1. Abu-Akel AM, Wood SJ, Hansen PC, Apperly IA. {{Perspective-taking abilities in the balance between autism tendencies and psychosis proneness}}. {Proc Biol Sci};2015 (Jun 7);282(1808)
Difficulties with the ability to appreciate the perspective of others (mentalizing) is central to both autism and schizophrenia spectrum disorders. While the disorders are diagnostically independent, they can co-occur in the same individual. The effect of such co-morbidity is hypothesized to worsen mentalizing abilities. The recent influential ‘diametric brain theory’, however, suggests that the disorders are etiologically and phenotypically diametrical, predicting opposing effects on one’s mentalizing abilities. To test these contrasting hypotheses, we evaluated the effect of psychosis and autism tendencies on the perspective-taking (PT) abilities of 201 neurotypical adults, on the assumption that autism tendencies and psychosis proneness are heritable dimensions of normal variation. We show that while both autism tendencies and psychosis proneness induce PT errors, their interaction reduced these errors. Our study is, to our knowledge, the first to observe that co-occurring autistic and psychotic traits can exert opposing influences on performance, producing a normalizing effect possibly by way of their diametrical effects on socio-cognitive abilities. This advances the notion that some individuals may, to some extent, be buffered against developing either illness or present fewer symptoms owing to a balanced expression of autistic and psychosis liability.
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2. Breitenkamp AF, Matthes J, Herzig S. {{Voltage-gated Calcium Channels and Autism Spectrum Disorders}}. {Curr Mol Pharmacol};2015 (May 6)
Autism spectrum disorder is a complex-genetic disease and its etiology is unknown for the majority of cases. So far, more than one hundred different susceptibility genes were detected. Voltage-gated calcium channels are among the candidates linked to autism spectrum disorder by results of genetic studies. Mutations of nearly all pore-forming and some auxiliary subunits of voltage gated calcium channels have been revealed from investigations of autism spectrum disorder patients and populations. Though there are only few electrophysiological characterizations of voltage-gated calcium channel mutations found in autistic patients these studies suggest their functional relevance. In summary, both genetic and functional data suggest a potential role of voltage-gated calcium channels in autism spectrum disorder. Future studies require refinement of the clinical and systems biological concepts of autism spectrum disorder and an appropriate holistic approach at the molecular level, e.g. regarding all facets of calcium channel functions.
3. Brown SS, Stanfield AC. {{Fragile X premutation carriers: A systematic review of neuroimaging findings}}. {J Neurol Sci};2015 (May 15);352(1-2):19-28.
BACKGROUND: Expansion of the CGG repeat region of the FMR1 gene from less than 45 repeats to between 55 and 200 repeats is known as the fragile X premutation. Carriers of the fragile X premutation may develop a neurodegenerative disease called fragile X-associated tremor/ataxia syndrome (FXTAS). Recent evidence suggests that premutation carriers experience other psychiatric difficulties throughout their lifespan. METHODS: Medline, EMBASE and PsychINFO were searched for all appropriate English language studies published between January 1990 and December 2013. 419 potentially relevant articles were identified and screened. 19 articles were included in the analysis. RESULTS: We discuss key structural magnetic resonance imaging (MRI) findings such as the MCP sign and white matter atrophy. Additionally, we discuss how functional MRI results have progressed our knowledge of how FXTAS may manifest, including reduced brain activation during social and memory tasks in multiple regions. LIMITATIONS: This systematic review may have been limited by the search for articles on just 3 scientific databases. Differing techniques and methods of analyses between research groups and primary research articles may have caused differences in results between studies. CONCLUSION: Current MRI studies into the fragile X premutation have been important in the diagnosis of FXTAS and identifying potential pathophysiological mechanisms. Associations with blood based measures have also demonstrated that neurodevelopmental and neurodegenerative aspects of the fragile X premutation could be functionally and pathologically separate. Larger longitudinal studies will be required to investigate these conclusions.
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4. Chakraborty S, Thomas P, Bhatia T, Nimgaonkar VL, Deshpande SN. {{Assessment of severity of autism using the Indian scale for assessment of autism}}. {Indian J Psychol Med};2015 (Apr-Jun);37(2):169-174.
