1. Abraham A, Milham MP, Di Martino A, Craddock RC, Samaras D, Thirion B, Varoquaux G. {{Deriving reproducible biomarkers from multi-site resting-state data: An Autism-based example}}. {Neuroimage};2017 (Feb 15);147:736-745.
Resting-state functional Magnetic Resonance Imaging (R-fMRI) holds the promise to reveal functional biomarkers of neuropsychiatric disorders. However, extracting such biomarkers is challenging for complex multi-faceted neuropathologies, such as autism spectrum disorders. Large multi-site datasets increase sample sizes to compensate for this complexity, at the cost of uncontrolled heterogeneity. This heterogeneity raises new challenges, akin to those face in realistic diagnostic applications. Here, we demonstrate the feasibility of inter-site classification of neuropsychiatric status, with an application to the Autism Brain Imaging Data Exchange (ABIDE) database, a large (N=871) multi-site autism dataset. For this purpose, we investigate pipelines that extract the most predictive biomarkers from the data. These R-fMRI pipelines build participant-specific connectomes from functionally-defined brain areas. Connectomes are then compared across participants to learn patterns of connectivity that differentiate typical controls from individuals with autism. We predict this neuropsychiatric status for participants from the same acquisition sites or different, unseen, ones. Good choices of methods for the various steps of the pipeline lead to 67% prediction accuracy on the full ABIDE data, which is significantly better than previously reported results. We perform extensive validation on multiple subsets of the data defined by different inclusion criteria. These enables detailed analysis of the factors contributing to successful connectome-based prediction. First, prediction accuracy improves as we include more subjects, up to the maximum amount of subjects available. Second, the definition of functional brain areas is of paramount importance for biomarker discovery: brain areas extracted from large R-fMRI datasets outperform reference atlases in the classification tasks.
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2. Beig A, Fine-Shamir N, Lindley D, Miller JM, Dahan A. {{Advantageous Solubility-Permeability Interplay When Using Amorphous Solid Dispersion (ASD) Formulation for the BCS Class IV P-gp Substrate Rifaximin: Simultaneous Increase of Both the Solubility and the Permeability}}. {AAPS J};2017 (Feb 15)
Rifaximin is a BCS class IV (low-solubility, low-permeability) drug and also a P-gp substrate. The aims of this work were to assess the efficiency of different rifaximin amorphous solid dispersion (ASDs) formulations in achieving and maintaining supersaturation and to investigate the consequent solubility-permeability interplay. Spray-dried rifaximin ASDs were prepared with different hydrophilic polymers and their ability to achieve and maintain supersaturation was assessed. Then, rifaximin’s apparent intestinal permeability was investigated as a function of increasing supersaturation both in vitro using the parallel artificial membrane permeability assay (PAMPA) and in vivo using the single-pass rat intestinal perfusion (SPIP) model. The efficiency of the different ASDs to achieve and maintain supersaturation of rifaximin was found to be highly polymer dependent, and the copovidone/HPC-SL formulation was found to be superior to the other two, allowing supersaturation of 200x that of the crystalline solubility for 20 h. In vitro, rifaximin flux was increased and the apparent permeability was constant as a function of increasing supersaturation level. In vivo, on the other hand, absorption rate coefficient (k a) was first constant as a function of increasing supersaturation, but at 250x, the crystalline solubility k a was doubled, similar to the k a in the presence of the strong P-gp inhibitor GF120918. In conclusion, a new and favorable nature of solubility-permeability interplay was revealed in this work: delivering high supersaturation level of the BCS class IV drug rifaximin via ASD, thereby saturating the drugs’ P-gp-mediated efflux transport, led to the favorable unique win-win situation, where both the solubility and the permeability increased simultaneously.
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3. Belin L, Henry L, Destays M, Hausberger M, Grandgeorge M. {{Simple Shapes Elicit Different Emotional Responses in Children with Autism Spectrum Disorder and Neurotypical Children and Adults}}. {Front Psychol};2017;8:91.
