1. {{International Society for Autism Research News}}. {Autism Res}. 2015; 8(5): 647.
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2. Althaus M, Groen Y, Wijers AA, Noltes H, Tucha O, Hoekstra PJ. {{Oxytocin enhances orienting to social information in a selective group of high-functioning male adults with autism spectrum disorder}}. {Neuropsychologia}. 2015; 79(Pt A): 53-69.
OBJECTIVE: The study investigated the effects of nasally administered oxytocin on neurophysiological orienting to empathy-evoking pictures in normally intelligent male adults with and without an autism spectrum disorder (ASD). It further investigated whether these effects might be moderated by the individual’s approach and avoidance tendencies. METHODS: All subjects participated in a randomised double-blind placebo controlled crossover trial where either oxytocin (OXT) or placebo was administered preceding the viewing of affective pictures.The pictures, selected from the International Affective Picture System (IAPS), represented a systematic variation of pleasant, unpleasant and neutral scenes with and without humans. Both cardiac (ECR) and cortical (LPP) evoked orienting responses were measured and both were enhanced for the pictures with humans, in particular for the unpleasant ones. RESULTS: No significant group differences were found, nor were there any treatment effects. Moderator analysis, however, demonstrated that OXT did enhance orienting to affective pictures with humansin male adults with ASD who are easily distressed when seeing others in stressful situations and in healthy males who are highly sensitive to anticipated punishment and criticism or have a low drive for goal achievement. CONCLUSION: Individual differences in stress-related avoidance tendencies should be taken into account when considering OXT as a treatment of social deficiencies in autism.
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3. Bijl N, Thys C, Wittevrongel C, De la Marche W, Devriendt K, Peeters H, Van Geet C, Freson K. {{Platelet studies in autism spectrum disorder patients and first-degree relatives}}. {Mol Autism}. 2015; 6: 57.
BACKGROUND: Platelets have been proven to be a useful cellular model to study some neuropathologies, due to the overlapping biological features between neurons and platelets as granule secreting cells. Altered platelet dense granule morphology was previously reported in three autism spectrum disorder (ASD) patients with chromosomal translocations that disrupted ASD candidate genes NBEA, SCAMP5, and AMYSIN, but a systematic analysis of platelet function in ASD is lacking in contrast to numerous reports of elevated serotonin levels in platelets and blood as potential biomarker for ASD. METHODS: We explored platelet count, size, epinephrine-induced activation, and dense granule ATP secretion in a cohort of 159 ASD patients, their 289 first-degree relatives (103 unaffected siblings, 99 mothers, and 87 fathers), 45 adult controls, and 65 pediatric controls. For each of the responses separately, a linear mixed model with gender as a covariate was used to compare the level between groups. We next investigated the correlation between platelet function outcomes and severity of impairments in social behavior (social responsiveness score (SRS)). RESULTS: The average platelet count was increased in ASD patients and siblings vs. controls (ASD 320.3 x 10(9)/L, p = 0.003; siblings 332.0 x 10(9)/L, p < 0.001; controls 283.0 x 10(9)/L). The maximal platelet secretion-dependent aggregation response to epinephrine was not significantly lower for ASD patients. However, secondary wave responses following stimulation with epinephrine were more frequently delayed or absent compared to controls (ASD 52 %, siblings 45 %, parents 53 %, controls 22 %, p = 0.002). In addition, stimulated release of ATP from dense granules was reduced in ASD patients, siblings, and parents vs. controls following activation of platelets with either collagen (ASD 1.54 muM, p = 0.001; siblings 1.51 muM, p < 0.001; parents 1.67 muM, p = 0.021; controls 2.03 muM) or ADP (ASD 0.96 muM, p = 0.003; siblings 1.00 muM, p = 0.012; parents 1.17 muM, p = 0.21; controls 1.40 muM). Plasma serotonin levels were increased for ASD patients (n = 20, p = 0.005) and siblings (n = 20, p = 0.0001) vs. controls (n = 16). No significant correlations were found in the different groups between SRS scores and count, size, epinephrine aggregation, or ATP release. CONCLUSIONS: We report increased platelet counts, decreased platelet ATP dense granule secretion, and increased serotonin plasma levels not only in ASD patients but also in their first-degree relatives. This suggests that potential genetic factors associated with platelet counts and granule secretion can be associated with, but are not fully penetrant for ASD. Lien vers le texte intégral (Open Access ou abonnement)
4. Cheslack-Postava K, Susser E, Liu K, Bearman PS. {{Can Sibling Sex Ratios Be Used as a Valid Test for the Prenatal Androgen Hypothesis of Autism Spectrum Disorders?}}. {PLoS One}. 2015; 10(10): e0141338.
