1. Achuta VS, Grym H, Putkonen N, Louhivuori V, Karkkainen V, Koistinaho J, Roybon L, Castren ML. {{Metabotropic glutamate receptor 5 responses dictate differentiation of neural progenitors to NMDA-responsive cells in fragile X syndrome}}. {Dev Neurobiol}. 2016.
Disrupted metabotropic glutamate receptor 5 (mGluR5) signaling is implicated in many neuropsychiatric disorders, including autism spectrum disorder, found in fragile X syndrome (FXS). Here we report that intracellular calcium responses to the group I mGluR agonist (S)-3,5-dihydroxyphenylglycine (DHPG) are augmented, and calcium-dependent mGluR5-mediated mechanisms alter the differentiation of neural progenitors in neurospheres derived from human induced pluripotent FXS stem cells and the brains of mouse model of FXS. Treatment with the mGluR5 antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP) prevents an abnormal clustering of DHPG-responsive cells that are responsive to activation of ionotropic receptors in mouse FXS neurospheres. MPEP also corrects morphological defects of differentiated cells and enhanced migration of neuron-like cells in mouse FXS neurospheres. Unlike in mouse neurospheres, MPEP increases the differentiation of DHPG-responsive radial glial cells as well as the subpopulation of cells responsive to both DHPG and activation of ionotropic receptors in human neurospheres. However, MPEP normalizes the FXS-specific increase in the differentiation of cells responsive only to N-methyl-D-aspartate (NMDA) present in human neurospheres. Exposure to MPEP prevents the accumulation of intermediate basal progenitors in embryonic FXS mouse brain suggesting that rescue effects of GluR5 antagonist are progenitor type-dependent and species-specific differences of basal progenitors may modify effects of MPEP on the cortical development. This article is protected by copyright. All rights reserved.
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2. Bennetto L, Keith JM, Allen PD, Luebke AE. {{Children with autism spectrum disorder have reduced otoacoustic emissions at the 1 kHz mid-frequency region}}. {Autism Res}. 2016.
Autism spectrum disorder (ASD) is a behaviorally diagnosed disorder of early onset characterized by impairment in social communication and restricted and repetitive behaviors. Some of the earliest signs of ASD involve auditory processing, and a recent study found that hearing thresholds in children with ASD in the mid-range frequencies were significantly related to receptive and expressive language measures. In addition, otoacoustic emissions have been used to detect reduced cochlear function in the presence of normal audiometric thresholds. We were interested then to know if otoacoustic emissions in children with normal audiometric thresholds would also reveal differences between children with ASD and typical developing (TD) controls in mid-frequency regions. Our objective was to specifically measure baseline afferent otoacoustic emissions (distortion-product otoacoustic emissions [DPOAEs]), transient-evoked otoacoustic emissions (TrOAEs), and efferent suppression, in 35 children with high-functioning ASD compared with 42 aged-matched TD controls. All participants were males 6-17 years old, with normal audiometry, and rigorously characterized via Autism Diagnostic Interview-Revised and Autism Diagnostic Observation Schedule. Children with ASD had greatly reduced DPOAE responses in the 1 kHz frequency range, yet had comparable DPOAE responses at 0.5 and 4-8 kHz regions. Furthermore, analysis of the spectral features of TrOAEs revealed significantly decreased emissions in ASD in similar frequencies. No significant differences were noted in DPOAE or TrOAE noise floors, middle ear muscle reflex activity, or efferent suppression between children with ASD and TD controls. In conclusion, attention to specific-frequency deficits using non-invasive measures of cochlear function may be important in auditory processing impairments found in ASD. Autism Res 2016. (c) 2016 International Society for Autism Research, Wiley Periodicals, Inc.
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3. Ellawadi AB, Fein D, Naigles LR. {{Category structure and processing in 6-year-old children with autism}}. {Autism Res}. 2016.
The ability to form categories is fundamental to understanding the world. Although individuals with autism spectrum disorder (ASD) are frequently described as having poor categorization abilities, there are mixed findings across research studies. This study investigated the categorization abilities of 6-year-old children with ASD as compared to their peers with typical language development (TD). We examined the impact of stimulus typicality, how representative a category member is of that category (e.g., sparrows are typical members of the category bird, whereas ostriches are atypical category members) on accuracy, reaction time, and performance stability. Both groups were more accurate in identifying typical category members than atypical ones. The accuracy of the children in the ASD group was affected by item ordering, indicating less stable performance. Furthermore, category structure was predicted by concurrent language levels in the TD group but by concurrent nonverbal IQ in the ASD group. Together these findings suggest that children with ASD process categories differently than their peers with TD.
