1. Emberti Gialloreti L, Curatolo P. {{Autism Spectrum Disorder: Why Do We Know So Little?}}. {Front Neurol};2018;9:670.
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2. Folsom TD, Higgins L, Markowski TW, Griffin TJ, Fatemi SH. {{Quantitative proteomics of forebrain subcellular fractions in fragile X mental retardation 1 knockout mice following acute treatment with 2-Methyl-6-(phenylethynyl)pyridine: Relevance to Developmental Study of Schizophrenia}}. {Synapse};2018 (Sep 3)
The fragile X mental retardation 1 knockout (Fmr1 KO) mouse replicates behavioral deficits associated with autism, fragile X syndrome, and schizophrenia. Less is known whether protein expression changes are consistent with findings in subjects with schizophrenia. In the current study we used liquid chromatography tandem mass spectrometry (LC-MS/MS) proteomics to determine the protein expression of four subcellular fractions in forebrains of Fmr1 KO mice vs. C57BL/6J mice and the effect of a negative allosteric modulator of mGluR5 – 2-Methyl-6-(phenylethynyl)pyridine (MPEP) – on protein expression. Strain- and treatment-specific differential expression of proteins was observed, many of which have previously been observed in brains of subjects with schizophrenia. Western blotting verified the direction and magnitude of change for several proteins in different subcellular fractions as follows: neurofilament light protein (NEFL) and 2′,3′-cyclic-nucleotide 3′-phosphodiesterase (CNP) in the total homogenate; heterogeneous nuclear ribonucleoproteins C1/C2 (HNRNPC) and heterogeneous nuclear ribonucleoprotein D0 (HNRNPD) in the nuclear fraction; excitatory amino acid transporter 2 (EAAT2) and ras-related protein rab 3a (RAB3A) in the synaptic fraction; and ras-related protein rab 35 (RAB35) and neuromodulin (GAP43) in the rough endoplasmic reticulum fraction. Individuals with FXS do not display symptoms of schizophrenia. However, the biomarkers that have been identified suggest that the Fmr1 KO model could potentially be useful in the study of schizophrenia. This article is protected by copyright. All rights reserved.
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3. Gabis LV, Shefer S, Gruber N, Raviv R, Cohen Y, Berkenstadt M, Ries-Levavi L, Pinhas-Hamiel O, Elizur S. {{[FROM GENETICS OF FRAGILE X SYNDROME TO DEVELOPMENT OF TARGETED AND PERSONALIZED DRUG THERAPY]}}. {Harefuah};2018 (Aug);157(8):529-533.
INTRODUCTION: At the end of the last century Fragile X syndrome was identified, and the main syndrome characteristics were discovered. The syndrome is caused from a flaw in the number of nucleotide repeats that encodes for a regulatory protein which is critical for neural connectivity and normal brain development. The syndrome is characterized by neurodevelopmental and intellectual disabilities, autism spectrum features and other clinical features associated with the same gene aberration. The number of trinucleotide repeats have a direct effect on the outcome and the need for genetic counseling. We advocate performing genetic tests for every child with developmental delay, learning disabilities, autism spectrum disorders and especially, intellectual impairment. It is also advisable to check the number of nucleotide repeats of the gene, in every woman suffering from infertility or early menopause. In addition, genetic testing should be performed on older adults manifesting early symptoms of Parkinson’s disease, balance instability, tremor or cognitive dysfunction with unknown etiology. Due to the tremendous progress in understanding the biological mechanisms of the syndrome, new molecules/drugs have been proposed and are tested, in order to find a way to bypass the defect mechanism underlying the disorder. We will review the most commonly used drugs in the treatment of Fragile X syndrome and many medications that are currently under investigation as a more targeted treatment.
4. Garcia-Cabezas MA, Barbas H, Zikopoulos B. {{Parallel Development of Chromatin Patterns, Neuron Morphology, and Connections: Potential for Disruption in Autism}}. {Front Neuroanat};2018;12:70.
The phenotype of neurons and their connections depend on complex genetic and epigenetic processes that regulate the expression of genes in the nucleus during development and throughout life. Here we examined the distribution of nuclear chromatin patters in relation to the epigenetic landscape, phenotype and connections of neurons with a focus on the primate cerebral cortex. We show that nuclear patterns of chromatin in cortical neurons are related to neuron size and cortical connections. Moreover, we point to evidence that reveals an orderly sequence of events during development, linking chromatin and gene expression patterns, neuron morphology, function, and connections across cortical areas and layers. Based on this synthesis, we posit that systematic studies of changes in chromatin patterns and epigenetic marks across cortical areas will provide novel insights on the development and evolution of cortical networks, and their disruption in connectivity disorders of developmental origin, like autism. Achieving this requires embedding and interpreting genetic, transcriptional, and epigenetic studies within a framework that takes into consideration distinct types of neurons, local circuit interactions, and interareal pathways. These features vary systematically across cortical areas in parallel with laminar structure and are differentially affected in disorders. Finally, based on evidence that autism-associated genetic polymorphisms are especially prominent in excitatory neurons and connectivity disruption affects mostly limbic cortices, we employ this systematic approach to propose novel, targeted studies of projection neurons in limbic areas to elucidate the emergence and time-course of developmental disruptions in autism.