BACKGROUND: Sibling sex ratios have been applied as an indirect test of a hypothesized association between prenatal testosterone levels and risk for autism, a developmental disorder disproportionately affecting males. Differences in sibling sex ratios between those with and without autism would provide evidence of a shared risk factor for autism and offspring sex. Conclusions related to prenatal testosterone, however, require additional assumptions. Here, we used directed acyclic graphs (DAGs) to clarify the elements required for a valid test of the hypothesis that sibling sex ratios differ between children with and without autism. We then conducted such a test using a large, population-based sample of children. METHODS: Over 1.1 million subjects, born in California from 1992-2007, and identified through birth records, were included. The association between autism diagnosis, determined using the administrative database of the California Department of Developmental Services, and the sex of the subsequent sibling was examined using generalized estimating equations. Sources of potential bias identified using DAGs were addressed. RESULTS: Among male children with autism, 52.2% of next-born siblings were brothers, versus 51.0% for unaffected males. For females with autism, 50.2% of following siblings were brothers versus 51.2% among control females. The relative risk of a subsequent male sibling associated with autism diagnosis was 1.02 (95% confidence interval: 0.99, 1.04). CONCLUSIONS: In a large, population-based sample we failed to find evidence suggesting an excess of brothers among children with autism while controlling for several threats to validity. This test cannot rule out a role of any given exposure, including prenatal testosterone, in either risk of autism or offspring sex ratio, but suggests against a common cause of both.
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5. Constantino JN, Charman T. {{Diagnosis of autism spectrum disorder: reconciling the syndrome, its diverse origins, and variation in expression}}. {Lancet Neurol}. 2015.
Recent discoveries about the pathogenesis and symptom structure of autism spectrum disorders (ASDs) are challenging traditional nosology and driving efforts to reconceptualise the diagnosis of autism, a goal made all the more pressing by new prospects for early identification, targeted intervention, and personalised-medicine approaches to specific autistic syndromes. Recognition that ASD represents the severe end of a continuous distribution of social communication abilities in the general population has stimulated attempts to standardise the measurement of autistic traits and to set appropriate clinical thresholds for diagnosis. Over the next decade, rapid advances in our understanding of symptom structure and the diversity of causes of ASD could be incorporated into the next evolution in the diagnosis of autism, with important implications for research, clinical practice, public health, and policy. As differential effects of personalised therapies are identified in relation to specific causes of autism, the benefits of an updated diagnostic nosology will translate into the delivery of more effective care for patients.
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6. Devinsky O, Asato M, Camfield P, Geller E, Kanner AM, Keller S, Kerr M, Kossoff EH, Lau H, Kothare S, Singh BK, Wirrell E. {{Delivery of epilepsy care to adults with intellectual and developmental disabilities}}. {Neurology}. 2015; 85(17): 1512-21.
Epilepsy is common in people with intellectual and developmental disabilities (IDD). In adulthood, patients with IDD and epilepsy (IDD-E) have neurologic, psychiatric, medical, and social challenges compounded by fragmented and limited care. With increasing neurologic disability, there is a higher frequency of epilepsy, especially symptomatic generalized and treatment-resistant epilepsies. The causes of IDD-E are increasingly recognized to be genetic based on chromosomal microarray analysis to identify copy number variants, gene panels (epilepsy, autism spectrum disorder, intellectual disability), and whole-exome sequencing. A specific genetic diagnosis may guide care by pointing to comorbid disorders and best therapy. Therapy to control seizures should be individualized, with drug selection based on seizure types, epilepsy syndrome, concomitant medications, and comorbid disorders. There are limited comparative antiepileptic drug data in the IDD-E population. Vagus nerve and responsive neural stimulation therapies and resective surgery should be considered. Among the many comorbid disorders that affect patients with IDD-E, psychiatric and sleep disorders are common but often unrecognized and typically not treated. Transition from holistic and coordinated pediatric to adult care is often a vulnerable period. Communication among adult health care providers is complex but essential to ensure best care when these patients are seen in outpatient, emergency room, and inpatient settings. We propose specific recommendations for minimum care standards for people with IDD-E.
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7. Frazier TW, Youngstrom EA, Hardan AY, Georgiades S, Constantino JN, Eng C. {{Quantitative autism symptom patterns recapitulate differential mechanisms of genetic transmission in single and multiple incidence families}}. {Mol Autism}. 2015; 6: 58.
