1. Dhossche DM, Ross CA, Stoppelbein L. {{The role of deprivation, abuse, and trauma in pediatric catatonia without a clear medical cause}}. {Acta Psychiatr Scand};2011 (Oct 24)
Dhossche DM, Ross CA, Stoppelbein L. The role of deprivation, abuse, and trauma in pediatric catatonia without a clear medical cause. Objective: Catatonia is considered a unique syndrome of motor signs, at times life-threatening when aggravated by autonomic dysfunction and fever, but eminently treatable with specific medical treatments, if recognized early. Catatonia commonly occurs in children and adolescents with a wide range of associated disorders. The role of deprivation, abuse, or trauma in the development of pediatric catatonia is examined. Method: Reports considering deprivation, abuse, or trauma as precipitants of catatonia in pediatric cases are culled from the classic writings on catatonia and from a selective review of modern contributions. Results: Kahlbaum gave trauma a central role in catatonia in many young adult cases. Kanner described children with psychogenic catalepsy. Anaclitic depression, a condition found by Spitz in deprived institutionalized children, strongly resembles stuporous catatonia. Leonhard considered lack of communication with the mother or substitute mother as an important risk factor for childhood catatonia. Children including those with autism who experience emotional and physical trauma sometimes develop catatonia. The clinical descriptions of children with classic catatonic syndromes and those of contemporary refugee children with a syndrome labeled Pervasive Refusal Syndrome are similar. Conclusion: The literature supports the view that deprivation, abuse, and trauma can precipitate catatonia in children and adolescents.
Lien vers le texte intégral (Open Access ou abonnement)
2. Santoro MR, Bray SM, Warren ST. {{Molecular Mechanisms of Fragile X Syndrome: A Twenty-Year Perspective}}. {Annu Rev Pathol};2011 (Jan 25)
Fragile X syndrome (FXS) is a common form of inherited intellectual disability and is one of the leading known causes of autism. The mutation responsible for FXS is a large expansion of the trinucleotide CGG repeat in the 5′ untranslated region of the X-linked gene FMR1. This expansion leads to DNA methylation of FMR1 and to transcriptional silencing, which results in the absence of the gene product, FMRP, a selective messenger RNA (mRNA)-binding protein that regulates the translation of a subset of dendritic mRNAs. FMRP is critical for mGluR (metabotropic glutamate receptor)-dependent long-term depression, as well as for other forms of synaptic plasticity; its absence causes excessive and persistent protein synthesis in postsynaptic dendrites and dysregulated synaptic function. Studies continue to refine our understanding of FMRP’s role in synaptic plasticity and to uncover new functions of this protein, which have illuminated therapeutic approaches for FXS. Expected final online publication date for the Annual Review of Pathology: Mechanisms of Disease Volume 7 is January 24, 2012. Please see http://www.annualreviews.org/catalog/pubdates.aspx for revised estimates.
Lien vers le texte intégral (Open Access ou abonnement)
3. Charles J, Harrison CM, Britt H. {{Management of children’s psychological problems in general practice 1970-1971, 1990-1991 and 2008-2009}}. {Aust N Z J Psychiatry};2011 (Oct 22)
Objective: The aim of this study was to examine changes over four decades in children’s psychological problems managed in Australian general practice and to describe recent management of these problems. Method: Analysis of GP encounters with children, using data from the BEACH study, an on-going, cross-sectional, national survey of general practice, provides contemporary results. Comparisons with two related studies: 1970-1971 (from published reports), and 1990-1991 (secondary analysis), describe changes over time. Results: Changes over time: psychological problems accounted for 2% of all children’s problems managed in 1971, 1.3% in 1990-1991 and 2.6% in 2008-2009. In 1971, non-organic enuresis accounted for 30% of children’s psychological problems but only 2.7% in 2008-2009. Insomnia showed a similar pattern. Between 1990-1991 and 2008-2009, ADHD increased from 0.8% to 14.7%, and from 2000-2001 to 2008-2009, autism spectrum disorders rose from 4.9% to 11%. Current practice: most common psychological problems managed for children less than 18 years were anxiety, depression, intellectual impairment and ADHD. Among children aged 0-5 years, sleep disturbance and intellectual impairment were the main problems, for 6-11 year olds, anxiety and ADHD, and for 12-17 year olds, depression. Boys were significantly more likely to be managed for intellectual impairment, ADHD and autism spectrum disorders than were girls, who were more likely to be managed for depression. The medication rate was low at 19 per 100 psychological problems although higher for depression and ADHD. Referrals were given at a high rate. Counselling was also provided often, except in management of ADHD. Conclusions: Access to the three studies allowed consideration of trends over a forty year period, showing the development of newly defined conditions which have replaced childhood diagnoses of past decades. The results demonstrate that GP involvement in children’s mental health care management has grown significantly over the past 20 years.