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5. Hollocks MJ, Lerh JW, Magiati I, Meiser-Stedman R, Brugha TS. {{Anxiety and depression in adults with autism spectrum disorder: a systematic review and meta-analysis}}. {Psychol Med};2018 (Sep 4):1-14.
Adults with autism spectrum disorder (ASD) are thought to be at disproportionate risk of developing mental health comorbidities, with anxiety and depression being considered most prominent amongst these. Yet, no systematic review has been carried out to date to examine rates of both anxiety and depression focusing specifically on adults with ASD. This systematic review and meta-analysis examined the rates of anxiety and depression in adults with ASD and the impact of factors such as assessment methods and presence of comorbid intellectual disability (ID) diagnosis on estimated prevalence rates. Electronic database searches for studies published between January 2000 and September 2017 identified a total of 35 studies, including 30 studies measuring anxiety (n = 26 070; mean age = 30.9, s.d. = 6.2 years) and 29 studies measuring depression (n = 26 117; mean age = 31.1, s.d. = 6.8 years). The pooled estimation of current and lifetime prevalence for adults with ASD were 27% and 42% for any anxiety disorder, and 23% and 37% for depressive disorder. Further analyses revealed that the use of questionnaire measures and the presence of ID may significantly influence estimates of prevalence. The current literature suffers from a high degree of heterogeneity in study method and an overreliance on clinical samples. These results highlight the importance of community-based studies and the identification and inclusion of well-characterized samples to reduce heterogeneity and bias in estimates of prevalence for comorbidity in adults with ASD and other populations with complex psychiatric presentations.
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6. Lee S, Chun HS, Lee J, Park HJ, Kim KT, Kim CH, Yoon S, Kim WK. {{Plausibility of the zebrafish embryos/larvae as an alternative animal model for autism: A comparison study of transcriptome changes}}. {PLoS One};2018;13(9):e0203543.
Autism spectrum disorder (ASD) is a serious neurodevelopmental disorder characterized by impaired or abnormal social interaction and communication and by restricted and repetitive behaviour. ASD is highly prevalent in Asia, Europe, and the United States, and the frequency of ASD is growing each year. Recent epidemiological studies have indicated that ASD may be caused or triggered by exposure to chemicals in the environment, such as those in the air or water. Thus, toxicological studies are needed to examine chemicals that might be implicated. However, the experimental efficiency of existing experimental models is limited, and many models represent challenges in terms of animal welfare. Thus, alternative ASD animal models are necessary. To address this, we examined the efficacy of the zebrafish embryo/larva as an alternative model of ASD. Specifically, we exposed zebrafish to valproic acid (0, 12.5, 25, 50, or 100 muM), which is a chemical known to induce autism-like effects. We then analysed subsequent developmental, behavioural, and transcriptomic changes. We found that 100 muM and 50 muM valproic acid decreased the hatching rate and locomotor activity of zebrafish embryos/larvae. Transcriptomic analysis revealed significant alterations in a number of genes associated with autism, such as adsl, mbd5, shank3, and tsc1b. Additionally, we found changes in gene ontology that were also reported in previous studies. Our findings indicate that zebrafish embryos/larvae and humans with ASD might have common physiological pathways, indicating that this animal model may represent an alternative tool for examining the causes of and potential treatments for this illness.
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7. Parsons L, Cordier R, Munro N, Joosten A. {{The feasibility and appropriateness of a peer-to-peer, play-based intervention for improving pragmatic language in children with autism spectrum disorder}}. {Int J Speech Lang Pathol};2018 (Sep 2):1-13.
