1. Bertolino B, Crupi R, Impellizzeri D, Bruschetta G, Cordaro M, Siracusa R, Esposito E, Cuzzocrea S. {{Beneficial Effects of Co-Ultramicronized Palmitoylethanolamide/Luteolin in a Mouse Model of Autism and in a Case Report of Autism}}. {CNS Neurosci Ther};2016 (Oct 4)
AIMS: Autism spectrum disorder (ASD) is a condition defined by social communication deficits and repetitive restrictive behaviors. Association of the fatty acid amide palmitoylethanolamide (PEA) with the flavonoid luteolin displays neuroprotective and antiinflammatory actions in different models of central nervous system pathologies. We hypothesized that association of PEA with luteolin might have therapeutic utility in ASD, and we employed a well-recognized autism animal model, namely sodium valproate administration, to evaluate cognitive and motor deficits. METHODS: Two sets of experiments were conducted. In the first, we investigated the effect of association of ultramicronized PEA with luteolin, co-ultramicronized PEA-LUT(R) (co-ultraPEA-LUT(R)) in a murine model of autistic behaviors, while in the second, the effect of co-ultraPEA-LUT(R) in a patient affected by ASD was examined. RESULTS: Co-ultraPEA-LUT(R) treatment ameliorated social and nonsocial behaviors in valproic acid-induced autistic mice and improved clinical picture with reduction in stereotypes in a 10-year-old male child. CONCLUSION: These data suggest that ASD symptomatology may be improved by agents documented to control activation of mast cells and microglia. Co-ultraPEA-LUT(R) might be a valid and safe therapy for the symptoms of ASD alone or in combination with other used drugs.
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2. Bradstreet LE, Hecht EE, King TZ, Turner JL, Robins DL. {{Associations between autistic traits and fractional anisotropy values in white matter tracts in a nonclinical sample of young adults}}. {Exp Brain Res};2016 (Oct 3)
Whereas a number of studies have examined relationships among brain activity, social cognitive skills, and autistic traits, fewer studies have evaluated whether structural connections among brain regions relate to these traits and skills. Uncinate fasciculus (UF) and inferior longitudinal fasciculus (ILF) are white matter tracts that may underpin the behavioral expression of these skills because they connect regions within or provide sensory information to brain areas implicated in social cognition, and structural differences in these tracts have been associated with autistic traits. We examined relationships among self-reported autistic traits, mentalizing, and water diffusivity in UF and ILF in a nonclinical sample of 24 young adults (mean age = 21.92 years, SD = 4.72 years; 15 women). We measured autistic traits using the Autism-Spectrum Quotient, and we measured mentalizing using the Dynamic Interactive Shapes Clips task. We used Tract-Based Spatial Statistics and randomize to examine relationships among fractional anisotropy (FA) values in bilateral ILF and UF, age, cognitive abilities, autistic traits, and mentalizing. Autistic traits were positively related to FA values in left ILF. No other relationships between FA values and other variables were significant. Results suggest that left ILF may be involved in the expression of autistic traits in individuals without clinical diagnoses.
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3. Brimberg L, Mader S, Jeganathan V, Berlin R, Coleman TR, Gregersen PK, Huerta PT, Volpe BT, Diamond B. {{Caspr2-reactive antibody cloned from a mother of an ASD child mediates an ASD-like phenotype in mice}}. {Mol Psychiatry};2016 (Oct 04)
Autism spectrum disorder (ASD) occurs in 1 in 68 births, preferentially affecting males. It encompasses a group of neurodevelopmental abnormalities characterized by impaired social interaction and communication, stereotypic behaviors and motor dysfunction. Although recent advances implicate maternal brain-reactive antibodies in a causative role in ASD, a definitive assessment of their pathogenic potential requires cloning of such antibodies. Here, we describe the isolation and characterization of monoclonal brain-reactive antibodies from blood of women with brain-reactive serology and a child with ASD. We further demonstrate that male but not female mice exposed in utero to the C6 monoclonal antibody, binding to contactin-associated protein-like 2 (Caspr2), display abnormal cortical development, decreased dendritic complexity of excitatory neurons and reduced numbers of inhibitory neurons in the hippocampus, as well as impairments in sociability, flexible learning and repetitive behavior. Anti-Caspr2 antibodies are frequent in women with brain-reactive serology and a child with ASD. Together these studies provide a methodology for obtaining monclonal brain-reactive antibodies from blood B cells, demonstrate that ASD can result from in utero exposure to maternal brain-reactive antibodies of single specificity and point toward the exciting possibility of prognostic and protective strategies.Molecular Psychiatry advance online publication, 4 October 2016; doi:10.1038/mp.2016.165.