Lien vers le texte intégral (Open Access ou abonnement)
4. Baird G, Douglas HR, Director A, Murphy MS. {{Recognising and diagnosing autism in children and young people: summary of NICE guidance}}. {BMJ};2011;343:d6360.
5. Blenner S, Reddy A, Augustyn M. {{Diagnosis and management of autism in childhood}}. {BMJ};2011;343:d6238.
6. Zwaigenbaum L. {{Assessment and diagnosis of autism spectrum disorders}}. {BMJ};2011;343:d6628.
7. Fu C, Cawthon B, Clinkscales W, Bruce A, Winzenburger P, Ess KC. {{GABAergic Interneuron Development and Function Is Modulated by the Tsc1 Gene}}. {Cereb Cortex};2011 (Oct 20)
Tuberous sclerosis complex (TSC) is a genetic disease with severe neurologic and psychiatric manifestations including epilepsy, developmental delay, and autism. Despite much progress in defining abnormal signaling pathways including the contribution of increased mTORC1 signaling, specific abnormalities that underlie the severe neurologic features in TSC remain poorly understood. We hypothesized that epilepsy and autism in TSC result from abnormalities of gamma-aminobutyric acidergic (GABAergic) interneurons. To test this hypothesis, we generated conditional knockout mice with selective deletion of the Tsc1 gene in GABAergic interneuron progenitor cells. These interneuron-specific Tsc1 conditional knockout (CKO) mice have impaired growth and decreased survival. Cortical and hippocampal GABAergic interneurons of CKO mice are enlarged and show increased mTORC1 signaling. Total numbers of GABAergic cells are reduced in the cortex with differential reduction of specific GABAergic subtypes. Ectopic clusters of cells with increased mTORC1 signaling are also seen suggesting impaired interneuron migration. The functional consequences of these cellular changes are evident in the decreased seizure threshold on exposure to the proconvulsant flurothyl. These findings support an important role for the Tsc1 gene during GABAergic interneuron development, function, and possibly migration.
Lien vers le texte intégral (Open Access ou abonnement)
8. Pratt K, Baird G, Gringras P. {{Ensuring successful admission to hospital for young people with learning difficulties, autism and challenging behaviour: a continuous quality improvement and change management programme}}. {Child Care Health Dev};2011 (Oct 21)
Background Children and young people with autism spectrum conditions frequently have adverse experiences in accessing health care. Methods An audit of experiences of families known to our tertiary service and hospital staff was conducted. A checklist asking about particular aspects of behaviour and communication was developed and incorporated into pre-admission planning. Results Awareness of the child/young person’s communication needs and behaviours, plus good preplanning by all staff involved and a team member allocated to ensure that the care plan is carried through, has resulted in a vastly improved ‘patient experience’ from the perspective of family and staff. Conclusion Children and young people with autism spectrum disorder, often with co-existing learning difficulties, vary greatly in their reactions to hospital admission. Preplanning that involves the family with a dedicated informed staff member can dramatically reduce distress and improve the patient and staff experience.