BACKGROUND: Previous studies have demonstrated aggregation of autistic traits in undiagnosed family members of children with autism spectrum disorder (ASD), which has significant implications for ASD risk in their offspring. This study capitalizes upon a large, quantitatively characterized clinical-epidemiologic family sample to establish the extent to which family transmission pattern and sex modulate ASD trait aggregation. METHODS: Data were analyzed from 5515 siblings (2657 non-ASD and 2858 ASD) included in the Interactive Autism Network. Autism symptom levels were measured using the Social Responsiveness Scale (SRS) and by computing Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition (DSM-5) symptom scores based on items from the SRS and Social Communication Questionnaire. Generalized estimating equation models evaluated the influence of family incidence types (single versus multiple incidence families; male-only ASD-affected families versus families with female ASD-affected children), diagnostic group (non-ASD children with and without a history of language delay with autistic speech and ASD-affected children), and sibling sex on ASD symptom levels. RESULTS: Non-ASD children manifested elevated ASD symptom burden when they were members of multiple incidence families-this effect was accentuated for male children in female ASD-containing families-or when they had a history of language delay with autistic qualities of speech. In this sample, ASD-affected children from multiple incidence families had lower symptom levels than their counterparts in single incidence families. Recurrence risk for ASD was higher for children from female ASD-containing families than for children from male-only families. CONCLUSIONS: Sex and patterns of family transmission modulate the risk of autism symptom burden in undiagnosed siblings of ASD-affected children. Identification of these symptoms/traits and their molecular genetic causes may have significant implications for genetic counseling and for understanding inherited liabilities that confer risk for ASD in successive generations. Autism symptom elevations were more dramatic in non-ASD children from multiple incidence families and those with a history of language delay and autistic qualities of speech, identifying sub-groups at substantially greater transmission risk. Higher symptom burden and greater recurrence in children from female ASD-containing families indicate that familial aggregation patterns are further qualified by sex-specific thresholds, supportive of the notion that females require a higher burden of deleterious liability to cross into categorical ASD diagnosis.
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8. Grove R, Roth I, Hoekstra RA. {{The motivation for special interests in individuals with autism and controls: Development and validation of the special interest motivation scale}}. {Autism Res}. 2015.
Clinical observations and first person accounts of living with autism suggest that individuals with autism are highly motivated to engage in special interests, and that these interests remain important throughout life. Previous research assessing special interests has mainly focused on parental reports of children with autism spectrum conditions (ASC). To better understand the significance of and motivations for engaging in special interests it is essential to use self-report ratings. This paper aims to systematically explore the motivations for engagement in special interests, and whether these differ in adults with ASC, first-degree relatives and general population controls. The Special Interest Motivation Scale (SIMS) was developed to assess motivation to engage in special interests. The internal structure of this scale was evaluated using factor analysis, and mean scores on the SIMS factors were subsequently compared across individuals with autism, parents and general population controls. Factor analysis indicated a 20-item SIMS containing five factors assessing Personal life values and goals; Intrinsic interest and knowledge; Prestige; Engagement and « flow » and Achievement. Individuals with autism were more motivated by Intrinsic interest and knowledge and by Engagement and flow than controls. The 20-item SIMS is a quick to administer measure that provides a reliable description of motivation to engage in special interests. This study indicates that individuals with ASC are highly motivated to engage in their special interest, and are more motivated than controls by intrinsic motivational factors, some of which are associated with positive affect. This has implications for research and clinical practice. Autism Res 2015. (c) 2015 International Society for Autism Research, Wiley Periodicals, Inc.
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9. Guillon Q, Afzali MH, Roge B, Baduel S, Kruck J, Hadjikhani N. {{The Importance of Networking in Autism Gaze Analysis}}. {PLoS One}. 2015; 10(10): e0141191.
Visual scanning of faces in individuals with Autism Spectrum Disorder (ASD) has been intensively studied using eye-tracking technology. However, most of studies have relied on the same analytic approach based on the quantification of fixation time, which may have failed to reveal some important features of the scanning strategies employed by individuals with ASD. In the present study, we examined the scanning of faces in a group of 20 preschoolers with ASD and their typically developing (TD) peers, using both classical fixation time approach and a new developed approach based on transition matrices and network analysis. We found between group differences in the eye region in terms of fixation time, with increased right eye fixation time for the ASD group and increased left eye fixation time for the TD group. Our complementary network approach revealed that the left eye might play the role of an anchor in the scanning strategies of TD children but not in that of children with ASD. In ASD, fixation time on the different facial parts was almost exclusively dependent on exploratory activity. Our study highlights the importance of developing innovative measures that bear the potential of revealing new properties of the scanning strategies employed by individuals with ASD.
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10. Henry J. {{Book Review: Essential first steps for parents of children with autism: Helping the littlest learners}}. {Can J Occup Ther}. 2015; 82(4): 234.
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11. Kana RK, Maximo JO, Williams DL, Keller TA, Schipul SE, Cherkassky VL, Minshew NJ, Just MA. {{Aberrant functioning of the theory-of-mind network in children and adolescents with autism}}. {Mol Autism}. 2015; 6: 59.
