1. Burgdorf J, Moskal JR, Brudzynski SM, Panksepp J. {{Rats selectively bred for low levels of play-induced 50 kHz vocalizations as a model for Autism Spectrum Disorders: A role for NMDA receptors}}. {Behav Brain Res};2013 (Apr 23)
Early childhood autism is characterized by deficits in social approach and play behaviors, socio-emotional relatedness, and communication/speech abnormalities, as well as repetitive behaviors. These core neuropsychological features of autism can be modeled in laboratory rats, and the results may be useful for drug discovery and therapeutic development. We review data that show that rats selectively bred for low rates of play-related pro-social ultrasonic vocalizations (USVs) can be used to model social deficit symptoms of autism. Low-line animals engage in less social contact time with conspecifics, show lower rates of play induced pro-social USVs, and show an increased proportion of non-frequency modulated (i.e. monotonous) ultrasonic vocalizations compared to non-selectively bred random-line animals. Gene expression patterns in the low-line animals show significant enrichment in autism-associated genes, and the NMDA receptor family was identified as a significant hub. Treatment of low-line animals with the NMDAR functional glycine site partial agonist, GLYX-13, rescued the deficits in play-induced pro-social 50-kHz USVs and reduced monotonous USVs. Since the NMDA receptor has been implicated in the genesis of autistic symptoms, it is possible that GLYX-13 may be of therapeutic value in the treatment of autism.
Lien vers le texte intégral (Open Access ou abonnement)
2. Cosar A, Ipcioglu OM. {{Re. Low folate and vitamin B nourishment is common in Omani children with newly diagnosed autism}}. {Nutrition};2013 (Apr 16)
Lien vers le texte intégral (Open Access ou abonnement)
3. Fatemi SH. {{Cerebellum and Autism}}. {Cerebellum};2013 (Apr 23)
Lien vers le texte intégral (Open Access ou abonnement)
4. Gentile I, Bravaccio C, Bonavolta R, Zappulo E, Scarica S, Riccio MP, Settimi A, Portella G, Pascotto A, Borgia G. {{Response to measles-mumps-rubella vaccine in children with autism spectrum disorders}}. {In Vivo};2013 (May-Jun);27(3):377-382.
Background/Aim: The etiology of autism spectrum disorders (ASD) is unknown. The measles-mumps-rubella (MMR) vaccination has been in the past implicated in ASD pathogenesis. The aim of our study was to evaluate the rate of seropositivity and the levels of antibodies against MMR antigens in a cohort of children with ASD compared to control children. PATIENTS AND METHODS: In a cohort of children with ASD and same-age healthy controls, we measured levels and seropositivity of antibodies against MMR. RESULTS: A total of 60 children, 31 with ASD and 29 controls were enrolled. The seropositivity rate and levels of all the three antibodies were similar in cases and controls. CONCLUSION: Children with ASD have a similar level and seropositivity rate of antibodies against the MMR vaccine to same-age controls. As persistent infections are typically associated with high antibody levels, our results support the arguments against a role of MMR vaccination as a causal factor or co-factor in development of ASD.
5. Gillespie-Smith K, Riby DM, Hancock PJ, Doherty-Sneddon G. {{Children with autism spectrum disorder (ASD) attend typically to faces and objects presented within their picture communication systems}}. {J Intellect Disabil Res};2013 (Apr 19)
BACKGROUND: Children with autism spectrum disorder (ASD) may require interventions for communication difficulties. One type of intervention is picture communication symbols which are proposed to improve comprehension of linguistic input for children with ASD. However, atypical attention to faces and objects is widely reported across the autism spectrum for several types of stimuli. METHOD: In this study we used eye-tracking methodology to explore fixation duration and time taken to fixate on the object and face areas within picture communication symbols. Twenty-one children with ASD were compared with typically developing matched groups. RESULTS: Children with ASD were shown to have similar fixation patterns on face and object areas compared with typically developing matched groups. CONCLUSIONS: It is proposed that children with ASD attend to the images in a manner that does not differentiate them from typically developing individuals. Therefore children with and without autism have the same opportunity to encode the available information. We discuss what this may imply for interventions using picture symbols.