BACKGROUND: The Indian Scale for Assessment of Autism (ISAA) was developed to assess the severity of autism among Indian cases. AIMS: The present study evaluated the ISAA in relation to the Childhood Autism Rating Scale (CARS) and the Developmental Disability- Children Global Assessment Scale (DD-CGAS). MATERIALS AND METHODS: Indian children with ICD 10 diagnoses of Autistic disorder (AD, n = 50), Intellectual Disability (ID, n = 50), Attention Deficit Hyperactivity Disorder (ADHD, n = 26), other psychiatric disorders (PD-N=25) and control children without psychiatric disorders (n = 65) were evaluated using the ISAA, DD-CGAS and the CARS (total n = 216). STATISTICAL ANALYSES: In addition to descriptive statistics and correlation, analysis of variance (ANOVA) was used to assess whether the ISAA scores were significantly different across diagnostic groups. RESULTS: Total ISAA scores were significantly higher among children diagnosed with autistic disorder compared to four other diagnostic groups. Total ISAA scores were significantly correlated with CARS scores and DD-CGAS scores. Groups sub-divided on the basis of recommended ISAA cutoff points of severity showed significant differences in CARS scores. CONCLUSION: The ISAA can thus be used to assess severity of AD among Indian children.
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5. Codina-Sola M, Rodriguez-Santiago B, Homs A, Santoyo J, Rigau M, Aznar-Lain G, Del Campo M, Gener B, Gabau E, Botella MP, Gutierrez-Arumi A, Antinolo G, Perez-Jurado LA, Cusco I. {{Integrated analysis of whole-exome sequencing and transcriptome profiling in males with autism spectrum disorders}}. {Mol Autism};2015;6:21.
BACKGROUND: Autism spectrum disorders (ASD) are a group of neurodevelopmental disorders with high heritability. Recent findings support a highly heterogeneous and complex genetic etiology including rare de novo and inherited mutations or chromosomal rearrangements as well as double or multiple hits. METHODS: We performed whole-exome sequencing (WES) and blood cell transcriptome by RNAseq in a subset of male patients with idiopathic ASD (n = 36) in order to identify causative genes, transcriptomic alterations, and susceptibility variants. RESULTS: We detected likely monogenic causes in seven cases: five de novo (SCN2A, MED13L, KCNV1, CUL3, and PTEN) and two inherited X-linked variants (MAOA and CDKL5). Transcriptomic analyses allowed the identification of intronic causative mutations missed by the usual filtering of WES and revealed functional consequences of some rare mutations. These included aberrant transcripts (PTEN, POLR3C), deregulated expression in 1.7% of mutated genes (that is, SEMA6B, MECP2, ANK3, CREBBP), allele-specific expression (FUS, MTOR, TAF1C), and non-sense-mediated decay (RIT1, ALG9). The analysis of rare inherited variants showed enrichment in relevant pathways such as the PI3K-Akt signaling and the axon guidance. CONCLUSIONS: Integrative analysis of WES and blood RNAseq data has proven to be an efficient strategy to identify likely monogenic forms of ASD (19% in our cohort), as well as additional rare inherited mutations that can contribute to ASD risk in a multifactorial manner. Blood transcriptomic data, besides validating 88% of expressed variants, allowed the identification of missed intronic mutations and revealed functional correlations of genetic variants, including changes in splicing, expression levels, and allelic expression.
