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. Dijkhuis RR, Ziermans TB, Van Rijn S, Staal WG, Swaab H. {{Self-regulation and quality of life in high-functioning young adults with autism}}. {Autism}. 2016.
BACKGROUND: Autism is generally associated with poor functional outcome but little is known about predictors of quality of life, especially during early adulthood. This study was conducted to assess subjective quality of life during early adulthood in high-functioning autism spectrum disorder and its relation with self-regulating abilities. Individuals with high-functioning autism spectrum disorder who progressed into post-secondary higher education (N = 75) were compared to a typical peer control group (N = 28) based on behavioral self-report questionnaires. The results indicated that individuals with high-functioning autism spectrum disorder reported significantly lower subjective quality of life than typical controls (p < 0.001, effect size (d) = 1.84). In addition, individuals with high-functioning autism spectrum disorder reported more problems with emotion processing (p < 0.05, effect size (d) = 0.79) and daily executive functioning (p < 0.001, effect size (d) = 1.29) than controls. A higher level of executive functioning problems was related to lower quality of life in the high-functioning autism spectrum disorder group, but no significant relation between level of emotion processing and subjective quality of life became apparent in the regression analysis. Our findings show that even in high-functioning young adults with autism, executive functioning, emotion processing, and subjective quality of life are low compared to typically developing peers. Furthermore, these results emphasize the importance of targeting executive functioning problems in individuals with autism to improve subjective quality of life. Lien vers le texte intégral (Open Access ou abonnement)
3. Gokoolparsadh A, Sutton GJ, Charamko A, Green NF, Pardy CJ, Voineagu I. {{Searching for convergent pathways in autism spectrum disorders: insights from human brain transcriptome studies}}. {Cell Mol Life Sci}. 2016.
Autism spectrum disorder (ASD) is one of the most heritable neuropsychiatric conditions. The complex genetic landscape of the disorder includes both common and rare variants at hundreds of genetic loci. This marked heterogeneity has thus far hampered efforts to develop genetic diagnostic panels and targeted pharmacological therapies. Here, we give an overview of the current literature on the genetic basis of ASD, and review recent human brain transcriptome studies and their role in identifying convergent pathways downstream of the heterogeneous genetic variants. We also discuss emerging evidence on the involvement of non-coding genomic regions and non-coding RNAs in ASD.
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4. Keefer A, Kreiser NL, Singh V, Blakeley-Smith A, Duncan A, Johnson C, Klinger L, Meyer A, Reaven J, Vasa RA. {{Intolerance of Uncertainty Predicts Anxiety Outcomes Following CBT in Youth with ASD}}. {J Autism Dev Disord}. 2016.
Modified cognitive-behavioral therapy (MCBT) has been demonstrated to reduce anxiety in youth with autism spectrum disorder (ASD). However, non-response rates are fairly high. Few studies have investigated factors associated with response. Intolerance of uncertainty (IU) is a treatment target for anxiety and worry in neurotypical populations and has been linked to anxiety and ASD. We sought to examine whether IU affects outcomes following MCBT in 43 children, ages 8-14 years, with ASD without intellectual disability. Consistent with prior data, there was a significant reduction in parent reported anxiety following MCBT. Higher levels of pre-intervention IU predicted higher anxiety and worry pre- and post-intervention. These findings suggest that targeting IU may improve outcomes following MCBT in youth with ASD and anxiety.
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5. 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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6. 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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7. Soares A, Shiozawa P, Trevizol AP, Paula CS, Lowenthal R, Cordeiro Q. {{Effects of augmentation agents in autistic disorder patients treated with risperidone: a systematic review and a meta-analysis}}. {Trends Psychiatry Psychother}. 2016; 38(2): 114-6.
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8. Stadnick N, Chlebowski C, Baker-Ericzen M, Dyson M, Garland A, Brookman-Frazee L. {{Psychiatric comorbidity in autism spectrum disorder: Correspondence between mental health clinician report and structured parent interview}}. {Autism}. 2016.
Publicly funded mental health services are critical in caring for children with autism spectrum disorder. Accurate identification of psychiatric comorbidity is necessary for effective mental health treatment. Little is known about psychiatric diagnosis for this population in routine mental health care. This study (1) examined correspondence between psychiatric diagnoses reported by mental health clinicians and those derived from a structured diagnostic interview and (2) identified predictors of agreement between clinician-reported and diagnostic interview-derived diagnoses in a sample of 197 children aged 4-14 years with autism spectrum disorder receiving mental health services. Data were drawn from a randomized effectiveness trial conducted in publicly funded mental health services. Non-autism spectrum disorder diagnoses were assessed using an adapted version of the Mini-International Neuropsychiatric Interview, parent version. Cohen’s kappa was calculated to examine agreement between Mini-International Neuropsychiatric Interview, parent version and clinician-reported diagnoses of comorbid conditions. Children met criteria for an average of 2.83 (standard deviation = 1.92) Mini-International Neuropsychiatric Interview, parent version diagnoses. Agreement was poor across all diagnostic categories (kappa values: 0.06-0.18). Logistic regression identified child gender and clinical characteristics as significant predictors of agreement for specific diagnoses. Results underscore the need for training mental health clinicians in targeted assessment of specific psychiatric disorders and prioritizing treatment development and testing for specific diagnoses to improve care for children with autism spectrum disorder served in publicly funded mental health settings.