Lien vers le texte intégral (Open Access ou abonnement)
6. Gongidi P, Johnson C, Dinan D. {{Scurvy in an autistic child: MRI findings}}. {Pediatr Radiol};2013 (Apr 19)
Scurvy results from a deficiency of vitamin C and is rarely seen in the United States. We describe the MRI findings of a case of scurvy in an autistic child with food-avoidant behavior. Advanced imaging is rarely performed in clinically well-understood disease entities such as scurvy. Typical radiographic findings are well described leading to definitive diagnosis, although the findings can be missed or misinterpreted given the rarity of scurvy in daily practice. To our knowledge, MRI features of scurvy in children in the US have been described in only one case report. This case of scurvy in an autistic child with food-avoidant behavior emphasizes that classic nutritional deficiencies, despite their rarity, must be included in the differential diagnosis of at-risk populations.
Lien vers le texte intégral (Open Access ou abonnement)
7. Isaksen J, Diseth TH, Schjolberg S, Skjeldal OH. {{Autism Spectrum Disorders – Are they really epidemic?}}. {Eur J Paediatr Neurol};2013 (Apr 17)
AIM: The aim of this paper is to report on how different external methodological factors influence estimates of ASD prevalence. METHODS: PubMed searches was conducted using the search terms, « Autism », « Autistic Disorder », « Autism Spectrum Disorders », « Asperger », « Prevalence » and « epidemiology », in combination. In total 49 studies were included. We also performed a manual search for and reviewed related articles referenced in the original articles. RESULTS: The reported prevalence rates of ASD vary widely, and so do the methodology used in the studies. CONCLUSION: There are reasons to argue that the methods used in some studies cause the high prevalence rates reported recently.
Lien vers le texte intégral (Open Access ou abonnement)
8. Kaat AJ, Gadow KD, Lecavalier L. {{Psychiatric Symptom Impairment in Children with Autism Spectrum Disorders}}. {J Abnorm Child Psychol};2013 (Apr 20)
The general aim of this study was to examine the relation of psychiatric symptom-induced impairment with other common parameters of mental health in children with autism spectrum disorder (ASD). Prevalence rates are used to illustrate the implications of different criteria for caseness. Parents/teachers completed DSM-IV-referenced rating scales for 6-12 year old children with ASD (N = 115), the majority of whom were boys (86 %). Most children were rated by parents (81 %) or teachers (86 %) as being socially or academically impaired by symptoms of at least one psychiatric disorder. The most common impairing conditions (parent/teacher) were attention-deficit/hyperactivity disorder (67 %/71 %), oppositional defiant disorder (35 %/33 %), and anxiety disorder (47 %/34 %), and the combined rates based on either informant were generally much higher. Agreement between symptom cutoff and impairment cutoff was acceptable for most disorders. A larger percentage of youth were impaired by psychiatric symptoms than met symptom cutoff criteria, and the discrepancy between impairment cutoff and clinical cutoff (impairment cutoff plus symptom cutoff) was even greater. Impairment was moderately to highly correlated with both number and severity of symptoms. Parents’ and teachers’ ratings indicated little agreement as to whether a child was impaired. Findings for youth with ASD were similar to non ASD child psychiatry outpatient referrals, but clearly different in several ways from comparable studies of community-based samples.
Lien vers le texte intégral (Open Access ou abonnement)
9. Lin Y, Tang C, He H, Duan R. {{Activation of mTOR Ameliorates Fragile X Premutation rCGG Repeat-Mediated Neurodegeneration}}. {PLoS One};2013;8(4):e62572.
