1. Beversdorf DQ, Stevens HE, Jones KL. {{Prenatal Stress, Maternal Immune Dysregulation, and Their Association With Autism Spectrum Disorders}}. {Curr Psychiatry Rep}. 2018; 20(9): 76.
PURPOSE OF REVIEW: While genetic factors are a major etiological contributor to autism spectrum disorder (ASD), evidence also supports a role for environmental factors. Herein, we will discuss two such factors that have been associated with a significant proportion of ASD risk: prenatal stress exposure and maternal immune dysregulation, and how sex and gender relate to these factors. RECENT FINDINGS: Recent evidence suggests that maternal stress susceptibility interacts with prenatal stress exposure to affect offspring neurodevelopment. Additionally, understanding of the impact of maternal immune dysfunction on ASD has recently been advanced by recognition of specific fetal brain proteins targeted by maternal autoantibodies, and identification of unique mid-gestational maternal immune profiles. Animal models have been developed to explore pathophysiology targeting both of these factors, with limited sex-specific effects observed. While prenatal stress and maternal immune dysregulation are associated with ASD, most cases of these prenatal exposures do not result in ASD, suggesting interaction with multiple other risks. We are beginning to understand the behavioral, pharmacopathological, and epigenetic effects related to these interactions, as well as potential mitigating factors. Sex differences of these risks have been understudied but are crucial for understanding the higher prevalence of ASD in boys. Continued growth in understanding of these mechanisms may ultimately allow for the identification of multiple potential points for prevention or intervention, and for a personalized medicine approach for this subset of environmental-associated ASD cases.
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2. Bitsika V, Sharpley CF. {{An exploration of the association between matrix reasoning and eating disturbance behavior in girls with autism spectrum disorder}}. {Psychology research and behavior management}. 2018; 11: 259-66.
Background: Although there have been suggestions that central coherence may be associated with eating disturbances (EBD) in children with autism spectrum disorder (ASD), relatively little attention has been given to specific aspects of IQ and EDB. Methods: The association between total IQ, perceptual and verbal composite scores and subtests was explored in a sample of 50 high-functioning girls with ASD (mean age = 9.7 years, SD = 2.4 years, range = 6 years to 14 years). Self-reports and mothers’ reports were collected about the girls’ EDB. Results: There were only isolated associations between mothers’ data and the girls’ IQ. Selected aspects of the girls’ self-reported EDB were significantly associated with matrix reasoning. Conclusion: The role of IQ, particularly matrix reasoning, in the assessment and treatment of EDB in girls with ASD, is highlighted by these findings.
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3. Jacquemont S, Pacini L, Jonch AE, Cencelli G, Rozenberg I, He Y, D’Andrea L, Pedini G, Eldeeb M, Willemsen R, Gasparini F, Tassone F, Hagerman R, Gomez-Mancilla B, Bagni C. {{Protein synthesis levels are increased in a subset of individuals with fragile X syndrome}}. {Hum Mol Genet}. 2018.
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4. Jia H, Li Y, Yu D. {{Attenuation of long-range temporal correlations of neuronal oscillations in young children with autism spectrum disorder}}. {Neuroimage Clin}. 2018; 20: 424-32.
Although autism spectrum disorder (ASD) was previously found to be associated with aberrant brain structure, neuronal amplitudes and spatial neuronal interactions, surprisingly little is known about the temporal dynamics of neuronal oscillations in this disease. Here, the hemoglobin concentration signals (i.e., oxy-Hb and deoxy-Hb) of young children with ASD and typically developing (TD) children were recorded via functional near infrared spectroscopy (fNIRS) when they were watching a cartoon. The long-range temporal correlations (LRTCs) of hemoglobin concentration signals were quantified using detrended fluctuation analysis (DFA). Compared with TD group, the DFA exponents of young children with ASD were significantly smaller over left temporal region for oxy-Hb signal, and over bilateral temporo-occipital regions for deoxy-Hb signals, indicating a shift-to-randomness of brain oscillations in the children with ASD. Testing the relationship between age and DFA exponents revealed that this association could be modulated by autism. The correlation coefficients between age and DFA exponents were significantly more positive in TD group, compared to those in ASD group over several brain regions. Furthermore, the DFA exponents of oxy-Hb in left temporal region were negatively correlated with autistic symptom severity. These results suggest that the decreased DFA exponent of hemoglobin concentration signals may be one of the pathologic changes in ASD, and studying the temporal structure of brain activity via fNIRS technique may provide physiological indicators for autism.
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5. Lowe MX, Stevenson RA, Barense MD, Cant JS, Ferber S. {{Relating the perception of visual ensemble statistics to individual levels of autistic traits}}. {Attention, perception & psychophysics}. 2018.
Integrating information across the visual field into an ensemble (e.g., seeing the forest from the trees) is an effective strategy to efficiently process the visual world, and one that is often impaired in autism spectrum disorder. Individual differences in sensory processing predict ensemble encoding, providing a potential mechanism for differing perceptual strategies across individuals, and possibly across diagnostic groups exhibiting atypical sensory processing. Here, we explore whether ensemble encoding is associated with traits associated with autism spectrum disorder (ASD). Participants (N=68) were presented with an ensemble display consisting of circles of varying sizes and colors, and were asked to remember the size of the red and blue circles, while ignoring the green circles. Participants were then cued to a target location after a brief delay, and instructed to report the remembered size of the circle they had previously viewed in that location, as ensemble information commonly biases memory for individual objects toward the probed mean of a set of similar objects. The Autism-spectrum Quotient (AQ) was completed to measure each individual’s level of autistic traits. We found that an individual’s level of ensemble perception, measured as their bias toward the probed mean, was negatively associated with a higher level of ASD traits. These results suggest that individuals with higher levels of ASD traits are less likely to integrate perceptual information. These findings may shed light on different perceptual processing within the autism spectrum, and provide insight into the relationship between individual differences and ensemble encoding.
