1. Blijd-Hoogewys EM, Bezemer ML, van Geert PL. {{Executive Functioning in Children with ASD: An Analysis of the BRIEF}}. {Journal of autism and developmental disorders}. 2014 Jul 5.
The Behavior Rating Inventory of Executive Functions (BRIEF) screens for executive function deficits in 5- to 18-year-olds. Data of three autism subgroups, according to DSM-IV-TR criteria (N = 35 Autistic Disorder, N = 27 Asperger’s Disorder and N = 65 PDD-NOS), were analyzed. The total group has elevated scores on almost all BRIEF scales. The Shift scale is clinically elevated, reflecting a deficit in cognitive flexibility. The BRIEF scales are not found to discriminate among the autism spectrum disorder (ASD) subgroups. The relation between BRIEF and IQ is complex. Possible influencing factors are discussed. Finally, it is recommended to omit the Negativity scale as a validity index in children with ASD and to consider a high score on this index as a unique characteristic of their BRIEF profile, reflecting rigidity problems.
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2. Cao X, Lin P, Jiang P, Li C. {{Characteristics of the gastrointestinal microbiome in children with autism spectrum disorder: a systematic review}}. {Shanghai archives of psychiatry}. 2013 Dec;25(6):342-53.
BACKGROUND: A high prevalence of gastrointestinal (GI) symptoms has been reported in children with Autism Spectrum Disorders (ASD). However, results from studies about the GI mircobiome of such children have been inconsistent. AIM: Integrate the results of studies that examine the distribution of different GI microorganisms in children with ASD. METHODS: Studies related to the GI microbiome in children with ASD were identified through PubMed, Embase, PsycINFO, ISI web of knowledge, Ovid/Medline, the Cochrane Library, the Chinese National Knowledge Infrastructure (CNKI) database, the Chongqing VIP database for Chinese Technical Periodicals, WANFANG DATA, and the China BioMedical Literature Service System (SinoMed). Studies were screened for inclusion following pre-defined inclusion and exclusion criteria. Software Review Manager 5.2.6 was used for statistical analysis. RESULTS: A total of 15 cross-sectional studies, all of which had relatively small samples, were included in the final analysis. Only one of the included studies was from China. Among the 15 studies, 11 studies (with a combined sample of 562 individuals) reported significant differences between ASD children and controls in the prevalence of GI bacteria, particularly bacteria in the Firmicutes, Bacteroidetes and Proteobacteria phyla. However, due to the substantial heterogeneity in methodology and the often contradictory results of different studies, it was not possible to pool the results into a meta-analysis. CONCLUSIONS: To date, studies on the GI microbiome in children with ASD are limited in quantity and quality. There does, however, appear to be a ‘signal’ suggesting significant differences in the GI microbiome between ASD children and children without ASD, so there would be value in continuing this line of research. To improve validity and decrease the heterogeneity of findings, future studies should enlarge sample sizes, standardize methods and assess relevant confounding variables, such as the severity of GI symptoms and the use of medications, special diets and supplements.
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3. Chen YW, Lin HC, Ng MC, Hsiao YH, Wang CC, Gean PW, Chen PS. {{Activation of mGluR2/3 underlies the effects of N-acetylcystein on amygdala-associated autism-like phenotypes in a valproate-induced rat model of autism}}. {Frontiers in behavioral neuroscience}. 2014;8:219.
Autism-like phenotypes in male valproate (VPA)-exposed offspring have been linked to high glutamatergic neurotransmission in the thalamic-amygdala pathway. Glial cystine/glutamate exchange (system Xc(-)), which exchanges extracellular cystine for intracellular glutamate, plays a significant role in the maintenance of extracellular glutamate. N-acetylcysteine (NAC) is a cystine prodrug that restores extracellular glutamate by stimulating system Xc(-). In this study, we examined the effects of NAC on autism-like phenotypes and neurotransmission in the thalamic-amygdala synapses, as well as the involvement of metabotropic glutamate receptors 2/3 (mGluR2/3). Valproate-treated rats received a single intraperitoneal injection of 500 mg/kg NaVPA on E12.5. On postnatal day 21 (P21), NAC or saline was administered once daily for 10 days. From day 8 to 10, NAC was given 1/2 h prior to behavioral testing. Chronic administration of NAC restored the duration and frequency of social interaction and ameliorated anxiety-like behaviors in VPA-exposed offspring. In amygdala slices, NAC treatment normalized the increased frequency of mEPSCs and decreased the paired pulse facilitation (PPF) induced by VPA exposure. The effects of NAC on social interaction and anxiety-like behavior in the VPA-exposed offspring were blocked after intra-amygdala infusion of mGluR2/3 antagonist LY341495. The expressions of mGluR2/3 protein and mGluR2 mRNA were significantly lower in the VPA-exposed offspring. In contrast, the mGluR3 mRNA level did not differ between the saline- and VPA-exposed offspring. These results provide the first evidence that the disruption of social interaction and enhanced presynaptic excitatory transmission in VPA-exposed offspring could be rescued by NAC, which depends on the activation of mGluR2/3.