Fragile X associated tremor/ataxia syndrome (FXTAS) is a late onset neurodegenerative disorder caused by aberrant expansion of CGG repeats in 5′ UTR of FMR1 gene. The elevated mRNA confers a toxic gain-of-function thought to be the critical event of pathogenesis. Expressing rCGG90 repeats of the human FMR1 5’UTR in Drosophila is sufficient to induce neurodegeneration. Rapamycin has been demonstrated to attenuate neurotoxicity by inducing autophagy in various animal models of neurodegenerative diseases. Surprisingly, we observed rapamycin exacerbated rCGG90-induced neurodegenerative phenotypes through an autophagy-independent mechanism. CGG90 expression levels of FXTAS flies exposed to rapamycin presented no significant differences. We further demonstrated that activation of the mammalian target of rapamycin (mTOR) signaling could suppress neurodegeneration of FXTAS. These findings indicate that rapamycin will exacerbate neurodegeneration, and that enhancing autophagy is insufficient to alleviate neurotoxicity in FXTAS. Moreover, these results suggest mTOR and its downstream molecules as new therapeutic targets for FXTAS by showing significant protection against neurodegeneration.
Lien vers le texte intégral (Open Access ou abonnement)
10. Mosca-Boidron AL, Valduga M, Thauvin-Robinet C, Lagarde N, Marle N, Henry C, Pinoit JM, Huet F, Beri-Deixheimer M, Ragon C, Gueneau L, Payet M, Callier P, Mugneret F, Jonveaux P, Faivre L. {{Additional Evidence to Support the Role of the 20q13.33 Region in Susceptibility to Autism}}. {Am J Med Genet A};2013 (Apr 23)
Lien vers le texte intégral (Open Access ou abonnement)
11. Pequegnat B, Sagermann M, Valliani M, Toh M, Chow H, Allen-Vercoe E, Monteiro MA. {{A vaccine and diagnostic target for Clostridium bolteae, an autism-associated bacterium}}. {Vaccine};2013 (Apr 18)
Constipation and diarrhea are common in autistic patients. Treatment with antibiotics against bacteria appears to partially alleviate autistic-related symptoms. Clostridium bolteae is a bacterium that has been shown to be overabundant in the intestinal tract of autistic children suffering from gastric intestinal ailments, and as such is an organism that could potentially aggravate gastrointestinal symptoms. We set out to investigate the cell-wall polysaccharides of C. bolteae in order to evaluate their structure and immunogenicity. Our explorations revealed that C. bolteae produces a conserved specific capsular polysaccharide comprised of rhamnose and mannose units: [–>3)-alpha-D-Manp-(1–>4)-beta-d-Rhap-(1–>], which is immunogenic in rabbits. These findings are the first description of a C. bolteae immunogen and indicate the prospect of using this polysaccharide as a vaccine to reduce or prevent C. bolteae colonization of the intestinal tract in autistic patients, and as a diagnostic marker for the rapid detection of C. bolteae in a clinical setting.
Lien vers le texte intégral (Open Access ou abonnement)
12. Poustka L, Brandeis D, Hohmann S, Holtmann M, Bolte S, Banaschewski T. {{Neurobiologically based interventions for autism spectrum disorders-rationale and new directions}}. {Restor Neurol Neurosci};2013 (Apr 17)
Autism spectrum disorders (ASD) are heterogeneous, neurodevelopmental disorders with early onset, characterized by a triad of impairments in reciprocal interaction and communication as well as repetitive and restricted interests and activities. Though underlying causes still remain largely unknown, there is now evidence for abnormal growth trajectories in the early brain development in ASD during vulnerable periods and subsequent impairment of neuronal organization and differentiation of neuronal networks. A growing number of studies over the last 10 years support the efficacy of behaviorally based interventions in ASD for the improvement of social communication and behavioral functioning. In contrast, research on neurobiologically based therapies for ASD is still at its beginnings. In this article, we will provide a selective overview of novel interventions and trainings based on neurobiological principles. Directions and options for future research on treatment aiming at restoration of normal plasticity in disrupted brain circuits in ASD are discussed.