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4. Duvekot J, Hoopen LW, Slappendel G, van der Ende J, Verhulst FC, van der Sijde A, Greaves-Lord K. {{Design and Cohort Characteristics of the Social Spectrum Study: A Multicenter Study of the Autism Spectrum Among Clinically Referred Children}}. {J Autism Dev Disord};2016 (Oct 3)
This paper provides an overview of the design and cohort characteristics of the Social Spectrum Study: a clinical cohort study that used a two-phase sampling design to identify children at risk for ASD. After screening 1281 children aged 2.5-10 years who had been consecutively referred to one of six mental health services in the Netherlands, children who screened positive for ASD (n = 428) and a random selection of screen negatives (n = 240) were invited to participate in diagnostic assessments and questionnaires regarding the child, family and society. A 1-year follow-up was also conducted. Results from this study may contribute to knowledge of the identification and characterization of children with ASD, family processes, and the impact of ASD on the family and society.
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5. Fernandez de Cossio L, Guzman A, van der Veldt S, Luheshi GN. {{Prenatal infection leads to ASD-like behavior and altered synaptic pruning in the mouse offspring}}. {Brain Behav Immun};2016 (Sep 30)
Environmental challenges to the maternal immune system during pregnancy have been associated with an increase in the frequency of neurodevelopmental disorders such as Autism Spectrum Disorders (ASD) appearing in the offspring. Microglia, the brain’s resident immune-cells, are now known to be critically involved in normal brain development, shaping connections between neurons by pruning superfluous synaptic spines. Our aim was to investigate whether maternal infection during critical stages of gestation compromises the role of microglia in sculpting neuronal circuits. Using a mouse model of maternal immune activation (MIA) induced by bacterial Lipopolysaccharide (LPS), we assayed the offspring’s behavior during postnatal development. Additionally, we quantified spines within the offspring’s brain and assessed alterations in some molecular signals involved in pruning. LPS-induced MIA led to behavioral changes relevant to ASD in the offspring in the absence of gross neurological problems. Prenatal LPS resulted in a significant increase in the number of spines in the granule cells of the dentate gyrus, as well as a reduction in hippocampal expression of the fractalkine microglial receptor (CX3CR1), involved in mediating the pruning process in the offspring. Interestingly, these changes were only noted in the male progeny of the LPS challenged dams. These results provide an early indicator that microglial function is altered in the brain of offspring from immune challenged mothers and that the effects in the brain appear to be specific along sex lines.
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6. Ida-Eto M, Hara N, Ohkawara T, Narita M. {{Mechanism of auditory hypersensitivity in human autism using autism model rats}}. {Pediatr Int};2016 (Oct 5)
BACKGROUND: Auditory hypersensitivity is one of the major complications accompanied by autism spectrum disorders. The aim of this study is to investigate whether auditory brain center is affected in autism model rats. METHODS: Autism model rats were prepared by prenatal exposure to thalidomide, which is administered to embryonic day 9 and 10 of pregnant rats. Superior olivary complex (SOC), a complex of auditory nuclei, was immunostained with anti-calbindin d28k antibody at postnatal day 50. RESULTS: In autism model rats, immunoreactivity of SOC was markedly decreased. Strength of immunostaining of auditory fibers in SOC was also weak in autism model rats. Surprisingly, when measured the size of medial nucleus of trapezoid body (MNTB), a nucleus exerting inhibitory function in SOC, the size of MNTB was significantly decreased in autism model rats. CONCLUSIONS: These results indicate that auditory hypersensitivity may be, in part, due to impairment of inhibitory processing exerted by auditory brain center. This article is protected by copyright. All rights reserved.
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7. Mazefsky CA, Day TN, Siegel M, White SW, Yu L, Pilkonis PA. {{Development of the Emotion Dysregulation Inventory: A PROMIS(R)ing Method for Creating Sensitive and Unbiased Questionnaires for Autism Spectrum Disorder}}. {J Autism Dev Disord};2016 (Oct 3)
The lack of sensitive measures suitable for use across the range of functioning in autism spectrum disorder (ASD) is a barrier to treatment development and monitoring. The Emotion Dysregulation Inventory (EDI) is a caregiver-report questionnaire designed to capture emotional distress and problems with emotion regulation in both minimally verbal and verbal individuals. The first two phases of the EDI’s development are described, including: (1) utilizing methods from the Patient-Reported Outcomes Measurement Information System (PROMIS(R)) project to develop the item pool and response options; and (2) assessment of the EDI in psychiatric inpatients with ASD. The results suggest that the EDI captures a wide range of emotion dysregulation, is sensitive to change, and is not biased by verbal or intellectual ability.
