1. Cheung AY, Horvath LM, Carrel L, Ellis J. {{X-chromosome inactivation in rett syndrome human induced pluripotent stem cells}}. {Front Psychiatry};2012;3:24.
Rett syndrome (RTT) is a neurodevelopmental disorder that affects girls due primarily to heterozygous mutations in the X-linked gene encoding methyl-CpG binding protein 2 (MECP2). Random X-chromosome inactivation (XCI) results in cellular mosaicism in which some cells express wild-type (WT) MECP2 while other cells express mutant MECP2. The generation of patient-specific human induced pluripotent stem cells (hiPSCs) facilitates the production of RTT-hiPSC-derived neurons in vitro to investigate disease mechanisms and identify novel drug treatments. The generation of RTT-hiPSCs has been reported by many laboratories, however, the XCI status of RTT-hiPSCs has been inconsistent. Some report RTT-hiPSCs retain the inactive X-chromosome (post-XCI) of the founder somatic cell allowing isogenic RTT-hiPSCs that express only the WT or mutant MECP2 allele to be isolated from the same patient. Post-XCI RTT-hiPSCs-derived neurons retain this allele-specific expression pattern of WT or mutant MECP2. Conversely, others report RTT-hiPSCs in which the inactive X-chromosome of the founder somatic cell reactivates (pre-XCI) upon reprogramming into RTT-hiPSCs. Pre-XCI RTT-hiPSC-derived neurons exhibit random XCI resulting in cellular mosaicism with respect to WT and mutant MECP2 expression. Here we review and attempt to interpret the inconsistencies in XCI status of RTT-hiPSCs generated to date by comparison to other pluripotent systems in vitro and in vivo and the methods used to analyze XCI. Finally, we discuss the relative strengths and weaknesses of post- and pre-XCI hiPSCs in the context of RTT, and other X-linked and autosomal disorders for translational medicine.
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2. Depape AM, Chen A, Hall GB, Trainor LJ. {{Use of prosody and information structure in high functioning adults with autism in relation to language ability}}. {Front Psychol};2012;3:72.
Abnormal prosody is a striking feature of the speech of those with Autism spectrum disorder (ASD), but previous reports suggest large variability among those with ASD. Here we show that part of this heterogeneity can be explained by level of language functioning. We recorded semi-spontaneous but controlled conversations in adults with and without ASD and measured features related to pitch and duration to determine (1) general use of prosodic features, (2) prosodic use in relation to marking information structure, specifically, the emphasis of new information in a sentence (focus) as opposed to information already given in the conversational context (topic), and (3) the relation between prosodic use and level of language functioning. We found that, compared to typical adults, those with ASD with high language functioning generally used a larger pitch range than controls but did not mark information structure, whereas those with moderate language functioning generally used a smaller pitch range than controls but marked information structure appropriately to a large extent. Both impaired general prosodic use and impaired marking of information structure would be expected to seriously impact social communication and thereby lead to increased difficulty in personal domains, such as making and keeping friendships, and in professional domains, such as competing for employment opportunities.
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3. Falter CM, Elliott MA, Bailey AJ. {{Enhanced visual temporal resolution in autism spectrum disorders}}. {PLoS One};2012;7(3):e32774.
Cognitive functions that rely on accurate sequencing of events, such as action planning and execution, verbal and nonverbal communication, and social interaction rely on well-tuned coding of temporal event-structure. Visual temporal event-structure coding was tested in 17 high-functioning adolescents and adults with autism spectrum disorder (ASD) and mental- and chronological-age matched typically-developing (TD) individuals using a perceptual simultaneity paradigm. Visual simultaneity thresholds were lower in individuals with ASD compared to TD individuals, suggesting that autism may be characterised by increased parsing of temporal event-structure, with a decreased capability for integration over time. Lower perceptual simultaneity thresholds in ASD were also related to increased developmental communication difficulties. These results are linked to detail-focussed and local processing bias.
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4. Heaton P, Reichenbacher L, Sauter D, Allen R, Scott S, Hill E. {{Measuring the effects of alexithymia on perception of emotional vocalizations in autistic spectrum disorder and typical development}}. {Psychol Med};2012 (Apr 4):1-7.
BACKGROUND: The results from recent studies suggest that alexithymia, a disorder characterized by impairments in understanding personal experiences of emotion, is frequently co-morbid with autism spectrum disorder (ASD). However, the extent that alexithymia is associated with primary deficits in recognizing external emotional cues, characteristic in ASD, has yet to be determined.MethodTwenty high-functioning adults with ASD and 20 age- and intelligence-matched typical controls categorized vocal and verbal expressions of emotion and completed an alexithymia assessment. RESULTS: Emotion recognition scores in the ASD group were significantly poorer than in the control group and performance was influenced by the severity of alexithymia and the psycho-acoustic complexity of the presented stimuli. For controls, the effect of complexity was significantly smaller than for the ASD group, although the association between total emotion recognition scores and alexithymia was still strong. CONCLUSIONS: Higher levels of alexithymia in the ASD group accounted for some, but not all, of the group difference in emotion recognition ability. However, alexithymia was insufficient to explain the different sensitivities of the two groups to the effects of psycho-acoustic complexity on performance. The results showing strong associations between emotion recognition and alexithymia scores in controls suggest a potential explanation for variability in emotion recognition in non-clinical populations.
