1. Baron-Cohen S, Johnson D, Asher J, Wheelwright S, Fisher SE, Gregersen PK, Allison C. {{Is synaesthesia more common in autism?}}. {Mol Autism};2013 (Nov 20);4(1):40.
BACKGROUND: Synaesthesia is a neurodevelopmental condition in which a sensation in one modality triggers a perception in a second modality. Autism (shorthand for Autism Spectrum Conditions) is a neurodevelopmental condition involving social-communication disability alongside resistance to change and unusually narrow interests or activities. Whilst on the surface they appear distinct, they have been suggested to share common atypical neural connectivity. METHODS: In the present study, we carried out the first prevalence study of synaesthesia in autism to formally test whether these conditions are independent. After exclusions, 164 adults with autism and 97 controls completed a synaesthesia questionnaire, autism spectrum quotient, and test of genuineness-revised (ToG-R) online. RESULTS: The rate of synaesthesia in adults with autism was 18.9% (31 out of 164), almost three times greater than in controls (7.22%, 7 out of 97, P <0.05). ToG-R proved unsuitable for synaesthetes with autism. CONCLUSIONS: The significant increase in synaesthesia prevalence in autism suggests that the two conditions may share some common underlying mechanisms. Future research is needed to develop more feasible validation methods of synaesthesia in autism.
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2. Casanova MF, El-Baz AS, Kamat SS, Dombroski BA, Khalifa F, Elnakib A, Soliman A, Allison-McNutt A, Switala AE. {{Focal cortical dysplasias in autism spectrum disorders}}. {Acta Neuropathol Commun};2013;1(1):67.
BACKGROUND: Previous reports indicate the presence of histological abnormalities in the brains of individuals with autism spectrum disorders (ASD) suggestive of a dysplastic process. In this study we identified areas of abnormal cortical thinning within the cerebral cortex of ASD individuals and examined the same for neuronal morphometric abnormalities by using computerized image analysis. RESULTS: The study analyzed celloidin-embedded and Nissl-stained serial full coronal brain sections of 7 autistic (ADI-R diagnosed) and 7 age/sex-matched neurotypicals. Sections were scanned and manually segmented before implementing an algorithm using Laplace’s equation to measure cortical width. Identified areas were then subjected to analysis for neuronal morphometry. Results of our study indicate the presence within our ASD population of circumscribed foci of diminished cortical width that varied among affected individuals both in terms of location and overall size with the frontal lobes being particularly involved. Spatial statistic indicated a reduction in size of neurons within affected areas. Granulometry confirmed the presence of smaller pyramidal cells and suggested a concomitant reduction in the total number of interneurons. CONCLUSIONS: The neuropathology is consistent with a diagnosis of focal cortical dysplasia (FCD). Results from the medical literature (e.g., heterotopias) and our own study suggest that the genesis of this cortical malformation seemingly resides in the heterochronic divisions of periventricular germinal cells. The end result is that during corticogenesis radially migrating neuroblasts (future pyramidal cells) are desynchronized in their development from those that follow a tangential route (interneurons). The possible presence of a pathological mechanism in common among different conditions expressing an autism-like phenotype argue in favor of considering ASD a « sequence » rather than a syndrome. Focal cortical dysplasias in ASD may serve to explain the high prevalence of seizures and sensory abnormalities in this patient population.
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3. Frackowiak J, Mazur-Kolecka B, Schanen NC, Brown WT, Wegiel J. {{The link between intraneuronal N-truncated amyloid-beta peptide and oxidatively modified lipids in idiopathic autism and dup(15q11.2-q13)/autism}}. {Acta Neuropathol Commun};2013;1(1):61.
BACKGROUND: Autism is a neurodevelopmental disorder of unknown etiopathogenesis associated with structural and functional abnormalities of neurons and increased formation of reactive oxygen species. Our previous study revealed enhanced accumulation of amino-terminally truncated amyloid-beta (Abeta) in brain neurons and glia in children and adults with autism. Verification of the hypothesis that intraneuronal Abeta may cause oxidative stress was the aim of this study. RESULTS: The relationships between neuronal Abeta and oxidative stress markers-4-hydroxy-2-nonenal (HNE) and malondialdehyde (MDA)-were examined in the frontal cortex from individuals aged 7-32 years with idiopathic autism or with chromosome 15q11.2-q13 duplications (dup(15)) with autism, and age-matched controls. Quantification of confocal microscopy images revealed significantly higher levels of neuronal N-truncated Abeta and HNE and MDA in idiopathic autism and dup(15)/autism than in controls. Lipid peroxidation products were detected in all mitochondria and lipofuscin deposits, in numerous autophagic vacuoles and lysosomes, and in less than 5% of synapses. Neuronal Abeta was co-localized with HNE and MDA, and increased Abeta levels correlated with higher levels of HNE and MDA. CONCLUSIONS: The results suggest a self-enhancing pathological process in autism that is initiated by intraneuronal deposition of N-truncated Abeta in childhood. The cascade of events includes altered APP metabolism and abnormal intracellular accumulation of N-terminally truncated Abeta which is a source of reactive oxygen species, which in turn increase the formation of lipid peroxidation products. The latter enhance Abeta deposition and sustain the cascade of changes contributing to metabolic and functional impairments of neurons in autism of an unknown etiology and caused by chromosome 15q11.2-q13 duplication.