BACKGROUND: Theory-of-mind (ToM), the ability to infer people’s thoughts and feelings, is a pivotal skill in effective social interactions. Individuals with autism spectrum disorders (ASD) have been found to have altered ToM skills, which significantly impacts the quality of their social interactions. Neuroimaging studies have reported altered activation of the ToM cortical network, especially in adults with autism, yet little is known about the brain responses underlying ToM in younger individuals with ASD. This functional magnetic resonance imaging (fMRI) study investigated the neural mechanisms underlying ToM in high-functioning children and adolescents with ASD and matched typically developing (TD) peers. METHODS: fMRI data were acquired from 13 participants with ASD and 13 TD control participants while they watched animations involving two « interacting » geometrical shapes. RESULTS: Participants with ASD showed significantly reduced activation, relative to TD controls, in regions considered part of the ToM network, the mirror network, and the cerebellum. Functional connectivity analyses revealed underconnectivity between frontal and posterior regions during task performance in the ASD participants. CONCLUSIONS: Overall, the findings of this study reveal disruptions in the brain circuitry underlying ToM in ASD at multiple levels, including decreased activation and decreased functional connectivity.
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12. Kern JK, Geier DA, Deth RC, Sykes LK, Hooker BS, Love JM, Bjorklund G, Chaigneau CG, Haley BE, Geier MR. {{Systematic Assessment of Research on Autism Spectrum Disorder and Mercury Reveals Conflicts of Interest and the Need for Transparency in Autism Research}}. {Sci Eng Ethics}. 2015.
Historically, entities with a vested interest in a product that critics have suggested is harmful have consistently used research to back their claims that the product is safe. Prominent examples are: tobacco, lead, bisphenol A, and atrazine. Research literature indicates that about 80-90 % of studies with industry affiliation found no harm from the product, while only about 10-20 % of studies without industry affiliation found no harm. In parallel to other historical debates, recent studies examining a possible relationship between mercury (Hg) exposure and autism spectrum disorder (ASD) show a similar dichotomy. Studies sponsored and supported by industry or entities with an apparent conflict of interest have most often shown no evidence of harm or no « consistent » evidence of harm, while studies without such affiliations report positive evidence of a Hg/autism association. The potentially causal relationship between Hg exposure and ASD differs from other toxic products since there is a broad coalition of entities for whom a conflict of interest arises. These include influential governmental public health entities, the pharmaceutical industry, and even the coal burning industry. This review includes a systematic literature search of original studies on the potential relationship between Hg and ASD from 1999 to date, finding that of the studies with public health and/or industry affiliation, 86 % reported no relationship between Hg and ASD. However, among studies without public health and/or industry affiliation, only 19 % find no relationship between Hg and ASD. The discrepancy in these results suggests a bias indicative of a conflict of interest.
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13. Kopp N, Climer S, Dougherty JD. {{Moving from capstones toward cornerstones: successes and challenges in applying systems biology to identify mechanisms of autism spectrum disorders}}. {Front Genet}. 2015; 6: 301.
The substantial progress in the last few years toward uncovering genetic causes and risk factors for autism spectrum disorders (ASDs) has opened new experimental avenues for identifying the underlying neurobiological mechanism of the condition. The bounty of genetic findings has led to a variety of data-driven exploratory analyses aimed at deriving new insights about the shared features of these genes. These approaches leverage data from a variety of different sources such as co-expression in transcriptomic studies, protein-protein interaction networks, gene ontologies (GOs) annotations, or multi-level combinations of all of these. Here, we review the recurrent themes emerging from these analyses and highlight some of the challenges going forward. Themes include findings that ASD associated genes discovered by a variety of methods have been shown to contain disproportionate amounts of neurite outgrowth/cytoskeletal, synaptic, and more recently Wnt-related and chromatin modifying genes. Expression studies have highlighted a disproportionate expression of ASD gene sets during mid fetal cortical development, particularly for rare variants, with multiple analyses highlighting the striatum and cortical projection and interneurons as well. While these explorations have highlighted potentially interesting relationships among these ASD-related genes, there are challenges in how to best transition these insights into empirically testable hypotheses. Nonetheless, defining shared molecular or cellular pathology downstream of the diverse genes associated with ASDs could provide the cornerstones needed to build toward broadly applicable therapeutic approaches.
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14. Kumar H, Sharma BM, Sharma B. {{Benefits of agomelatine in behavioral, neurochemical and blood brain barrier alterations in prenatal valproic acid induced autism spectrum disorder}}. {Neurochem Int}. 2015.