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4. Cubells JF. {{Prevalence of autism spectrum disorders in China}}. {Shanghai archives of psychiatry}. 2013 Jun;25(3):176-7.
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5. Dekker V, Nauta MH, Mulder EJ, Timmerman ME, de Bildt A. {{A randomized controlled study of a social skills training for preadolescent children with autism spectrum disorders: generalization of skills by training parents and teachers?}}. {BMC psychiatry}. 2014 Jul 2;14(1):189.
BACKGROUND: Social skills training (SST) is a common intervention for children with autism spectrum disorders (ASDs) to improve their social and communication skills. Despite the fact that SSTs are often applied in clinical practice, the evidence for the effectiveness of these trainings for children with ASD is inconclusive. Moreover, long term outcome and generalization of learned skills are little evaluated. Additionally, there is no research on the influence of involvement of parents and teachers on effectiveness of SST and on the generalization of learned social skills to daily life. We expect parent and teacher involvement in SST to enhance treatment efficacy and to facilitate generalization of learned skills to daily life.Method/design: In a randomized controlled trial (RCT) with three conditions, 120 participants with ASD at the end of primary school (10-12 years of calendar age) have been randomized to SST, SST-PTI (SST with Parent & Teacher Involvement), or care-as-usual. The SST consists of 18 group sessions of 1.5 hours for the children. In the SST-PTI condition, parents additionally participate in 8 parent sessions and parents and teachers are actively involved in homework assignments. Assessment takes place at three moments: before and immediately after the intervention period and at 6 months follow-up. Primary outcome is socialization, as an aspect of adaptive functioning. Secondary outcomes focus on specific social skills children learn during SST and on more general social skills pertaining to home and community settings from a multi-informant perspective. Additionally, possible predictors of treatment outcome will be assessed. DISCUSSION: The current study is an RCT study evaluating SST in a large sample of Dutch children with ASD in a specific age range (10-12 years). Strengths of the study are the use of one manualized protocol, application of standardized and internationally used rating instruments, use of multiple raters, investigation of generalization of learned skills to daily life, and the evaluation of efficacy in the longer term by follow-up measures at 6 months after the end of training.Trial registration: NTR2405.
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6. Ewbank MP, Rhodes G, von dem Hagen EA, Powell TE, Bright N, Stoyanova RS, Baron-Cohen S, Calder AJ. {{Repetition Suppression in Ventral Visual Cortex Is Diminished as a Function of Increasing Autistic Traits}}. {Cerebral cortex (New York, NY : 1991)}. 2014 Jul 1.
Repeated viewing of a stimulus causes a change in perceptual sensitivity, known as a visual aftereffect. Similarly, in neuroimaging, repetitions of the same stimulus result in a reduction in the neural response, known as repetition suppression (RS). Previous research shows that aftereffects for faces are reduced in both children with autism and in first-degree relatives. With functional magnetic resonance imaging, we found that the magnitude of RS to faces in neurotypical participants was negatively correlated with individual differences in autistic traits. We replicated this finding in a second experiment, while additional experiments showed that autistic traits also negatively predicted RS to images of scenes and simple geometric shapes. These findings suggest that a core aspect of neural function-the brain’s response to repetition-is modulated by autistic traits.
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7. Galloway JN, Shaw C, Yu P, Parghi D, Poidevin M, Jin P, Nelson DL. {{CGG repeats in RNA modulate expression of TDP-43 in mouse and fly models of fragile X tremor ataxia syndrome}}. {Human molecular genetics}. 2014 Jun 30.
