1. Clayton TA. {{Metabolic differences underlying two distinct rat urinary phenotypes, a suggested role for gut microbial metabolism of phenylalanine and a possible connection to autism}}. {FEBS Lett};2012 (Apr 5);586(7):956-961.
A novel explanation is proposed for the metabolic differences underlying two distinct rat urinary compositional phenotypes i.e. that these may arise from differences in the gut microbially-mediated metabolism of phenylalanine. As part of this hypothesis, it is further suggested that elements of the mammalian gut microbiota may convert phenylalanine to cinnamic acid, either by means of an ammonia lyase-type reaction or by means of a three step route via phenylpyruvate and phenyllactate. The wider significance of such conversions is discussed with similar metabolism of tryptophan and subsequent glycine conjugation potentially explaining the origin of trans-indolylacryloylglycine, a postulated marker for autism.
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2. Divan G, Vajaratkar V, Desai MU, Strik-Lievers L, Patel V. {{Challenges, Coping Strategies, and Unmet Needs of Families with a Child with Autism Spectrum Disorder in Goa, India}}. {Autism Res};2012 (Mar 30)
Autism Spectrum Disorders (ASD) are increasingly recognized in developing countries like India. However, little is known about the experiences of parents raising a child with ASD. This study aimed to describe the experiences of families in Goa, India with a view to understanding the unmet needs of families raising a child with ASD. Twenty in-depth interviews and nine focus group discussions were carried out with families of children with ASD and key community stakeholders such as special educators, teachers, and parents of typically developing children. This qualitative data was triangulated to explore the experiences, life impact, and unmet needs of raising a child with ASD. Key findings suggest that raising a child with ASD puts a tremendous strain on families due to competing commitments, often leading to initial social withdrawal with later reintegration into social networks. Second, the impact is multidimensional, involving the personal sphere but also extending into the wider community with negative experiences of discrimination. Third, parents actively respond to these challenges through a range of approaches with help from existing and new social support networks and health care providers. Fourth, professionals from the health, education, and religious sectors have a low awareness of the unique needs of families living with ASD which leads to a considerable economic and emotional burden on families. Finally, as a consequence of these experiences, several unmet needs can be identified, notably for supporting increasingly isolated families and the limited access to multidisciplinary evidence-based services for ASD. Autism Res 2012,**:**-**. (c) 2012 International Society for Autism Research, Wiley Periodicals, Inc.
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3. Emerson E, Yasamy MT, Saxena S. {{Scaling up support for children with developmental disabilities in low- and middle-income countries}}. {J Appl Res Intellect Disabil};2012 (Mar);25(2):96-98.
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4. Estigarribia B, Martin GE, Roberts JE. {{Cognitive, Environmental, and Linguistic Predictors of Syntax in Fragile X Syndrome and Down Syndrome}}. {J Speech Lang Hear Res};2012 (Apr 3)
PURPOSE: We examined which cognitive, environmental, and speech/language variables predict expressive syntax in boys with fragile X syndrome (FXS), Down syndrome (DS), and typical development (TD), and whether predictive relationships differed by group. METHOD: We obtained Index of Productive Syntax scores for 18 boys with FXS only, 20 boys with both FXS and autism spectrum disorder, 27 boys with DS, and 25 younger TD boys of similar nonverbal mental age (MA). Predictors included group (diagnosis), nonverbal cognition, phonological working memory (PWM), maternal education, speech intelligibility, and expressive vocabulary. We addressed the research questions via hierarchical linear regression. RESULTS: Diagnostic group, nonverbal cognition, and PWM predicted 56% of the variance in syntactic ability, with approximately three-fourths of the predicted variance explained by group membership alone. The other factors did not contribute any additional significant variance in this final model. There was no evidence that predictor effects differed by group. CONCLUSIONS: Nonverbal cognition and PWM have an effect on expressive syntax beyond that of diagnostic group. These effects are estimated to be the same in FXS, DS, and TD. We discuss explanations for residual variance and the relative role of different predictors.