Valproic acid administration during gestational period causes behavior and biochemical deficits similar to those observed in humans with autism spectrum disorder. Although worldwide prevalence of autism spectrum disorder has been increased continuously, therapeutic agents to ameliorate the social impairment are very limited. The present study has been structured to investigate the therapeutic potential of melatonin receptor agonist, agomelatine in prenatal valproic acid (Pre-VPA) induced autism spectrum disorder in animals. Pre-VPA has produced reduction in social interaction (three chamber social behavior apparatus), spontaneous alteration (Y-Maze), exploratory activity (Hole board test), intestinal motility, serotonin levels (prefrontal cortex and ileum) and prefrontal cortex mitochondrial complex activity (complex I, II, IV). Furthermore, Pre-VPA has increased locomotor activity (actophotometer), anxiety, brain oxidative stress (thiobarbituric acid reactive species, glutathione, and catalase), nitrosative stress (nitrite/nitrate), inflammation (brain and ileum myeloperoxidase activity), calcium levels and blood brain barrier leakage in animals. Treatment with agomelatine has significantly attenuated Pre-VPA induced reduction in social interaction, spontaneous alteration, exploratory activity intestinal motility, serotonin levels and prefrontal cortex mitochondrial complex activity. Furthermore, agomelatine also attenuated Pre-VPA induced increase in locomotion, anxiety, brain oxidative stress, nitrosative stress, inflammation, calcium levels and blood brain barrier leakage. It is concluded that, Pre-VPA has induced autism spectrum disorder, which was attenuated by agomelatine. Agomelatine has shown ameliorative effect on behavioral, neurochemical and blood brain barrier alteration in Pre-VPA exposed animals. Thus melatonin receptor agonists may provide beneficial therapeutic strategy for managing autism spectrum disorder.
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15. Lim CK, Essa MM, de Paula Martins R, Lovejoy DB, Bilgin AA, Waly MI, Al-Farsi YM, Al-Sharbati M, Al-Shaffae MA, Guillemin GJ. {{Altered kynurenine pathway metabolism in autism: Implication for immune-induced glutamatergic activity}}. {Autism Res}. 2015.
Dysfunction of the serotoninergic and glutamatergic systems is implicated in the pathogenesis of autism spectrum disorder (ASD) together with various neuroinflammatory mediators. As the kynurenine pathway (KP) of tryptophan degradation is activated in neuroinflammatory states, we hypothesized that there may be a link between inflammation in ASD and enhanced KP activation resulting in reduced serotonin synthesis from tryptophan and production of KP metabolites capable of modulating glutamatergic activity. A cross-sectional study of 15 different Omani families with newly diagnosed children with ASD (n = 15) and their age-matched healthy siblings (n = 12) was designed. Immunological profile and the KP metabolic signature were characterized in the study participants. Our data indicated that there were alterations to the KP in ASD. Specifically, increased production of the downstream metabolite, quinolinic acid, which is capable of enhancing glutamatergic neurotransmission was noted. Correlation studies also demonstrated that the presence of inflammation induced KP activation in ASD. Until now, previous studies have failed to establish a link between inflammation, glutamatergic activity, and the KP. Our findings also suggest that increased quinolinic acid may be linked to 16p11.2 mutations leading to abnormal glutamatergic activity associated with ASD pathogenesis and may help rationalize the efficacy of sulforaphane treatment in ASD. Autism Res 2015. (c) 2015 International Society for Autism Research, Wiley Periodicals, Inc.
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16. McDuffie A, Oakes A, Machalicek W, Ma M, Bullard L, Nelson S, Abbeduto L. {{Early language intervention using distance video-teleconferencing: A pilot study of young males with fragile X syndrome and their mothers}}. {Am J Speech Lang Pathol}. 2015.
Purpose: This study examined the effects of a naturalistic parent-implemented language intervention on the use of verbally responsive language by mothers of six young males with fragile X syndrome (FXS). The intervention included parent education sessions and clinician coaching delivered onsite and by distance video-teleconferencing. Method: A single-case multiple baseline across participants was used to examine intervention effects on maternal use of language support strategies. A nonparametric analysis was used to evaluate the relative effectiveness of onsite compared to distance coaching sessions. Results: Mothers increased their use of utterances that followed into their child’s focus of attention and prompted child communication acts. Intervention effects were not observed for maternal contingent responses to child communication possibly due to the limited number of spontaneous communication acts children produced. Children showed moderate increases in the use of prompted communication acts while intervention effects on spontaneous communication acts were more modest and variable. Comparable increases in maternal strategy use were observed during onsite and distance sessions. Conclusion: No previous study has examined a distance-delivered parent-implemented language intervention for young males with FXS. Mothers were able to increase their use of verbally responsive language. Intervention efficacy might be enhanced by incorporating an AAC device for some children and a more concerted focus on increasing the frequency of child communication acts. Findings provide preliminary support for the efficacy of the distance delivery format.
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17. McMahon CM, Henderson HA, Newell L, Jaime M, Mundy P. {{Metacognitive Awareness of Facial Affect in Higher-Functioning Children and Adolescents with Autism Spectrum Disorder}}. {J Autism Dev Disord}. 2015.
Higher-functioning participants with and without autism spectrum disorder (ASD) viewed a series of face stimuli, made decisions regarding the affect of each face, and indicated their confidence in each decision. Confidence significantly predicted accuracy across all participants, but this relation was stronger for participants with typical development than participants with ASD. In the hierarchical linear modeling analysis, there were no differences in face processing accuracy between participants with and without ASD, but participants with ASD were more confident in their decisions. These results suggest that individuals with ASD have metacognitive impairments and are overconfident in face processing. Additionally, greater metacognitive awareness was predictive of better face processing accuracy, suggesting that metacognition may be a pivotal skill to teach in interventions.