Determining the molecular mechanism(s) leading to Purkinje neuron loss in the neurodegenerative disorder fragile X-associated tremor/ataxia syndrome (FXTAS) is limited by the complex morphology of this cell type. Purkinje neurons are notoriously difficult to isolate and maintain in culture presenting considerable difficultly to identify molecular changes in response to expanded CGG repeat (rCGG)-containing mRNA that induces neurotoxicity in FXTAS. Several studies have uncovered a number of RNA-binding proteins involved in translation that aberrantly interact with the CGG-containing RNA; however, whether these interactions alter the translational profile of cells has not been investigated. Here we employ bacTRAP translational profiling to demonstrate that Purkinje neurons ectopically expressing 90 CGG repeats exhibit a dramatic change in their translational profile even prior to the onset of rCGG-induced phenotypes. This approach identified approximately 500 transcripts that are differentially associated with ribosomes in r(CGG)90-expressing mice. Functional annotation cluster analysis revealed broad ontologies enriched in the r(CGG)90 list, including RNA binding and response to stress. Intriguingly, a transcript for the Tardbp gene, implicated in a number of other neurodegenerative disorders, exhibits altered association with ribosomes in the presence of r(CGG)90 repeats. We therefore tested and showed that reduced association of Tardbp mRNA with the ribosomes results in a loss of TDP-43 protein expression in r(CGG)90-expressing Purkinje neurons. Furthermore, we showed that TDP-43 could modulate the rCGG repeat-mediated toxicity in a Drosophila model that we developed previously. These findings together suggest that translational dysregulation may be an underlying mechanism of rCGG-induced neurotoxicity in FXTAS.
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8. Heyvaert M, Saenen L, Campbell JM, Maes B, Onghena P. {{Efficacy of behavioral interventions for reducing problem behavior in persons with autism: An updated quantitative synthesis of single-subject research}}. {Research in developmental disabilities}. 2014 Jun 30;35(10):2463-76.
Problem or challenging behaviors are highly prevalent among persons with autism and bring along major risks for the individual with autism and his/her family. In order to reduce the problem behavior, several behavioral interventions are used. We conducted a quantitative synthesis of single-subject studies to examine the efficacy of behavioral interventions for reducing problem behavior in persons with autism. Two hundred and thirteen studies representing 358 persons with autism met the inclusion criteria and were included in the statistical analyses. Overall, we found that behavioral interventions were on average effective in reducing problem behavior in individuals with autism, but some interventions were significantly more effective than others. The results further showed that the use of positive (nonaversive) behavioral interventions was increasing over time. The behavioral interventions were on average equally effective regardless of the type of problem behavior that was targeted. Interventions preceded by a functional analysis reduced problem behavior significantly more than interventions not preceded by a functional analysis. Finally, treatment and experimental characteristics, but not participant characteristics, were statistically significant moderators of the behavioral treatment effectiveness.
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9. Hyman SE. {{How far can mice carry autism research?}}. {Cell}. 2014 Jul 3;158(1):13-4.
In the face of growing controversy about the utility of genetic mouse models of human disease, Rothwell et al. report on a shared mechanism by which two different neuroligin-3 mutations, associated with autism spectrum disorders in humans, produce an enhancement in motor learning. The open question is how much we can learn about human ills from such models.
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10. Jivraj J, Sacrey LA, Newton A, Nicholas D, Zwaigenbaum L. {{Assessing the influence of researcher-partner involvement on the process and outcomes of participatory research in autism spectrum disorder and neurodevelopmental disorders: A scoping review}}. {Autism : the international journal of research and practice}. 2014 Jul 2.
Participatory research aims to increase the relevance and broaden the implementation of health research by involving those affected by the outcomes of health studies. Few studies within the field of neurodevelopmental disorders, particularly autism spectrum disorders, have involved autistic individuals as partners. This study sought to identify and characterize published participatory research partnerships between researchers and individuals with autism spectrum disorder or other neurodevelopmental disorders and examine the influence of participatory research partnerships on the research process and reported study outcomes. A search of databases and review of gray literature identified seven studies that described participatory research partnerships between academic researchers and individuals with autism spectrum disorder or other neurodevelopmental disorders. A comparative analysis of the studies revealed two key themes: (1) variations in the participatory research design and (2) limitations during the reporting of the depth of the partner’s involvement. Both themes potentially limit the application and generalizability of the findings. The results of the review are discussed in relation to the use of evaluative frameworks for such participatory research studies to determine the potential benefits of participatory research partnerships within the neurodevelopmental and autism spectrum disorder populations.