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5. Fountain C, Winter AS, Bearman PS. {{Six Developmental Trajectories Characterize Children With Autism}}. {Pediatrics};2012 (Apr 2)
OBJECTIVE:The goal of this study was to describe the typical longitudinal developmental trajectories of social and communication functioning in children with autism and to determine the correlates of these trajectories.METHODS:Children with autism who were born in California from 1992 through 2001 and enrolled with the California Department of Developmental Services were identified. Subjects with <4 evaluations present in the database were excluded, resulting in a sample of 6975 children aged 2 to 14 years. Score sequences were constructed based on 9 evaluative items for social, communication, and repetitive behavior functioning. Typical trajectories were identified by using group-based latent trajectory modeling, and multinomial logistic regression models were used to determine the odds of classification within each trajectory varied by individual and family-level factors.RESULTS:Six typical patterns of social, communication, and repetitive behavior functioning were identified. These trajectories displayed significant heterogeneity in developmental pathways, and children whose symptoms were least severe at first diagnosis tended to improve more rapidly than those severely affected. One group of approximately 10% of children experienced rapid gains, moving from severely affected to high functioning. Socioeconomic factors were correlated with trajectory outcomes; children with non-Hispanic, white, well-educated mothers were more likely to be high functioning, and minority children with less-educated mothers or intellectual disabilities were very unlikely to experience rapid gains.CONCLUSIONS:Children with autism have heterogeneous developmental pathways. One group of children evidenced remarkable developmental change over time. Understanding what drives these outcomes is thus critical.
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6. Hedges DJ, Hamilton-Nelson KL, Sacharow SJ, Nations L, Beecham GW, Kozhekbaeva ZM, Butler BL, Cukier HN, Whitehead PL, Ma D, Jaworski JM, Nathanson L, Lee JM, Hauser SL, Oksenberg JR, Cuccaro ML, Haines JL, Gilbert JR, Pericak-Vance MA. {{Evidence of novel fine-scale structural variation at autism spectrum disorder candidate loci}}. {Mol Autism};2012 (Apr 2);3(1):2.
ABSTRACT: BACKGROUND: Autism spectrum disorders (ASD) represent a group of neurodevelopmental disorders characterized by a core set of social-communicative and behavioral impairments. Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the brain, acting primarily via the GABA receptors (GABR). Multiple lines of evidence, including altered GABA and GABA receptor expression in autistic patients, indicate that the GABAergic system may be involved in the etiology of autism. METHODS: As copy number variations (CNVs), particularly rare and de novo CNVs, have now been implicated in ASD risk, we examined the GABA receptors and genes in related pathways for structural variation that may be associated with autism. We further extended our candidate gene set to include 19 genes and regions that had either been directly implicated in the autism literature or were directly related (via function or ancestry) to these primary candidates. For the high resolution CNV screen we employed custom-designed 244 k comparative genomic hybridization (CGH) arrays. Collectively, our probes spanned a total of 11 Mb of GABA-related and additional candidate regions with a density of approximately one probe every 200 nucleotides, allowing a theoretical resolution for detection of CNVs of approximately 1 kb or greater on average. One hundred and sixty-eight autism cases and 149 control individuals were screened for structural variants. Prioritized CNV events were confirmed using quantitative PCR, and confirmed loci were evaluated on an additional set of 170 cases and 170 control individuals that were not included in the original discovery set. Loci that remained interesting were subsequently screened via quantitative PCR on an additional set of 755 cases and 1,809 unaffected family members. RESULTS: Results include rare deletions in autistic individuals at JAKMIP1, NRXN1, Neuroligin4Y, OXTR, and ABAT. Common insertion/deletion polymorphisms were detected at several loci, including GABBR2 and NRXN3. Overall, statistically significant enrichment in affected vs. unaffected individuals was observed for NRXN1 deletions. CONCLUSIONS: These results provide additional support for the role of rare structural variation in ASD.
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7. Khanna R, Jariwala K, West-Strum D. {{Use and cost of psychotropic drugs among recipients with autism in a state Medicaid fee-for-service programme}}. {J Intellect Disabil Res};2012 (Apr 4)
Background There has been a significant increase in the prevalence of autism in the USA in the past few decades. The purpose of this study was to provide recent estimates of psychotropic drug use and costs among individuals with autism enrolled in Medicaid programme. Method A cross-sectional analysis of 2007 Mississippi (MS) Medicaid fee-for-service (FFS) programme administrative-claims data was performed. Study sample included recipients (<65 years) who had a medical services claim with a diagnosis of autism in 2007. Psychotropic drug patterns of use and costs were studied. Factors predicting the use of psychotropic drugs were identified using logistic regression analyses. Average number and cost of psychotropic drug claims per recipient were reported. Costs were reported from the perspective of MS Medicaid. Results In 2007, there were 1330 recipients with a diagnosis of autism in MS Medicaid FFS programme. Among these recipients, 66.32% had a claim for psychotropic drug during the year. Roughly 39% of recipients with autism had a claim for antipsychotics, 31.58% for stimulants, 19.55% for antidepressants, 19.40% for other psychotropics and 14.81% for anxiolytics/hypnotics/sedatives. Results from regression analyses highlighted variation in psychotropic drug use by demographic and co-morbid factors. There were a total of 12 618 claims for psychotropic drugs filled by recipients with autism in 2007, at an average of 14 (+/-12) claims per recipient. The total cost of these claims paid for by MS Medicaid FFS programme was approximately $2 million. Antipsychotics accounted for more than half ( approximately 58%) of the total costs, and had the highest average cost per claim ($291 +/- 205). Conclusions The results of this study indicate a high use of psychotropic drugs among individuals with autism enrolled in a state Medicaid programme. There is an urgent need to study the risk-benefit profile of these drugs in this growing population. Psychotropic drug use was found to vary by demographic and co-morbid factors. Among the different classes of psychotropic drugs, antipsychotics were the most commonly used and had the highest cost per claim.