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18. Munde V, Vlaskamp C, Ter Haar A. {{Social-emotional instability in individuals with Rett syndrome: parents’ experiences with second stage behaviour}}. {J Intellect Disabil Res}. 2015.
BACKGROUND: While the medical profession often terms behaviours in individuals with Rett syndrome (RTT) in the second stage as ‘autistic-like’, parents disagree with this description. The present study focuses on a comparison of parents’ experiences with the social-emotional behaviour of the child with RTT in the second and subsequent stages. METHOD: In collaboration with the Dutch Rett Syndrome Organization, 51 parents of children with RTT in the Netherlands took part in the present study. Parents completed an online questionnaire to clarify their experiences of the social-emotional behaviour of their children during and after the second stage of RTT. Both quantitative and qualitative analysis techniques have been used. RESULTS: The results of the paired-samples t-test show that parents see significantly less social-emotional behaviour in the children during the second stage of RTT than in the subsequent stages. Parents reported that their children did not seek as much interaction. From the parents’ descriptions, it would seem that the children are willing but unable to interact with their environment. CONCLUSIONS: Like previous research, our study leads to doubts about the appropriateness of the label ‘autistic-like’ for the behaviour of individuals in the second stage of RTT. While behaviours of individuals with autism and individuals with RTT may resemble each other, quality and intentions may differ. Still, future studies are needed for further clarification.
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19. Patel I, Erickson SR, Caldwell CH, Woolford SJ, Bagozzi RP, Chang J, Balkrishnan R. {{Predictors of medication adherence and persistence in Medicaid enrollees with developmental disabilities and type 2 diabetes}}. {Res Social Adm Pharm}. 2015.
BACKGROUND: The prevalence of diabetes mellitus is high among patients with developmental disabilities (cerebral palsy, autism, Down’s syndrome and cognitive disabilities). OBJECTIVES: The purpose of this study was to examine the racial health disparities in medication adherence and medication persistence in developmentally disabled adults with type 2 diabetes enrolled in Medicaid. METHODS: This was a retrospective cohort study using the MarketScan(R) Multi-State Medicaid Database. Adults aged 18-64 years with a prior diagnosis of a developmental disability (cerebral palsy/autism/down’s/cognitive disabilities) and a new diagnosis of type 2 diabetes enrolled in Medicaid from January 1, 2004 and December 31, 2006, were included. Adults were included if they had a continuous enrollment for at least 12 months and were excluded if they were dual eligible. Anti-diabetes medication adherence and diabetes medication persistence were measured using multivariate logistic regression and the Cox-proportional hazard regression, respectively. RESULTS: The study population comprised of 1529 patients. Although overall diabetes medication adherence in this population was optimal, African Americans had significantly lower odds (25%) of adhering to anti-diabetes medications compared to Caucasians (OR = 0.75, 95% CI = 0.58-0.97, P < 0.05). Also, after controlling for other covariates, the rate of discontinuation was higher in African Americans compared to Caucasians (hazard ratio = 1.03, 95% CI = 0.91-1.18, P < 0.629). CONCLUSION: In this study, racial disparities were found in anti-diabetes medication adherence among Medicaid enrollees with developmental disabilities (DD). Studies conducted in the future should examine predictors that impact access to care, availability of primary and specialized care, social support as well as beliefs of racial minority populations with developmental disabilities and chronic conditions like diabetes to optimize medication use outcomes in this especially vulnerable population. Lien vers le texte intégral (Open Access ou abonnement)
20. Randel A, Adlof S, Klusek J, Roberts J. {{Teaching reading to youth with fragile X syndrome: Should phonemic awareness and phonics instruction be used?}}. {EBP Briefs}. 2015; 9(6): 47-61.
CLINICAL QUESTION: Would a child with fragile X syndrome benefit more from phonemic awareness and phonics instruction or whole-word training to increase reading skills? METHOD: Systematic review. STUDY SOURCES: PsycINFO. SEARCH TERMS: Fragile X or Down Syndrome or Cognitive Impairment or Cognitive Deficit or Cognitive Disability or Intellectual Disorder or Intellectual Delay or Intellectual Disability or Mental Retardation AND Whole Word or Sight Word or Phonological Awareness or Phonics. NUMBER OF STUDIES INCLUDED: FXS = 0; DS = 6; ID = 17. PRIMARY RESULTS: There are currently no published peer-reviewed treatment studies testing reading interventions for children with fragile X syndrome.Phonological awareness and reading outcomes are correlated in children with fragile X syndrome, similar to the pattern seen in typical development.There is converging empirical evidence that phonologically-based approaches, often included as part of a comprehensive program, can be beneficial with children and adolescents with other developmental disabilities, including Down syndrome, intellectual disabilities, and autism spectrum disorder. CONCLUSIONS: There is a need for more research to determine what types of reading interventions are beneficial when working with children with fragile X syndrome. Given the lack of published empirical research in this area, clinicians should rely on existing evidence-based treatment data and professional judgment when determining which course of treatment to implement.
