1. Barton EE, Harris B, Leech N, Stiff L, Choi G, Joel T. {{An Analysis of State Autism Educational Assessment Practices and Requirements}}. {J Autism Dev Disord};2015 (Sep 12)
States differ in the procedures and criteria used to identify ASD. These differences are likely to impact the prevalence and age of identification for children with ASD. The purpose of the current study was to examine the specific state variations in ASD identification and eligibility criteria requirements. We examined variations by state in autism assessment practices and the proportion of children eligible for special education services under the autism category. Overall, our findings suggest that ASD identification practices vary across states, but most states use federal guidelines, at least in part, to set their requirements. Implications and recommendations for policy and practice are discussed.
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2. Deschrijver E, Bardi L, Wiersema JR, Brass M. {{Behavioral measures of implicit theory of mind in adults with high functioning autism}}. {Cogn Neurosci};2015 (Sep 14)
Theory of mind (ToM) research has shown that adults with high functioning autism (HFA) demonstrate typical performance on tasks that require explicit belief reasoning, despite clear social difficulties in everyday life situations. In the current study, we used implicit belief manipulations that are task-irrelevant and therefore less susceptible to strategies. In a ball detection task, it was shown that neurotypical individuals detect a ball faster if an agent believed the ball was present. We predicted that adults with high functioning autism (HFA) would not show this effect. While we found a numerical difference in the hypothesized direction, we did not find a reliable group. Interestingly, the implicit ToM-index showed a strong negative correlation with both self-reported and observational measures of social difficulties in the HFA group. This suggests that the relationship between implicit ToM reasoning and the symptomatology of HFA might be subtler than assumed.
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3. Fox-Edmiston E, Van de Water J. {{Maternal Anti-Fetal Brain IgG Autoantibodies and Autism Spectrum Disorder: Current Knowledge and its Implications for Potential Therapeutics}}. {CNS Drugs};2015 (Sep 14)
Several studies have found a correlation between the presence of circulating maternal autoantibodies and neuronal dysfunction in the neonate. Specifically, maternal anti-brain autoantibodies, which may access the fetal compartment during gestation, have been identified as one risk factor for developing autism spectrum disorder (ASD). Studies by our laboratory elucidated seven neurodevelopmental proteins recognized by maternal autoantibodies whose presence is associated with a diagnosis of maternal autoantibody-related (MAR) autism in the child. While the specific process of anti-brain autoantibody generation is unclear and the detailed pathogenic mechanisms are currently unknown, identification of the maternal autoantibody targets increases the therapeutic possibilities. The potential therapies discussed in this review provide a framework for possible future medical interventions.
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4. Harrison AJ, Gamsiz ED, Berkowitz IC, Nagpal S, Jerskey BA. {{Genetic variation in the oxytocin receptor gene is associated with a social phenotype in autism spectrum disorders}}. {Am J Med Genet B Neuropsychiatr Genet};2015 (Sep 14)
Oxytocin regulates social behavior in animal models. Research supports an association between genetic variation in the oxytocin receptor gene (OXTR) and autism spectrum disorders (ASD). In this study, we examine the association between the OXTR gene and a specific social phenotype within ASD. This genotype-phenotype investigation may provide insight into how OXTR conveys risk for social impairment. The current study investigated 10 SNPS in the OXTR gene that have been previously shown to be associated with ASD. We examine the association of these SNPs with both a social phenotype and a repetitive behavior phenotype comprised of behaviors commonly impaired in ASD in the Simons simplex collection (SSC). Using a large sample to examine the association between OXTR and ASD (n = range: 485-1002), we find evidence to support a relation between two OXTR SNPs and the examined social phenotype among children diagnosed with ASD. Greater impairment on the social responsiveness scale standardized total score and on several subdomains was observed among individuals with one or more copies of the minor frequency allele in both rs7632287 and rs237884. Linkage disequilibrium (LD) mapping suggests that these two SNPs are in LD within and overlapping the 3′ untranslated region (3′-UTR) of the OXTR gene. These two SNPs were also associated with greater impairment on the repetitive behavior scale. Results of this study indicate that social impairment and repetitive behaviors in ASD are associated with genomic variation in the 3’UTR of the OXTR gene. These variants may be linked to an allele that alters stability of the mRNA message although further work is necessary to test this hypothesis. (c) 2015 Wiley Periodicals, Inc.