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8. Kubas B, Kulak W, Sobaniec W, Tarasow E, Lebkowska U, Walecki J. {{Metabolite alterations in autistic children: a 1H MR spectroscopy study}}. {Adv Med Sci};2012 (Apr 3):1-5.
Purpose: The purpose of this study was to assess the role of proton magnetic resonance spectroscopy (1H MRS) in the detection of changes in cerebral metabolite levels in autistic children.Material and methods: Study group consisted of 12 children, aged 8-15 years, who were under the care of Pediatric Neurology Department and Pediatric Rehabilitation Department of Medical University of Bialystok. The diagnosis of autism was established by neurologist, psychiatrist and psychologist in every case. All patients matched the clinical criteria of the disease according to International Statistical Classification of Diseases and Related Health Problems (ICD-10). The control group included 16 healthy children aged 7-17. 1H MRS was performed with a single-voxel method (TE-36, TR-1500, NEX-192). The volume of interest (VOI) was located in the frontal lobe regions, separately on each side.Results: We showed lower N-acetylaspartate/creatine (NAA/Cr), gamma-aminobutyric acid /creatine (GABA/Cr) and glutamate/creatine (Glx/Cr) in the frontal lobes in the study group comparing with healthy controls. The ratio of myoinositol/creatine (mI/Cr) was increased in autistic children. No differences in choline/creatine (Cho/Cr) ratio in study group and controls were found. There was a correlation between age and NAA/Cr in autistic children (R=0.593 p=0.041). No significant differences in metabolite ratios between right and left hemisphere in ASD and controls were found.Conclusions:1H MRS can provide important information regarding abnormal brain metabolism. Differences in NAA/Cr, GABA/Cr, Glx/Cr and mI/Cr may contribute to the pathogenesis of autism.
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9. Nesbitt M, Carranza A, Kasem AJ, Arnold JC, Bareng R, Friedman NJ, Gilboa M. {{Index of Suspicion * Case 1: Abdominal Pain, Fever, and Cough in a 3-year-old Boy * Case 2: Emesis, Irritability in 9-year-old Boy Who Has Autism * Case 3: Skin Lesions and Pulmonary Nodules in a 17-year-old Boy}}. {Pediatr Rev};2012 (Apr);33(4):179-185.
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10. Rhode M. {{Whose memories are they and where do they go? Problems surrounding internalization in children on the autistic spectrum}}. {Int J Psychoanal};2012 (Apr);93(2):355-376.
Recent work in neuroscience has highlighted the contrast between ‘procedural’ memory for bodily experiences and skills, which is unconscious though unrepressed, and verbalizable, ‘declarative’ memory, which includes autobiographical memory. Autobiographical memory is weak in people with autistic spectrum disorder, who frequently turn to self-generated sensations for reassurance that they continue to exist. The author suggests that, instead of internalizing shared experiences leading to growth, children with autism can feel that they add to themselves by taking over the qualities of others through the ‘annexation’ of physical properties that leads to a damaged object and can trigger a particular sort of negative therapeutic reaction. Clinical illustrations drawn from the treatment of two children on the autistic spectrum illustrate some ramifications of these processes in relation to the sense of a separate identity and the capacity to access memories.
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11. Tierney CD, Gupta VB, Angel AP, Augustyn M. {{Teasing out specific language impairment from an autism spectrum disorder}}. {J Dev Behav Pediatr};2012 (Apr);33(3):272-274.