According to the literature, simple shapes induce emotional responses. Current evaluations suggest that humans consider angular shapes as « bad » and curvilinear forms as « good, » but no behavioral data are available to support this hypothesis. Atypical development, such as autism spectrum disorder (ASD), could modify humans’ perception of visual stimuli and thereby their emotional effect. This study assessed the effects of simple stimuli (i.e., jagged edges shape, disk, star, spiral, eye-like shape, and head character) on the emotional responses of different groups of humans. First, we assessed the effects of a looming movement on neurotypical adults’ emotional responses. Second, we assessed the effects of atypical development on emotional responses by comparing the reactions of neurotypical children and of children with ASD. We used different methodological approaches: self-evaluation through questionnaires and direct observation of participants’ behavior. We found that (1) neurotypical adults tended to perceive looming stimuli negatively as they associated more negative feelings with them although few behavioral responses could be evidenced and (2) the emotional responses of neurotypical children and of children with ASD differed significantly. Neurotypical children perceived the spiral stimulus positively, i.e., a curvilinear shape, whereas children with ASD perceived the jagged edges stimulus positively, i.e., an angular shape. Although neurotypical children and children with ASD presented some behavioral responses in common, children with ASD smiled and vocalized more than did neurotypical children during stimuli presentations. We discuss our results in relation to the literature on humans’ perception of simple shapes and we stress the importance of studying behavioral components for visual cognition research.
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4. Cahill L. {{A New Link Between Autism and Masculinity}}. {JAMA Psychiatry};2017 (Feb 08)
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5. Chowdhury MR, Chauhan S, Dabral A, Thelma BK, Gupta N, Kabra M. {{Validation of Polymerase Chain Reaction-Based Assay to Detect Actual Number of CGG Repeats in FMR1 Gene in Indian Fragile X Syndrome Patients}}. {J Child Neurol};2017 (Mar);32(4):371-378.
Molecular genetic testing for fragile X (FX) is complicated due to the large variation in the size of CGG expansion. The aim of this study was to apply this new technique using AmplideX FMR1 PCR assay, which is considered a better diagnostic tool for detecting expanded alleles in Indian population. The primary objective was to identify the carrier status of females and to correlate the instability of premutation alleles in females with the repeat sizes. 24 children with FX based on rapid PCR and 29 female relatives of these patients were included. Out of the 29 females screened, those whose child (or children) was affected by FX, were all premutation carriers confirming their role in transmission. The smallest PM allele that expanded into FM in the next generation was 78 repeats and the smallest PM allele detected was 63 repeats, and when transmitted from mother to offspring remained in the premutation range. In 4 families, the repeat size of the allele reduced from PM to normal repeat numbers in their daughters and in 1 case to borderline PM range. Thus, apart from the reduced turnaround time, this PCR based assay offers advantage by its sensitivity to detect CGG repeats in the intermediate region and lower range of premutation alleles. It also provides added information of AGG interruptions, which may have an impact on the counseling of women with intermediate and PM alleles.
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6. Diebo BG, Gammal I, Ha Y, Yoon SH, Chang JW, Kim B, Matsumoto M, Yamato Y, Takeuchi D, Hosogane N, Yagi M, Taneichi H, Schwab F, Lafage V, Ames C. {{Role of Ethnicity in Alignment Compensation: Propensity Matched Analysis of Differential Compensatory Mechanism Recruitment Patterns for Sagittal Malalignment in 288 ASD Patients From Japan, Korea, and United States}}. {Spine (Phila Pa 1976)};2017 (Feb 15);42(4):E234-E240.
