediators of the evolutionarily conserved cell danger response (CDR). CONCLUSIONS: The data show that antipurinergic therapy improves the multisystem, ASD-like features of both the environmental MIA, and the genetic Fragile X models. These abnormalities appeared to be traceable to mitochondria and regulated by purinergic signaling.
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15. Pantelis PC, Byrge L, Tyszka JM, Adolphs R, Kennedy DP. {{A specific hypoactivation of right temporo-parietal junction/posterior superior temporal sulcus in response to socially awkward situations in autism}}. {Soc Cogn Affect Neurosci}. 2015.
People with autism spectrum disorders (ASD) often have difficulty comprehending social situations in the complex, dynamic contexts encountered in the real world. To study the social brain under conditions which approximate naturalistic situations, we measured brain activity with fMRI while participants watched a full-length episode of the sitcom The Office. Having quantified the degree of social awkwardness at each moment of the episode, as judged by an independent sample of controls, we found that both individuals with ASD and control participants showed reliable activation of several brain regions commonly associated with social perception and cognition (e.g., those comprising the « mentalizing network ») during the more awkward moments. However, individuals with ASD showed less activity than controls in a region near right temporo-parietal junction (RTPJ) extending into the posterior end of the right superior temporal sulcus (RSTS). Further analyses suggested that, despite the free-form nature of the experimental design, this group difference was specific to this RTPJ/RSTS area of the mentalizing network; other regions of interest showed similar activity across groups with respect to both location and magnitude. These findings add support to a body of evidence suggesting that RTPJ/RSTS plays a special role in social processes across modalities and may function atypically in individuals with ASD navigating the social world.
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16. Pucilowska J, Vithayathil J, Tavares EJ, Kelly C, Karlo JC, Landreth GE. {{The 16p11.2 Deletion Mouse Model of Autism Exhibits Altered Cortical Progenitor Proliferation and Brain Cytoarchitecture Linked to the ERK MAPK Pathway}}. {J Neurosci}. 2015; 35(7): 3190-200.
Autism spectrum disorders are complex, highly heritable neurodevelopmental disorders affecting approximately 1 in 100 children. Copy number variations of human chromosomal region 16p11.2 are genetically linked to 1% of autism-related disorders. This interval contains the MAPK3 gene, which encodes the MAP kinase, ERK1. Mutations in upstream elements regulating the ERK pathway are genetically linked to autism and other disorders of cognition including the neuro-cardio-facial cutaneous syndromes and copy number variations. We report that a murine model of human 16p11.2 deletion exhibits a reduction in brain size and perturbations in cortical cytoarchitecture. We observed enhanced progenitor proliferation and premature cell cycle exit, which are a consequence of altered levels of downstream ERK effectors cyclin D1 and p27(Kip1) during mid-neurogenesis. The increased progenitor proliferation and cell cycle withdrawal resulted in premature depletion of progenitor pools, altering the number and frequency of neurons ultimately populating cortical lamina. Specifically, we found a reduced number of upper layer pyramidal neurons and an increase in layer VI corticothalamic projection neurons, reflecting the altered cortical progenitor proliferation dynamics in these mice. Importantly, we observed a paradoxical increase in ERK signaling in mid-neurogenesis in the 16p11.2del mice, which is coincident with the development of aberrant cortical cytoarchitecture. The 16p11.2del mice exhibit anxiety-like behaviors and impaired memory. Our findings provide evidence of ERK dysregulation, developmental abnormalities in neurogenesis, and behavioral impairment associated with the 16p11.2 chromosomal deletion.
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17. Romaniello R, Saettini F, Panzeri E, Arrigoni F, Bassi MT, Borgatti R. {{A de-novo STXBP1 gene mutation in a patient showing the Rett syndrome phenotype}}. {Neuroreport}. 2015.