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4. Gomez-Mancilla B, Berry-Kravis E, Hagerman R, von Raison F, Apostol G, Ufer M, Gasparini F, Jacquemont S. {{Development of mavoglurant and its potential for the treatment of fragile X syndrome}}. {Expert Opin Investig Drugs};2013 (Nov 20)
Introduction: Fragile X syndrome (FXS) is the most common inherited cause of intellectual disability. With no curative treatment available, current therapeutic approaches are aimed at symptom management. FXS is caused by silencing the FMR1 gene, which encodes FMRP; as loss of FMRP leads to the development of symptoms associated with FXS. Areas covered: In this evaluation, the authors examine the role of the metabotropic glutamate receptor 5 (mGluR5) in the pathophysiology of FXS, and its suitability as a target for rescuing the disease state. Furthermore, the authors review the evidence from preclinical studies of pharmacological interventions targeting mGluR5 in FXS. Lastly, the authors assess the findings from clinical studies in FXS, in particular the use of the Aberrant Behavior Checklist-Community Edition (ABC-C) and the recently developed ABC-C for FXS scale, as clinical endpoints to assess disease modification in this patient population. Expert opinion: There is cautious optimism for the successful treatment of the core behavioral and cognitive symptoms of FXS based on preclinical data in animal models and early studies in humans. However, the association between mGluR5-heightened responsiveness and the clinical phenotype in humans remains to be demonstrated. Many questions regarding the optimal treatment and outcome measures of FXS remain unanswered.
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5. Hamilton PJ, Campbell NG, Sharma S, Erreger K, Hansen FH, Saunders C, Belovich AN, Sahai MA, Cook EH, Gether U, McHaourab HS, Matthies HJ, Sutcliffe JS, Galli A. {{Drosophila melanogaster: a novel animal model for the behavioral characterization of autism-associated mutations in the dopamine transporter gene}}. {Mol Psychiatry};2013 (Dec);18(12):1235.
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6. Kenworthy L, Anthony LG, Naiman DQ, Cannon L, Wills MC, Luong-Tran C, Werner MA, Alexander KC, Strang J, Bal E, Sokoloff JL, Wallace GL. {{Randomized controlled effectiveness trial of executive function intervention for children on the autism spectrum}}. {J Child Psychol Psychiatry};2013 (Nov 21)
BACKGROUND: Unstuck and On Target (UOT) is an executive function (EF) intervention for children with autism spectrum disorders (ASD) targeting insistence on sameness, flexibility, goal-setting, and planning through a cognitive-behavioral program of self-regulatory scripts, guided/faded practice, and visual/verbal cueing. UOT is contextually-based because it is implemented in school and at home, the contexts in which a child uses EF skills. METHODS: To evaluate the effectiveness of UOT compared with a social skills intervention (SS), 3rd-5th graders with ASD (mean IQ = 108; UOT n = 47; SS n = 20) received interventions delivered by school staff in small group sessions. Students were matched for gender, age, race, IQ, ASD symptomotolgy, medication status, and parents’ education. Interventions were matched for ‘dose’ of intervention and training. Measures of pre-post change included classroom observations, parent/teacher report, and direct child measures of problem-solving, EF, and social skills. Schools were randomized and evaluators, but not parents or teachers, were blinded to intervention type. RESULTS: Interventions were administered with high fidelity. Children in both groups improved with intervention, but mean change scores from pre- to postintervention indicated significantly greater improvements for UOT than SS groups in: problem-solving, flexibility, and planning/organizing. Also, classroom observations revealed that participants in UOT made greater improvements than SS participants in their ability to follow rules, make transitions, and be flexible. Children in both groups made equivalent improvements in social skills. CONCLUSIONS: These data support the effectiveness of the first contextually-based EF intervention for children with ASD. UOT improved classroom behavior, flexibility, and problem-solving in children with ASD. Individuals with variable background/training in ASD successfully implemented UOT in mainstream educational settings.