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6. Furlano R, Kelley EA, Hall L, Wilson DE. {{Self-perception of competencies in adolescents with autism spectrum disorders}}. {Autism Res};2015 (May 13)
Research has demonstrated that, despite difficulties in multiple domains, children with autism spectrum disorders (ASD) show a lack of awareness of these difficulties. A misunderstanding of poor competencies may make it difficult for individuals to adjust their behaviour in accordance with feedback and may lead to greater impairments over time. This study examined self-perceptions of adolescents with ASD (n = 19) and typically developing (TD) mental-age-matched controls (n = 22) using actual performance on objective academic tasks as the basis for ratings. Before completing the tasks, participants were asked how well they thought they would do (pre-task prediction). After completing each task, they were asked how well they thought they did (immediate post-performance) and how well they would do in the future (hypothetical future post-performance). Adolescents with ASD had more positively biased self-perceptions of competence than TD controls. The ASD group tended to overestimate their performance on all ratings of self-perceptions (pre-task prediction, immediate, and hypothetical future post-performance). In contrast, while the TD group was quite accurate at estimating their performance immediately before and after performing the task, they showed some tendency to overestimate their future performance. Future investigation is needed to systematically examine possible mechanisms that may be contributing to these biased self-perceptions. Autism Res 2015. (c) 2015 International Society for Autism Research, Wiley Periodicals, Inc.
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7. Gockley J, Willsey AJ, Dong S, Dougherty JD, Constantino JN, Sanders SJ. {{The female protective effect in autism spectrum disorder is not mediated by a single genetic locus}}. {Mol Autism};2015;6:25.
BACKGROUND: A 4:1 male to female sex bias has consistently been observed in autism spectrum disorder (ASD). Epidemiological and genetic studies suggest a female protective effect (FPE) may account for part of this bias; however, the mechanism of such protection is unknown. Quantitative assessment of ASD symptoms using the Social Responsiveness Scale (SRS) shows a bimodal distribution unique to females in multiplex families. This leads to the hypothesis that a single, common genetic locus on chromosome X might mediate the FPE and produce the ASD sex bias. Such a locus would represent a major therapeutic target and is likely to have been missed by conventional genome-wide association study (GWAS) analysis. METHODS: To explore this possibility, we performed an association study in affected versus unaffected females, considering three tiers of single nucleotide polymorphisms (SNPs) as follows: 1) regions of chromosome X that escape X-inactivation, 2) all of chromosome X, and 3) genome-wide. RESULTS: No evidence of a SNP meeting the criteria for a single FPE locus was observed, despite the analysis being well powered to detect this effect. CONCLUSIONS: The results do not support the hypothesis that the FPE is mediated by a single genetic locus; however, this does not exclude the possibility of multiple genetic loci playing a role in the FPE.
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8. Hirschler-Guttenberg Y, Feldman R, Ostfeld-Etzion S, Laor N, Golan O. {{Self- and Co-regulation of Anger and Fear in Preschoolers with Autism Spectrum Disorders: The Role of Maternal Parenting Style and Temperament}}. {J Autism Dev Disord};2015 (May 13)
Emotion regulation (ER) difficulties are a major concern in children with autism spectrum disorder (ASD). Maternal temperament and parenting style have significant effects on children’s ER. However, these effects have not been studied in children with ASD. Forty preschoolers with ASD and their mothers and forty matched controls engaged in fear and anger ER paradigms, micro-coded for child self- and co-regulatory behaviors and parent’s regulation-facilitation. Mothers’ parenting style and temperament were self-reported. In the ASD group only, maternal authoritarian style predicted higher self-regulation and lower co-regulation of anger and maternal authoritative style predicted higher self-regulation of fear. Maternal temperament did not predict child’s ER. Findings emphasize the importance of maternal flexible parenting style in facilitating ER among children with ASD.
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9. Kadak MT, Demirel OF, Gokalp B, Erdogdu Z, Demirel A. {{Relationship between temperament-character and autistic trait in parents of children with autistic spectrum disorder}}. {Int J Psychiatry Clin Pract};2015 (May 12):1-20.
OBJECTIVE: Previous studies revealed distinct features for autism with higher harm avoidance and lower reward dependence, novelty seeking. It is assumed that high harm aviodance, low novelty seeking, reward dependance, cooperativeness and self-directedness are related with broad autism phenotype as in autistic individual. METHOD: This study examined association between Temperament and Character Inventory (TCI) and The Autism Spectrum Quotient (AQ) and in parents of children with ASD. RESULT: There was significant correlation between total AQ and total harm avoidance, cooperativeness, self-directedness (p < 0.05). In the stepwise analysis, self-directedness and education emerged significantly (F(2,67)= 19.71, p < .005). This model modestly explained 35 % of variance (Adjusted R2= .350). CONCLUSION: Our findings suggest that self-directedness may be autistic trait.