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11. Keita L, Guy J, Berthiaume C, Mottron L, Bertone A. {{An early origin for detailed perception in Autism Spectrum Disorder: biased sensitivity for high-spatial frequency information}}. {Scientific reports}. 2014;4:5475.
Autistics demonstrate superior performances on several visuo-spatial tasks where local or detailed information processing is advantageous. Altered spatial filtering properties at an early level of visuo-spatial analysis may be a plausible perceptual origin for such detailed perception in Autism Spectrum Disorder. In this study, contrast sensitivity for both luminance and texture-defined vertically-oriented sine-wave gratings were measured across a range of spatial frequencies (0.5, 1, 2, 4 & 8 cpd) for autistics and non-autistic participants. Contrast sensitivity functions and peak frequency ratios were plotted and compared across groups. Results demonstrated that autistic participants were more sensitivity to luminance-defined, high spatial frequency gratings (8 cpd). A group difference in peak distribution was also observed as 35% of autistic participants manifested peak sensitivity for luminance-defined gratings of 4 cpd, compared to only 7% for the comparison group. These findings support that locally-biased perception in Autism Spectrum Disorder originates, at least in part, from differences in response properties of early spatial mechanisms favouring detailed spatial information processing.
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12. Kotey S, Ertel K, Whitcomb B. {{Co-occurrence of Autism and Asthma in a Nationally-Representative Sample of Children in the United States}}. {Journal of autism and developmental disorders}. 2014 Jul 6.
Few large epidemiological studies have examined the co-occurrence of autism and asthma. We performed a cross-sectional study to examine this association using the 2007 National Survey of Children’s Health dataset (n = 77,951). We controlled for confounders and tested for autism-secondhand smoke interaction. Prevalence of asthma and autism were 14.5 % (n = 11,335) and 1.81 % (n = 1,412) respectively. Unadjusted odds ratio (OR) for asthma among autistic children was 1.35 (95 % CI 1.18-1.55). Adjusting for covariates (age, gender, body mass index, race, brain injury, secondhand smoke and socio-economic status) attenuated the OR to 1.19 (95 % CI 1.03-1.36). Autism-secondhand smoke interaction was insignificant (p = 0.38). Asthma is approximately 35 % more common in autistic children; screening may be an efficient approach to reduce risk of morbidity due to asthma.
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13. Kuhn M, Bransfield R. {{Divergent opinions of proper Lyme disease diagnosis and implications for children co-morbid with autism spectrum disorder}}. {Medical hypotheses}. 2014 Jun 16.
This paper proposes that some children with an autism spectrum disorder (ASD) in the United States have undiagnosed Lyme disease and different testing criteria used by commercial laboratories may be producing false negative results. Two testing protocols will be evaluated; first, the Centers for Disease Control (CDC) and Infectious Disease Society of America (IDSA) approved two-tiered Enzyme Immunoassay (EIA) or Immunofluorescence Assay (IFA) followed by an IgM and/or IgG Western Blot test. Second, a clinical diagnosis (flu like symptoms, joint pain, fatigue, neurological symptoms, etc.) possibly followed by a Western Blot with a broader criteria for positive bands [1]. The hypothesis proposes that the former criteria may be producing false negative results for some individuals diagnosed with an ASD. Through an online survey parents of 48 children who have a diagnosis of an ASD and have been diagnosed with Lyme disease were asked to fill out the Autism Treatment Evaluation Checklist (ATEC) before they started antibiotic therapy and after treatment. Of the 48 parents surveyed 45 of them (94%) indicated their child initially tested negative using the two-tiered CDC/IDSA approved test. The parents sought a second physician who diagnosed their child with Lyme disease using the wider range of Western Blot bands. The children were treated with antibiotics and their scores on the ATEC improved. Anecdotal data indicated that some of the children achieved previously unattained developmental milestones after antibiotic therapy began. Protein bands OSP-A and/or OSP-B (Western Blot band 31) and (Western Blot band 34) were found in 44 of 48 patients. These two bands are so specific to Borrelia burgdorferi that they were targeted for use in vaccine trials, yet are not included in the IDSA interpretation of the Western Blot.
