1. Aleyasin SA, Salamat F, Mirakhori M. {{Haplotype Analysis of DXS548 and FRAXAC1 Microsatellite Loci in Iranian Patients with Fragile X Syndrome}}. {Iranian journal of child neurology}. 2018; 12(1): 36-46.
Objective: Fragile X syndrome (FXS) is the most common cause of inherited mental retardation caused by expansion of a (CGG) repeat region up to 1000 repeat in 5′ region of the FMR1 gene located in FRAXA locus Xq27.3. To better understand the mechanism involved in expansion of CGG region, the molecular characteristic of the flanking microsatellite markers in the region must be clarify in different populations. We aimed to examine the potential association between specific haplotype and the expanded AC-repeat region in cases and controls chromosomes. Materials & Methods: Forty unrelated FXS males and 62 unrelated normal males originating from various regions of Iran were haplotyped by analyzing two CA-repeat markers, FRAXAC1 and DXS548. Results: Significant linkage disequilibrium was obtained between DXS548 and FRAXAC1 specific marker alleles and CGG repeat expansion among 40 fragile X cases compared to 62 normal controls. The frequencies of DXS548 and FRAXAC1 longer alleles in patients were significantly higher than that in control group. Two FRAXAC1 long alleles were only observed in cases, possibly due to concatenated mutations. The increase of heterozygosities in fragile X cases (DXS548 78.6%, FRAXAC1 64.6%) in comparison to the controls (DXS548 63.0%, FRAXAC1 47.0%) showed a multimodal distribution of fragile X associated alleles. Conclusion: Haplotype analyses with DXS548 and FRAXAC1 markers represented that haplotype distribution in the normal controls and FXS patients were significantly different, representing a weak founder effect.
2. Bolte S, Mahdi S, de Vries PJ, Granlund M, Robison JE, Shulman C, Swedo S, Tonge B, Wong V, Zwaigenbaum L, Segerer W, Selb M. {{The Gestalt of functioning in autism spectrum disorder: Results of the international conference to develop final consensus International Classification of Functioning, Disability and Health core sets}}. {Autism}. 2018: 1362361318755522.
Autism spectrum disorder is associated with diverse social, educational, and occupational challenges. To date, no standardized, internationally accepted tools exist to assess autism spectrum disorder-related functioning. World Health Organization’s International Classification of Functioning, Disability and Health can serve as foundation for developing such tools. This study aimed to identify a comprehensive, a common brief, and three age-appropriate brief autism spectrum disorder Core Sets. Four international preparatory studies yielded in total 164 second-level International Classification of Functioning, Disability and Health candidate categories. Based on this evidence, 20 international autism spectrum disorder experts applied an established iterative decision-making consensus process to select from the candidate categories the most relevant ones to constitute the autism spectrum disorder Core Sets. The consensus process generated 111 second-level International Classification of Functioning, Disability and Health categories in the Comprehensive Core Set for autism spectrum disorder-one body structure, 20 body functions, 59 activities and participation categories, and 31 environmental factors. The Common Brief Core Set comprised 60 categories, while the age-appropriate core sets included 73 categories in the preschool version (0- to 5-year-old children), 81 in the school-age version (6- to 16-year-old children and adolescents), and 79 in the older adolescent and adult version (17-year-old individuals). The autism spectrum disorder Core Sets mark a milestone toward the standardized assessment of autism spectrum disorder-related functioning in educational, administrative, clinical, and research settings.
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3. Bou Khalil R. {{The potential role of insulin-like growth factor-1 and zinc in brain growth of autism spectrum disorder children}}. {Autism}. 2018: 1362361317753565.
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4. Goh DA, Gan D, Kung J, Baron-Cohen S, Allison C, Chen H, Saw SM, Chong YS, Rajadurai VS, Tan KH, Shek PCL, Yap F, Broekman BFP, Magiati I. {{Child, Maternal and Demographic Factors Influencing Caregiver-Reported Autistic Trait Symptomatology in Toddlers}}. {J Autism Dev Disord}. 2018.
Current research on children’s autistic traits in the general population relies predominantly on caregiver-report, yet the extent to which individual, caregiver or demographic characteristics are associated with informants’ ratings has not been sufficiently explored. In this study, caregivers of 396 Singaporean two-year-olds from a birth cohort study completed the Quantitative Checklist for Autism in Toddlers. Children’s gender, cognitive functioning and birth order, maternal age, and ethnic group membership were not significant predictors of caregiver-reported autistic traits. Poorer child language development and higher maternal depressive symptoms significantly predicted more social-communicative autistic traits, while lower maternal education predicted more behavioural autistic traits. Children’s language and informants’ educational level and depressive symptomatology may need to be considered in caregiver-reports of autistic traits.