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4. Erickson SR, Spoutz P, Dorsch M, Bleske B. {{Cardiovascular risk and treatment for adults with intellectual or developmental disabilities}}. {Int J Cardiol}. 2016; 221: 371-5.
BACKGROUND: People with intellectual/developmental disabilities (IDDs) face the development of cardiovascular disease (CVD) similar to the general population. The purpose of this study was to describe and compare the presence of CVD risk factors, the atherosclerotic cardiovascular (ASCVD) risk score, and medication prescribing patterns for medications to treat related risk factors for patients with IDD and those without. METHODS: This was a retrospective study of patients age 18years and older of a health system’s primary care medicine practices. The IDD group had documentation of a diagnosis related to IDD. The comparison group was a random sample of patients from the same practices who had no indication of IDD. Patient characteristics included demographics, smoking status, cholesterol, and blood pressure. The presence of a diagnosis of hypertension, hyperlipidemia, diabetes, coronary artery disease, history of stroke or myocardial infarction, and related medication therapy were documented. The dependent variable was the estimated 10-year primary risk of ASCVD. RESULTS: The IDD group included 78 patients while the GenMed group included 187. There were no significant differences in the prevalence of risk-related diagnoses or in blood pressure and cholesterol between the two groups. The estimated 10-year ASCVD risk was significantly higher in the GenMed group compared to the IDD group (p=0.02). Prescribing was similar between the groups. The regression analysis found that group assignment was not significantly associated with ASCVD risk, while age, gender, and race were. CONCLUSIONS: CV risk and related treatment among patients with IDD was similar to that of the general population.
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5. Fernandes LC, Gillberg CI, Cederlund M, Hagberg B, Gillberg C, Billstedt E. {{Aspects of Sexuality in Adolescents and Adults Diagnosed with Autism Spectrum Disorders in Childhood}}. {J Autism Dev Disord}. 2016.
The literature concerning sexuality in autism spectrum disorders (ASDs) is limited regarding inappropriate sexual behaviours and paraphilias and its relation to age, verbal ability, symptom severity, intellectual ability, or adaptive functioning. A cohort of 184 adolescents and young adults (ages 15-39 years) with ASD diagnosed in childhood, including both low and high functioning individuals, was examined. The large majority were found to have a sexual interest and showed interest towards the opposite sex. Inappropriate sexual behaviours and paraphilias were reported for about a fourth of the individuals. No relationships were found between inappropriate sexual behaviours and any of the background variables listed above. However, associations were found between paraphilias and ASD symptom severity, intellectual ability, and adaptive functioning.
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6. Homs A, Codina-Sola M, Rodriguez-Santiago B, Villanueva CM, Monk D, Cusco I, Perez-Jurado LA. {{Genetic and epigenetic methylation defects and implication of the ERMN gene in autism spectrum disorders}}. {Transl Psychiatry}. 2016; 6(7): e855.
Autism spectrum disorders (ASD) are highly heritable and genetically complex conditions. Although highly penetrant mutations in multiple genes have been identified, they account for the etiology of <1/3 of cases. There is also strong evidence for environmental contribution to ASD, which can be mediated by still poorly explored epigenetic modifications. We searched for methylation changes on blood DNA of 53 male ASD patients and 757 healthy controls using a methylomic array (450K Illumina), correlated the variants with transcriptional alterations in blood RNAseq data, and performed a case-control association study of the relevant findings in a larger cohort (394 cases and 500 controls). We found 700 differentially methylated CpGs, most of them hypomethylated in the ASD group (83.9%), with cis-acting expression changes at 7.6% of locations. Relevant findings included: (1) hypomethylation caused by rare genetic variants (meSNVs) at six loci (ERMN, USP24, METTL21C, PDE10A, STX16 and DBT) significantly associated with ASD (q-value <0.05); and (2) clustered epimutations associated to transcriptional changes in single-ASD patients (n=4). All meSNVs and clustered epimutations were inherited from unaffected parents. Resequencing of the top candidate genes also revealed a significant load of deleterious mutations affecting ERMN in ASD compared with controls. Our data indicate that inherited methylation alterations detectable in blood DNA, due to either genetic or epigenetic defects, can affect gene expression and contribute to ASD susceptibility most likely in an additive manner, and implicate ERMN as a novel ASD gene. Lien vers le texte intégral (Open Access ou abonnement)
7. Khaled EM, Meguid NA, Bjorklund G, Gouda A, Bahary MH, Hashish A, Sallam NM, Chirumbolo S, El-Bana MA. {{Altered urinary porphyrins and mercury exposure as biomarkers for autism severity in Egyptian children with autism spectrum disorder}}. {Metab Brain Dis}. 2016.
Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder that affects social, communication, and behavioral development. Recent evidence supported but also questioned the hypothetical role of compounds containing mercury (Hg) as contributors to the development of ASD. Specific alterations in the urinary excretion of porphyrin-containing ring catabolites have been associated with exposure to Hg in ASD patients. In the present study, the level of urinary porphyrins, as biomarkers of Hg toxicity in children with ASD, was evaluated, and its correlation with severity of the autistic behavior further explored. A total of 100 children was enrolled in the present study. They were classified into three groups: children with ASD (40), healthy controls (40), and healthy siblings of the ASD children (20). Children with ASD were diagnosed using DSM-IV-TR, ADI-R, and CARS tests. Urinary porphyrins were evaluated within the three groups using high-performance liquid chromatography (HPLC), after plasma evaluation of mercury (Hg) and lead (Pb) in the same groups. Results showed that children with ASD had significantly higher levels of Hg, Pb, and the porphyrins pentacarboxyporphyrin, coproporphyrin, precoproporphyrin, uroporphyrins, and hexacarboxyporphyrin compared to healthy controls and healthy siblings of the ASD children. However, there was no significant statistical difference in the level of heptacarboxyporphyrin among the three groups, while a significant positive correlation between the levels of coproporphyrin and precoproporphyrin and autism severity was observed. Mothers of ASD children showed a higher percentage of dental amalgam restorations compared to the mothers of healthy controls suggesting that high Hg levels in children with ASD may relate to the increased exposure to Hg from maternal dental amalgam during pregnancy and lactation. The results showed that the ASD children in the present study had increased blood Hg and Pb levels compared with healthy control children indicating that disordered porphyrin metabolism might interfere with the pathology associated with the autistic neurologic phenotype. The present study indicates that coproporphyrin and precoproporhyrin may be utilized as possible biomarkers for heavy metal exposure and autism severity in children with ASD.
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8. Lopata C, Donnelly JP, Jordan AK, Thomeer ML, McDonald CA, Rodgers JD. {{Brief Report: Parent-Teacher Discrepancies on the Developmental Social Disorders Scale (BASC-2) in the Assessment of High-Functioning Children with ASD}}. {J Autism Dev Disord}. 2016.
This study compared parent and teacher ratings of ASD-related symptoms of 120 high-functioning children, ages 6-12 years with ASD (HFASD) using the Developmental Social Disorders (DSD) scale of the BASC-2. DSD ratings (parent and teacher) were significantly higher than normative estimates. The cross-informant comparison was significantly higher for parents (vs. teachers), and correlations (ICC and Pearson) between the informant groups were significant (but low in magnitude). Agreement among parents and teachers accurately placed 81 % of cases above the at-risk cutpoint for symptoms of ASD, and agreement was highest in the at-risk range of perceived symptoms. Additional analyses indicated a significant difference in the trend across the parent-teacher discrepancies, and no significant moderators of the discrepancies. Implications for assessment are provided.
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9. Menassa DA, Sloan C, Chance SA. {{Primary olfactory cortex in autism and epilepsy: Increased glial cells in autism}}. {Brain Pathol}. 2016.
BACKGROUND: Autism Spectrum Disorder is characterized by sensory anomalies including impaired olfactory identification. 30% of individuals with autism have a clinical diagnosis of epilepsy. Primary olfactory cortex (piriform cortex) is central to olfactory identification and is an epileptogenic structure. Cytoarchitectural changes in olfactory cortex may underlie olfactory differences seen in autism. METHODS: Primary olfactory cortex was sampled from 17 post-mortem autism cases with and without epilepsy, 11 epilepsy cases without autism and 11 typically developed cases. Stereological and neuropathological methods were used to quantify glial, pyramidal and non-pyramidal cell densities in layers of the piriform as well as identify pathological differences in this area and its neighbouring region, the olfactory tubercle. RESULTS: We found increased layer II glial cell densities in autism with and without epilepsy, which were negatively correlated with age and positively correlated with levels of corpora amylacea in layer I. These changes were also associated with greater symptom severity and did not extend to the olfactory tubercle. CONCLUSION: Glial cell organisation may follow an altered trajectory of development with age in autism. The findings are consistent with other studies implicating increased glial cells in the autism brain. Altered cytoarchitecture may contribute to sensory deficits observed in affected individuals. This study provides evidence that autism is linked to alterations in the cytoarchitectural structure that underlies primary sensory processes and is not restricted to heteromodal (‘higher’) cognitive centres. This article is protected by copyright. All rights reserved.