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5. Jin Y, Wee CY, Shi F, Thung KH, Ni D, Yap PT, Shen D. {{Identification of infants at high-risk for autism spectrum disorder using multiparameter multiscale white matter connectivity networks}}. {Hum Brain Mapp};2015 (Sep 14)
Autism spectrum disorder (ASD) is a wide range of disabilities that cause life-long cognitive impairment and social, communication, and behavioral challenges. Early diagnosis and medical intervention are important for improving the life quality of autistic patients. However, in the current practice, diagnosis often has to be delayed until the behavioral symptoms become evident during childhood. In this study, we demonstrate the feasibility of using machine learning techniques for identifying high-risk ASD infants at as early as six months after birth. This is based on the observation that ASD-induced abnormalities in white matter (WM) tracts and whole-brain connectivity have already started to appear within 24 months after birth. In particular, we propose a novel multikernel support vector machine classification framework by using the connectivity features gathered from WM connectivity networks, which are generated via multiscale regions of interest (ROIs) and multiple diffusion statistics such as fractional anisotropy, mean diffusivity, and average fiber length. Our proposed framework achieves an accuracy of 76% and an area of 0.80 under the receiver operating characteristic curve (AUC), in comparison to the accuracy of 70% and the AUC of 70% provided by the best single-parameter single-scale network. The improvement in accuracy is mainly due to the complementary information provided by multiparameter multiscale networks. In addition, our framework also provides the potential imaging connectomic markers and an objective means for early ASD diagnosis. Hum Brain Mapp, 2015. (c) 2015 Wiley Periodicals, Inc.
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6. Krach S, Kamp-Becker I, Einhauser W, Sommer J, Frassle S, Jansen A, Rademacher L, Muller-Pinzler L, Gazzola V, Paulus FM. {{Evidence from pupillometry and fMRI indicates reduced neural response during vicarious social pain but not physical pain in autism}}. {Hum Brain Mapp};2015 (Sep 14)
Autism spectrum disorder (ASD) is characterized by substantial social deficits. The notion that dysfunctions in neural circuits involved in sharing another’s affect explain these deficits is appealing, but has received only modest experimental support. Here we evaluated a complex paradigm on the vicarious social pain of embarrassment to probe social deficits in ASD as to whether it is more potent than paradigms currently in use. To do so we acquired pupillometry and fMRI in young adults with ASD and matched healthy controls. During a simple vicarious physical pain task no differences emerged between groups in behavior, pupillometry, and neural activation of the anterior insula (AIC) and anterior cingulate cortex (ACC). In contrast, processing complex vicarious social pain yielded reduced responses in ASD on all physiological measures of sharing another’s affect. The reduced activity within the AIC was thereby explained by the severity of autistic symptoms in the social and affective domain. Additionally, behavioral responses lacked correspondence with the anterior cingulate and anterior insula cortex activity found in controls. Instead, behavioral responses in ASD were associated with hippocampal activity. The observed dissociation echoes the clinical observations that deficits in ASD are most pronounced in complex social situations and simple tasks may not probe the dysfunctions in neural pathways involved in sharing affect. Our results are highly relevant because individuals with ASD may have preserved abilities to share another’s physical pain but still have problems with the vicarious representation of more complex emotions that matter in life. Hum Brain Mapp, 2015. (c) 2015 Wiley Periodicals, Inc.