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5. Grabrucker S, Haderspeck JC, Sauer AK, Kittelberger N, Asoglu H, Abaei A, Rasche V, Schon M, Boeckers TM, Grabrucker AM. {{Brain Lateralization in Mice Is Associated with Zinc Signaling and Altered in Prenatal Zinc Deficient Mice That Display Features of Autism Spectrum Disorder}}. {Front Mol Neurosci}. 2017; 10: 450.
A number of studies have reported changes in the hemispheric dominance in autism spectrum disorder (ASD) patients on functional, biochemical, and morphological level. Since asymmetry of the brain is also found in many vertebrates, we analyzed whether prenatal zinc deficient (PZD) mice, a mouse model with ASD like behavior, show alterations regarding brain lateralization on molecular and behavioral level. Our results show that hemisphere-specific expression of marker genes is abolished in PZD mice on mRNA and protein level. Using magnetic resonance imaging, we found an increased striatal volume in PZD mice with no change in total brain volume. Moreover, behavioral patterns associated with striatal lateralization are altered and the lateralized expression of dopamine receptor 1 (DR1) in the striatum of PZD mice was changed. We conclude that zinc signaling during brain development has a critical role in the establishment of brain lateralization in mice.
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6. Hendry A, Jones EJH, Bedford R, Gliga T, Charman T, Johnson MH. {{Developmental change in look durations predicts later effortful control in toddlers at familial risk for ASD}}. {J Neurodev Disord}. 2018; 10(1): 3.
BACKGROUND: Difficulties with executive functioning (EF) are common in individuals with a range of developmental disorders, including autism spectrum disorder (ASD). Interventions that target underlying mechanisms of EF early in development could be broadly beneficial, but require infant markers of such mechanisms in order to be feasible. Prospective studies of infants at high familial risk (HR) for ASD have revealed a surprising tendency for HR toddlers to show longer epochs of attention to faces than low-risk (LR) controls. In typical development, decreases in look durations towards the end of the first year of life are driven by the development of executive attention-a foundational component of EF. Here, we test the hypothesis that prolonged attention to visual stimuli (including faces) in HR toddlers reflects early differences in the development of executive attention. METHODS: In a longitudinal prospective study, we used eye-tracking to record HR and LR infants’ looking behaviour to social and non-social visual stimuli at ages 9 and 15 months. At age 3 years, we assessed children with a battery of clinical research measures and collected parental report of effortful control (EC)-a temperament trait closely associated with EF and similarly contingent on executive attention. RESULTS: Consistent with previous studies, we found an attenuated reduction in peak look durations to faces between 9 and 15 months for the HR group compared with the LR group, and lower EC amongst the HR-ASD group. In line with our hypothesis, change in peak look duration to faces between 9 and 15 months was negatively associated with EC at age 3. CONCLUSIONS: We suggest that for HR toddlers, disruption to the early development of executive attention results in an attenuated reduction in looking time to faces. Effects may be more apparent for faces due to early biases to orient towards them; further, attention difficulties may interact with earlier emerging differences in social information processing. Our finding that prolonged attention to faces may be an early indicator of disruption to the executive attention system is of potential value in screening for infants at risk for later EF difficulties and for evaluation of intervention outcomes.
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7. Hogeveen J, Krug MK, Elliott MV, Solomon M. {{Insula-Retrosplenial Cortex Overconnectivity Increases Internalizing via Reduced Insight in Autism}}. {Biol Psychiatry}. 2018.