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14. Majdalany LM, Wilder DA, Greif A, Mathisen D, Saini V. {{Comparing massed-trial instruction, distributed-trial instruction, and task interspersal to teach tacts to children with autism spectrum disorders}}. {Journal of applied behavior analysis}. 2014 Jul 3.
Although massed-trial instruction, distributed-trial instruction, and task interspersal have been shown to be effective methods of teaching skills to children with autism spectrum disorders, they have not been directly compared. In the current study, we taught 6 children to tact shapes of countries using these methods to determine which would result in the quickest acquisition. Five of the 6 participants acquired the targets in the massed-trial condition before the other 2 conditions.
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15. Maskey M, Lowry J, Rodgers J, McConachie H, Parr JR. {{Reducing Specific Phobia/Fear in Young People with Autism Spectrum Disorders (ASDs) through a Virtual Reality Environment Intervention}}. {PloS one}. 2014;9(7):e100374.
Anxiety is common in children with autism spectrum disorders (ASD), with specific fears and phobias one of the most frequent subtypes. Specific fears and phobias can have a serious impact on young people with ASD and their families. In this study we developed and evaluated a unique treatment combining cognitive behaviour therapy (CBT) with graduated exposure in a virtual reality environment (VRE). Nine verbally fluent boys with an ASD diagnosis and no reported learning disability, aged 7 to 13 years old, were recruited. Each had anxiety around a specific situation (e.g. crowded buses) or stimulus (e.g. pigeons). An individualised scene was recreated in our ‘wrap-around’ VRE. In the VRE participants were coached by a psychologist in cognitive and behavioural techniques (e.g. relaxation and breathing exercises) while the exposure to the phobia/fear stimulus was gradually increased as the child felt ready. Each child received four 20-30 minute sessions. After participating in the study, eight of the nine children were able to tackle their phobia situation. Four of the participants completely overcame their phobia. Treatment effects were maintained at 12 months. These results provide evidence that CBT with VRE can be a highly effective treatment for specific phobia/fear for some young people with ASD. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN58483069.
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16. McStay RL, Trembath D, Dissanayake C. {{Stress and Family Quality of Life in Parents of Children with Autism Spectrum Disorder: Parent Gender and the Double ABCX Model}}. {Journal of autism and developmental disorders}. 2014 Jul 6.
Past research has supported the utility of the Double ABCX model of family adaptation for parents raising a child with autism spectrum disorder (ASD). What remains unclear is the impact of family-related variables on outcomes in both mothers and fathers within the same family. We explored the potential predictors of maternal and paternal stress and family quality of life in an Australian sample of 196 parents of children with ASD aged 3-16 years. Using a cross-sectional design, parents completed questionnaires assessing factors within the Double ABCX model attributed to family adaptation. Findings provide further evidence of the negative impact of child externalising behaviours and highlight the importance of family sense of coherence on positive parental outcomes.
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17. Naganathan AN, Munoz V. {{Thermodynamics of Downhill Folding: Multi-Probe Analysis of PDD, a Protein that Folds over a Marginal Free Energy Barrier}}. {The journal of physical chemistry B}. 2014 Jul 2.
Downhill folding proteins fold in microseconds by crossing a very low or no free energy barrier (<3 RT), and exhibit a complex unfolding behavior in equilibrium. Such unfolding complexity is due to the weak thermodynamic coupling that exists between the various structural segments of these proteins, and it is manifested in unfolding curves that differ depending on the structural probe employed to monitor the process. Probe-dependent unfolding has important practical implications because it permits to investigate the folding energy landscape in detail using multi-probe thermodynamic experiments. This type of thermodynamic behavior has been investigated in depth on the protein BBL, an example of extreme (one-state) downhill folding in which there is no free energy barrier at any condition, including the denaturation midpoint. However, an open question is to what extent is such thermodynamic behavior observed on less extreme downhill folders. Here we perform a multi-probe spectroscopic characterization of the microsecond folder PDD, a structural and functional homolog of BBL that folds within the downhill regime, but is not an example of one-state downhill folding; rather at the denaturation midpoint PDD folds by crossing an incipient free energy barrier. Model-free analysis of the unfolding curves from four different spectroscopic probes together with differential scanning calorimetry reveals a dispersion of ~9 K in the apparent melting temperature and also marked differences in unfolding broadness (from ~50 to ~130 kJ mol-1 when analyzed with a two-state model), confirming that such properties are also observed on less extreme downhill folders. We subsequently perform a global quantitative analysis of the unfolding data of PDD using the same ME statistical mechanical model that was used before for the BBL domain. The analysis shows that this simple model captures all of the features observed on the unfolding of PDD (i.e. the intensity and temperature dependence of the different spectroscopic signals). From the model we estimate a free energy landscape for PDD in which the maximal thermodynamic barrier (i.e. at the denaturation midpoint) is only ~0.5 RT, consistently with previous independent estimates. Our results highlight that multi-probe unfolding experiments in equilibrium combined with statistical mechanical modeling provide important insights into the structural events that take place during the unfolding process of downhill proteins, and thus effectively probe the free energy landscape of these proteins.