STUDY DESIGN: Retrospective review of adult spinal deformity patients in a multiethnic database. OBJECTIVE: To investigate the role of ethnicity on recruitment of compensatory mechanisms for sagittal spinal deformity. SUMMARY OF BACKGROUND DATA: While the impacts of age, sex, and pelvic morphology on the ability to compensate for sagittal malalignment have been investigated, the role of ethnicity in compensatory mechanism recruitment is poorly understood. METHODS: Patients from USA (85% Caucasian) >25 y/o were propensity matched by age, sex, and pelvic incidence with patients from Korea and Japan. Only primary patients or those with existing fusion below T12 were retained for analysis. Groups were subclassified by deformity severity (aligned: sagittal vertical axis (SVA) <50 mm; moderate malalignment: SVA 50-100 mm; severe malalignment: SVA >100 mm). Radiographic measurements including pelvic retroversion, thoracic kyphosis, loss of lumbar lordosis (PI minus LL), cervical lordosis, and cervical SVA were compared between the groups. RESULTS: There were 288 patients (96 each in USA, KOR, JPN), with similar age (64-67 yr) and PI (49-53 degrees ). USA had smaller pelvic incidence minus lumbar lordosis in every alignment group (P <0.05). In moderate malalignment, JPN had more pelvic retroversion than USA (30 degrees vs. 20 degrees ), and KOR had more thoracic hypokyphosis than USA (15 vs. 31 degrees ). In severe malalignment, JPN had more pelvic retroversion than USA (39 degrees vs. 27 degrees ), and KOR had more thoracic hypokyphosis than USA (15 degrees vs. 31 degrees ). KOR had smaller cSVA than USA in both aligned (11 vs. 27 mm) and moderate (19 vs. 31 mm) malalignment. In severe malalignment, KOR had less cervical lordosis (13 degrees KOR vs. 15 degrees USA vs. 27 degrees JPN). All differences with P <0.05. CONCLUSION: Compensation for sagittal is ethnicity dependent. Korean patients favor thoracic compensation via hypokyphosis, and Japanese patients favor pelvic compensation via retroversion. Patient ethnicity should be considered when evaluating the sagittal plane and surgical correction strategies. LEVEL OF EVIDENCE: 3. Lien vers le texte intégral (Open Access ou abonnement)
7. Ecker C, Andrews DS, Gudbrandsen CM, Marquand AF, Ginestet CE, Daly EM, Murphy CM, Lai MC, Lombardo MV, Ruigrok AN, Bullmore ET, Suckling J, Williams SC, Baron-Cohen S, Craig MC, Murphy DG. {{Association Between the Probability of Autism Spectrum Disorder and Normative Sex-Related Phenotypic Diversity in Brain Structure}}. {JAMA Psychiatry};2017 (Feb 08)
Importance: Autism spectrum disorder (ASD) is 2 to 5 times more common in male individuals than in female individuals. While the male preponderant prevalence of ASD might partially be explained by sex differences in clinical symptoms, etiological models suggest that the biological male phenotype carries a higher intrinsic risk for ASD than the female phenotype. To our knowledge, this hypothesis has never been tested directly, and the neurobiological mechanisms that modulate ASD risk in male individuals and female individuals remain elusive. Objectives: To examine the probability of ASD as a function of normative sex-related phenotypic diversity in brain structure and to identify the patterns of sex-related neuroanatomical variability associated with low or high probability of ASD. Design, Setting, and Participants: This study examined a cross-sectional sample of 98 right-handed, high-functioning adults with ASD and 98 matched neurotypical control individuals aged 18 to 42 years. A multivariate probabilistic classification approach was used to develop a predictive model of biological sex based on cortical thickness measures assessed via magnetic resonance imaging in neurotypical controls. This normative model was subsequently applied to individuals with ASD. The study dates were June 2005 to October 2009, and this analysis was conducted between June 2015 and July 2016. Main Outcomes and Measures: Sample and population ASD probability estimates as a function of normative sex-related diversity in brain structure, as well as neuroanatomical patterns associated with low or high ASD probability in male individuals and female individuals. Results: Among the 98 individuals with ASD, 49 were male and 49 female, with a mean (SD) age of 26.88 (7.18) years. Among the 98 controls, 51 were male and 47 female, with a mean (SD) age of 27.39 (6.44) years. The sample probability of ASD increased significantly with predictive probabilities for the male neuroanatomical brain phenotype. For example, biological female individuals with a more male-typic pattern of brain anatomy were significantly (ie, 3 times) more likely to have ASD than biological female individuals with a characteristically female brain phenotype (P = .72 vs .24, respectively; chi21 = 20.26; P < .001; difference in P values, 0.48; 95% CI, 0.29-0.68). This finding translates to an estimated variability in population prevalence from 0.2% to 1.3%, respectively. Moreover, the patterns of neuroanatomical variability carrying low or high ASD probability were sex specific (eg, in inferior temporal regions, where ASD has different neurobiological underpinnings in male individuals and female individuals). Conclusions and Relevance: These findings highlight the need for considering normative sex-related phenotypic diversity when determining an individual's risk for ASD and provide important novel insights into the neurobiological mechanisms mediating sex differences in ASD prevalence. Lien vers le texte intégral (Open Access ou abonnement)