BACKGROUND: Internalizing symptoms like anxiety and depression are common and impairing in autism spectrum disorder (ASD). Here, we test the hypothesis that aberrant functional connectivity among three brain networks (salience network [SN], default mode network [DMN], and frontoparietal network [FPN]) plays a role in the pathophysiology of internalizing in ASD. METHODS: We examined the association between resting-state functional connectivity and internalizing in 102 adolescents and young adults with ASD (n = 49) or typical development (n = 53). Seed-to-target functional connectivity was contrasted between adolescents and young adults with ASD and typically developing subjects using a recent parcellation of the human cerebral cortex, and connections that were aberrant in ASD were analyzed dimensionally as a function of parent-reported internalizing symptoms. RESULTS: Three connections demonstrated robust overconnectivity in ASD: 1) the anterior insula to the retrosplenial cortex (i.e., SN-DMN), 2) the anterior insula to the frontal pole (i.e., SN-FPN), and 3) the dorsolateral prefrontal cortex to the retrosplenial cortex (i.e., FPN-DMN). These differences remained significant after controlling for age, and no age-related effects survived correction. The SN-DMN connection was associated with greater internalizing in ASD, mediated by a bigger difference between self- and parent-reported internalizing. Control analyses found that the other two connections were not associated with internalizing, and SN-DMN connectivity was not associated with a well-matched control measure (externalizing symptoms). CONCLUSIONS: The present findings provide novel evidence for a specific link between SN-DMN overconnectivity and internalizing in ASD. Further, the mediation results suggest that intact anterior insula-retrosplenial connectivity may play a role in an individual’s generating insight into his or her own psychopathology.
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8. Katsnelson A. {{Modeling autism}}. {Lab animal}. 2018; 47(2): 41-4.
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9. Kerns CM, Moskowitz LJ, Rosen T, Drahota A, Wainer A, Josephson AR, Soorya L, Cohn E, Chacko A, Lerner MD. {{A Multisite, Multidisciplinary Delphi Consensus Study Describing « Usual Care » Intervention Strategies for School-Age to Transition-Age Youth With Autism}}. {J Clin Child Adolesc Psychol}. 2018: 1-22.
Understanding usual care is important to reduce health disparities and improve the dissemination of evidence-based practices for youth (ages 7-22 years) with autism spectrum disorder (ASD). A barrier to describing « usual ASD care » is the lack of a common vocabulary and inventory of the practices used by a diverse provider field. To address this barrier, we gathered input from expert providers to develop an inventory of usual care practices and assess expert familiarity and perceptions of these practices as interventions for anxiety, externalizing, and social difficulties in ASD. Purposeful sampling recruited 66 expert ASD providers representing multiple disciplines from 5 sites. Via a 2-round Delphi poll, experts reviewed, suggested revisions to and rated 49 literature-derived practices on several dimensions (familiarity, usefulness, common use, research support). A revised list of 55 practices and anonymous summary of group characteristics and ratings was then returned for further review. Results yielded 55 intervention practices, 48 of which were identified as « familiar » approaches by consensus (>/= 75% endorsement). Greater variation was observed in practices identified by consensus as most often used, useful, and research supported, depending upon the target problem. Findings provide an inventory of practices, reflective of the multidisciplinary language and approaches of expert ASD providers. This inventory may be used to better assess what constitutes usual care for youth with ASD in the United States. Moreover, findings offer insights from clinical experts regarding the range and acceptability of practices that may inform and ground treatment research, dissemination, and implementation efforts.
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10. Knoth IS, Lajnef T, Rigoulot S, Lacourse K, Vannasing P, Michaud JL, Jacquemont S, Major P, Jerbi K, Lippe S. {{Auditory repetition suppression alterations in relation to cognitive functioning in fragile X syndrome: a combined EEG and machine learning approach}}. {J Neurodev Disord}. 2018; 10(1): 4.
BACKGROUND: Fragile X syndrome (FXS) is a neurodevelopmental genetic disorder causing cognitive and behavioural deficits. Repetition suppression (RS), a learning phenomenon in which stimulus repetitions result in diminished brain activity, has been found to be impaired in FXS. Alterations in RS have been associated with behavioural problems in FXS; however, relations between RS and intellectual functioning have not yet been elucidated. METHODS: EEG was recorded in 14 FXS participants and 25 neurotypical controls during an auditory habituation paradigm using repeatedly presented pseudowords. Non-phased locked signal energy was compared across presentations and between groups using linear mixed models (LMMs) in order to investigate RS effects across repetitions and brain areas and a possible relation to non-verbal IQ (NVIQ) in FXS. In addition, we explored group differences according to NVIQ and we probed the feasibility of training a support vector machine to predict cognitive functioning levels across FXS participants based on single-trial RS features. RESULTS: LMM analyses showed that repetition effects differ between groups (FXS vs. controls) as well as with respect to NVIQ in FXS. When exploring group differences in RS patterns, we found that neurotypical controls revealed the expected pattern of RS between the first and second presentations of a pseudoword. More importantly, while FXS participants in the 42 NVIQ group showed a delayed RS response after several presentations. Concordantly, single-trial estimates of repetition effects over the first four repetitions provided the highest decoding accuracies in the classification between the FXS participant groups. CONCLUSION: Electrophysiological measures of repetition effects provide a non-invasive and unbiased measure of brain responses sensitive to cognitive functioning levels, which may be useful for clinical trials in FXS.