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10. Kastner A, Begemann M, Michel TM, Everts S, Stepniak B, Bach C, Poustka L, Becker J, Banaschewski T, Dose M, Ehrenreich H. {{Autism beyond diagnostic categories: characterization of autistic phenotypes in schizophrenia}}. {BMC Psychiatry};2015 (May 13);15(1):115.
BACKGROUND: Behavioral phenotypical continua from health to disease suggest common underlying mechanisms with quantitative rather than qualitative differences. Until recently, autism spectrum disorders and schizophrenia were considered distinct nosologic entities. However, emerging evidence contributes to the blurring of symptomatic and genetic boundaries between these conditions. The present study aimed at quantifying behavioral phenotypes shared by autism spectrum disorders and schizophrenia to prepare the ground for biological pathway analyses. METHODS: Specific items of the Positive and Negative Syndrome Scale were employed and summed up to form a dimensional autism severity score (PAUSS). The score was created in a schizophrenia sample (N = 1156) and validated in adult high-functioning autism spectrum disorder (ASD) patients (N = 165). To this end, the Autism Diagnostic Observation Schedule (ADOS), the Autism (AQ) and Empathy Quotient (EQ) self-rating questionnaires were applied back to back with the newly developed PAUSS. RESULTS: PAUSS differentiated between ASD, schizophrenia and a disease-control sample and substantially correlated with the Autism Diagnostic Observation Schedule. Patients with ADOS scores >/=12 obtained highest, those with scores <7 lowest PAUSS values. AQ and EQ were not found to vary dependent on ADOS diagnosis. ROC curves for ADOS and PAUSS resulted in AuC values of 0.9 and 0.8, whereas AQ and EQ performed at chance level in the prediction of ASD. CONCLUSIONS: This work underscores the convergence of schizophrenia negative symptoms and autistic phenotypes. PAUSS evolved as a measure capturing the continuous nature of autistic behaviors. The definition of extreme-groups based on the dimensional PAUSS may permit future investigations of genetic constellations modulating autistic phenotypes.
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11. Kieffer E, Nicod JC, Gardes N, Kastner C, Becker N, Celebi C, Pirrello O, Rongieres C, Koscinski I, Gosset P, Moutou C. {{Improving preimplantation genetic diagnosis for Fragile X syndrome: two new powerful single-round multiplex indirect and direct tests}}. {Eur J Hum Genet};2015 (May 13)
Fragile X syndrome (FraX) is caused by the expansion of an unstable CGG repeat located in the Fragile X mental retardation 1 gene (FMR1) gene. Preimplantation genetic diagnosis (PGD) can be proposed to couples at risk of transmitting the disease, that is, when the female carries a premutation or a full mutation. We describe two new single-cell, single-round multiplex PCR for indirect and direct diagnosis of FraX on biopsied embryos. These tests include five unpublished, highly heterozygous simple sequence repeats, and the co-amplification of non-expanded CGG repeats for the direct test. Heterozygosity of the new markers ranged from 69 to 81%. The mean rate of non-informative marker included in the tests was low (26% and 23% for the new indirect and direct tests, respectively). This strategy allows offering a PGD for FraX to 96% of couples requesting it in our centre. A conclusive genotype was obtained in all cells with a rate of cells presenting an allele dropout ranging from 17% for the indirect test to 26% for the direct test. The new indirect test was applied for eight PGD cycles: 32 embryos were analysed, 9 were transferred and 3 healthy babies were born. By multiplexing these highly informative markers, robustness of the diagnosis is improved and the loss of potentially healthy embryos (because they are non-diagnosed or misdiagnosed) is limited. This may increase the chances of success of couples requesting a PGD for FraX, in particular, when premature ovarian insufficiency in premutated women leads to a reduced number of embryos available for analysis.European Journal of Human Genetics advance online publication, 13 May 2015; doi:10.1038/ejhg.2015.96.