21. Rice ML. {{Specific Language Impairment, Nonverbal IQ, ADHD, ASD, Cochlear Implants, Bilingualism and Dialectal Variants: Defining the boundaries, clarifying clinical conditions and sorting out causes}}. {J Speech Lang Hear Res}. 2015.
Purpose: The purpose of this paper is to provide an overview of a collection of invited papers on the topic « Specific Language Impairment (SLI) in Children with Concomitant Health Conditions or Nonmainstream Language Backgrounds. » Topics include SLI, Attention Deficit/Hyperactivity Disorder (ADHD), Autism Spectrum Disorder (ASD), Cochlear Implants (CI), Bilingualism and Dialectal language learning contexts. Method: The topic is timely due to current debates about the diagnosis of SLI. An overarching comparative conceptual framework is provided for comparisons of SLI to other clinical conditions. Comparisons of SLI in children with low normal or normal nonverbal IQ illustrate the unexpected outcomes of 2 x 2 comparison designs. Results: Comparative studies reveal unexpected relationships among speech, language, cognitive and social dimensions of children’s development, as well as precise ways to identify children with SLI who are bilingual or dialect speakers. Conclusions: The diagnosis of SLI is essential for elucidating possible causal pathways of language impairments, risks for language impairments, assessments for identification of language impairments, linguistic dimensions of language impairments, and long-term outcomes. Although children’s language acquisition is robust under high levels of risk, unexplained individual variations in language acquisition lead to persistent language impairments.
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22. Sato JR, Balardin J, Vidal MC, Fujita A. {{Identification of segregated regions in the functional brain connectome of autistic patients by a combination of fuzzy spectral clustering and entropy analysis}}. {J Psychiatry Neurosci}. 2015; 41(1): 140364.
BACKGROUND: Several neuroimaging studies support the model of abnormal development of brain connectivity in patients with autism-spectrum disorders (ASD). In this study, we aimed to test the hypothesis of reduced functional network segregation in autistic patients compared with controls. METHODS: Functional MRI data from children acquired under a resting-state protocol (Autism Brain Imaging Data Exchange [ABIDE]) were submitted to both fuzzy spectral clustering (FSC) with entropy analysis and graph modularity analysis. RESULTS: We included data from 814 children in our analysis. We identified 5 regions of interest comprising the motor, temporal and occipitotemporal cortices with increased entropy (p < 0.05) in the clustering structure (i.e., more segregation in the controls). Moreover, we noticed a statistically reduced modularity (p < 0.001) in the autistic patients compared with the controls. Significantly reduced eigenvector centrality values (p < 0.05) in the patients were observed in the same regions that were identified in the FSC analysis. LIMITATIONS: There is considerable heterogeneity in the fMRI acquisition protocols among the sites that contributed to the ABIDE data set (e.g., scanner type, pulse sequence, duration of scan and resting-state protocol). Moreover, the sites differed in many variables related to sample characterization (e.g., age, IQ and ASD diagnostic criteria). Therefore, we cannot rule out the possibility that additional differences in functional network organization would be found in a more homogeneous data sample of individuals with ASD. CONCLUSION: Our results suggest that the organization of the whole-brain functional network in patients with ASD is different from that observed in controls, which implies a reduced modularity of the brain functional networks involved in sensorimotor, social, affective and cognitive processing. Lien vers Pubmed
23. Siniscalco D. {{Commentary: The Impact of Neuroimmune Alterations in Autism Spectrum Disorder}}. {Front Psychiatry}. 2015; 6: 145.
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24. Siu WK, Lam CW, Gao WW, Tang VH, Jin DY, Mak CM. {{Unmasking a novel disease gene NEO1 associated with autism spectrum disorders by a hemizygous deletion on chromosome 15 and a functional polymorphism}}. {Behav Brain Res}. 2015.