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18. Nuvia SD, Bringas ME, Atzori M, Flores G. {{Prefrontal cortex, hippocampus, and basolateral amygdala plasticity in a rat model of autism spectrum}}. {Synapse (New York, NY)}. 2014 Jul 1.
We aimed to investigate the effect of prenatal administration of valproic acid (VPA) (500 mg/kg) at embryonic day 12.5 on the anatomical properties of the prefrontal cortex, hippocampus, and basolateral amygdala, at three different ages: immediately after weaning (postnatal day 21 [PD21]), pre-pubertal (PD35) and post-pubertal (PD70) ages in a rat model of autistic spectrum disorder. Quantitative analysis of the thickness of the prefrontal cortex revealed a reduced size at all study ages in the cingulate 1 area of the prefrontal cortex and CA1 of the dorsal hippocampus in prenatally exposed animals compared to controls. At the level of the basolateral amygdala, a reduction in the size was observed at PD35 and PD70 in the VPA group. In addition, a reduced thickness was observed in the prelimbic region of the prefrontal cortex in VPA animals at PD35. Interestingly, no differences in cortical thickness were observed between control and VPA animals in the infralimbic region of the prefrontal at any age. Our results suggest that prenatal exposure to VPA differentially alters cortical limbic regions anatomical parameters, with implication in the autistic spectrum disorder. Synapse, 2014. (c) 2014 Wiley Periodicals, Inc.
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19. Papagiannopoulou EA, Chitty KM, Hermens DF, Hickie IB, Lagopoulos J. {{A systematic review and meta-analysis of eye-tracking studies in children with autism spectrum disorders}}. {Social neuroscience}. 2014 Jul 2:1-23.
Aberrant eye gaze mechanisms have been implicated in autism spectrum disorders (ASD). Studies of eye movements in children with ASD reveal diminished eye gaze duration and lack of specific eye gaze fixation to the eyes and/or mouth compared with controls. However, findings to date have been contradictory. We examined eye-tracking studies on face processing in children with ASD and conducted meta-analyses to examine whether these children demonstrate atypical fixation on primary facial regions. Twenty eye-tracking studies in children with ASD were reviewed, of which the results from 14 studies were incorporated in the meta-analyses that evaluated fixation duration on (i) eyes (eight studies) and (ii) mouth (six studies). The results reveal that children with ASD have significantly reduced gaze fixation to the eye region of faces. The results of the meta-analyses indicate that ASD patients have significant impairments in gaze fixation to the eyes. On the other hand, no significant difference was uncovered in terms of fixation to the mouth region; however, this finding needs to be interpreted with caution because of the significant heterogeneity in the mouth fixation studies. The findings of this meta-analysis add further clarity to an expanding literature and suggest that specific eye gaze fixation to the eye region may represent a robust biomarker for the condition. The heterogeneity associated with the mouth fixation data precludes any definitive statement as to the robustness of these findings.
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20. Pennington ML, Cullinan D, Southern LB. {{Defining autism: variability in state education agency definitions of and evaluations for autism spectrum disorders}}. {Autism research and treatment}. 2014;2014:327271.