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8. Miller LE, Burke JD, Troyb E, Knoch K, Herlihy LE, Fein DA. {{Preschool predictors of school-age academic achievement in autism spectrum disorder}}. {Clin Neuropsychol};2016 (Oct 5):1-22.
OBJECTIVE: Characterization of academic functioning in children with autism spectrum disorder (ASD), particularly predictors of achievement, may have important implications for intervention. The current study aimed to characterize achievement profiles, confirm associations between academic ability and concurrent intellectual and social skills, and explore preschool predictors of school-age academic achievement in a sample of children with ASD. METHOD: Children with ASD (n = 26) were evaluated at the approximate ages of two, four, and ten. Multiple regression was used to predict school-age academic achievement in reading and mathematics from both concurrent (i.e. school-age) and preschool variables. RESULTS: Children with ASD demonstrated a weakness in reading comprehension relative to word reading. There was a smaller difference between mathematics skills; math reasoning was lower than numerical operations, but this did not quite reach trend level significance. Concurrent IQ and social skills were associated with school-age academic achievement across domains. Preschool verbal abilities significantly predicted school-age reading comprehension, above and beyond concurrent IQ, and early motor functioning predicted later math skills. CONCLUSIONS: Specific developmental features of early ASD predict specific aspects of school-age achievement. Early intervention targeting language and motor skills may improve later achievement in this population.
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9. Mujkanovic E, Memisevic H, Zecic S, Biscevic I. {{MOTHERS’ SATISFACTION WITH TREATMENT OPPORTUNITIES FOR THEIR CHILDREN WITH AUTISM SPECTRUM DISORDER IN BOSNIA AND HERZEGOVINA}}. {Mater Sociomed};2016 (Jul 24);28(4):288-291.
AIM: The goal of this study was to examine the general satisfaction of mothers of children with autism spectrum disorder (ASD) with treatment opportunities for their children in Bosnia and Herzegovina. An additional goal was to assess the level of mothers’ satisfaction with their own involvement in the creation and implementation of Individual Education Plans. METHODS: The sample consisted of 98 mothers of children with ASD. Mothers answered to questions related to their perceived satisfaction with treatment options. RESULTS: The results of this study indicated that mothers are generally satisfied with educational opportunities for their children (61.2%). However, their satisfaction with involvement in the creation and implementation of Individual Education Programs was much lower (35.7%). Most comments of the mothers were that the treatment options should be more widely available and that the educational programs could be improved. CONCLUSIONS: Parents of children with ASD should have more information on the treatment options available for their children. More educational opportunities need to be offered to children with ASD in Bosnia and Herzegovina.
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10. Must A, Eliasziw M, Phillips SM, Curtin C, Kral TV, Segal M, Sherwood NE, Sikich L, Stanish HI, Bandini LG. {{The Effect of Age on the Prevalence of Obesity among US Youth with Autism Spectrum Disorder}}. {Child Obes};2016 (Oct 5)
BACKGROUND: We sought to assess the association between age and the prevalence of obesity among children with and without autism spectrum disorder (ASD) in the 2011-2012 National Survey of Children’s Health. METHODS: Analyses were restricted to 43,777 children, ages 10-17, with valid measures of parent-reported weight, height, and ASD status. Exploratory analyses describe the impact of sex, race/ethnicity, and household income on the relationship between age and obesity in ASD. RESULTS: Although the overall prevalence of obesity among children with ASD was significantly (p < 0.001) higher than among children without ASD (23.1% vs. 14.1%, 95% confidence interval for difference 3.6 to 14.4), child age significantly (p = 0.035) modified this difference. In a multivariable logistic regression analysis, adjusted for sex, race/ethnicity, and household income, the odds of obesity among children with ASD compared with children without ASD increased monotonically from ages 10 to 17 years. This pattern arose due to a consistently high prevalence of obesity among children with ASD and a decline in prevalence with advancing age among children without ASD. These findings were replicated using a propensity score analysis. Exploratory analyses suggested that the age-related change in obesity disparity between children with and without ASD may be further modified by sex, race/ethnicity, and household income. CONCLUSIONS: The patterns of prevalence observed with increasing age among children with and without ASD were unexpected. A better understanding of the etiological and maintenance factors for obesity in youth with ASD is needed to develop interventions tailored to the specific needs of these children. Lien vers le texte intégral (Open Access ou abonnement)
11. Tonacci A, Billeci L, Ruta L, Tartarisco G, Pioggia G, Gangemi S. {{A systematic review of the association between allergic asthma and autism}}. {Minerva Pediatr};2016 (Oct 05)
