1. Ahmad SF, Nadeem A, Ansari MA, Bakheet SA, Attia SM, Zoheir KM, Al-Ayadhi LY, Alzahrani MZ, Alsaad AM, Alotaibi MR, Abd-Allah AR. {{Imbalance between the anti- and pro-inflammatory milieu in blood leukocytes of autistic children}}. {Mol Immunol};2016 (Dec 24);82:57-65.
Accumulating evidence suggests an association between immune dysfunction and autism disorders in a significant subset of children. In addition, an imbalance between pro- and anti-inflammatory pathways has been proposed to play an important role in the pathogenesis of several neurodevelopmental disorders including autism; however, the role of anti-inflammatory molecules IL-27 and CTLA-4 and pro-inflammatory cytokines IL-21 and IL-22 has not previously been explored in autistic children. In the current study, we investigated the expression of IL-21, IL-22, IL-27, and CD152 (CTLA-4) following an in-vitro immunological challenge of peripheral blood mononuclear cells (PBMCs) from children with autism (AU) or typically-developing children (TD) with phorbol-12-myristate 13-acetate (PMA) and ionomycin. In our study, cells from children with AU had increased IL-21 and IL-22 and decreased CTLA-4 expression on CD4+ T cells as compared with cells from the TD control. Similarly, AU cells showed decreased IL-27 production by CD14+ cells compared to that of TD control cells. These results were confirmed by real-time PCR and western blot analyses. Our study shows dysregulation of the immune balance in cells from autistic children as depicted by enhanced pro-inflammatory cytokines, ‘IL-21/IL-22’ and decreased anti-inflammatory molecules, ‘IL-27/CTLA-4’. Thus, further study of this immune imbalance in autistic children is warranted in order to facilitate development of biomarkers and therapeutics.
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2. Barrett G. {{Letter re: CSF concentrations of 5-methyltetrahydrofolate in a cohort of young children with autism}}. {Neurology};2017 (Jan 03);88(1):110-111.
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3. Bhandari R, Kuhad A. {{Resveratrol suppresses neuroinflammation in the experimental paradigm of autism spectrum disorders}}. {Neurochem Int};2016 (Dec 23)
BACKGROUND: Neuronal dysfunction caused by neuroinflammation triggered by the stimulation of matrix metalloproteinases and the subsequent release of pro-inflammatory cytokines, as a result of oxidative stress and mitochondrial dysfunction, is one of the probable mechanisms involved in the pathogenesis of autism spectrum disorders (ASD). The aim of the present study was to explore the ameliorative potential of resveratrol on neuroinflammation in the experimental paradigm of neuroinflammatory model of ASD in rats. METHOD: 1M Propanoic acid (PPA) (4 mul) was infused over 10 min into the anterior portion of the lateral ventricle to induce ASD like symptoms in rats. Resveratrol (5, 10 and 15 mg/kg) was administered starting from the 2nd day of the surgery and continued upto 28th day. Rats were tested for various behavioural paradigms such as social interaction, stereotypy, locomotor activity, anxiety, novelty, depression, spatial learning, memory, repetitive and pervasive behaviour between the 7th day and 28th day. In addition, biochemical tests for oxidative stress, mitochondrial complexes, TNF-alpha and MMP-9 were also assessed. RESULTS: Treatment with resveratrol for four weeks restored, significantly and dose dependently, all the neurological, sensory, behavioural, biochemical and molecular deficits in PPA induced autistic phenotype in rats. CONCLUSION: The major finding of the study is that resveratrol restored the core and associated symptoms of autistic phenotype by suppressing oxidative-nitrosative stress, mitochondrial dysfunction, TNF-alpha and MMP-9 expression in PPA induced ASD in rats. Therefore, resveratrol might serve as an adjunct potential therapeutic agent for amelioration of neurobehavioural and biochemical deficits associated with autism spectrum disorders.
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4. Ghiassian S, Greiner R, Jin P, Brown MR. {{Using Functional or Structural Magnetic Resonance Images and Personal Characteristic Data to Identify ADHD and Autism}}. {PLoS One};2016;11(12):e0166934.