This study reports on a 9-year-old girl who developed West syndrome and showed clinical features fulfilling the main revised diagnostic criteria for typical Rett syndrome (hand washing, severe cognitive impairment with absence of language, ataxic gait, progressive scoliosis and autistic features). Mutation analyses for methyl-CpG-binding protein 2 (MECP2), cyclin-dependent kinase-like 5 (CDKL5/STK9), ARX and Forkhead box G1 (FOXG1) genes were carried out, with negative results. A known de-novo c.1217G>A missense mutation in exon 14 leading to the substitution of a conserved residue, p.R406H in domain3b of the syntaxin-binding protein 1 (STXBP1) gene, was detected. The STXBP1 gene encodes the syntaxin-binding protein 1, a neuron-specific protein involved in synaptic vesicle release at both glutaminergic and GABAergic synapses. This function is also affected by MECP2 gene mutations, which are known to lead to a decrease in glutamate and GABA receptors’ density. It is possible to speculate that the impairment in synaptic plasticity represents the pathogenic link between MECP2 and STXBP1 gene mutations. On reviewing the clinical features of the reported patients with the same mutation in the STXBP1 gene, it has been observed that poor eye contact, tremour, dyskinesia, head/hand stereotypies and both cognitive and motor progressive deterioration are common symptoms, although never considered as indicative of a Rett syndrome phenotype. In conclusion, the case described here suggests a relationship between the Rett syndrome and the STXBP1 gene not described so far, making the search for STXBP1 gene mutations advisable in patients with Rett syndrome and early onset of epilepsy.
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18. Rutherford MD, Walsh JA, Lee V. {{Brief Report: Infants Developing with ASD Show a Unique Developmental Pattern of Facial Feature Scanning}}. {J Autism Dev Disord}. 2015.
Infants are interested in eyes, but look preferentially at mouths toward the end of the first year, when word learning begins. Language delays are characteristic of children developing with autism spectrum disorder (ASD). We measured how infants at risk for ASD, control infants, and infants who later reached ASD criterion scanned facial features. Development differed across groups. The preference for the eyes region decreased with age in infants who were at risk of ASD. For the control group the change in feature preference was marginally significant for a quadratic model, reflecting a decrease in the preference for eyes at 9 months followed by a recovery. The infants who later reached ASD criterion did not show a significant change across time.
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19. Talbott MR, Nelson CA, Tager-Flusberg H. {{Diary Reports of Concerns in Mothers of Infant Siblings of Children with Autism Across the First Year of Life}}. {J Autism Dev Disord}. 2015.
We examined the home-based concerns reported by mothers of infant siblings of children with autism across the first year of life. At all three ages measured, mothers of high-risk infants were significantly more likely than mothers of low-risk infants to report language, social communication, and restricted and repetitive behavior concerns but were not more likely to report general, medically based concerns. At 6 and 9 months of age, maternal concerns were poorly related to infant or family variables. At 12 months of age, there were moderate correlations between maternal concerns and infant behavior, and concerns were associated with the proband’s autism symptoms and mothers’ concurrent depressive symptoms. These findings highlight the need to examine high-risk infants’ development in the family context.
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20. Turville C, Golden I. {{Autism and vaccination: The value of the evidence base of a recent meta-analysis}}. {Vaccine}. 2015.
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21. van Bon BW, Coe BP, Bernier R, Green C, Gerdts J, Witherspoon K, Kleefstra T, Willemsen MH, Kumar R, Bosco P, Fichera M, Li D, Amaral D, Cristofoli F, Peeters H, Haan E, Romano C, Mefford HC, Scheffer I, Gecz J, de Vries BB, Eichler EE. {{Disruptive de novo mutations of DYRK1A lead to a syndromic form of autism and ID}}. {Mol Psychiatry}. 2015.
Dual-specificity tyrosine-(Y)-phosphorylation-regulated kinase 1 A (DYRK1A) maps to the Down syndrome critical region; copy number increase of this gene is thought to have a major role in the neurocognitive deficits associated with Trisomy 21. Truncation of DYRK1A in patients with developmental delay (DD) and autism spectrum disorder (ASD) suggests a different pathology associated with loss-of-function mutations. To understand the phenotypic spectrum associated with DYRK1A mutations, we resequenced the gene in 7162 ASD/DD patients (2446 previously reported) and 2169 unaffected siblings and performed a detailed phenotypic assessment on nine patients. Comparison of our data and published cases with 8696 controls identified a significant enrichment of DYRK1A truncating mutations (P=0.00851) and an excess of de novo mutations (P=2.53 x 10-10) among ASD/intellectual disability (ID) patients. Phenotypic comparison of all novel (n=5) and recontacted (n=3) cases with previous case reports, including larger CNV and translocation events (n=7), identified a syndromal disorder among the 15 patients. It was characterized by ID, ASD, microcephaly, intrauterine growth retardation, febrile seizures in infancy, impaired speech, stereotypic behavior, hypertonia and a specific facial gestalt. We conclude that mutations in DYRK1A define a syndromic form of ASD and ID with neurodevelopmental defects consistent with murine and Drosophila knockout models.Molecular Psychiatry advance online publication, 24 February 2015; doi:10.1038/mp.2015.5.