CASE:: Marcus is a handsome, sweet, 7(1/2)-year-old boy with a significant history of delayed development, specifically in speech and language skills, as well as difficulties with social interactions that have led other specialists to be concerned about a diagnosis of an autism spectrum disorder.He has been seen in our primary care practice since birth. He was born full-term after vaginal delivery weighing 6 pounds, 6 ounces. There were no pregnancy or delivery complications noted. Genetic testing revealed normal chromosomes, fragile X, and microarray testing. Marcus was a picky eater and good sleeper and had delays in toilet training.There is no family history of attention-deficit hyperactivity disorder (ADHD), autism, or substance abuse. Maternal grandmother and mother have a history of learning difficulties, and his father and a paternal uncle have a history of depression and anxiety. Marcus lives in a supportive environment with his mother, father, and sister.Marcus was noted to have significantly delayed language, stuttering, and immediate echolalia as a toddler. Gross and fine motor milestones were met on time, but he did not talk or follow directions until 4 to 5 years old. As a younger child, he would pretend to talk on the phone or mow the grass with a pretend lawn mower, but other household activities were not of interest to Marcus.Currently, he enjoys puzzles, reading, and board games. He likes to play with other children and can interact with familiar adults. Marcus is reported to initiate social interactions, although he has difficulty in understanding personal space. Imaginative play is preferred over other types. He seeks out adult attention and will bring objects over to an adult especially to share his perceived accomplishment. Marcus has difficulty in playing cooperatively with his sister.He is independent with activities of daily living. Marcus is noted to have auditory defensiveness including covering his ears to loud noises and becoming distressed. Parents feel he is immature and inattentive for his age. Marcus responds well when a routine is followed.Previous testing about 2 years ago revealed significant language deficits on the Clinical Evaluation of Language Functioning with average scores on the Woodcock Johnson Achievement Testing and Test of Nonverbal Intelligence Version 3. Marcus was not referred for early intervention and he did not attend preschool. In a regular education Kindergarten, he received speech and occupational therapy along with reading and math support.Comments from teachers or evaluator include the following: Marcus looked to his peers for clues about what he should be doing. Marcus has great difficulty in understanding requests but seems to be interested in pleasing his teacher and others. Marcus’ language difficulty makes socialization with his peers problematic; however, he is interested in interacting with them and they seem to accept him willingly. Marcus has intent to communicate with others but relies on visual support to decipher social situations. Marcus has difficulty in attending to details and moves from activity to activity quickly. His short attention span is likely impacting not only learning but also his ability to socially interact with peers.On the day you see him for his 7-year-old checkup, he brought many toys over to show his father and interrupted your conversation to get your attention intermittently throughout the examination. He immediately pointed out a lit ceiling tile with Nemo illuminated to show his father. Marcus does not have any notable or significant repetitive motor mannerisms or stereotypies reported or observed. Marcus’ gesture use was appropriate for age and included both symbolic (directing eye gaze and pointing) and concrete (hands up to be picked up and touching an item rather than pointing to it) gestures. Play observed today, although immature for age, was novel, imaginative, and functional. Answers to questions did not always match the question posed. He had a difficult time waiting for his turn before interrupting a conversation. Visual cues were helpful in understanding what was expected of him and what was going on socially.Marcus’ speech is notable for persistent stuttering and difficulty in turn-taking in conversation. He gets frustrated easily and has a hard time being understood. He continues to confuse pronouns and makes some grammatical errors. He is able to follow simple directions but has a hard time following complex or multistep directions with accuracy. Nonverbal communication includes pointing to objects of interest in order to share the experience (« Look mom! »). He will point to identify an object and can follow a point across the room. He is able to use his eye contact to direct yours to moderate social interactions.Marcus has a special interest in Thomas the Tank Engine Train and Disney movies but is able to move away from those topics to engage in other play interests. Repetitive behaviors are not noted. Toe walking, hand flapping, or spinning, or unusual hand motions or observation of objects were not observed.Difficulties noted today include delays in his receptive and expressive language, poor intelligibility, dysfluency, and impaired motor planning. He recently underwent an audiogram which was normal. You decide to refer to a specialist for further evaluation.
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12. Yates D. {{Neurological disorders: Microglia – major players in Rett syndrome?}}. {Nat Rev Neurosci};2012 (Apr 4)
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13. Zachariah RM, Rastegar M. {{Linking Epigenetics to Human Disease and Rett Syndrome: The Emerging Novel and Challenging Concepts in MeCP2 Research}}. {Neural Plast};2012;2012:415825.
Epigenetics refer to inheritable changes beyond DNA sequence that control cell identity and morphology. Epigenetics play key roles in development and cell fate commitments and highly impact the etiology of many human diseases. A well-known link between epigenetics and human disease is the X-linked MECP2 gene, mutations in which lead to the neurological disorder, Rett Syndrome. Despite the fact that MeCP2 was discovered about 20 years ago, our current knowledge about its molecular function is not comprehensive. While MeCP2 was originally found to bind methylated DNA and interact with repressor complexes to inhibit and silence its genomic targets, recent studies have challenged this idea. Indeed, depending on its interacting protein partners and target genes, MeCP2 can act either as an activator or as a repressor. Furthermore, it is becoming evident that although Rett Syndrome is a progressive and postnatal neurological disorder, the consequences of MeCP2 deficiencies initiate much earlier and before birth. To comprehend the novel and challenging concepts in MeCP2 research and to design effective therapeutic strategies for Rett Syndrome, a targeted collaborative effort from scientists in multiple research areas to clinicians is required.