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11. LaMarca K, Gevirtz R, Lincoln AJ, Pineda JA. {{Facilitating Neurofeedback in Children with Autism and Intellectual Impairments Using TAGteach}}. {J Autism Dev Disord}. 2018.
Individuals with autism and intellectual impairments tend to be excluded from research due to their difficulties with methodological compliance. This study focuses on using Teaching with Acoustic Guidance-TAGteach-to behaviorally prepare children with autism and a IQ Lien vers le texte intégral (Open Access ou abonnement)
12. Levaot Y, Meiri G, Dinstein I, Menashe I, Shoham-Vardi I. {{Autism Prevalence and Severity in Bedouin-Arab and Jewish Communities in Southern Israel}}. {Community mental health journal}. 2018.
The vast majority of autism spectrum disorder (ASD) research focuses on Caucasian populations in western world countries. While it is assumed that autism rates are similar across ethnic groups regardless of genetic background and environmental exposures, few studies have specifically examined how autism prevalence and severity may differ between majority and minority populations with distinct characteristics. Therefore, we evaluated ethnic differences in ASD prevalence and severity of Bedouin-Arab and Jewish children in the south of Israel. We compared demographic and clinical characteristics of 104 children from a Bedouin-Arab minority with 214 Jewish children who were referred to the main ASD clinic in Southern Israel with suspected communication disorders. Data were obtained from medical records. Jewish children’s referral rates were almost 6 times more than that of Bedouin-Arab referral rates (21:1000 and 3.6:1000, respectively). The percentage of high functioning children with ASD was much higher in Jewish than in Bedouin-Arab children (29.6 and 2.6%, respectively). Bedouin-Arab children showed more severe autistic manifestations. Moreover, Bedouin-Arab children were more likely than Jewish children to have additional diagnosis of intellectual disability (14.5 and 6.9%, respectively). Autism prevalence and severity differs markedly between the Bedouin-Arab and Jewish populations in the south of Israel. Most striking is the almost complete absence of children with high-functioning autism in the Bedouin community. A better understanding of the causes for autism prevalence and severity differences across ethnic groups is crucial for revealing the impact of multiple genetic and environmental factors that may affect autism development in each group.
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13. Michaelsen-Preusse K, Feuge J, Korte M. {{Imbalance of synaptic actin dynamics as a key to fragile X syndrome?}}. {The Journal of physiology}. 2018.
Our experiences and memories define who we are, and evidence has accumulated that memory formation is dependent on functional and structural adaptations of synaptic structures in our brain. Especially dendritic spines, the postsynaptic compartments of synapses show a strong structure-to-function relationship and a high degree of structural plasticity. Although the molecular mechanisms are not completely understood, it is known that these modifications are highly dependent on the actin cytoskeleton, the major cytoskeletal component of the spine. Given the crucial involvement of actin in these mechanisms, dysregulations of spine actin dynamics (reflected by alterations in dendritic spine morphology) can be found in a variety of neurological disorders ranging from schizophrenia to several forms of autism spectrum disorders such as fragile X syndrome (FXS). FXS is caused by a single mutation leading to an inactivation of the X-linked fragile X mental retardation 1 gene and loss of its gene product, the RNA-binding protein fragile X mental retardation protein 1 (FMRP), which normally can be found both pre- and postsynaptically. FMRP is involved in mRNA transport as well as regulation of local translation at the synapse, and although hundreds of FMRP-target mRNAs could be identified only a very few interactions between FMRP and actin-regulating proteins have been reported and validated. In this review we give an overview of recent work by our lab and others providing evidence that dysregulated actin dynamics might indeed be at the very base of a deeper understanding of neurological disorders ranging from cognitive impairment to the autism spectrum.
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14. Nunes AS, Peatfield N, Vakorin V, Doesburg SM. {{Idiosyncratic organization of cortical networks in autism spectrum disorder}}. {Neuroimage}. 2018.