BACKGROUND: Autism spectrum disorders (ASD) are neurodevelopment disorders with a high degree of heritability, but the genetic basis is exceedingly heterogeneous. Microdeletion of chromosome 15q24 has been described as a recurrent genomic imbalance in ASD patients. Of interest, neuronal migration genes are of particular relevance to the pathogenesis of ASD. NEO1 is located in 15q24 and encodes for neogenin, a membrane receptor involved in cortical interneuron migration and axon guidance. We postulated that the ASD patient has one copy of the NEO1 gene deleted and the other copy disrupted by intrageneic mutation. RESULTS: We identify genetic changes in both alleles of NEO1 in two individuals from a cohort of 66Han Chinese patients with ASD. In one patient, we detected a hemizygous 1.97-Mb deletion at 15q23q24.1 encompassing the NEO1 gene, a missense variant in NEO1, c.3388C>T (p.Arg1130Cys), and a duplication, c.2204-14_2204-2dup, in the acceptor splice site of intron 14 of NEO1. Furthermore, we identified a second patient was a compound heterozygote for NEO1. A novel missense variant in NEO1, c.302G>A (p.Arg101His), in addition to c.3388C>T and c.2204-14_2204-2dup was detected in the second patient. The c.3388C>T is a single nucleotide polymorphism with allele frequency of 0.045 in Han Chinese individuals. In silico and functional analyses indicated that p.Arg1130Cys, located in the nuclear localization signal (NLS) domain of neogenin led to defective nuclear translocation of neogenin. CONCLUSIONS: The hemizygous 15q deletion unmasks the recessive functional polymorphism in NEO1 which plays a pivotal role in cortical interneuron development. Our study provides the first evidence linking NEO1 with ASD in humans.
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25. Tager-Flusberg H. {{Risk Factors Associated with Language in Autism Spectrum Disorder: Clues to Underlying Mechanisms}}. {J Speech Lang Hear Res}. 2015.
Purpose: Identifying risk factors associated with neurodevelopmental disorders is an important line of research, as it will lead to the earlier identification of children who could benefit from interventions that support optimal developmental outcomes. The primary goal of this review is to summarize research on risk factors associated with autism spectrum disorder. Method: The review focused on studies on infants who have older siblings with ASD, with particular emphasis on risk factors associated with language impairments that affect the majority of children with ASD. Findings from this body of work were compared to the literature on SLI. Results: A wide range of risk factors has been found for ASD, including demographic (e.g., male, family history), behavioral (e.g., gesture, motor) and neural risk markers (e.g., atypical lateralization for speech and reduced functional connectivity). Environmental factors, such as caregiver interaction were not found to predict language outcomes. Many of the risk markers for ASD are also found in studies of risk for SLI including demographic, behavioral and neural factors. Conclusions: There are significant gaps in the literature, and limitations in the current research that preclude direct cross-syndrome comparisons. Future research directions are outlined that could address these limitations.
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26. Volkmar FR, McPartland JC. {{Moving beyond a categorical diagnosis of autism}}. {Lancet Neurol}. 2015.
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27. Yatawara CJ, Einfeld SL, Hickie IB, Davenport TA, Guastella AJ. {{The effect of oxytocin nasal spray on social interaction deficits observed in young children with autism: a randomized clinical crossover trial}}. {Mol Psychiatry}. 2015.
Interventions for autism are limited. The synthetic hormone oxytocin may provide a potential treatment to improve core social and behavioral difficulties in autism, but its efficacy has yet to be evaluated in young children who potentially may benefit to a greater extent. We investigated the efficacy, tolerability and safety of oxytocin treatment in young children with autism using a double-blind, randomized, placebo-controlled, crossover, clinical trial. Thirty-one children with autism received 12 International Units (IU) of oxytocin and placebo nasal spray morning and night (24 IU per day) for 5 weeks, with a 4-week washout period between each treatment. Compared with placebo, oxytocin led to significant improvements on the primary outcome of caregiver-rated social responsiveness. Overall, nasal spray was well tolerated, and the most common reported adverse events were thirst, urination and constipation. This study is the first clinical trial to support the potential of oxytocin as an early intervention for young children with autism to help improve social interaction deficits.Molecular Psychiatry advance online publication, 27 October 2015; doi:10.1038/mp.2015.162.
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28. Ziats MN, Grosvenor LP, Rennert OM. {{Functional genomics of human brain development and implications for autism spectrum disorders}}. {Transl Psychiatry}. 2015; 5: e665.
Transcription of the inherited DNA sequence into copies of messenger RNA is the most fundamental process by which the genome functions to guide development. Encoded sequence information, inherited epigenetic marks and environmental influences all converge at the level of mRNA gene expression to allow for cell-type-specific, tissue-specific, spatial and temporal patterns of expression. Thus, the transcriptome represents a complex interplay between inherited genomic structure, dynamic experiential demands and external signals. This property makes transcriptome studies uniquely positioned to provide insight into complex genetic-epigenetic-environmental processes such as human brain development, and disorders with non-Mendelian genetic etiologies such as autism spectrum disorders. In this review, we describe recent studies exploring the unique functional genomics profile of the human brain during neurodevelopment. We then highlight two emerging areas of research with great potential to increase our understanding of functional neurogenomics-non-coding RNA expression and gene interaction networks. Finally, we review previous functional genomics studies of autism spectrum disorder in this context, and discuss how investigations at the level of functional genomics are beginning to identify convergent molecular mechanisms underlying this genetically heterogeneous disorder.