A clinical tool that can diagnose psychiatric illness using functional or structural magnetic resonance (MR) brain images has the potential to greatly assist physicians and improve treatment efficacy. Working toward the goal of automated diagnosis, we propose an approach for automated classification of ADHD and autism based on histogram of oriented gradients (HOG) features extracted from MR brain images, as well as personal characteristic data features. We describe a learning algorithm that can produce effective classifiers for ADHD and autism when run on two large public datasets. The algorithm is able to distinguish ADHD from control with hold-out accuracy of 69.6% (over baseline 55.0%) using personal characteristics and structural brain scan features when trained on the ADHD-200 dataset (769 participants in training set, 171 in test set). It is able to distinguish autism from control with hold-out accuracy of 65.0% (over baseline 51.6%) using functional images with personal characteristic data when trained on the Autism Brain Imaging Data Exchange (ABIDE) dataset (889 participants in training set, 222 in test set). These results outperform all previously presented methods on both datasets. To our knowledge, this is the first demonstration of a single automated learning process that can produce classifiers for distinguishing patients vs. controls from brain imaging data with above-chance accuracy on large datasets for two different psychiatric illnesses (ADHD and autism). Working toward clinical applications requires robustness against real-world conditions, including the substantial variability that often exists among data collected at different institutions. It is therefore important that our algorithm was successful with the large ADHD-200 and ABIDE datasets, which include data from hundreds of participants collected at multiple institutions. While the resulting classifiers are not yet clinically relevant, this work shows that there is a signal in the (f)MRI data that a learning algorithm is able to find. We anticipate this will lead to yet more accurate classifiers, over these and other psychiatric disorders, working toward the goal of a clinical tool for high accuracy differential diagnosis.
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5. Sethi NK. {{Letter re: Autism and epilepsy: A population-based nationwide cohort study}}. {Neurology};2017 (Jan 03);88(1):110.
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6. Shoffner J. {{Author response: CSF concentrations of 5-methyltetrahydrofolate in a cohort of young children with autism}}. {Neurology};2017 (Jan 03);88(1):111.
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7. Sundelin HE, Ludvigsson JF. {{Author response: Autism and epilepsy: A population-based nationwide cohort study}}. {Neurology};2017 (Jan 03);88(1):110.
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8. Tomchek S, Koenig KP, Arbesman M, Lieberman D. {{Occupational Therapy Interventions for Adolescents With Autism Spectrum Disorder}}. {Am J Occup Ther};2017 (Jan/Feb);71(1):7101395010p7101395011-7101395010p7101395013.
Evidence Connection articles provide a clinical application of systematic reviews developed in conjunction with the American Occupational Therapy Association’s (AOTA’s) Evidence-Based Practice Project. In this Evidence Connection article, we describe a case report of an adolescent with autism spectrum disorder. The occupational therapy assessment and treatment processes for school, home, community, and transition settings are described. Findings from the systematic reviews on this topic were published in the September/October 2015 issue of the American Journal of Occupational Therapy and in AOTA’s Occupational Therapy Practice Guidelines for Individuals With Autism Spectrum Disorder. Each article in this series summarizes the evidence from the published reviews on a given topic and presents an application of the evidence to a related clinical case. Evidence Connection articles illustrate how the research evidence from the reviews can be used to inform and guide clinical decision making.
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9. Weiss EM, Gschaidbauer B, Kaufmann L, Fink A, Schulter G, Mittenecker E, Papousek I. {{Age-related differences in inhibitory control and memory updating in boys with Asperger syndrome}}. {Eur Arch Psychiatry Clin Neurosci};2016 (Dec 26)
Deficits in specific executive domains are highly prevalent in autism spectrum disorder; however, age-related improvements in executive functions (reflecting prefrontal maturational changes) have been reported even in individuals diagnosed with autism. The current study examined two components of cognitive flexibility (inhibition of prepotent responses and memory monitoring/updating) by using a random-motor-generation task (MPT) in a group of 23 boys with Asperger syndrome (AS) and 23 matched healthy controls. We found poorer inhibition and more repetitive responses in younger AS children solely, but comparable memory monitoring/updating skills across groups. Overall, our findings correspond well with previous studies and reveal that even in AS specific EFs may improve with age and, thus, call for a more differentiated view of executive (dys) function profiles in children diagnosed with AS. Tests such as the random-motor-generation task may help to disentangle more specific processes of executive deficits in autism spectrum disorder as compared to the more classical tests.