Lien vers le texte intégral (Open Access ou abonnement)
13. Pozo P, Sarria E, Brioso A. {{Family quality of life and psychological well-being in parents of children with autism spectrum disorders: a double ABCX model}}. {J Intellect Disabil Res};2013 (Apr 19)
BACKGROUND: This study examined family quality of life (FQOL) and psychological well-being from a multidimensional perspective. The proposed model was based on the double ABCX model, with severity of the disorder, behaviour problems, social support, sense of coherence (SOC) and coping strategies as components. METHOD: One hundred and eighteen parents (59 mothers and 59 fathers) with a child diagnosed with autism spectrum disorders (ASD) participated in the study. Separate path analyses were performed to evaluate models of FQOL and psychological well-being for mothers and fathers. RESULTS: In all models, behaviour problems had a negative indirect effect on adaptation (FQOL and psychological well-being) through SOC. For both mothers and fathers, the severity of the disorder and social support played significant roles in FQOL models. Coping strategies were related with adaptation, active avoidance coping with FQOL for fathers and positive and problem-focused coping with psychological well-being for mothers. CONCLUSIONS: The results of this study highlight the value of the multidimensional approach. The specific patterns of results for mothers and fathers contribute to comprehension of the psychological adaptation of parents. Findings could be taken into account in interventions with families.
Lien vers le texte intégral (Open Access ou abonnement)
14. Rai D, Lee BK, Dalman C, Golding J, Lewis G, Magnusson C. {{Parental depression, maternal antidepressant use during pregnancy, and risk of autism spectrum disorders: population based case-control study}}. {BMJ};2013;346:f2059.
OBJECTIVE: To study the association between parental depression and maternal antidepressant use during pregnancy with autism spectrum disorders in offspring. DESIGN: Population based nested case-control study. SETTING: Stockholm County, Sweden, 2001-07. PARTICIPANTS: 4429 cases of autism spectrum disorder (1828 with and 2601 without intellectual disability) and 43 277 age and sex matched controls in the full sample (1679 cases of autism spectrum disorder and 16 845 controls with data on maternal antidepressant use nested within a cohort (n=589 114) of young people aged 0-17 years. MAIN OUTCOME MEASURE: A diagnosis of autism spectrum disorder, with or without intellectual disability. EXPOSURES: Parental depression and other characteristics prospectively recorded in administrative registers before the birth of the child. Maternal antidepressant use, recorded at the first antenatal interview, was available for children born from 1995 onwards. RESULTS: A history of maternal (adjusted odds ratio 1.49, 95% confidence interval 1.08 to 2.08) but not paternal depression was associated with an increased risk of autism spectrum disorders in offspring. In the subsample with available data on drugs, this association was confined to women reporting antidepressant use during pregnancy (3.34, 1.50 to 7.47, P=0.003), irrespective of whether selective serotonin reuptake inhibitors (SSRIs) or non-selective monoamine reuptake inhibitors were reported. All associations were higher in cases of autism without intellectual disability, there being no evidence of an increased risk of autism with intellectual disability. Assuming an unconfounded, causal association, antidepressant use during pregnancy explained 0.6% of the cases of autism spectrum disorder. CONCLUSIONS: In utero exposure to both SSRIs and non-selective monoamine reuptake inhibitors (tricyclic antidepressants) was associated with an increased risk of autism spectrum disorders, particularly without intellectual disability. Whether this association is causal or reflects the risk of autism with severe depression during pregnancy requires further research. However, assuming causality, antidepressant use during pregnancy is unlikely to have contributed significantly towards the dramatic increase in observed prevalence of autism spectrum disorders as it explained less than 1% of cases.
15. Ricci S, Businaro R, Ippoliti F, Lo Vasco VR, Massoni F, Onofri E, Troili GM, Pontecorvi V, Morelli M, Rapp Ricciardi M, Archer T. {{Altered Cytokine and BDNF Levels in Autism Spectrum Disorder}}. {Neurotox Res};2013 (Apr 19)
The contribution of neuroimmune functioning and brain-derived neurotrophic factor (BDNF) to functional dysregulation in autism spectrum disorder was assessed in 29 patients under treatment in two specialized centers of Basilicata (Chiaromonte and Matera), Southern Italy, through analysis of serum levels of cytokines and BDNF. Elevated levels of the pro-inflammatory cytokine, including interleukin-1, interleukin-6, interleukin-12, interleukin-23, tumor necrosis factor-alpha and BDNF were observed, regardless of age and gender. Comparisons were made with age- and gender-related healthy controls. The present findings reinforce current notions regarding immunoexcitotoxic mechanisms contributing to the pathophysiology of autistic disorder.