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12. Lai MC, Baron-Cohen S, Buxbaum JD. {{Understanding autism in the light of sex/gender}}. {Mol Autism};2015;6:24.
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13. Lee PF, Thomas RE, Lee PA. {{Approach to autism spectrum disorder: Using the new DSM-V diagnostic criteria and the CanMEDS-FM framework}}. {Can Fam Physician};2015 (May);61(5):421-424.
OBJECTIVE: To review the diagnostic criteria for autism spectrum disorder (ASD) from the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-V), and to develop an approach to managing ASD using the CanMEDS- Family Medicine (CanMEDS-FM) framework. SOURCES OF INFORMATION: The DSM-V from the American Psychiatric Association, published in May 2013, provides new diagnostic criteria for ASD. The College of Family Physicians of Canada’s CanMEDS-FM framework provides a blueprint that can guide the complex management of ASD. We used data from the Centers for Disease Control and Prevention to determine the prevalence of ASD, and we used the comprehensive systematic review and meta-analysis completed by the UK National Institute for Health and Care Excellence for their guidelines on ASD to assess the evidence for more than 100 interventions. MAIN MESSAGE: The prevalence of ASD was 1 in 88 in 2008 in the United States according to data from the Centers for Disease Control and Prevention. The ASD classification in the fourth edition of the DSM included autism, Asperger syndrome, pervasive developmental disorder, and childhood disintegrative disorder. The new DSM-V revision incorporates all these disorders into one ASD umbrella term with different severity levels. The management of ASD is complex and requires a multidisciplinary team effort and continuity of care. The CanMEDS-FM roles provide a framework for management. CONCLUSION: Family physicians are the key leaders of the multidisciplinary care team for ASD, and the CanMEDS-FM framework provides a comprehensive guide to help manage a child with ASD and to help the child’s family.
14. Levin IP, Gaeth GJ, Foley-Nicpon M, Yegorova V, Cederberg C, Yan H. {{Extending decision making competence to special populations: a pilot study of persons on the autism spectrum}}. {Front Psychol};2015;6:539.
The area of decision making has much to offer in our effort to understand special populations. This pilot study is an example of just such a project, where we illustrate how traditional decision making tools and tasks can be used to uncover strengths and weaknesses within a growing population of young adults with autism. In this pilot project we extended accounts of autistic behavior such as those derived from « theory of mind » to predict key components of decision making in high-functioning young adults on the autism spectrum. A battery of tests was administered to 15 high-functioning college students with autism spectrum disorder (ASD), focusing on decision making competence (DMC) and other aspects of decision making related to known deficits associated with autism. Data from this group were compared to data from unselected college students receiving the same measures. First, as a test of a key social deficit associated with autism, the target group scored much lower on the Empathy Quotient scale. Traditional elements of decision making competency such as Numeracy and application of decision rules were comparable across groups. However, there were differences in thinking style, with the ASD group showing lesser ability and engagement in intuitive thinking, and they showed lower levels of risk taking. For comparisons within the ASD group, autobiographical reports concerning individual lifestyles and outcomes were used to derive a scale of Social Functioning. The lowest scoring individuals showed the lowest levels of intuitive thinking, the lowest perceived levels of others’ endorsement of socially undesirable behaviors, and the lowest ability to discriminate between « good » and « bad » risks. Results are discussed in terms of interventions that might aid high-functioning young adults with ASD in their everyday decision making.
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15. Little LM, Ausderau K, Sideris J, Baranek GT. {{Activity Participation and Sensory Features Among Children with Autism Spectrum Disorders}}. {J Autism Dev Disord};2015 (May 15)
Sensory features are highly prevalent among children with autism spectrum disorders (ASD) and have been shown to cluster into four patterns of response, including hyperresponsiveness, hyporesponsiveness, enhanced perception, and sensory interests, repetitions and seeking behaviors. Given the lack of large-scale research on the differential effects of sensory response patterns on children’s participation in specific activities, this study investigated the extent to which sensory response patterns impacted six dimensions of children’s activity participation as measured by the Home and Community Activities Scale among a large, national sample of school aged children with ASD (n = 674). Using mixed model regression, results showed that sensory response patterns differentially impacted dimensions of activity participation, and associations were moderated by a number of child characteristics.
