1. Anitha A, Nakamura K, Thanseem I, Matsuzaki H, Miyachi T, Tsujii M, Iwata Y, Suzuki K, Sugiyama T, Mori N. {{Downregulation of the Expression of Mitochondrial Electron Transport Complex Genes in Autism Brains}}. {Brain Pathol};2012 (Oct 23)
Mitochondrial dysfunction (MtD) and abnormal brain bioenergetics have been implicated in autism, suggesting possible candidate genes in the electron transport chain (ETC). We compared the expression of 84 ETC genes in the postmortem brains of autism patients and controls. Brain tissues from the anterior cingulate gyrus, motor cortex, and thalamus of autism patients (n=8) and controls (n=10) were obtained from Autism Tissue Program, U.S.A. Quantitative real-time PCR Arrays were used to quantify gene expression. We observed reduced expression of several ETC genes in autism brains compared to controls. 11 genes of Complex I, five genes each of Complex III and Complex IV, and seven genes of Complex V showed brain region-specific reduced expression in autism. ATP5A1 (Complex V), ATP5G3 (Complex V) and NDUFA5 (Complex I) showed consistently reduced expression in all the brain regions of autism patients. Upon silencing ATP5A1, the expression of mitogen-activated protein kinase 13 (MAPK13), a p38 MAPK responsive to stress stimuli, was upregulated in HEK 293 cells. This could have been induced by oxidative stress due to impaired ATP synthesis. We report new candidate genes involved in abnormal brain bioenergetics in autism, supporting the hypothesis that mitochondria, critical for neurodevelopment, may play a role in autism.
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2. Aoki Y, Abe O, Yahata N, Kuwabara H, Natsubori T, Iwashiro N, Takano Y, Inoue H, Kawakubo Y, Gonoi W, Sasaki H, Murakami M, Katsura M, Nippashi Y, Takao H, Kunimatsu A, Matsuzaki H, Tsuchiya KJ, Kato N, Kasai K, Yamasue H. {{Absence of age-related prefrontal NAA change in adults with autism spectrum disorders}}. {Transl Psychiatry};2012;2:e178.
Atypical trajectory of brain growth in autism spectrum disorders (ASDs) has been recognized as a potential etiology of an atypical course of behavioral development. Numerous neuroimaging studies have focused on childhood to investigate atypical age-related change of brain structure and function, because it is a period of neuron and synapse maturation. Recent studies, however, have shown that the atypical age-related structural change of autistic brain expands beyond childhood and constitutes neural underpinnings for lifelong difficulty to behavioral adaptation. Thus, we examined effects of aging on neurochemical aspects of brain maturation using 3-T proton magnetic resonance spectroscopy ((1)H-MRS) with single voxel in the medial prefrontal cortex (PFC) in 24 adult men with non-medicated high-functioning ASDs and 25 age-, IQ- and parental-socioeconomic-background-matched men with typical development (TD). Multivariate analyses of covariance demonstrated significantly high N-acetylaspartate (NAA) level in the ASD subjects compared with the TD subjects (F=4.83, P=0.033). The low NAA level showed a significant positive correlation with advanced age in the TD group (r=-0.618, P=0.001), but was not evident among the ASD individuals (r=0.258, P=0.223). Fisher’s r-to-z transformation showed a significant difference in the correlations between the ASD and TD groups (Z=-3.23, P=0.001), which indicated that the age-NAA relationship was significantly specific to people with TD. The current (1)H-MRS study provided new evidence that atypical age-related change of neurochemical aspects of brain maturation in ASD individuals expands beyond childhood and persists during adulthood.
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3. Beaudet AL. {{Neuroscience. Preventable forms of autism?}}. {Science};2012 (Oct 19);338(6105):342-343.
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4. Bhattacharya A, Kaphzan H, Alvarez-Dieppa AC, Murphy JP, Pierre P, Klann E. {{Genetic Removal of p70 S6 Kinase 1 Corrects Molecular, Synaptic, and Behavioral Phenotypes in Fragile X Syndrome Mice}}. {Neuron};2012 (Oct 18);76(2):325-337.
Fragile X syndrome (FXS) is the leading inherited cause of autism and intellectual disability. Aberrant synaptic translation has been implicated in the etiology of FXS, but most lines of research on therapeutic strategies have targeted protein synthesis indirectly, far upstream of the translation machinery. We sought to perturb p70 ribosomal S6 kinase 1 (S6K1), a key translation initiation and elongation regulator, in FXS model mice. We found that genetic reduction of S6K1 prevented elevated phosphorylation of translational control molecules, exaggerated protein synthesis, enhanced mGluR-dependent long-term depression (LTD), weight gain, and macro-orchidism in FXS model mice. In addition, S6K1 deletion prevented immature dendritic spine morphology and multiple behavioral phenotypes, including social interaction deficits, impaired novel object recognition, and behavioral inflexibility. Our results support the model that dysregulated protein synthesis is the key causal factor in FXS and that restoration of normal translation can stabilize peripheral and neurological function in FXS.