Lien vers le texte intégral (Open Access ou abonnement)
16. Taddei S, Contena B. {{Brief Report: Cognitive Performance in Autism and Asperger’s Syndrome: What are the Differences?}}. {J Autism Dev Disord};2013 (Apr 23)
Autism spectrum disorders include autistic and Asperger’s Syndrome (AS), often studied in terms of executive functions (EF), with controversial results. Using Planning Attention Simultaneous Successive theory (PASS; Das et al. in Assessment of cognitive processes: the PASS theory of intelligence. Allyn and Bacon, Boston, MA, 1994), this research compares the cognitive profiles obtained by the Cognitive Assessment System (CAS; Naglieri and Das in Cognitive assessment system. Riverside, Itasca, IL, 1997) of 15 subjects with typical development, 18 with autistic disorder and 20 with AS. Results highlight lower profiles for children with autistic and AS compared with typical development and even lower Planning and Attention processes for the group with autistic disorders than that with Asperger’s. Subjects with Asperger’s diagnosis do not differ from those with typical development as regards Simultaneous and Successive processes. Results are discussed in the light of current studies about EF.
Lien vers le texte intégral (Open Access ou abonnement)
17. Todd PK, Oh SY, Krans A, He F, Sellier C, Frazer M, Renoux AJ, Chen KC, Scaglione KM, Basrur V, Elenitoba-Johnson K, Vonsattel JP, Louis ED, Sutton MA, Taylor JP, Mills RE, Charlet-Berguerand N, Paulson HL. {{CGG Repeat-Associated Translation Mediates Neurodegeneration in Fragile X Tremor Ataxia Syndrome}}. {Neuron};2013 (Apr 17)
Fragile X-associated tremor ataxia syndrome (FXTAS) results from a CGG repeat expansion in the 5′ UTR of FMR1. This repeat is thought to elicit toxicity as RNA, yet disease brains contain ubiquitin-positive neuronal inclusions, a pathologic hallmark of protein-mediated neurodegeneration. We explain this paradox by demonstrating that CGG repeats trigger repeat-associated non-AUG-initiated (RAN) translation of a cryptic polyglycine-containing protein, FMRpolyG. FMRpolyG accumulates in ubiquitin-positive inclusions in Drosophila, cell culture, mouse disease models, and FXTAS patient brains. CGG RAN translation occurs in at least two of three possible reading frames at repeat sizes ranging from normal (25) to pathogenic (90), but inclusion formation only occurs with expanded repeats. In Drosophila, CGG repeat toxicity is suppressed by eliminating RAN translation and enhanced by increased polyglycine protein production. These studies expand the growing list of nucleotide repeat disorders in which RAN translation occurs and provide evidence that RAN translation contributes to neurodegeneration.