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16. Luschekina EA, Haerdinova OY, Novototsky-Vlasov VY, Luschekin VS, Strelets VB. {{[EEG synchronisation in autistic children. Analysis of coherency]}}. {Zh Vyssh Nerv Deiat Im I P Pavlova};2015 (Jan-Feb);65(1):72-81.
EEG study of 5-7 years boys with autism revealed lower values of coherence in background delta, theta and alpha bands and higher values of coherence in background beta 1, beta 2 and gamma bands. Healthy boys showed higher values of beta and gamma coherence during cognitive task. Autistic persons demonstrated higher values of theta coherence during cognitive task.
17. Nordahl CW, Iosif AM, Young GS, Perry LM, Dougherty R, Lee A, Li D, Buonocore MH, Simon T, Rogers S, Wandell B, Amaral DG. {{Sex differences in the corpus callosum in preschool-aged children with autism spectrum disorder}}. {Mol Autism};2015;6:26.
BACKGROUND: Abnormalities in the corpus callosum have been reported in individuals with autism spectrum disorder (ASD), but few studies have evaluated young children. Sex differences in callosal organization and diffusion characteristics have also not been evaluated fully in ASD. METHODS: Structural and diffusion-weighted images were acquired in 139 preschool-aged children with ASD (112 males/27 females) and 82 typically developing (TD) controls (53 males/29 females). Longitudinal scanning at two additional annual time points was carried out in a subset of these participants. Callosal organization was evaluated using two approaches: 1) diffusion tensor imaging (DTI) tractography to define subregions based on cortical projection zones and 2) as a comparison to previous studies, midsagittal area analysis using Witelson subdivisions. Diffusion measures of callosal fibers were also evaluated. RESULTS: Analyses of cortical projection zone subregions revealed sex differences in the patterns of altered callosal organization. Relative to their sex-specific TD counterparts, both males and females with ASD had smaller regions dedicated to fibers projecting to superior frontal cortex, but patterns differed in callosal subregions projecting to other parts of frontal cortex. While males with ASD had a smaller callosal region dedicated to the orbitofrontal cortex, females with ASD had a smaller callosal region dedicated to the anterior frontal cortex. There were also sex differences in diffusion properties of callosal fibers. While no alterations were observed in males with ASD relative to TD males, mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were all increased in females with ASD relative to TD females. Analyses of Witelson subdivisions revealed a decrease in midsagittal area of the corpus callosum in both males and females with ASD but no regional differences in specific subdivisions. Longitudinal analyses revealed no diagnostic or sex differences in the growth rate or change in diffusion measures of the corpus callosum from 3 to 5 years of age. CONCLUSIONS: There are sex differences in the pattern of altered corpus callosum neuroanatomy in preschool-aged children with ASD.
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18. Rao VS, Raman V, Mysore AV. {{Issues related to obtaining intelligence quotient-matched controls in autism research}}. {Indian J Psychol Med};2015 (Apr-Jun);37(2):149-153.
BACKGROUND: Intelligence Quotient (IQ) is considered to be an index of global cognitive functioning and has traditionally been used as a fulcral measure in case-control studies in neuro-developmental disorders such as autism. AIM: The aim is to highlight the issues of « matching for IQ » with controls in autism research. MATERIALS AND METHODS: Percentile scores on the Coloured Progressive Matrices of 20 children with autism in the age range of 5 to 12 years have been graphically compared with 21 age matched typically developing children. RESULTS AND CONCLUSIONS: The percentile scores of the so-called high functioning children with autism from special schools were well below that of typically developing children. There are many challenges when using IQ in case-control studies of autism. Alternative approaches need to be considered.