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22. Van Eylen L, Boets B, Steyaert J, Wagemans J, Noens I. {{Executive functioning in autism spectrum disorders: influence of task and sample characteristics and relation to symptom severity}}. {Eur Child Adolesc Psychiatry}. 2015.
Impaired executive functioning (EF) has been proposed to underlie symptoms of autism spectrum disorders (ASD). However, insight in the EF profile of ASD individuals is hampered due to task impurity and inconsistent findings. To elucidate these inconsistencies, we investigated the influence of task and sample characteristics on EF in ASD, with an extended test battery designed to reduce task impurity. Additionally, we studied the relation between EF and ASD symptoms. EF (inhibition, cognitive flexibility, generativity, working memory and planning) was measured in open-ended versus structured assessment situations, while controlling for possible confounding EF and non-EF variables. The performance of 50 individuals with ASD was compared with that of 50 age, gender and IQ matched typically developing (TD) individuals. The effects of group (ASD versus TD), age (children versus adolescents) and gender were examined, as well as the correlation between age, IQ, ASD symptoms and EF. Individuals with ASD showed impairments in all EF domains, but deficits were more pronounced in open-ended compared to structured settings. Group differences did not depend on gender and only occasionally on participants’ age. This suggests that inconsistencies between studies largely result from differences in task characteristics and less from differences in the investigated sample features. However, age and IQ strongly correlated with EF, indicating that group differences in these factors should be controlled for when studying EF. Finally, EF correlated with both social and non-social ASD symptoms, but further research is needed to clarify the nature of this relationship.
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23. van Iterson L, de Jong PF, Zijlstra BJ. {{Pediatric epilepsy and comorbid reading disorders, math disorders, or autism spectrum disorders: Impact of epilepsy on cognitive patterns}}. {Epilepsy Behav}. 2015; 44C: 159-68.
INTRODUCTION: In pediatric epilepsy, comorbidities are reported to be frequent. The present study focusedon the cognitive patterns of children with isolated epilepsy, children with isolated neurodevelopmental disorders (reading disorders, math disorders, autism spectrum disorders), and children with epilepsy and these neurodevelopmental disorders as comorbidities. METHODS: Based on two samples of referred children, one with epilepsy, reading disorders, math disorders, or ASDs occurring in « isolation » (n=117) and one with reading disorders, math disorders, and ASDs occurring comorbid with epilepsy (n=171), cognitive patterns were compared. The patterns displayed by verbal and nonverbal abilities from the WISC series were studied with repeated measures ANOVA. Thereafter, an exploratory 2 *3 *2 factorial analysis was done to study the independent contribution of the type of comorbidity and of the presence or absence of epilepsy to the VIQ-PIQ pattern. RESULTS: In isolated epilepsy, a VIQ>PIQ pattern was found, which was not seen in the other disorders. When epilepsy and another disorder co-occurred, patterns were altered. They resembled partly the pattern seen in isolated epilepsy and partly the pattern seen in the isolated neurodevelopmental disorder. In comorbid reading disorders, the VIQ>PIQ pattern was mitigated; in comorbid math disorders, it was exacerbated. In comorbid ASDs, no clear pattern emerged. In the presence of epilepsy, patterns characteristic of isolated disorders appeared systematically shifted toward relatively lowered performance abilities or relatively spared verbal abilities. The similar « impact » exerted by epilepsy on the patterns of the various conditions suggested shared mechanisms.
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24. Wong LM, Tassone F, Rivera SM, Simon TJ. {{Temporal dynamics of attentional selection in adult male carriers of the fragile X premutation allele and adult controls}}. {Front Hum Neurosci}. 2015; 9: 37.