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6. Murphy D, Glaser K, Hayward H, Eklund H, Cadman T, Findon J, Woodhouse E, Ashwood K, Beecham J, Bolton P, McEwen F, Wilson E, Ecker C, Wong I, Simonoff E, Russell A, McCarthy J, Chaplin E, Young S, Asherson P. Programme Grants for Applied Research. Crossing the divide: a longitudinal study of effective treatments for people with autism and attention deficit hyperactivity disorder across the lifespan. Southampton (UK): NIHR Journals Library
Copyright (c) Queen’s Printer and Controller of HMSO 2018. This work was produced by Murphy et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK.; 2018.
7. Pascual-Belda A, Diaz-Parra A, Moratal D. {{Evaluating Functional Connectivity Alterations in Autism Spectrum Disorder Using Network-Based Statistics}}. {Diagnostics (Basel, Switzerland)}. 2018; 8(3).
The study of resting-state functional brain networks is a powerful tool to understand the neurological bases of a variety of disorders such as Autism Spectrum Disorder (ASD). In this work, we have studied the differences in functional brain connectivity between a group of 74 ASD subjects and a group of 82 typical-development (TD) subjects using functional magnetic resonance imaging (fMRI). We have used a network approach whereby the brain is divided into discrete regions or nodes that interact with each other through connections or edges. Functional brain networks were estimated using the Pearson’s correlation coefficient and compared by means of the Network-Based Statistic (NBS) method. The obtained results reveal a combination of both overconnectivity and underconnectivity, with the presence of networks in which the connectivity levels differ significantly between ASD and TD groups. The alterations mainly affect the temporal and frontal lobe, as well as the limbic system, especially those regions related with social interaction and emotion management functions. These results are concordant with the clinical profile of the disorder and can contribute to the elucidation of its neurological basis, encouraging the development of new clinical approaches.
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8. Rosenberg A, Sunkara A. {{Does attenuated divisive normalization affect gaze processing in autism spectrum disorder? A commentary on Palmer et al. (2018)}}. {Cortex}. 2018.
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9. Wang W, Liu J, Shi S, Liu T, Ma L, Ma X, Tian J, Gong Q, Wang M. {{Altered Resting-State Functional Activity in Patients With Autism Spectrum Disorder: A Quantitative Meta-Analysis}}. {Frontiers in neurology}. 2018; 9: 556.
Background: There is accumulating evidence showing that patients with autism spectrum disorder (ASD) have obvious changes in resting-state functional brain activity. So far, there have been no meta-analyses of the resting-state brain activity alterations in patients with ASD. We attempted to explore the resting-state functional activity changes in patients with ASD, possibly providing a new perspective for investigating the pathophysiology of patients with ASD. Methods: We screened relevant studies published before August 2017 in PubMed, Ovid, Web of Science, China National Knowledge Infrastructure (CNKI), and the Wan-fang database. Fifteen resting-state functional neural activity datasets (including 382 patients and 348 healthy controls) were included. Through the use of the effect-size signed differential mapping (ES-SDM) method, we carried out a meta-analysis of resting-state functional activity studies of patients with ASD. Results: Compared with healthy controls, patients with ASD showed hyperactivity in the right supplementary motor area, middle frontal gyrus, inferior frontal gyrus, the left precentral gyrus, and the bilateral cerebellum hemispheric lobule (VIII/IX), and hypoactivity in the right middle temporal gyrus, superior temporal gyrus, and the left precuneus, posterior cingulate cortex, median cingulate cortex, and bilateral cerebellum (crus I). Conclusion: This meta-analysis indicates that patients with ASD have significant and robust resting-state brain activity alterations in the language comprehension network, inferior-posterior cerebellum, default mode network (DMN), and cerebellar crus I. These brain regions may serve as specific regions of interest for further studies of ASD, which will allow us to further clarify the neurobiological mechanisms in patients with ASD.
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10. Zhang F, Kang Y, Wang M, Li Y, Xu T, Yang W, Song H, Wu H, Shu Q, Jin P. {{Fragile X mental retardation protein modulates the stability of its m6A-marked messenger RNA targets}}. {Hum Mol Genet}. 2018.
N6-methyladenosine (m6A) is the most prevalent internal modification of mammalian messenger RNAs (mRNAs) and long non-coding RNAs. The biological functions of this reversible RNA modification can be interpreted by cytoplasmic and nuclear « m6A reader » proteins to fine-tune gene expression, such as mRNA degradation and translation initiation. Here we profiled transcriptome-wide m6A sites in adult mouse cerebral cortex, underscoring that m6A is a widespread epitranscriptomic modification in brain. Interestingly, the mRNA targets of fragile X mental retardation protein (FMRP), a selective RNA-binding protein, are enriched for m6A marks. Loss of functional FMRP leads to Fragile X syndrome (FXS), the most common inherited form of intellectual disability. Transcriptome-wide gene expression profiling identified 2,035 genes differentially expressed in the absence of FMRP in cortex, and 92.5% of 174 downregulated FMRP targets are marked by m6A. Biochemical analyses indicate that FMRP binds to the m6A sites of its mRNA targets and interacts with m6A reader YTHDF2 in an RNA-independent manner. FMRP maintains the stability of its mRNA targets while YTHDF2 promotes the degradation of these mRNAs. These data together suggest that FMRP regulates the stability of its m6A-marked mRNA targets through YTHDF2, which could potentially contribute to the molecular pathogenesis of FXS.