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5. Drahota A, Stadnick N, Brookman-Frazee L. {{Therapist Perspectives on Training in a Package of Evidence-Based Practice Strategies for Children with Autism Spectrum Disorders Served in Community Mental Health Clinics}}. {Adm Policy Ment Health};2012 (Oct 21)
Therapist perspectives regarding delivery of evidence-based practice (EBP) strategies are needed to understand the feasibility of implementation in routine service settings. This qualitative study examined the perspectives of 13 therapists receiving training and delivering a package of EBPs to children with autism spectrum disorders (ASDs) in community mental health clinics. Therapists perceived the training and intervention delivery as effective at improving their clinical skills, the psychotherapy process, and child and family outcomes. Results expand parent pilot study findings, and add to the literature on training community providers and limited research on training providers to deliver EBPs to children with ASD.
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6. Kalkman HO. {{A review of the evidence for the canonical Wnt pathway in autism spectrum disorders}}. {Mol Autism};2012 (Oct 19);3(1):10.
ABSTRACT: Microdeletion and microduplication copy number variations are found in patients with autism spectrum disorder and in a number of cases they include genes that are involved in the canonical Wnt signaling pathway (for example, FZD9, BCL9 or CDH8). Association studies investigating WNT2, DISC1, MET, DOCK4 or AHI1 also provide evidence that the canonical Wnt pathway might be affected in autism. Prenatal medication with sodium-valproate or antidepressant drugs increases autism risk. In animal studies, it has been found that these medications promote Wnt signaling, including among others an increase in Wnt2 gene expression. Notably, the available genetic information indicates that not only canonical Wnt pathway activation, but also inhibition seems to increase autism risk. The canonical Wnt pathway plays a role in dendrite growth and suboptimal activity negatively affects the dendritic arbor. In principle, this provides a logical explanation as to why both hypo- and hyperactivity may generate a similar set of behavioral and cognitive symptoms. However, without a validated biomarker to stratify for deviant canonical Wnt pathway activity, it is probably too dangerous to treat patients with compounds that modify pathway activity.
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7. Laugeson EA. {{Review: social skills groups may improve social competence in children and adolescents with autism spectrum disorder}}. {Evid Based Ment Health};2012 (Oct 23)
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8. Nava C, Lamari F, Heron D, Mignot C, Rastetter A, Keren B, Cohen D, Faudet A, Bouteiller D, Gilleron M, Jacquette A, Whalen S, Afenjar A, Perisse D, Laurent C, Dupuits C, Gautier C, Gerard M, Huguet G, Caillet S, Leheup B, Leboyer M, Gillberg C, Delorme R, Bourgeron T, Brice A, Depienne C. {{Analysis of the chromosome X exome in patients with autism spectrum disorders identified novel candidate genes, including TMLHE}}. {Transl Psychiatry};2012;2:e179.
The striking excess of affected males in autism spectrum disorders (ASD) suggests that genes located on chromosome X contribute to the etiology of these disorders. To identify new X-linked genes associated with ASD, we analyzed the entire chromosome X exome by next-generation sequencing in 12 unrelated families with two affected males. Thirty-six possibly deleterious variants in 33 candidate genes were found, including PHF8 and HUWE1, previously implicated in intellectual disability (ID). A nonsense mutation in TMLHE, which encodes the varepsilon-N-trimethyllysine hydroxylase catalyzing the first step of carnitine biosynthesis, was identified in two brothers with autism and ID. By screening the TMLHE coding sequence in 501 male patients with ASD, we identified two additional missense substitutions not found in controls and not reported in databases. Functional analyses confirmed that the mutations were associated with a loss-of-function and led to an increase in trimethyllysine, the precursor of carnitine biosynthesis, in the plasma of patients. This study supports the hypothesis that rare variants on the X chromosome are involved in the etiology of ASD and contribute to the sex-ratio disequilibrium.
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9. Paula-Perez I. {{Differential diagnosis between obsessive compulsive disorder and restrictive and repetitive behavioural patterns, activities and interests in autism spectrum disorders}}. {Rev Psiquiatr Salud Ment};2012 (Sep 13)
INTRODUCTION: The obsessive compulsive disorder (OCD) and the restricted and repetitive patterns of behavior, interests and activities inherent to autism spectrum disorders (ASD) share a number of features that can make the differential diagnosis between them extremely difficult and lead to erroneous overdiagnosis of OCD in people with autism. DEVELOPMENT: In both cases there may appear to have a fixation on routine, ritualized patterns of verbal and nonverbal behavior, resistance to change, and highly restrictive interests, which becomes a real challenge for differentiating rituals, stereotypes and adherence to routines in ASD from obsessions and compulsions in OCD. This article provides key points to clarify this differential diagnosis through the analysis of emotional valence, content, function and psychological theories that explain the obsessions and compulsions in OCD, and the desire for sameness, stereotyped movements and limited interest in autism. CONCLUSION: The terms « obsession » and « compulsion » should no longer be used when referring to patterns of behavior, interests or restricted and repetitive activities in autism due to syntonic characteristics, low perception of personal responsibility and low neutralizing efforts. Treatment focuses on changing the environment, the use of socio-communicative compensatory strategies and behavioral modification techniques to improve cognitive and behavioral flexibility. When there is comorbidity between, exposure behavioral and response prevention techniques are then used, followed by others of more cognitive orientation if necessary.