8. Esposito G, Hiroi N, Scattoni ML. {{Cry, baby, cry: Expression of Distress as a Biomarker and Modulator in Autism Spectrum Disorder}}. {Int J Neuropsychopharmacol};2017 (Feb 15)
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9. Frye RE, Wynne R, Rose S, Slattery J, Delhey L, Tippett M, Kahler SG, Bennuri SC, Melnyk S, Sequeira JM, Quadros E. {{Thyroid dysfunction in children with autism spectrum disorder is associated with folate receptor alpha autoimmune disorder}}. {J Neuroendocrinol};2017 (Feb 15)
Folate receptor alpha (FRalpha) autoantibodies (FRAAs) are prevalent in Autism Spectrum Disorder (ASD). FRAAs disrupt folate transport across the blood-brain barrier by binding to the FRalpha. Thyroid dysfunction is frequently found in children with ASD. We measured blocking and binding FRAAs and thyroid stimulating hormone (TSH), free T4 (FT4), total T3 (TT3), reverse T3 (rT3), thyroid releasing hormone (TRH) and other metabolites in 87 children with ASD, 84 of whom also underwent behavior and cognition testing and in 42 of whom FRAAs, TSH and FT4 were measured at two time points. To better understand the significance of the FRalpha in relation to thyroid development, we examined FRalpha expression on prenatal and postnatal thyroid. TSH, TT3 and rT3 were above the normal range in 7%, 33% and 51% of the participants and TRH was below the normal range in 13% of the participants. FT4 was rarely outside the normal range. TSH concentration was positively and the FT4/TSH, TT3/TSH and rT3/TSH ratios were inversely related to blocking FRAA titers. On repeated measurements, change in TSH and FT4/TSH ratio were found to correspond to change in blocking FRAA titers. TSH and the FT4/TSH, TT3/TSH and rT3/TSH ratios were related to irritability on the Aberrant Behavior Checklist and several scales of the Social Responsiveness Scale (SRS), while TT3 was associated with SRS subscales and TRH were related to Vineland Adaptive Behavior Scale subscales. The thyroid showed significant FRalpha expression during the early prenatal period but expression decreased significantly in later gestation and postnatal thyroid tissue. This study suggests that thyroid dysfunction in ASD may be related to the blocking FRAA. The high expression of FRalpha in the early fetal thyroid suggests that fetal and neonatal exposure to maternal FRAAs could affect the development of the thyroid and may contribute to the pathology in ASD. This article is protected by copyright. All rights reserved.
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10. Hajiabolhasani-Nargani Z, Najafi M, Mehrabi T. {{Effect of mobile parenting skills education on anxiety of the mothers with autistic children}}. {Iran J Nurs Midwifery Res};2016 (Nov-Dec);21(6):572-576.
BACKGROUND: The parents of autistic children suffer from anxiety and tension. Unawareness of parenting skills required for autistic children (parenting) doubles their anxiety. Researchers have recently considered research on mobile education, especially mobile text messages. The present study aimed to investigate the effect of mobile parenting skills education on the anxiety of mothers with autistic children. MATERIALS AND METHODS: This is a clinical trial conducted on 64 mothers of children suffering from autism who had a medical file. The participants were recruited by convenient sampling in selected autism centers in Isfahan, Iran. Then, the participants were randomly assigned into two 32-subject groups of study and control. Spielberger Anxiety Inventory was adopted for the mothers. The book « Parenting skills for the mothers with autistic children » was distributed in the study and control group, and then, the study group underwent a structured mobile text messages education. Sixty text messages were sent daily to the participants in the study group for two months. Data were analyzed by Mann-Whitney, Chi-square, independent t-test, and paired t-test using Statistical Package for the Social Sciences version 16. RESULTS: The obtained results showed a significant decrease in mothers’ anxiety mean score after intervention in the study group compared to control group (P = 0.04). There was also a significant reduction in mothers’ anxiety mean score after intervention, compared to before intervention (P < 0.001). CONCLUSIONS: Mobile parenting skills education, especially through text messages, could reduce the level of anxiety among the mothers with autistic children. Lien vers le texte intégral (Open Access ou abonnement)
11. Hampton S, Rabagliati H, Sorace A, Fletcher-Watson S. {{Autism and Bilingualism: A Qualitative Interview Study of Parents’ Perspectives and Experiences}}. {J Speech Lang Hear Res};2017 (Feb 14):1-12.