Lien vers le texte intégral (Open Access ou abonnement)
9. Hua X, Thompson PM, Leow AD, Madsen SK, Caplan R, Alger JR, O’Neill J, Joshi K, Smalley SL, Toga AW, Levitt JG. {{Brain growth rate abnormalities visualized in adolescents with autism}}. {Hum Brain Mapp};2011 (Oct 20)
Autism spectrum disorder is a heterogeneous disorder of brain development with wide ranging cognitive deficits. Typically diagnosed before age 3, autism spectrum disorder is behaviorally defined but patients are thought to have protracted alterations in brain maturation. With longitudinal magnetic resonance imaging (MRI), we mapped an anomalous developmental trajectory of the brains of autistic compared with those of typically developing children and adolescents. Using tensor-based morphometry, we created 3D maps visualizing regional tissue growth rates based on longitudinal brain MRI scans of 13 autistic and seven typically developing boys (mean age/interscan interval: autism 12.0 +/- 2.3 years/2.9 +/- 0.9 years; control 12.3 +/- 2.4/2.8 +/- 0.8). The typically developing boys demonstrated strong whole brain white matter growth during this period, but the autistic boys showed abnormally slowed white matter development (P = 0.03, corrected), especially in the parietal (P = 0.008), temporal (P = 0.03), and occipital lobes (P = 0.02). We also visualized abnormal overgrowth in autism in gray matter structures such as the putamen and anterior cingulate cortex. Our findings reveal aberrant growth rates in brain regions implicated in social impairment, communication deficits and repetitive behaviors in autism, suggesting that growth rate abnormalities persist into adolescence. Tensor-based morphometry revealed persisting growth rate anomalies long after diagnosis, which has implications for evaluation of therapeutic effects. Hum Brain Mapp, 2011. (c) 2011 Wiley Periodicals, Inc.
Lien vers le texte intégral (Open Access ou abonnement)
10. Fernandopulle N. {{Measurement of autism: a review of four screening measures}}. {Indian J Psychol Med};2011 (Jan);33(1):5-10.
Using a key word search on electronic databases, two relevant journals and relevant review references, four measures of autistic symptoms (Childhood Asperger Syndrome Test, Autism Behavior Checklist, Social Communication Questionnaire, Social Responsiveness Scale) were reviewed with reference to their ability to discriminate the three major components of autism and measure across the whole spectrum of autism. None of the reviewed measures were able to effectively tap into and differentiate between all points on the spectrum. Further work is required to assess the sensitivity of the measures to independence between domains. The development of a measure sensitive to symptom change/continuity across development may be useful.
Lien vers le texte intégral (Open Access ou abonnement)
11. Ludlow A, Skelly C, Rohleder P. {{Challenges Faced by Parents of Children Diagnosed With Autism Spectrum Disorder}}. {J Health Psychol};2011 (Oct 21)
Few studies address the daily challenges faced by parents of children diagnosed with autism spectrum disorder. This article reports on a qualitative interview study with 20 parents exploring their experiences, challenges faced, and what has helped them to cope. A thematic analysis of the data identified five core categories: Dealing with challenging behaviour; dealing with judgements from others; lack of support; impact upon the family; coping and the importance of appropriate support. The findings emphasize where the parents themselves believe they still require additional support. It raises key strategies and resources that parents have found helpful.
Lien vers le texte intégral (Open Access ou abonnement)
12. Carayol J, Schellenberg GD, Dombroski B, Genin E, Rousseau F, Dawson G. {{Autism risk assessment in siblings of affected children using sex-specific genetic scores}}. {Mol Autism};2011 (Oct 21);2(1):17.
ABSTRACT: BACKGROUND: The inheritance pattern in most cases of autism is complex. The risk of autism is increased in siblings of children with autism and previous studies have indicated that the level of risk can be further identified by the accumulation of multiple susceptibility single nucleotide polymorphisms (SNPs) allowing for the identification of a higher-risk subgroup among siblings. As a result of the sex difference in the prevalence of autism, we explored the potential for identifying sex-specific autism susceptibility SNPs in siblings of children with autism and the ability to develop a sex-specific risk assessment genetic scoring system. METHODS: SNPs were chosen from genes known to be associated with autism. These markers were evaluated using an exploratory sample of 480 families from the Autism Genetic Resource Exchange (AGRE) repository. A reproducibility index (RI) was proposed and calculated in all children with autism and in males and females separately. Differing genetic scoring models were then constructed to develop a sex-specific genetic score model designed to identify individuals with a higher risk of autism. The ability of the genetic scores to identify high-risk children was then evaluated and replicated in an independent sample of 351 affected and 90 unaffected siblings from families with at least 1 child with autism. RESULTS: We identified three risk SNPs that had a high RI in males, two SNPs with a high RI in females, and three SNPs with a high RI in both sexes. Using these results, genetic scoring models for males and females were developed which demonstrated a significant association with autism (p = 2.2×10-6 and 1.9×10-5, respectively). CONCLUSIONS: Our results demonstrate that individual susceptibility associated SNPs for autism may have important differential sex effects. We also show that a sex-specific risk score based on the presence of multiple susceptibility associated SNPs allow for the identification of subgroups of siblings of children with autism who have a significantly higher risk of autism.