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7. Lozano R, Martinez-Cerdeno V, Hagerman RJ. {{Advances In The Understanding Of The Gabaergic Neurobiology Of Fmr1 Expanded Alleles Leading To Targeted Treatments For Fragile X Spectrum Disorder}}. {Curr Pharm Des};2015 (Sep 14)
Fragile X spectrum disorder (FXSD) includes; fragile x syndrome (FXS), fragile X-associated tremor ataxia syndrome (FXTAS) and fragile X-associated primary ovarian insufficiency (FXPOI), as well as, other medical, psychiatric and neurobehavioral problems associated with the premutation and gray zone alleles. FXS is the most common monogenetic cause of autism (ASD) and intellectual disability (ID). The understanding of the neurobiology of FXS has led to many targeted treatment trials in FXS that may also benefit those with ASD from etiologies other than fragile X mutations. The first wave of phase II clinical trials in FXS were designed to target the mGluR5 pathway, however the results did not show significant efficacy and were terminated. Recent animal and human studies have shown that many of the symptoms in FXSD particularly in FXS are related to a down-regulation of the GABA system. The advances in the understanding of the GABA system in FXS have shifted the focus of treatment trials to GABA agonists and a new wave of promising clinical trials is under way. Ganaxolone and allopregnanolone (GABA agonists) have been studied in individuals with FXSD and are currently in phase II trials. Both allopregnanolone and ganaxolone may be efficacious in treatment of FXS and FXTAS, respectively. The animal and human studies that have led to an understanding of the GABA system in FXSD are reviewed. Allopregnanolone, ganaxolone, Riluzole, gaboxadol, tiagabine, and vigabatrin are potential GABAergic treatments, which are also discussed. The lessons learned from the initial trials have not only shifted the targeted system, but also have refined the design of clinical trials. The results of these new trials will likely impact further clinical trials for FXS and other genetic disorders associated with ASD.
8. Miodovnik A, Harstad E, Sideridis G, Huntington N. {{Timing of the Diagnosis of Attention-Deficit/Hyperactivity Disorder and Autism Spectrum Disorder}}. {Pediatrics};2015 (Sep 14)
BACKGROUND AND OBJECTIVE: Symptoms of inattention, hyperactivity, and impulsivity are core features of attention-deficit/hyperactivity disorder (ADHD). However, children with autism spectrum disorder (ASD) often present with similar symptoms and may receive a diagnosis of ADHD first. We investigated the relationship between the timing of ADHD diagnosis in children with ASD and the age at ASD diagnosis. METHODS: Data were drawn from the 2011-2012 National Survey of Children’s Health, which asked parents to provide the age(s) at which their child received a diagnosis of ADHD and/or ASD. Using weighted prevalence estimates, we examined the association between a previous diagnosis of ADHD and the age at ASD diagnosis, while controlling for factors known to influence the timing of ASD diagnosis. RESULTS: Our study consisted of 1496 children with a current diagnosis of ASD as reported by parents of children ages 2 to 17 years. Approximately 20% of these children had initially been diagnosed with ADHD. Children diagnosed with ADHD before ASD were diagnosed with ASD approximately 3 years (95% confidence interval 2.3-3.5) after children in whom ADHD was diagnosed at the same time or after ASD. The children with ADHD diagnosed first were nearly 30 times more likely to receive their ASD diagnosis after age 6 (95% confidence interval 11.2-77.8). The delay in ASD diagnosis was consistent across childhood and independent of ASD severity. CONCLUSION: To avoid potential delays in ASD diagnosis, clinicians should consider ASD in young children presenting with ADHD symptoms.
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9. Strifert K. {{An epigenetic basis for autism spectrum disorder risk and oral contraceptive use}}. {Med Hypotheses};2015 (Sep 6)
In the United States 1 in 68 children are diagnosed with autism spectrum disorder (ASD). Although the etiology is unknown, many scientists believe ASD is caused by a combination of genetic and environmental factors and/or epigenetic factors. The widespread use of oral contraceptives is one environmental risk factor that has been greatly overlooked in the biomedical literature. Oral contraceptives, synthetic hormones created to imitate natural human hormones and disrupt endogenous endocrine function to inhibit pregnancy, may be causing the harmful neurodevelopmental effects that result in the increased prevalence of ASD. It is conceivable that the synthetic hormones repeatedly assault the oocyte causing persistent changes in expression of the estrogen receptor beta gene. Ethinylestradiol, a known endocrine disruptor, may trigger DNA methylation of the estrogen receptor beta gene causing decreased mRNA resulting in impaired brain estrogen signaling in progeny. In addition, it is possible the deleterious effects are transgenerational as the estrogen receptor gene and many of its targets may be imprinted and the methylation marks protected from global demethylation and preserved through fertilization and beyond to progeny generations. This article will delineate the hypothesis that ethinylestradiol activates DNA methylation of the estrogen receptor beta gene causing decreased mRNA resulting in diminished brain estrogen signaling in offspring of mothers exposed to oral contraceptives. Considering the detrimental epigenetic and transgenerational effects proposed, it calls for further study.