Purpose: Research into how bilingual parents of children with autism spectrum disorder (ASD) make choices about their children’s language environment is scarce. This study aimed to explore this issue, focusing on understanding how bilingual parents of children with ASD may make different language exposure choices compared with bilingual parents of children without ASD. Method: Semistructured qualitative interviews were conducted with 17 bilingual parents with a child with ASD and 18 bilingual parents with a typically developing (TD) child. Results: Thematic analysis revealed that, in contrast to parents of TD children, parents with a child with ASD expressed concerns that a bilingual environment would cause confusion for their child and exacerbate language delays. This was particularly common for parents of children with lower verbal ability. Parents also identified potential benefits of bilingualism, particularly in terms of maintaining a close and affectionate bond with their child. Conclusions: Parents of children with ASD have concerns about bilingualism not present for parents of TD children, and these concerns are greater for parents of children with lower verbal ability. Future research in this area should take into account factors such as parent-child bonds as well as communication and language development.
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12. Hazlett HC, Gu H, Munsell BC, Kim SH, Styner M, Wolff JJ, Elison JT, Swanson MR, Zhu H, Botteron KN, Collins DL, Constantino JN, Dager SR, Estes AM, Evans AC, Fonov VS, Gerig G, Kostopoulos P, McKinstry RC, Pandey J, Paterson S, Pruett JR, Schultz RT, Shaw DW, Zwaigenbaum L, Piven J. {{Early brain development in infants at high risk for autism spectrum disorder}}. {Nature};2017 (Feb 15);542(7641):348-351.
Brain enlargement has been observed in children with autism spectrum disorder (ASD), but the timing of this phenomenon, and the relationship between ASD and the appearance of behavioural symptoms, are unknown. Retrospective head circumference and longitudinal brain volume studies of two-year olds followed up at four years of age have provided evidence that increased brain volume may emerge early in development. Studies of infants at high familial risk of autism can provide insight into the early development of autism and have shown that characteristic social deficits in ASD emerge during the latter part of the first and in the second year of life. These observations suggest that prospective brain-imaging studies of infants at high familial risk of ASD might identify early postnatal changes in brain volume that occur before an ASD diagnosis. In this prospective neuroimaging study of 106 infants at high familial risk of ASD and 42 low-risk infants, we show that hyperexpansion of the cortical surface area between 6 and 12 months of age precedes brain volume overgrowth observed between 12 and 24 months in 15 high-risk infants who were diagnosed with autism at 24 months. Brain volume overgrowth was linked to the emergence and severity of autistic social deficits. A deep-learning algorithm that primarily uses surface area information from magnetic resonance imaging of the brain of 6-12-month-old individuals predicted the diagnosis of autism in individual high-risk children at 24 months (with a positive predictive value of 81% and a sensitivity of 88%). These findings demonstrate that early brain changes occur during the period in which autistic behaviours are first emerging.