BACKGROUND: Autism Spectrum Disorder represents a burdensome condition in early childhood, with a number of risk factors proposed to explain its pathogenesis, most of which without a reliable scientific basis. Allergic asthma is likely to be one of the possible comorbilities of autism. EVIDENCE ACQUISITION: In this paper, the relationship between autism and allergic asthma was analyzed through a systematic literature review, conducted according to the PRISMA guidelines. The review was performed on PubMed and Science Direct database and covered the period January 1, 2004- July 9, 2016. The search was limited to articles published in peer-reviewed journals. The obtained results were sorted by relevance and the most significant case-control, epidemiological and nationwide-based works associating autism and allergic asthma in humans were selected. EVIDENCE SYNTHESIS: A slight correlation between these conditions has been found in more than a half studies selected, suggesting a possible association between the two diseases. Small sample sizes of some works and some methodological limitations rise uncertainty about this link. CONCLUSIONS: Autism Spectrum Disorder and asthma could be associated conditions, as evidenced by the higher prevalence of asthma in autistic children with respect to typically developed controls, with also a verisimilar biological basis. Despite that, future studies are required to provide more reliable data, also by employing animal models, to better clarify this, still unsure, relationship. Methods for study selection and inclusion criteria were specified in advance and documented in PROSPERO protocol #CRD42014012851.
12. Watson LR. {{Autism Spectrum Disorder: From Pensieve to Crystal Ball}}. {Semin Speech Lang};2016 (Nov);37(4):231-238.
In the next decade, professionals in communication sciences and disorders will encounter a wealth of needs, opportunities, and challenges in research and practice related to autism spectrum disorder. What lies ahead will reflect both transformations of and continuities with past perspectives (psychodynamic, biological, and learning theory). Among our largest challenges as individuals and as a discipline will be to determine the most important needs to address and the most productive opportunities to seize. Interprofessional collaboration, community engagement, and partnerships among researchers, practitioners, and community stakeholder are all strategies that can better guide our selection of priorities.
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13. Yamada T, Itahashi T, Nakamura M, Watanabe H, Kuroda M, Ohta H, Kanai C, Kato N, Hashimoto RI. {{Altered functional organization within the insular cortex in adult males with high-functioning autism spectrum disorder: evidence from connectivity-based parcellation}}. {Mol Autism};2016;7:41.
BACKGROUND: The insular cortex comprises multiple functionally differentiated sub-regions, each of which has different patterns of connectivity with other brain regions. Such diverse connectivity patterns are thought to underlie a wide range of insular functions, including cognitive, affective, and sensorimotor processing, many of which are abnormal in autism spectrum disorder (ASD). Although past neuroimaging studies of ASD have shown structural and functional abnormalities in the insula, possible alterations in the sub-regional organization of the insula and the functional characteristics of each sub-region have not been examined in the ASD brain. METHODS: Resting-state functional magnetic resonance imaging (rs-fMRI) data were acquired from 36 adult males with ASD and 38 matched typically developed (TD) controls. A data-driven clustering analysis was applied to rs-fMRI data of voxels in the left and right insula to automatically group voxels with similar intrinsic connectivity pattern into a cluster. After determining the optimal number of clusters based on information theoretic measures of variation of information and mutual information, functional parcellation patterns in both the left and the right insula were compared between the TD and ASD groups. Furthermore, functional profiles of each sub-region were meta-analytically decoded using Neurosynth and were compared between the groups. RESULTS: We observed notable alterations in the anterior sector of the left insula and the middle ventral sub-region of the right insula in the ASD brain. Meta-analytic decoding revealed that whereas the anterior sector of the left insula contained two functionally differentiated sub-regions for cognitive, sensorimotor, and emotional/affective functions in TD brain, only a single functional cluster for cognitive and sensorimotor functions was identified in the anterior sector in the ASD brain. In the right insula, the middle ventral sub-region, which is primarily specialized for sensory- and auditory-related functions, showed a significant volumetric increase in the ASD brain compared with the TD brain. CONCLUSIONS: The results indicate an altered organization of sub-regions in specific parts of the left and right insula of the ASD brain. The alterations in the left and right insula may constitute neural substrates underlying abnormalities in emotional/affective and sensory functions in ASD.