Carriers of the fragile X premutation allele (fXPCs) have an expanded CGG trinucleotide repeat size within the FMR1 gene and are at increased risk of developing fragile x-associated tremor/ataxia syndrome (FXTAS). Previous research has shown that male fXPCs with FXTAS exhibit cognitive decline, predominantly in executive functions such as inhibitory control and working memory. Recent evidence suggests fXPCs may also exhibit impairments in processing temporal information. The attentional blink (AB) task is often used to examine the dynamics of attentional selection, but disagreements exist as to whether the AB is due to excessive or insufficient attentional control. In this study, we used a variant of the AB task and neuropsychological testing to explore the dynamics of attentional selection, relate AB performance to attentional control, and determine whether fXPCs exhibited temporal and/or attentional control impairments. Participants were adult male fXPCs, aged 18-48 years and asymptomatic for FXTAS (n = 19) and age-matched male controls (n = 20). We found that fXPCs did not differ from controls in the AB task, indicating that the temporal dynamics of attentional selection were intact. However, they were impaired in the letter-number sequencing task, a test of executive working memory. In the combined fXPC and control group, letter-number sequencing performance correlated positively with AB magnitude. This finding supports models that posit the AB is due to excess attentional control. In our two-pronged analysis approach, in control participants we replicated a previously observed effect and demonstrated that it persists under more stringent theoretical constraints, and we enhance our understanding of fXPCs by demonstrating that at least some aspects of temporal processing may be spared.
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25. Yan CL, Zhang J, Hou Y. {{Decreased plasma levels of lipoxin A4 in children with autism spectrum disorders}}. {Neuroreport}. 2015.
The aim of this study was to evaluate the plasma levels of lipoxin A4 (LXA4), a mediator involved in the resolution of inflammation in Chinese children with autism spectrum disorders (ASD). From January 2013 to June 2014, a total of 150 children (75 confirmed ASD cases and 75 their age-matched and sex-matched control cases) participated in this study after consent was obtained from their parents. Clinical information was collected. Plasma levels of LXA4 were measured at baseline. The severity of ASD was assessed at admission using the Childhood Autism Rating Scale total score. The results indicated that the mean plasma levels of LXA4 were significantly lower in autistic children compared with the normal children (P<0.0001). There was a significant negative relationship between circulating LXA4 levels and severity of autism evaluated by Childhood Autism Rating Scale scores (P=0.006) after adjustment for the possible covariates. On the basis of the receiver operating characteristic curve, the optimal cutoff value of plasma LXA4 levels as an indicator for an auxiliary diagnosis of ASD was projected to be 81.5 pg/ml, which yielded a sensitivity of 90.7% and a specificity of 76.0%, with the area under the curve at 0.911 (95% confidence interval, 0.867-0.955). These results suggested that autistic children had lower plasma LXA4 levels, suggesting an increased susceptibility to recurring inflammation in these samples.
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26. Young LJ, Barrett CE. {{Neuroscience. Can oxytocin treat autism?}}. {Science}. 2015; 347(6224): 825-6.
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27. Zantomio D, Chana G, Laskaris L, Testa R, Everall I, Pantelis C, Skafidas E. {{Convergent evidence for mGluR5 in synaptic and neuroinflammatory pathways implicated in ASD}}. {Neurosci Biobehav Rev}. 2015.
The pathogenesis of Autism spectrum disorder (ASD), a serious neurodevelopmental disorder, is poorly understood. We review evidence for alterations in glutamatergic signalling in the aetiology of ASD, with a focus on the metabotropic glutamate receptor-5 (mGluR5). mGluR5 signalling is important for synapse formation, neuroplasticity and long term potentiation as well as neuroprotection and has been shown to have a regulatory role in neuroinflammation. Evidence for neuroinflammation in ASD is supported by increase in pro-inflammatory cytokines in the blood and cerebrospinal fluid (CSF) and increased number and activation of microglia in postmortem dorsolateral prefrontal cortex (DLPFC). mGlur5 signalling has also been shown to downregulate microglial activation. Therefore, we focus on the mGluR5 as a potential unifying explanation for synapse alteration and neuroinflammation seen in ASD. Data from mGluR5 knockout mouse models, syndromic and non syndromic forms of ASD are discussed in relation to how alterations in mGluR5 are associated with ASD symptoms. This review supports altered mGluR5 functioning as a convergent point in ASD pathogenesis and indicates more research is warranted into mGluR5 as a potential therapeutic target.