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7. O’Keefe JA, Orias AA, Khan H, Hall DA, Berry-Kravis E, Wimmer MA. {{Implementation of a markerless motion analysis method to quantify hyperkinesis in males with fragile X syndrome}}. {Gait Posture};2013 (Oct 28)
Hyperactive behavior – and implicitly, motion – in Fragile X syndrome (FXS) has been historically described using behavioral rating scales. While rating scales are the current standard outcome measures used in clinical research, they have limitations including their qualitative nature and subjectivity. The advent of new motion capture technologies has provided the opportunity to develop quantitative methods for measuring hyperactive motion. The hypotheses for this study were that a novel markerless motion analysis method (1) can quantitatively measure kinematic parameters, (2) can differentiate the level of hyperkinesis between control and FXS populations, and (3) will correlate with blind-reviewer synchronous video-capture methods and behavioral rating scale scores. Twenty young males (7-control, 13-FXS; ages 9-32) were studied using a standardized protocol in a markerless motion analysis suite. Behavioral scale questionnaires were filled out by parents and those scores were correlated with motion parameters (frequency and total traveled distance) of body segments during 30s of story listening while standing in the observation space. The markerless system was able to track subjects and the two populations displayed significantly different quantities of motion, with larger amounts of motion in the FXS group (p<0.05). Pearson’s correlation coefficients between frequency counts obtained from the markerless system and rater-based video capture were between 0.969 and 0.996 (p<0.001). Significant correlations between rating scale scores and motion parameters ranged from 0.462</=r</=0.568 (p</=0.040). These results suggest feasibility and validity of a markerless system as a non-invasive method able to quantify motion in individuals with hyperkinesis.
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8. Sorensen MJ, Gronborg TK, Christensen J, Parner ET, Vestergaard M, Schendel D, Pedersen LH. {{Antidepressant exposure in pregnancy and risk of autism spectrum disorders}}. {Clin Epidemiol};2013;5:449-459.
BACKGROUND: Both the use of antidepressant medication during pregnancy and the prevalence of autism spectrum disorder have increased during recent years. A causal link has recently been suggested, but the association may be confounded by the underlying indication for antidepressant use. We investigated the association between maternal use of antidepressant medication in pregnancy and autism, controlling for potential confounding factors. METHODS: We identified all children born alive in Denmark 1996-2006 (n=668,468) and their parents in the Danish Civil Registration System. We obtained information on the mother’s prescriptions filled during pregnancy from the Danish National Prescription Registry, and on diagnoses of autism spectrum disorders in the children and diagnoses of psychiatric disorders in the parents from the Danish Psychiatric Central Register. In a cohort analysis, we estimated hazard ratios of autism spectrum disorders in children exposed to antidepressant medication during pregnancy compared with children who were not exposed, using Cox proportional hazards regression analysis. Furthermore, we estimated the risk for autism spectrum disorder in a sibling design. RESULTS: Children exposed prenatally to antidepressants had an adjusted hazard ratio of 1.5 (95% confidence interval [CI] 1.2-1.9) for autism spectrum disorder compared with unexposed children. Restricting the analysis to children of women with a diagnosis of affective disorder, the adjusted hazard ratio was 1.2 (95% CI 0.7-2.1), and the risk was further reduced when exposed children were compared with their unexposed siblings (adjusted hazard ratio 1.1; 95% CI 0.5-2.3). CONCLUSION: After controlling for important confounding factors, there was no significant association between prenatal exposure to antidepressant medication and autism spectrum disorders in the offspring.
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9. Vaiouli P, Grimmet K, Ruich LJ. {{« Bill is now singing »: Joint engagement and the emergence of social communication of three young children with autism}}. {Autism};2013 (Nov 19)
Young children with autism spectrum disorder meet significant challenges in joint attention skills and in social communication. A child-centered, improvisational, music therapy intervention model was implemented to promote engagement in three young children with autism in a kindergarten classroom. A multiple baseline design compared the children’s performance through three phases of intervention: focus on faces, response to joint attention, and initiation of joint attention. A complimentary qualitative analysis of teacher and parent experiences allowed for an in-depth understanding of the role of social environment in supporting emerging social communication skills among three children. As all children showed improvement in joint attention and actions of social engagement, this study bears evidence on the potential of music therapy as a promising intervention for promoting social skills of young children with autism spectrum disorder.
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10. Weiss JA, Wingsiong A, Lunsky Y. {{Defining crisis in families of individuals with autism spectrum disorders}}. {Autism};2013 (Nov 19)
Parents of children diagnosed with autism spectrum disorder often report higher levels of depression, anxiety, and mental health-related issues. The combination of stressors and family adjustment difficulties can cause distress which may develop into a crisis. Understanding crisis in the family is important to mental health practice since it can serve as a guide in delivering service to at-risk families. This study investigated the subjective experience of crisis in 155 mothers of children diagnosed with autism spectrum disorder. Thematic analysis revealed that crisis is characterized by factors influencing four major areas: demands, internal capabilities, external resources, and subjective appraisal. Understanding what crisis means to families of individuals with autism spectrum disorder can help inform effective preventative and crisis services.