Neuroimaging studies of Autism Spectrum Disorder (ASD) have yielded inconsistent results indicating either increases or decreases in functional connectivity, or both. Recent findings suggest that these seemingly divergent results might be underpinned by greater inter-individual variability in brain network connectivity in ASD. We tested the hypothesis that the spatial patterns of intrinsic connectivity networks (ICNs) are more idiosyncratic in ASD, and demonstrated that this increased variability is associated with symptomatology. We estimated whole brain functional connectivity based on resting state functional magnetic resonance imaging (fMRI) data obtained from the Autism Brain Imaging Data Exchange I & II (ABIDE I & II) repository: 422 (69 females) participants with ASD and 424 (59 females) typically developing (TD) participants between 6 and 30 years of age. We clustered individuals’ patterns of resting state functional connectivity into seven networks, each representing an ICN, and assessed the heterogeneity of each vertex on the cortical surface across individuals in terms of its incorporation into a particular ICN. We found that the incorporation of individual anatomical locations (vertices) to a common network was less consistent across individuals in ASD, indicating a more idiosyncratic organization of ICNs in the ASD brain. This spatial shifting effect was particularly pronounced in the Sensory-Motor Network (SMN) and the Default Mode Network (DMN). We also found that this idiosyncrasy in large-scale brain network organization was correlated with ASD symptomatology (ADOS). These results support the view that idiosyncratic functional connectivity is a hallmark of the ASD brain. We provide the first evidence that the anatomical organization of ICNs is idiosyncratic in ASD, as well as providing evidence that such abnormalities in brain network organization may contribute to the symptoms of ASD.
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15. Ocakoglu FT, Kose S, Ozbaran B, Onay H. {{The oxytocin receptor gene polymorphism -rs237902- is associated with the severity of autism spectrum disorder: A pilot study}}. {Asian J Psychiatr}. 2018.
INTRODUCTION: Previous studies showed the association of Autism Spectrum Disorder (ASD) and oxytocin receptor (OXTR) gene. We aimed to explore the OXTR gene single nucleotide polymorphisms (SNPs) across the ASD severity categories based on DSM-5. METHOD: The whole encoding regions of the human OXTR gene were sequenced to identify the SNPs in 100 Turkish children with ASD. Genotypes of detected SNPs were also compared with the Childhood Autism Rating Scale (CARS) scores. RESULTS: Disease severity of the patients carrying GA and AA genotypes (GA/AA) of rs237902 were found more severe compared to those carrying GG genotype (chi(2)=6.456, df=2, p=.040). This finding was more powerful in boys (chi(2)=9.288, df=2, p=.010). Similarly, GA/AA genotypes of rs237902 were found associated with higher CARS scores in boys (U=650.5, r=0.24, p=.021). CONCLUSION: Significant relationship between the ASD severity categories of DSM-5 and rs237902 was shown for the first time.
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16. Ouellette-Kuntz H, Martin L, McKenzie K. {{Rate of deficit accumulation in home care users with intellectual and developmental disabilities}}. {Annals of epidemiology}. 2018.
PURPOSE: To identify factors associated with the rate of deficit accumulation in a population of adults with intellectual and developmental disabilities (IDD). METHODS: A longitudinal analysis of administratively held clinical data collected at routine home care assessments across Ontario (Canada) using the Resident Assessment Instrument for Home Care (RAI-HC) was conducted using a cohort comprised of 5074 adults with IDD 18-99 years of age who had at least two home care assessments between April 1, 2003 and March 31, 2015. Rates of deficit accumulation were calculated across variables of interest. Incidence rate ratios and 95% confidence intervals are presented. Negative binomial regression models using a generalized estimating equation (GEE) approach were developed. RESULTS: Increasing age, Down syndrome, and living in a group home were significant predictors of deficit accumulation. Rates of deficit accumulation tended to be higher among prefrail and frail individuals; however, impaired cognition and impairment in activities of daily living were associated with slower deficit accumulation. The relationship between provision of nursing and therapy services and deficit accumulation is unclear. CONCLUSIONS: Frailty should be monitored among adults with IDD starting at age 40 years, those with Down syndrome, and those who live in group homes.
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17. Ring M, Gaigg SB, Altgassen M, Barr P, Bowler DM. {{Allocentric Versus Egocentric Spatial Memory in Adults with Autism Spectrum Disorder}}. {J Autism Dev Disord}. 2018.