Lien vers le texte intégral (Open Access ou abonnement)
13. Mercimek-Mahmutoglu S, Dunbar M, Friesen A, Garret S, Hartnett C, Huh L, Sinclair G, Stockler S, Wellington S, Pouwels PJ, Salomons GS, Jakobs C. {{Evaluation of two year treatment outcome and limited impact of arginine restriction in a patient with GAMT deficiency}}. {Mol Genet Metab};2011 (Oct 6)
A 4-year-old female with history of developmental regression and autistic features was diagnosed with guanidinoacetate methyltransferase deficiency at age 21months. Upon treatment, she showed improvements in her developmental milestones, sensorial-neural hearing loss and brain atrophy on cranial-MRI. The creatine/choline ratio increased 82% in basal ganglia and 88% in white matter on cranial MR-spectroscopy. The CSF guanidinoacetate decreased 80% after six months of ornithine and creatine supplementation and an additional 8% after 18months of additional arginine restricted diet. We report the most favorable clinical and biochemical outcome on treatment in our patient.
Lien vers le texte intégral (Open Access ou abonnement)
14. Aldinger KA, Plummer JT, Qiu S, Levitt P. {{SnapShot: Genetics of Autism}}. {Neuron};2011 (Oct 20);72(2):418-418 e411.
Lien vers le texte intégral (Open Access ou abonnement)
15. Kana RK, Libero LE, Moore MS. {{Disrupted cortical connectivity theory as an explanatory model for autism spectrum disorders}}. {Phys Life Rev};2011 (Oct 13)
Recent findings of neurological functioning in autism spectrum disorder (ASD) point to altered brain connectivity as a key feature of its pathophysiology. The cortical underconnectivity theory of ASD (Just et al., 2004) provides an integrated framework for addressing these new findings. This theory suggests that weaker functional connections among brain areas in those with ASD hamper their ability to accomplish complex cognitive and social tasks successfully. We will discuss this theory, but will modify the term underconnectivity to ‘disrupted cortical connectivity’ to capture patterns of both under- and over-connectivity in the brain. In this paper, we will review the existing literature on ASD to marshal supporting evidence for hypotheses formulated on the disrupted cortical connectivity theory. These hypotheses are: 1) underconnectivity in ASD is manifested mainly in long-distance cortical as well as subcortical connections rather than in short-distance cortical connections; 2) underconnectivity in ASD is manifested only in complex cognitive and social functions and not in low-level sensory and perceptual tasks; 3) functional underconnectivity in ASD may be the result of underlying anatomical abnormalities, such as problems in the integrity of white matter; 4) the ASD brain adapts to underconnectivity through compensatory strategies such as overconnectivity mainly in frontal and in posterior brain areas. This may be manifested as deficits in tasks that require frontal-parietal integration. While overconnectivity can be tested by examining the cortical minicolumn organization, long-distance underconnectivity can be tested by cognitively demanding tasks; and 5) functional underconnectivity in brain areas in ASD will be seen not only during complex tasks but also during task-free resting states. We will also discuss some empirical predictions that can be tested in future studies, such as: 1) how disrupted connectivity relates to cognitive impairments in skills such as Theory-of-Mind, cognitive flexibility, and information processing; and 2) how connection abnormalities relate to, and may determine, behavioral symptoms hallmarked by the triad of Impairments in ASD. Furthermore, we will relate the disrupted cortical connectivity model to existing cognitive and neural models of ASD.
Lien vers le texte intégral (Open Access ou abonnement)
16. Cook D, Del Rayo Sanchez-Carbente M, Lachance C, Radzioch D, Tremblay S, Khandjian EW, Desgroseillers L, Murai KK. {{Fragile X Related Protein 1 Clusters with Ribosomes and Messenger RNAs at a Subset of Dendritic Spines in the Mouse Hippocampus}}. {PLoS One};2011;6(10):e26120.