Lien vers le texte intégral (Open Access ou abonnement)
18. Villalon J, Jahanshad N, Beaton E, Toga AW, Thompson PM, Simon TJ. {{White matter microstructural abnormalities in girls with chromosome 22q11.2 deletion syndrome, Fragile X or Turner syndrome as evidenced by diffusion tensor imaging}}. {Neuroimage};2013 (Apr 18)
Children with chromosome 22q11.2 deletion syndrome (22q11.2DS), Fragile X syndrome (FXS), or Turner syndrome (TS) are considered to belong to distinct genetic groups, as each disorder is caused by separate genetic alterations. Even so, they have similar cognitive and behavioral dysfunctions, particularly in visuospatial and numerical abilities. To assess evidence for common underlying neural microstructural alterations, we set out to determine whether these groups have partially overlapping white matter abnormalities, relative to typically developing controls. We scanned 101 female children between 7 and 14years old: 25 with 22q11.2DS, 18 with FXS, 17 with TS, and 41 aged-matched controls using diffusion tensor imaging (DTI). Anisotropy and diffusivity measures were calculated and all brain scans were nonlinearly aligned to population and site-specific templates. We performed voxel-based statistical comparisons of the DTI-derived metrics between each disease group and the controls, while adjusting for age. Girls with 22q11.2DS showed lower fractional anisotropy (FA) than controls in the association fibers of the superior and inferior longitudinal fasciculi, the splenium of the corpus callosum, and the corticospinal tract. FA was abnormally lower in girls with FXS in the posterior limbs of the internal capsule, posterior thalami, and precentral gyrus. Girls with TS had lower FA in the inferior longitudinal fasciculus, right internal capsule and left cerebellar peduncle. Partially overlapping neurodevelopmental anomalies were detected in all three neurogenetic disorders. Altered white matter integrity in the superior and inferior longitudinal fasciculi and thalamic to frontal tracts may contribute to the behavioral characteristics of all of these disorders.
Lien vers le texte intégral (Open Access ou abonnement)
19. Wong CC, Meaburn EL, Ronald A, Price TS, Jeffries AR, Schalkwyk LC, Plomin R, Mill J. {{Methylomic analysis of monozygotic twins discordant for autism spectrum disorder and related behavioural traits}}. {Mol Psychiatry};2013 (Apr 23)
Autism spectrum disorder (ASD) defines a group of common, complex neurodevelopmental disorders. Although the aetiology of ASD has a strong genetic component, there is considerable monozygotic (MZ) twin discordance indicating a role for non-genetic factors. Because MZ twins share an identical DNA sequence, disease-discordant MZ twin pairs provide an ideal model for examining the contribution of environmentally driven epigenetic factors in disease. We performed a genome-wide analysis of DNA methylation in a sample of 50 MZ twin pairs (100 individuals) sampled from a representative population cohort that included twins discordant and concordant for ASD, ASD-associated traits and no autistic phenotype. Within-twin and between-group analyses identified numerous differentially methylated regions associated with ASD. In addition, we report significant correlations between DNA methylation and quantitatively measured autistic trait scores across our sample cohort. This study represents the first systematic epigenomic analyses of MZ twins discordant for ASD and implicates a role for altered DNA methylation in autism.Molecular Psychiatry advance online publication, 23 April 2013; doi:10.1038/mp.2013.41.
Lien vers le texte intégral (Open Access ou abonnement)
20. Ziats MN, Rennert OM. {{The Cerebellum in Autism: Pathogenic or an Anatomical Beacon?}}. {Cerebellum};2013 (Apr 21)
Lien vers le texte intégral (Open Access ou abonnement)
21. Zurawicz E, Kaluzna-Czaplinska J, Rynkowski J. {{Chromatographic methods in the study of autism}}. {Biomed Chromatogr};2013 (Apr 22)
Research into biomarkers of autism is a new means of medical intervention in this disease. Chromatographic techniques, especially coupled with mass spectrometry, are widely used in determination of biomarkers and assessment of effectiveness of autism therapy owing to their sensitivity and selectivity. Among the chromatographic techniques gas chromatography and liquid chromatography, especially high-performance liquid chromatography, have found application in clinical trials. The high-performance liquid chromatography technique allows an analysis of liquid samples with a wide range of molecules, small and large, providing an opportunity to perform advanced assays within a short time frame. Gas chromatography with the appropriate preparation of samples (gaseous and liquid) and a selection of analysis conditions enables the separation of thermally stable, volatile and non-volatile organic substances in short runtimes. The chromatographic techniques that are currently used in metabolic studies in autism are designed to identify abnormalities in three areas: the metabolism of neurotransmitters, nutritional and metabolic status and manifestations of oxidative stress. This review presents a necessary theoretical introduction and examples of applications of chromatographic studies of disorder markers in autism. Copyright (c) 2013 John Wiley & Sons, Ltd.