Individuals with autism spectrum disorder (ASD) present difficulties in forming relations among items and context. This capacity for relational binding is also involved in spatial navigation and research on this topic in ASD is scarce and inconclusive. Using a computerised version of the Morris Water Maze task, ASD participants showed particular difficulties in performing viewpoint independent (allocentric) navigation, leaving viewpoint dependent navigation (egocentric) intact. Further analyses showed that navigation deficits were not related to poor visual short-term memory or mental rotation in the ASD group. The results further confirm the need of autistic individuals for support at retrieval and have important implications for the design of signposts and maps.
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18. Rochette AC, Soulieres I, Berthiaume C, Godbout R. {{NREM sleep EEG activity and procedural memory: A comparison between young neurotypical and autistic adults without sleep complaints}}. {Autism Res}. 2018.
Delta EEG activity (0.75-3.75 Hz) during non-Rapid eye movement (NREM) sleep reflects the thalamo-cortical system contribution to memory consolidation. The functional integrity of this system is thought to be compromised in the Autism spectrum disorder (ASD). This lead us to investigate the topography of NREM sleep Delta EEG activity in young adults with ASD and typically-developed individuals (TYP). The relationship between Delta EEG activity and sensory-motor procedural information was also examined using a rotary pursuit task. Two dependent variables were computed: a learning index (performance increase across trials) and a performance index (average performance for all trials). The ASD group showed less Delta EEG activity during NREM sleep over the parieto-occipital recording sites compared to the TYP group. Delta EEG activity dropped more abruptly from frontal to posterior regions in the ASD group. Both groups of participants learned the task at a similar rate but the ASD group performed less well in terms of contact time with the target. Delta EEG activity during NREM sleep, especially during stage 2, correlated positively with the learning index for electrodes located all over the cortex in the TYP group, but only in the frontal region in the ASD group. Delta EEG activity, especially during stage 2, correlated positively with the performance index, but in the ASD group only. These results reveal an atypical thalamo-cortical functioning over the parieto-occipital region in ASD. They also point toward an atypical relationship between the frontal area and the encoding of sensory-motor procedural memory in ASD. Autism Res 2018. (c) 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Slow EEG waves recorded from the scalp during sleep are thought to facilitate learning and memory during daytime. We compared these EEG waves in young autistic adults to typically-developing young adults. We found less slow EEG waves in the ASD group and the pattern of relationship with memory differed between groups. This suggests atypicalities in the way sleep mechanisms are associated with learning and performance in a sensory-motor procedural memory task in ASD individuals.
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19. Saldarriaga W, Forero-Forero JV, Gonzalez-Teshima LY, Fandino-Losada A, Isaza C, Tovar-Cuevas JR, Silva M, Choudhary NS, Tang HT, Aguilar-Gaxiola S, Hagerman RJ, Tassone F. {{Genetic cluster of fragile X syndrome in a Colombian district}}. {Journal of human genetics}. 2018.
BACKGROUND: Fragile X syndrome (FXS) is the most common cause of inherited intellectual disabilities and autism. The reported prevalence of the full mutation (FM) gene FMR1 in the general population is 0.2-0.4 per 1000 males and 0.125-0.4 per 1000 females. Population screening for FMR1 expanded alleles has been performed in newborns and in an adult population. However, it has never been carried out in an entire town. Ricaurte is a Colombian district with 1186 habitants, with a high prevalence of FXS, which was first described by cytogenetic techniques in 1999. METHODS: Using a PCR-based approach, screening for FXS was performed on blood spot samples obtained from 926 (502 males and 424 females) inhabitants from Ricaurte, accounting for 78% of total population. RESULTS: A high prevalence of carriers of the expanded allele was observed in all FXS mutation categories. Using the Bayesian methods the carrier frequency of FM was 48.2 (95% Credibility Region CR: 36.3-61.5) per 1000 males and 20.5 (95% CR:13.5-28.6) per 1000 females; the frequency of premutation carrier was 14.1 (95% RC: 8.0-21.7) per 1000 males (95% RC: 8.0-21.7 per 1000 males) and 35.9 (95% RC: 26.5-46.2) per 1000 for females (95% RC: 26.5-46.2 per 1000 females), and gray zone carrier was 13.4 (95% RC: 7.4-20.7) per 1000 males (95% RC: 7.4-20.7 per 1000 males) and 42.2 (95% RC: 32.2-53.8) per 1000 for females (95% RC: 32.2-53.8 per 1000 females). Differences in carrier frequencies were observed for premutation and FM alleles between natives and non-natives. CONCLUSIONS: This study shows that in Ricaurte the carrier frequencies of FMR1 expanded alleles (premutations and FMs) are higher than those reported in the literature, suggesting that Ricaurte constitutes a genetic cluster of FXS.