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13. Jeter K, Zlomke K, Shawler P, Sullivan M. {{Comprehensive Psychometric Analysis of the Eyberg Child Behavior Inventory in Children with Autism Spectrum Disorder}}. {J Autism Dev Disord};2017 (Feb 15)
Many assessment measures have only been validated for one specific diagnostic population, which is costly and reduces the clinical utility of assessments. The Eyberg Child Behavior Inventory (ECBI) is one popular measure designed to assess disruptive behavior problems in youth. The ECBI has sound psychometric properties in typically developing youth, but the factor structure has never been examined in children with autism spectrum disorder (ASD). Therefore, the current study conducted a comprehensive psychometric analysis of the ECBI in children with ASD. Retrospective data from a nationally representative sample was collected from 335 children with ASD ages 2-12 years old. A four factor solution was identified for this sample. Implications of these findings and directions for future research are discussed.
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14. Kim H, Keifer CM, Rodriguez-Seijas C, Eaton NR, Lerner MD, Gadow KD. {{Structural hierarchy of autism spectrum disorder symptoms: an integrative framework}}. {J Child Psychol Psychiatry};2017 (Feb 14)
BACKGROUND: In an attempt to resolve questions regarding the symptom classification of autism spectrum disorder (ASD), previous research generally aimed to demonstrate superiority of one model over another. Rather than adjudicating which model may be optimal, we propose an alternative approach that integrates competing models using Goldberg’s bass-ackwards method, providing a comprehensive understanding of the underlying symptom structure of ASD. METHODS: The study sample comprised 3,825 individuals, consecutive referrals to a university hospital developmental disabilities specialty clinic or a child psychiatry outpatient clinic. This study analyzed DSM-IV-referenced ASD symptom statements from parent and teacher versions of the Child and Adolescent Symptom Inventory-4R. A series of exploratory structural equation models was conducted in order to produce interpretable latent factors that account for multivariate covariance. RESULTS: Results indicated that ASD symptoms were structured into an interpretable hierarchy across multiple informants. This hierarchy includes five levels; key features of ASD bifurcate into different constructs with increasing specificity. CONCLUSIONS: This is the first study to examine an underlying structural hierarchy of ASD symptomatology using the bass-ackwards method. This hierarchy demonstrates how core features of ASD relate at differing levels of resolution, providing a model for conceptualizing ASD heterogeneity and a structure for integrating divergent theories of cognitive processes and behavioral features that define the disorder. These findings suggest that a more coherent and complete understanding of the structure of ASD symptoms may be reflected in a metastructure rather than at one level of resolution.
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15. Okamoto Y, Kosaka H, Kitada R, Seki A, Tanabe HC, Hayashi MJ, Kochiyama T, Saito DN, Yanaka HT, Munesue T, Ishitobi M, Omori M, Wada Y, Okazawa H, Koeda T, Sadato N. {{Age-dependent atypicalities in body- and face-sensitive activation of the EBA and FFA in individuals with ASD}}. {Neurosci Res};2017 (Feb 10)
Individuals with autism spectrum disorder (ASD) have difficuly in recognizing bodies and faces, which are more pronounced in children than adults. If such difficulties originate from dysfunction of the extrastriate body area (EBA) and the fusiform face area (FFA), activation in these regions might be more atypical in children than in adults. We preformed functional magnetic resonance imaging while children and adults with ASD and age-matched typically developed (TD) individuals observed face, body, car, and scene. To examine various aspects, we performed individual region of interest (ROI) analysis, as well as conventional random effect group analysis. At individual ROI analysis, we examined the ratio of participants showing a category-sensitive response, the size of regions, location and activation patterns among the four object categories. Adults with ASD showed no atypicalities in activation of the EBA and FFA, whereas children with ASD showed atypical activation in these regions. Specifically, a smaller percentage of children with ASD showed face-sensitive activation of the FFA than TD children. Moreover, the size of the EBA was smaller in children with ASD than in TD children. Our results revealed atypicalities in both the FFA and EBA in children with ASD but not in adults with ASD.
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16. Otsuka S, Uono S, Yoshimura S, Zhao S, Toichi M. {{Emotion Perception Mediates the Predictive Relationship Between Verbal Ability and Functional Outcome in High-Functioning Adults with Autism Spectrum Disorder}}. {J Autism Dev Disord};2017 (Feb 13)
The aim of this study was to identify specific cognitive abilities that predict functional outcome in high-functioning adults with autism spectrum disorder (ASD), and to clarify the contribution of those abilities and their relationships. In total, 41 adults with ASD performed cognitive tasks in a broad range of neuro- and social cognitive domains, and information concerning functional outcomes was obtained. Regression analyses revealed that emotion perception and verbal generativity predicted adaptive functioning directly, and the former mediated between the other two. These findings provide the first evidence of a triadic relationship among neuro- and social cognition and functional outcome in this population. Our results suggest that psychosocial interventions targeting these cognitive abilities could benefit social adaptation in adults with ASD.