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5. Hoffman GE, Le WW, Entezam A, Otsuka N, Tong ZB, Nelson L, Flaws JA, McDonald JH, Jafar S, Usdin K. {{Ovarian Abnormalities in a Mouse Model of Fragile X Primary Ovarian Insufficiency}}. {J Histochem Cytochem};2012 (Apr 2)
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6. 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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7. Kidd SA, Corbett BA, Granger DA, Boyce WT, Anders TF, Tager IB. {{Daytime Secretion of Salivary Cortisol and Alpha-Amylase in Preschool-Aged Children with Autism and Typically Developing Children}}. {J Autism Dev Disord};2012 (Apr 4)
We examined daytime salivary cortisol and salivary alpha-amylase (sAA) secretion levels and variability in preschool-aged children with autism (AUT) and typically developing children (TYP). Fifty-two subjects (26 AUT and 26 TYP) were enrolled. Salivary samples were obtained at waking, midday, and bedtime on two consecutive days at three phases (baseline, 3 months later, 6 months later). There were modest increases in waking cortisol and sAA levels in AUT relative to TYP, but the increases were not statistically significant. Important differences were observed in cortisol and sAA variability between AUT and TYP. There was also a graded response among AUT by functional status-cortisol and sAA secretion levels were higher when IQ was lower.
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8. Schieve LA, Rice C, Yeargin-Allsopp M, Boyle CA, Kogan MD, Drews C, Devine O. {{Parent-Reported Prevalence of Autism Spectrum Disorders in US-Born Children: An Assessment of Changes within Birth Cohorts from the 2003 to the 2007 National Survey of Children’s Health}}. {Matern Child Health J};2012 (Apr 4)
The prevalence of autism spectrum disorders (ASD) from the 2007 National Survey of Children’s Health (NSCH) was twice the 2003 NSCH estimate for autism. From each NSCH, we selected children born in the US from 1990 to 2000. We estimated autism prevalence within each 1-year birth cohort to hold genetic and non-genetic prenatal factors constant. Prevalence differences across surveys thus reflect survey measurement changes and/or external identification effects. In 2003, parents were asked whether their child was ever diagnosed with autism. In 2007, parents were asked whether their child was ever diagnosed with an ASD and whether s/he currently had an ASD. For the 1997-2000 birth cohorts (children aged 3-6 years in 2003 and 7-10 years in 2007), relative increases between 2003 autism estimates and 2007 ASD estimates were 200-600 %. For the 1990-1996 birth cohorts (children aged 7-13 years in 2003) increases were lower; nonetheless, differences between 2003 estimates and 2007 « ever ASD » estimates were >100 % for 6 cohorts and differences between 2003 estimates and 2007 « current ASD » estimates were >80 % for 3 cohorts. The magnitude of most birth cohort-specific differences suggests continuing diagnosis of children in the community played a sizable role in the 2003-2007 ASD prevalence increase. While some increase was expected for 1997-2000 cohorts, because some children have later diagnoses coinciding with school entry, increases were also observed for children ages >/=7 years in 2003. Given past ASD subtype studies, the 2003 « autism » question might have missed a modest amount (</=33 %) of ASDs other than autistic disorder.
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9. Treasure J. {{Coherence and other autistic spectrum traits and eating disorders: Building from mechanism to treatment. The Birgit Olsson lecture}}. {Nord J Psychiatry};2012 (Apr 2)
Treasure J. Coherence and other autistic spectrum traits and eating disorders: Building from mechanism to treatment. The Birgit Olsson lecture. Nord J Psychiatry 2012; Early Online:1-5. Aim: To revisit Gillberg’s hypothesis proposed in 1992, which was that anorexia nervosa should be considered within the spectrum of autistic disorders. Method: A search was made of the literature relating to the behavioural traits, and cognitive, emotional and neuroanatomical intermediate phenotypes that are shared between autistic spectrum disorders (ASD) and anorexia nervosa. Results: People with eating disorders in the acute phase (less so after recovery) share some behavioural traits (social impairment and restricted and repetitive behaviours) and intermediate phenotypes (weak central coherence, and impaired set shifting and theory of mind) with people in the autistic spectrum. Conclusion: Behavioural and intermediate neuropsychological traits are shared between eating disorders and ASD. In part, these are familial but also they are accentuated by the illness state and may be secondary to starvation. These traits have implications for prognosis and treatment.
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10. Waligorska A, Pisula E, Waligorski M, Letachowicz M. {{The AutismPro system in supporting treatment of children with autism in Poland}}. {Pediatr Int};2012 (Apr 2)
Background: The efficacy of early intervention programs for children with autism has been emphasized in many studies. However, access people with autism to professional services in Poland is very limited and the burden of supporting child’s development often falls on parents, especially in families with low socio-economical status and families living far away from big cities. Using the Internet resources in planning and delivering individualized intervention may be useful. The study examined the effects of a home program of intervention based on the AutismPro system with elements of consultative therapy. Methods: Ten families of children with a diagnosis of autism participated in the project; 9 of them completed the 6 month program of intervention. Parents were taught to use the AutismPro system and implement the intervention techniques in a home setting. Modification of the intervention program to suit individual children’s needs and evaluations of children’s progress were performed during consultation meetings with therapists. The pre- and posttreatment measurement of child development was performed using the Psychoeducational Profile-Revised (PEP-R). Results: Children involved in the study progressed in total PEP-R scores and on the PEP-R subtest of fine motor, gross motor, nonverbal and verbal cognitive skills and eye-hand integration. Parents expressed positive opinions on the program. Conclusions: The results suggest that an intervention which combines the use of the Internet support tool and professional consultations may provide benefits to the children with autism. There are however methodological limitations of the study to be taken into account, when interpreting the results. (c) 2012 The Authors. Pediatrics International (c) 2012 Japan Pediatric Society.
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11. Yates D. {{Neurological disorders: Microglia – major players in Rett syndrome?}}. {Nat Rev Neurosci};2012 (Apr 4)