The formation and storage of memories in neuronal networks relies on new protein synthesis, which can occur locally at synapses using translational machinery present in dendrites and at spines. These new proteins support long-lasting changes in synapse strength and size in response to high levels of synaptic activity. To ensure that proteins are made at the appropriate time and location to enable these synaptic changes, messenger RNA (mRNA) translation is tightly controlled by dendritic RNA-binding proteins. Fragile X Related Protein 1 (FXR1P) is an RNA-binding protein with high homology to Fragile X Mental Retardation Protein (FMRP) and is known to repress and activate mRNA translation in non-neuronal cells. However, unlike FMRP, very little is known about the role of FXR1P in the central nervous system. To understand if FXR1P is positioned to regulate local mRNA translation in dendrites and at synapses, we investigated the expression and targeting of FXR1P in developing hippocampal neurons in vivo and in vitro. We found that FXR1P was highly expressed during hippocampal development and co-localized with ribosomes and mRNAs in the dendrite and at a subset of spines in mouse hippocampal neurons. Our data indicate that FXR1P is properly positioned to control local protein synthesis in the dendrite and at synapses in the central nervous system.
Lien vers le texte intégral (Open Access ou abonnement)
17. Sheridan SD, Theriault KM, Reis SA, Zhou F, Madison JM, Daheron L, Loring JF, Haggarty SJ. {{Epigenetic characterization of the FMR1 gene and aberrant neurodevelopment in human induced pluripotent stem cell models of fragile x syndrome}}. {PLoS One};2011;6(10):e26203.
Fragile X syndrome (FXS) is the most common inherited cause of intellectual disability. In addition to cognitive deficits, FXS patients exhibit hyperactivity, attention deficits, social difficulties, anxiety, and other autistic-like behaviors. FXS is caused by an expanded CGG trinucleotide repeat in the 5′ untranslated region of the Fragile X Mental Retardation (FMR1) gene leading to epigenetic silencing and loss of expression of the Fragile X Mental Retardation protein (FMRP). Despite the known relationship between FMR1 CGG repeat expansion and FMR1 silencing, the epigenetic modifications observed at the FMR1 locus, and the consequences of the loss of FMRP on human neurodevelopment and neuronal function remain poorly understood. To address these limitations, we report on the generation of induced pluripotent stem cell (iPSC) lines from multiple patients with FXS and the characterization of their differentiation into post-mitotic neurons and glia. We show that clones from reprogrammed FXS patient fibroblast lines exhibit variation with respect to the predominant CGG-repeat length in the FMR1 gene. In two cases, iPSC clones contained predominant CGG-repeat lengths shorter than measured in corresponding input population of fibroblasts. In another instance, reprogramming a mosaic patient having both normal and pre-mutation length CGG repeats resulted in genetically matched iPSC clonal lines differing in FMR1 promoter CpG methylation and FMRP expression. Using this panel of patient-specific, FXS iPSC models, we demonstrate aberrant neuronal differentiation from FXS iPSCs that is directly correlated with epigenetic modification of the FMR1 gene and a loss of FMRP expression. Overall, these findings provide evidence for a key role for FMRP early in human neurodevelopment prior to synaptogenesis and have implications for modeling of FXS using iPSC technology. By revealing disease-associated cellular phenotypes in human neurons, these iPSC models will aid in the discovery of novel therapeutics for FXS and other autism-spectrum disorders sharing common pathophysiology.
Lien vers le texte intégral (Open Access ou abonnement)
18. Guex P, Halfon O. {{[Hegemonic model of autism: epistemological crossroads between medicine, family and politics]}}. {Rev Med Suisse};2011 (Sep 21);7(309):1813-1816.
The aim of this article is to make a contribution to the regional reflection with regard to autism spectrum disorders (ASDs) at a key moment in which the authorities are requested by the users, professionals in the fields of health, pedagogy and education to put forward a structured answer to a multitude of expressed needs. The question for the creation of a competence pole of an academic tertiary level is posed in order to advise in the best possible way the families who do not know how to orient themselves in the maze and contradictions of the proposed solutions and to help the professionals who are submerged by an ever increasing demand of services exceeding the means of the existing institutions and who cannot justify their choices among the various existing theoretical and scientific models.