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10. Windham GC, Lyall K, Anderson M, Kharrazi M. {{Autism Spectrum Disorder Risk in Relation to Maternal Mid-Pregnancy Serum Hormone and Protein Markers from Prenatal Screening in California}}. {J Autism Dev Disord};2015 (Sep 14)
We examined prenatal screening markers and offspring autism spectrum disorder (ASD) using California statewide data on singleton births in 1996 and 2002. Second trimester levels of unconjugated estriol (uE3), human chorionic gonadotropin (hCG), and maternal serum alpha-fetoprotein (MSAFP) were compared between mothers of children with ASD (n = 2586) and of non-cases (n = 600,103). Adjusted odds ratios (AOR) were calculated by logistic regression. Lower uE3 (AOR for < 10th percentile vs. 25th-74th percentiles = 1.21, 95 % CI 1.06-1.37), and higher MSAFP (AOR = 1.21, 95 % CI 1.07-1.37 for > 90th percentile) were significantly associated with ASD. A U-shaped relationship was seen for hCG (AOR = 1.16, 95 % CI 1.02-1.32 for < 10th percentile; AOR = 1.19, 95 % CI 1.05-1.36 for > 90th percentile). Our results further support prenatal hormone involvement in ASD risk.
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11. Zeedyk SM, Cohen SR, Eisenhower A, Blacher J. {{Perceived Social Competence and Loneliness Among Young Children with ASD: Child, Parent and Teacher Reports}}. {J Autism Dev Disord};2015 (Sep 12)
Perceived loneliness and social competence were assessed for 127 children with ASD without comorbid ID, 4-7 years old, through child self-report. Using an abbreviated version of the Loneliness and Social Dissatisfaction Questionnaire (LSDQ; Cassidy and Asher in Child Dev 63:250-365, 1992), the majority of children reported friendships, yet a considerable proportion also reported social difficulties. Factor analysis of the abbreviated LSDQ identified three factors, which were significantly associated with parent- and teacher-reported variables. Regression analyses revealed parent-reported social skills deficits and teacher-reported conflict in the student-teacher relationship to be associated with child-reported loneliness. Implications for practice are discussed.
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12. Zerbo O, Yoshida C, Gunderson EP, Dorward K, Croen LA. {{Interpregnancy Interval and Risk of Autism Spectrum Disorders}}. {Pediatrics};2015 (Sep 14)
OBJECTIVE: To determine whether subsequent births after short and long interpregnancy intervals (IPIs) are associated with risk of autism spectrum disorder (ASD). METHOD: We assessed the association between IPI and ASD risk in a cohort of 45 261 children born at Kaiser Permanente Northern California (KPNC) between 2000 and 2009. Children with ASD were identified from International Classification of Diseases, Revision 9 diagnostic codes 299.0, 299.8, and 299.9 recorded in KPNC electronic medical records. IPI was defined as the time from the birth of the first child to the conception of the second child. Survival analysis and logistic regression models were used to evaluate the association between IPI and risk of ASD in second-born children. RESULTS: Children born after an IPI of <12 months or >/=72 months had a 2- to 3-fold increased ASD risk compared with children born after an interval of 36 to 47 months. Respective adjusted hazard ratios (95% confidence intervals) were as follows: <6 months, 3.0 (1.9-4.7); 6 to 8 months, 2.1 (1.4-3.3); 9 to 11 months, 1.9 (1.3-2.1); 12 to 23 months, 1.5 (1.1-2.1); and >/=72 months, 2.4 (1.5-3.7). The results are not explained by maternal BMI or change in BMI between pregnancies or by parental age, maternal antidepressant medication use, or unfavorable events occurring during the first or second pregnancy. CONCLUSIONS: Children born after interpregnancy intervals <2 years or >6 years may be at increased risk of ASD. The mechanism explaining this association is unknown, and more research is needed.