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19. Real Fernandez F, Di Pisa M, Rossi G, Auberger N, Lequin O, Larregola M, Benchohra A, Mansuy C, Chassaing G, Lolli F, Hayek J, Lavielle S, Rovero P, Mallet JM, Papini AM. {{Antibody Recognition In Multiple Sclerosis And Rett Syndrome Using A Collection Of Linear And Cyclic N-glucosylated antigenic probes}}. {Biopolymers};2015 (May 13)
Antibody detection in autoimmune disorders such as Multiple Sclerosis (MS) and Rett syndrome (RTT) can be achieved more efficiently using synthetic peptides. The previously developed synthetic antigenic probe CSF114(Glc), a type I’ beta-turn N-glucosylated peptide structure, is able to recognize antibodies in MS and RTT patients’ sera as a sign of immune system derangement. We report herein the design, synthesis, conformational analysis, and immunological evaluation of a collection of glycopeptide analogs of CSF114(Glc) to characterize the specific role of secondary structures in MS and RTT antibody recognition. Therefore, we synthesized a series of linear and cyclic short glucosylated sequences, mimicking different beta-turn conformations, which were evaluated in inhibition enzyme-linked immunosorbent assays (ELISA). Calculated IC50 ranking analysis allowed the selection of the candidate octapeptide containing two (S)-2-amino-4-pentynoic acid (L-Pra) residues Ac-Pra-RRN(Glc)GHT-Pra-NH2 , with an IC50 in the nanomolar range. This peptide was adequately modified for solid-phase ELISA (SP-ELISA) and surface plasmon resonance (SPR) experiments. Pra-RRN(Glc)GHT-Pra-NH2 peptide was modified with an alkyl chain linked to the N-terminus, favoring immobilization on solid phase in SP-ELISA and differentiating IgG antibody recognition between patients and healthy blood donors with a high specificity. However, this peptide displayed a loss in IgM specificity and sensitivity. Moreover, an analog was obtained after modification of the octapeptide candidate Ac-Pra-RRN(Glc)GHT-Pra-NH2 to favor immobilization on SPR sensor chips. SPR technology allowed us to determine its affinity (KD = 16.4 nM), 2.3-times lower than the affinity of the original glucopeptide CSF114(Glc) (KD = 7.1 nM). This article is protected by copyright. All rights reserved.
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20. Saleh M, Nashaat NH, Fahim C, Ibrahim AS, Meguid N. {{MRI Surface-Based Brain Morphometry in Egyptian Autistic and Typically Developing Children}}. {Folia Phoniatr Logop};2015 (May 6);67(1):29-35.
OBJECTIVES: The verbal abilities of autistic children differ from those of typically developing ones and they also differ among autistic children themselves. Neuroanatomical changes and an abnormal organization of functional networks are expected to accompany such a neurodevelopmental disorder. The aim of this study was to delineate the brain neuroanatomical changes in Egyptian children with autism and to compare them with previous studies in order to add more insight into the global brain imaging deviations linked to autism. PATIENTS AND METHODS: Twenty-five autistic children and 25 typically developing children underwent MRI. Further analysis was performed using surface-based morphometry to obtain cortical thickness, brain volume, and cortical complexity. RESULTS: MRI analysis results revealed significantly greater cortical thickness, cortical complexity, and gray matter volume in the autistic as compared to the control group. On the other hand, the white matter volume was significantly smaller. CONCLUSION: These findings generally align with findings in previous studies, except for occasional differences. (c) 2015 S. Karger AG, Basel.
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21. Sreedaran P, Ashok MV. {{Asperger syndrome in India: findings from a case-series with respect to clinical profile and comorbidity}}. {Indian J Psychol Med};2015 (Apr-Jun);37(2):212-214.
Asperger syndrome (AS) is an autism spectrum disorder with a high rate of psychiatric comorbidity. We describe the clinical profile and psychiatric comorbidity in a series of affected individuals referred to an Indian general hospital psychiatry setting. Gilliam Asperger’s disorder scale was used to evaluate the clinical characteristics while Mini-International Neuropsychiatric Interview (MINI)-KID and MINI-PLUS were used to assess psychiatric comorbidity. The profile of subjects with AS in our case-series appears similar to that published elsewhere with high rates of psychiatric comorbidity. Mental health professionals should evaluate for psychiatric comorbidity in individuals with autism spectrum disorders.