In light of the steady rise in the prevalence of students with autism, this study examined the definition of autism published by state education agencies (SEAs), as well as SEA-indicated evaluation procedures for determining student qualification for autism. We compared components of each SEA definition to aspects of autism from two authoritative sources: Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) and Individuals with Disabilities Education Improvement Act (IDEA-2004). We also compared SEA-indicated evaluation procedures across SEAs to evaluation procedures noted in IDEA-2004. Results indicated that many more SEA definitions incorporate IDEA-2004 features than DSM-IV-TR features. However, despite similar foundations, SEA definitions of autism displayed considerable variability. Evaluation procedures were found to vary even more across SEAs. Moreover, within any particular SEA there often was little concordance between the definition (what autism is) and evaluation procedures (how autism is recognized). Recommendations for state and federal policy changes are discussed.
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21. Rothwell PE, Fuccillo MV, Maxeiner S, Hayton SJ, Gokce O, Lim BK, Fowler SC, Malenka RC, Sudhof TC. {{Autism-associated neuroligin-3 mutations commonly impair striatal circuits to boost repetitive behaviors}}. {Cell}. 2014 Jul 3;158(1):198-212.
In humans, neuroligin-3 mutations are associated with autism, whereas in mice, the corresponding mutations produce robust synaptic and behavioral changes. However, different neuroligin-3 mutations cause largely distinct phenotypes in mice, and no causal relationship links a specific synaptic dysfunction to a behavioral change. Using rotarod motor learning as a proxy for acquired repetitive behaviors in mice, we found that different neuroligin-3 mutations uniformly enhanced formation of repetitive motor routines. Surprisingly, neuroligin-3 mutations caused this phenotype not via changes in the cerebellum or dorsal striatum but via a selective synaptic impairment in the nucleus accumbens/ventral striatum. Here, neuroligin-3 mutations increased rotarod learning by specifically impeding synaptic inhibition onto D1-dopamine receptor-expressing but not D2-dopamine receptor-expressing medium spiny neurons. Our data thus suggest that different autism-associated neuroligin-3 mutations cause a common increase in acquired repetitive behaviors by impairing a specific striatal synapse and thereby provide a plausible circuit substrate for autism pathophysiology. PAPERFLICK:
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22. Signorini C, Leoncini S, De Felice C, Pecorelli A, Meloni I, Ariani F, Mari F, Amabile S, Paccagnini E, Gentile M, Belmonte G, Zollo G, Valacchi G, Durand T, Galano JM, Ciccoli L, Renieri A, Hayek J. {{Redox imbalance and morphological changes in skin fibroblasts in typical rett syndrome}}. {Oxidative medicine and cellular longevity}. 2014;2014:195935.
Evidence of oxidative stress has been reported in the blood of patients with Rett syndrome (RTT), a neurodevelopmental disorder mainly caused by mutations in the gene encoding the Methyl-CpG-binding protein 2. Little is known regarding the redox status in RTT cellular systems and its relationship with the morphological phenotype. In RTT patients (n = 16) we investigated four different oxidative stress markers, F2-Isoprostanes (F2-IsoPs), F4-Neuroprostanes (F4-NeuroPs), nonprotein bound iron (NPBI), and (4-HNE PAs), and glutathione in one of the most accessible cells, that is, skin fibroblasts, and searched for possible changes in cellular/intracellular structure and qualitative modifications of synthesized collagen. Significantly increased F4-NeuroPs (12-folds), F2-IsoPs (7.5-folds) NPBI (2.3-folds), 4-HNE PAs (1.48-folds), and GSSG (1.44-folds) were detected, with significantly decreased GSH (-43.6%) and GSH/GSSG ratio (-3.05 folds). A marked dilation of the rough endoplasmic reticulum cisternae, associated with several cytoplasmic multilamellar bodies, was detectable in RTT fibroblasts. Colocalization of collagen I and collagen III, as well as the percentage of type I collagen as derived by semiquantitative immunofluorescence staining analyses, appears to be significantly reduced in RTT cells. Our findings indicate the presence of a redox imbalance and previously unrecognized morphological skin fibroblast abnormalities in RTT patients.
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23. Stewart LT. {{Cell adhesion proteins and the pathogenesis of autism spectrum disorders}}. {Journal of neurophysiology}. 2014 Jul 2.
Current theories on the pathogenesis of Autism Spectrum Disorders (ASD) maintain that the associated cognitive and behavioral symptoms are caused by aberrant synaptic transmission affecting specific brain circuits. Transgenic mouse models have implicated the involvement of cell adhesion proteins in synaptic dysfunction and ASD pathogenesis. Recently, Aoto et al. has shown that alternatively spliced neurexin proteins affect the efficacy of AMPA excitatory currents in both cultured neuronal networks and acute hippocampal slices constituting an ASD-related elecrophysiological phenotype.