PURPOSE: This study trialled a play-based, peer-to-peer intervention with children with autism spectrum disorder (ASD) to identify suitable instruments for measuring changes in pragmatic language following the intervention, and evaluate preliminary effectiveness. It also aimed to investigate the appropriateness of the intervention for participants. METHOD: Ten children with ASD, their typically developing peers, and parents participated. The Pragmatics Observational Measure (POM), Social Emotional Evaluation (SEE) and Profiling Elements of Prosody in Speech Communication (PEPS-C) measured the participant’s social communication skills before, after, and 2-months following the intervention. Parent interviews were conducted two months after the intervention and responses were analysed using a thematic approach. RESULT: Children demonstrated gains in pragmatic language on the POM (chi(2)(3) = 11.160, p = 0.011) and related higher-level language on the SEE (chi(2)(2) = 6.686, p = 0.035). The PEPS-C did not produce any significant results. Parent interview responses indicated the intervention was appropriate for the children and families involved. CONCLUSION: The intervention warrants further investigation of effectiveness with a more robust research design. Consideration should be given to using observational measures of pragmatic language away from the clinic environment to evaluate generalisation, and future development of the intervention might consider variations in playmates and group size.
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8. Sun C, Zou M, Wang X, Xia W, Ma Y, Liang S, Hao Y, Wu L, Fu S. {{FADS1-FADS2 and ELOVL2 gene polymorphisms in susceptibility to autism spectrum disorders in Chinese children}}. {BMC Psychiatry};2018 (Sep 4);18(1):283.
BACKGROUD: Autism spectrum disorders (ASD) are a complex group of neurodevelopmental disorders with a genetic basis. The role of long-chain polyunsaturated fatty acids (LC-PUFAs) and the occurrence of autism has been the focus of many recent studies. The present study investigates whether genetic variants of the fatty acid desaturase (FADS) 1/2 and elongation of very long-chain fatty acids protein (ELOVL) 2 genes, which are involved in LC-PUFA metabolism, are associated with ASD risk. METHODS: A cohort of 243 ASD patients and 243 unrelated healthy controls were enrolled in this case control study. Sixteen tag single nucleotide polymorphisms from the FADS1-2 and ELOVL2 genes were genotyped using the Sequenom Mass Array. RESULTS: There were significant differences in allelic distribution of FADS2 rs526126 (OR = 0.55, 95% CI = 0.42-0.72, pFDR < 0.05) between autistic children and controls. FADS2 rs526126 and ELOVL2 rs10498676 were associated with decreased ASD risk in recessive model (OR = 0.07, 95% CI = 0.02-0.22, pFDR < 0.01; OR = 0.56, 95% CI = 0.35-0.89, pFDR = 0.042), while ELOVL2 rs17606561, rs3756963, and rs9468304 were associated with increased ASD risk in overdominant model (OR = 1.63, 95% CI = 1.12-2.36, pFDR = 0.036; OR = 1.64, 95% CI = 1.14-2.37, pFDR = 0.039; OR = 1.75, 95% CI = 1.22-2.50, pFDR = 0.017). The A/A genotype of rs10498676 was correlated with a decline in the Autism Diagnostic Interview-Revised communication (verbal and nonverbal) domain. CONCLUSIONS: These findings provide evidence of an association between FADS2 and ELOVL2 polymorphisms and ASD susceptibility in Chinese children. Lien vers le texte intégral (Open Access ou abonnement)
9. Tinsley M. {{Drinking, Drug Use, and Addiction in the Autism Community ELIZABETH KUNREUTHER & ANN PALMER London: Jessica Kingsley Publishers, 2017 ISBN: 9781785927492, 192 pp. Paperback. Price: $39.99}}. {Drug Alcohol Rev};2018 (Sep);37(6):818-819.
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10. Yamagata B, Itahashi T, Nakamura M, Mimura M, Hashimoto RI, Kato N, Aoki Y. {{White matter endophenotypes and correlates for the clinical diagnosis of autism spectrum disorder}}. {Soc Cogn Affect Neurosci};2018 (Sep 4);13(7):765-773.
Since prior diffusion tensor imaging (DTI) studies reported no significant differences in white matter organizations between individuals with autism spectrum disorder (ASD) and their unaffected siblings, the neural correlates for developing a clinical diagnosis among people with endophenotypes remain undetermined. We obtained DTI data from a total of 60 participants consisting of 30 people with endophenotypes and 30 people without. We first followed a conventional approach by comparing individuals with ASD and their unaffected siblings. Using region-of-interest approach, we then performed bootstrapping to examine whether the differences in white matter organizations between individuals with ASD and their unaffected siblings were substantially large, considering the distribution of differences between typically developing (TD) siblings. Conventional approaches revealed no significant differences in white matter organizations between individuals with ASD and their unaffected siblings. Bootstrapping revealed a significantly large difference in axial diffusivity in the left stria terminalis between individuals with ASD and their unaffected siblings after accounting for the distribution of differences in axial diffusivity among TD siblings (99.998 percentile). The results remained significant after controlling for multiple comparisons with Bonferroni method. We assumed that one aspect of this tract was associated with the development of a clinical diagnosis.