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10. Plumb AM, Plexico LW. {{Autism Spectrum Disorders: Experience, Training and Confidence Levels of School-Based Speech-Language Pathologists}}. {Lang Speech Hear Serv Sch};2012 (Oct 19)
PURPOSE: To investigate the graduate training experiences of school-based speech-language pathologists (SLPs) working with children with autism spectrum disorders (ASDs). Comparisons were made between recent graduates (post-2006) and pre-2006 graduates to investigate if differences existed in their academic and clinical experiences or their confidence in working with this population. METHOD: A 47-item, web-based, national survey was created to address the purposes of this investigation. Participants were recruited through e-mail and listservs for ASHA special interest divisions 1 (Language, Learning, and Education) and 16 (School-Based Issues). RESULTS: Recent graduates reported a greater amount of graduate coursework relating to ASDs than pre-2006 graduates. However, the pre-2006 graduates reported significantly greater confidence in the areas of counseling parents of children who exhibit « red flags » of ASDs and addressing social communication, as well as literacy and academics in intervention. CONCLUSIONS: Results of the current survey indicated an increase in the amount of pre-professional training that SLPs receive relating to ASDs. Nonetheless, the majority reported that they could have benefitted from additional clinical experience and training working with children with ASDs. The greater degree of confidence reported by the pre-2006 graduates highlights the importance of experience and continuing education for professionals in the field.
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11. Post SG, Pomeroy J, Keirns CC, Cover VI, Dorn ML, Boroson L, Boroson F, Coulehan A, Coulehan J, Covell K, Kubasek K, Luchsinger E, Nichols S, Parles J, Schreiber L, Tetenbaum SP, Walsh RA. {{Brief Report: Stony Brook Guidelines on the Ethics of the Care of People with Autism and Their Families}}. {J Autism Dev Disord};2012 (Oct 20)
The increased prevalence of autism spectrum disorders (ASD), with associated societal and clinical impacts, calls for a broad community-based dialogue on treatment related ethical and social issues. The Stony Brook Guidelines, based on a community dialogue process with affected individuals, families and professionals, identify and discuss the following topics: treatment goals and happiness, distributive justice, managing the hopes for a cure, sibling responsibilities, intimacy and sex, diagnostic ethics, and research ethics. Our guidelines, based not on « top-down » imposition of professional expertise but rather on « bottom-up » grass roots attention to the voices of affected individuals and families speaking from experience, can inform clinical practice and are also meaningful for the wider social conversation emerging over the treatment of individuals with ASD.
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12. Spooren W, Lindemann L, Ghosh A, Santarelli L. {{Synapse dysfunction in autism: a molecular medicine approach to drug discovery in neurodevelopmental disorders}}. {Trends Pharmacol Sci};2012 (Oct 17)
Autism and autism spectrum disorders (ASDs) affect millions of individuals worldwide. Despite increased autism diagnoses over the past 30 years, therapeutic intervention is often ‘trial and error’. This approach has identified some beneficial agents, but complex heterogeneous disorders require a more personalized treatment regimen. Many ASD risk factors are genetic, implicating impaired synaptic development and function. Monogenetic disorders (e.g., fragile X syndrome, Rett syndrome, and neurofibromatosis) that have phenotypic overlap with autism provide insights into ASD pathology through the identification novel drug targets (e.g., glutamatergic receptors). Encouragingly, some of these novel drug targets provide symptomatic improvement, even in patients who have lived with ASDs for protracted periods of time. Consequently, a targeted drug discovery approach is expected to deliver improved agents for the treatment and management of ASDs. Here, we review the opportunities and challenges in drug development for autism and provide insight into the neurobiology of ASDs.
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13. Wilson KP. {{Incorporating Video Modeling into School-Based Intervention for Students with Autism Spectrum Disorders}}. {Lang Speech Hear Serv Sch};2012 (Oct 19)
PURPOSE: Video modeling is an intervention strategy that has been shown to be effective in improving the social and communication skills of students with autism spectrum disorders, or ASD. The purpose of this tutorial is to outline empirically supported, step-by-step instructions for the use of video modeling by school-based SLPs serving students with ASD. METHOD: This tutorial draws from the many reviews and meta-analyses of the video modeling literature conducted over the past decade, presenting empirically supported considerations for school-based SLPs planning to incorporate video modeling into their service delivery for students with ASD. The five overarching procedural phases presented in this tutorial are: (1) preparation; (2) recording the video model; (3) implementing the video modeling intervention; (4) monitoring the student’s response to the intervention; and (5) planning next steps. Conclusions/Implications Video modeling is not only a promising intervention strategy for students with ASD, but it is also a practical and efficient tool, well-suited to the school setting. This tutorial will facilitate school-based SLPs’ incorporation of this empirically supported intervention into their existing strategies for intervention.