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24. Taurines R, Schwenck C, Lyttwin B, Schecklmann M, Jans T, Reefschlager L, Geissler J, Gerlach M, Romanos M. {{Oxytocin plasma concentrations in children and adolescents with autism spectrum disorder: correlation with autistic symptomatology}}. {Attention deficit and hyperactivity disorders}. 2014 Jul 3.
Findings from research in animal models and humans have shown a clear role for the neuropeptide oxytocin (OT) on complex social behaviors. This is also true in the context of autism spectrum disorder (ASD). Previous studies on peripheral OT concentrations in children and young adults have reported conflicting results with the initial studies presenting mainly decreased OT plasma levels in ASD compared to healthy controls. Our study therefore aimed to further investigate changes in peripheral OT concentrations as a potential surrogate for the effects observed in the central nervous system (CNS) in ASD. OT plasma concentrations were assessed in 19 male children and adolescents with ASD, all with an IQ > 70 (age 10.7 +/- 3.8 years), 17 healthy male children (age 13.6 +/- 2.1 years) and 19 young male patients with attention deficit hyperactivity disorder (ADHD) as a clinical control group (age 10.4 +/- 1.9 years) using a validated radioimmunoassay. Analysis of covariance revealed significant group differences in OT plasma concentrations (F(2, 48) = 9.574, p < 0.001, eta 2 = 0.285; plasma concentrations ASD 19.61 +/- 7.12 pg/ml, ADHD 8.05 +/- 5.49 pg/ml, healthy controls 14.43 +/- 9.64 pg/ml). Post hoc analyses showed significantly higher concentrations in children with ASD compared to ADHD (p < 0.001). After Bonferroni correction, there was no significant difference in ASD in comparison with healthy controls (p = 0.132). A significant strong correlation between plasma OT and autistic symptomatology, assessed by the Autism Diagnostic Observation Schedule, was observed in the ASD group (p = 0.013, r = 0.603). Patients with ADHD differed from healthy control children by significantly decreased OT concentrations (p = 0.014). No significant influences of the covariates age, IQ, medication and comorbidity could be seen. Our preliminary results point to a correlation of OT plasma concentrations with autistic symptom load in children with ASD and a modulation of the OT system also in the etiologically and phenotypically overlapping disorder ADHD. Further studies in humans and animal models are warranted to clarify the complex association of the OT system with social impairments as well as stress-related and depressive behavior and whether peripheral findings reflect primary changes of OT synthesis and/or release in relevant areas of the CNS.
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25. Tejada MI, Glover G, Martinez F, Guitart M, de Diego-Otero Y, Fernandez-Carvajal I, Ramos FJ, Hernandez-Chico C, Pintado E, Rosell J, Calvo MT, Ayuso C, Ramos-Arroyo MA, Maortua H, Mila M. {{Molecular testing for fragile x: analysis of 5062 tests from 1105 fragile x families-performed in 12 clinical laboratories in Spain}}. {BioMed research international}. 2014;2014:195793.
Fragile X syndrome is the most common inherited form of intellectual disability. Here we report on a study based on a collaborative registry, involving 12 Spanish centres, of molecular diagnostic tests in 1105 fragile X families comprising 5062 individuals, of whom, 1655 carried a full mutation or were mosaic, three cases had deletions, 1840 had a premutation, and 102 had intermediate alleles. Two patients with the full mutation also had Klinefelter syndrome. We have used this registry to assess the risk of expansion from parents to children. From mothers with premutation, the overall rate of allele expansion to full mutation is 52.5%, and we found that this rate is higher for male than female offspring (63.6% versus 45.6%; P < 0.001). Furthermore, in mothers with intermediate alleles (45-54 repeats), there were 10 cases of expansion to a premutation allele, and for the smallest premutation alleles (55-59 repeats), there was a 6.4% risk of expansion to a full mutation, with 56 repeats being the smallest allele that expanded to a full mutation allele in a single meiosis. Hence, in our series the risk for alleles of <59 repeats is somewhat higher than in other published series. These findings are important for genetic counselling.