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17. Park SM, Park HR, Lee JH. {{MAPK3 at the Autism-Linked Human 16p11.2 Locus Influences Precise Synaptic Target Selection at Drosophila Larval Neuromuscular Junctions}}. {Mol Cells};2017 (Feb 15)
Proper synaptic function in neural circuits requires precise pairings between correct pre- and post-synaptic partners. Errors in this process may underlie development of neuropsychiatric disorders, such as autism spectrum disorder (ASD). Development of ASD can be influenced by genetic factors, including copy number variations (CNVs). In this study, we focused on a CNV occurring at the 16p11.2 locus in the human genome and investigated potential defects in synaptic connectivity caused by reduced activities of genes located in this region at Drosophila larval neuromuscular junctions, a well-established model synapse with stereotypic synaptic structures. A mutation of rolled, a Drosophila homolog of human mitogen-activated protein kinase 3 (MAPK3) at the 16p11.2 locus, caused ectopic innervation of axonal branches and their abnormal defasciculation. The specificity of these phenotypes was confirmed by expression of wild-type rolled in the mutant background. Albeit to a lesser extent, we also observed ectopic innervation patterns in mutants defective in Cdk2, Gaq, and Gp93, all of which were expected to interact with Rolled MAPK3. A further genetic analysis in double heterozygous combinations revealed a synergistic interaction between rolled and Gp93. In addition, results from RT-qPCR analyses indicated consistently reduced rolled mRNA levels in Cdk2, Gaq, and Gp93 mutants. Taken together, these data suggest a central role of MAPK3 in regulating the precise targeting of presynaptic axons to proper postsynaptic targets, a critical step that may be altered significantly in ASD.
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18. Patzlaff NE, Nemec KM, Malone SG, Li Y, Zhao X. {{Fragile X related protein 1 (FXR1P) regulates proliferation of adult neural stem cells}}. {Hum Mol Genet};2017 (Feb 15)
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19. Zaidman-Zait A, Curle D, Jamieson JR, Chia R, Kozak FK. {{Health-Related Quality of Life Among Young Children With Cochlear Implants and Developmental Disabilities}}. {Ear Hear};2017 (Feb 15)
OBJECTIVE: The present study examined differences in health-related quality of life (HRQoL) between deaf children with cochlear implants (CI) with and without developmental disabilities (DD) and differences across HRQoL domains within both groups of children. METHODS: Ninety-two parents of children with CI aged 3-7 years participated in this cross-sectional study. Of these children, 43 had DD (i.e., CI-DD group) and 49 had no DD or chronic illness, demonstrating overall typical development (i.e., CI-TD group). Parents of children in both groups completed the KINDL, a generic HRQoL questionnaire. Parents also provided anecdotal comments to open-ended questions, and parent comments were evaluated on a CI benefits scale to assess parent-perceived benefits of CI for the deaf children with and without disabilities. RESULTS: Children in the CI-DD group had significantly lower HRQoL compared to children in the CI-TD group, including lower scores on the self-esteem, friend, school, and family HRQoL subscales. No significant differences among groups were found on the physical well-being and emotional well-being subscales. For the CI-TD group, age at implantation correlated negatively with self-esteem and school HRQoL subscales. In the CI-DD group, children’s current age correlated negatively with family and with the total HRQoL scores. Parent anecdotal comments and scores on the CI-benefits scale indicated strong parent perceptions of benefits of implantation for children in both groups. CONCLUSION: Based on parents’ proxy report, findings suggest that having DD affects multiple domains of HRQoL among young children with CIs above and beyond that of the CI itself. Parents of deaf children with DD may need greater support through the CI process and follow-up than parents of deaf children without DD.