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22. Uno Y, Uchiyama T, Kurosawa M, Aleksic B, Ozaki N. {{Early exposure to the combined measles-mumps-rubella vaccine and thimerosal-containing vaccines and risk of autism spectrum disorder}}. {Vaccine};2015 (May 15);33(21):2511-2516.
OBJECTIVE: This case-control study investigated the relationship between the risk of Autism Spectrum Disorder (ASD) onset, and early exposure to the combined Measles-Mumps-Rubella (MMR) vaccine and thimerosal consumption measured from vaccinations in the highly genetically homogenous Japanese population. METHODS: Vaccination histories at 1, 3, 6, 12, 18, 24, and 36 months from birth were investigated in ASD cases (189 samples), and controls (224 samples) matching age and sex in each case. Crude odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated to determine relationship between MMR vaccination and ASD. The differences in mean values of the thimerosal dosage between cases and controls were analyzed using an unpaired t-test. MMR vaccination and thimerosal dosage were also investigated using a conditional multiple-regression model. RESULTS: There were no significant differences in MMR vaccination and thimerosal dosage between cases and controls at any age. Furthermore, the ORs (95% CIs) of MMR vaccination and thimerosal dosage associated with ASD in the conditional multiple regression model were, respectively, 0.875 (0.345-2.222) and 1.205 (0.862-1.683) at age 18 months, 0.724 (0.421-1.243) and 1.343 (0.997-1.808) at 24 months, and 1.040 (0.648-1.668) and 0.844 (0.632-1.128) at 36 months. Thus, there were no significant differences. CONCLUSIONS: No convincing evidence was found in this study that MMR vaccination and increasing thimerosal dose were associated with an increased risk of ASD onset.
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23. Werling DM, Geschwind DH. {{Recurrence rates provide evidence for sex-differential, familial genetic liability for autism spectrum disorders in multiplex families and twins}}. {Mol Autism};2015;6:27.
BACKGROUND: Autism spectrum disorders (ASDs) are more prevalent in males, suggesting a multiple threshold liability model in which females are, on average, protected by sex-differential mechanisms. Under this model, autistic females are predicted to carry a more penetrant risk variant load than males and to share this greater genetic liability with their siblings. However, reported ASD recurrence rates have not demonstrated significantly increased risk to siblings of affected girls. Here, we characterize recurrence patterns in multiplex families from the Autism Genetics Resource Exchange (AGRE) to determine if risk in these families follows a female protective model. METHODS: We assess recurrence rates and quantitative traits in full siblings from 1,120 multiplex nuclear families and concordance rates in 305 twin pairs from AGRE. We consider the first two affected children per family, and one randomly selected autistic twin per pair, as probands. We then compare recurrence rates and phenotypes between males and females and between twin pairs or families with at least one female proband (female-containing (FC)) versus those with only male probands (male-only (MO)). RESULTS: Among children born after two probands, we observe significantly higher recurrence in males (47.5%) than in females (21.1%; relative risk, RR = 2.25; adjusted P = 6.22e-08) and in siblings of female (44.3%) versus siblings of male probands (30.4%; RR = 1.46; adj. P = 0.036). This sex-differential recurrence is also robust in dizygotic twin pairs (males = 61.5%, females = 19.1%; RR = 3.23; adj. P = 7.66e-09). Additionally, we find a significant negative relationship between interbirth interval and ASD recurrence that is driven by children in MO families. CONCLUSIONS: By classifying families as MO or FC using two probands instead of one, we observe significant recurrence rate differences between families harboring sex-differential familial liability. However, a significant sex difference in risk to children within FC families suggests that female protective mechanisms are still operative in families carrying high genetic risk loads. Furthermore, the male-specific relationship between shorter interbirth intervals and increased ASD risk is consistent with a potentially greater contribution from environmental factors in males versus higher genetic risk in affected females and their families. Understanding the mechanisms driving these sex-differential risk profiles will be useful for treatment development and prevention.