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20. Simmons DR, Todorova GK. {{Local Versus Global Processing in Autism: Special Section Editorial}}. {J Autism Dev Disord}. 2018.
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21. Tordjman S, Cohen D, Anderson GM, Botbol M, Canitano R, Coulon N, Roubertoux PL. {{Repint of « Reframing autism as a behavioral syndrome and not a specific mental disorder: Implications of genetic and phenotypic heterogeneity »}}. {Neurosci Biobehav Rev}. 2018.
Clinical and molecular genetics have advanced current knowledge on genetic disorders associated with autism. A review of diverse genetic disorders associated with autism is presented and for the first time discussed extensively with regard to possible common underlying mechanisms leading to a similar cognitive-behavioral phenotype of autism. The possible role of interactions between genetic and environmental factors, including epigenetic mechanisms, is in particular examined. Finally, the pertinence of distinguishing non-syndromic autism (isolated autism) from syndromic autism (autism associated with genetic disorders) will be reconsidered. Given the high genetic and etiological heterogeneity of autism, autism can be viewed as a behavioral syndrome related to known genetic disorders (syndromic autism) or currently unknown disorders (apparent non-syndromic autism), rather than a specific categorical mental disorder. It highlights the need to study autism phenotype and developmental trajectory through a multidimensional, non-categorical approach with multivariate analyses within autism spectrum disorder but also across mental disorders, and to conduct systematically clinical genetic examination searching for genetic disorders in all individuals (children but also adults) with autism.
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22. Yasue M, Nakagami A, Nakagaki K, Ichinohe N, Kawai N. {{Inequity aversion is observed in common marmosets but not in marmoset models of autism induced by prenatal exposure to valproic acid}}. {Behav Brain Res}. 2018; 343: 36-40.
Humans and various nonhuman primates respond negatively to inequity not in their favor (i.e., inequity aversion), when inequity between two individuals is introduced. Common marmosets, a highly prosocial species, further discriminated between human actors who reciprocated in social exchanges, and those who did not. Conversely, marmoset models of autism, induced via prenatal exposure to valproic acid (VPA marmosets), did not discriminate. Interestingly, previous studies of inequity aversion in marmosets have produced negative results, or were limited to males. Recent studies suggest that inequity aversion is highly influenced by the tasks employed. Here we show inequity aversion in both male and female marmosets using a novel task which required a relatively long duration of response. Marmosets were required to hold a spoon for 2s to receive a reward. Marmosets successfully performed the task when they observed an unfamiliar conspecific partner obtaining the same reward (equity test). However, when they witnessed the partner receiving a more attractive reward for equal effort (inequity test), unexposed marmosets, which were not exposed to either valproic acid or saline during the fetal period refused to respond. This inequity aversion was not observed in unexposed marmosets when the partner was absent.In contrast, marmosets with fetal exposure to valproic acid (VPA marmosets) successfully executed the task irrespective of their partners’ reward conditions. As prenatal exposure to valproic acid is a well-known procedure to induce autism spectrum disorder (ASD)-like behaviors in rodents, we propose that VPA marmosets failed to show inequity aversion due to weak social motivation or interest towards others.
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23. Zaboski BA, Storch EA. {{Comorbid autism spectrum disorder and anxiety disorders: a brief review}}. {Future neurology}. 2018; 13(1): 31-7.
Appearing in 40% of the cases of autism spectrum disorder (ASD), comorbid anxiety presents unique challenges for practitioners by amplifying problem behaviors such as social skills deficits, resistance to change and repetitive behaviors. Furthermore, comorbid ASD/anxiety strains familial relationships and increases parental stress. Research indicates that the neurobiological interactions between anxiety and ASD require comprehensive assessment approaches, modified cognitive behavioral therapy and carefully managed pharmacological interventions. Meta-analyses indicate that cognitive behavioral therapy with exposure is an effective treatment option when adequately accounting for social, familial and cognitive variables. The purpose of this focused review is to update readers on the latest research advances in comorbid ASD and anxiety, including prevalence, assessment, psychosocial and pharmacological treatment.