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10. Olsen J, Liew Z. {{Commentary: Acetaminophen use in pregnancy and neurodevelopment: attention function and autism spectrum symptoms}}. {Int J Epidemiol}. 2016.
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11. Parisi L, Di Filippo T, Roccella M. {{The Quality of Life in Girls with Rett Syndrome}}. {Ment Illn}. 2016; 8(1): 6302.
Nowadays, quality of life is receiving an increasing attention in all scientific areas. Rett syndrome (RTT) is a rare neurological development, affecting mainly females. The congenital disease affects the central nervous system, and is one of the most common causes of severe intellectual disability. The aim of our study is to evaluate the effect of RTT on the quality of life of people who are affected. Both parents of 18 subjects, all female, diagnosed with RTT, took part in the research. Quality of life was assessed using the Italian version of the Impact of Childhood Illness Scale. This scale consists of 30 questions that investigate the effect of illness on children, parents and families. For each question, the parent was asked to rate two variables: frequency and importance. Another questionnaire was administered to obtain medical history, diagnostic and therapeutic data of the persons with RTT. Our data show that RTT has a considerable impact on both the child’s development and the entire family. Parents’ answers demonstrated that their child’s illness had consequences for the child and how the family coped with it. For this reason, attention should be directed at psychological and social aspects, as well as attitudes, manners, reactions and effects such disturbances can have on the entire family.
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12. Schelinski S, Roswandowitz C, von Kriegstein K. {{Voice identity processing in autism spectrum disorder}}. {Autism Res}. 2016.
People with autism spectrum disorder (ASD) have difficulties in identifying another person by face and voice. This might contribute considerably to the development of social cognition and interaction difficulties. The characteristics of the voice recognition deficit in ASD are unknown. Here, we used a comprehensive behavioral test battery to systematically investigate voice processing in high-functioning ASD (n = 16) and typically developed pair-wise matched controls (n = 16). The ASD group had particular difficulties with discriminating, learning, and recognizing unfamiliar voices, while recognizing famous voices was relatively intact. Tests on acoustic processing abilities showed that the ASD group had a specific deficit in vocal pitch perception that was dissociable from otherwise intact acoustic processing (i.e., musical pitch, musical, and vocal timbre perception). Our results allow a characterization of the voice recognition deficit in ASD: The findings indicate that in high-functioning ASD, the difficulty to recognize voices is particularly pronounced for learning novel voices and the recognition of unfamiliar peoples’ voices. This pattern might be indicative of difficulties with integrating the acoustic characteristics of the voice into a coherent percept-a function that has been previously associated with voice-selective regions in the posterior superior temporal sulcus/gyrus of the human brain. Autism Res 2016. (c) 2016 International Society for Autism Research, Wiley Periodicals, Inc.
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13. van der Plas E, Dupuis A, Arnold P, Crosbie J, Schachar R. {{Association of Autism Spectrum Disorder with Obsessive-Compulsive and Attention-Deficit/Hyperactivity Traits and Response Inhibition in a Community Sample}}. {J Autism Dev Disord}. 2016.
We examined co-occurrence of autism spectrum disorder (ASD) with (traits of) attention-deficit/hyperactivity (ADHD), obsessive-compulsive (OCD) and inhibition deficits in a community sample (n = 16,676) and tested whether having a sibling with ASD manifested in increased features of ADHD, OCD or inhibition deficits. Individuals with ASD had increased ADHD and OCD traits compared with individuals without ASD. Individuals with a sibling with ASD exhibited more ADHD traits than did individuals whose sibling did not have ASD. The « sibling effect » on manifestation of ADHD traits was observed in individuals with and without ASD. Having a sibling with ASD did not affect OCD traits. Inhibition was impaired in individuals with ASD who had a sibling with ASD only.
