1. Abruzzo PM, Ghezzo A, Bolotta A, Ferreri C, Minguzzi R, Vignini A, Visconti P, Marini M. {{Perspective Biological Markers for Autism Spectrum Disorders: Advantages of the Use of Receiver Operating Characteristic Curves in Evaluating Marker Sensitivity and Specificity}}. {Dis Markers};2015;2015:329607.
Autism Spectrum Disorders (ASD) are a heterogeneous group of neurodevelopmental disorders. Recognized causes of ASD include genetic factors, metabolic diseases, toxic and environmental factors, and a combination of these. Available tests fail to recognize genetic abnormalities in about 70% of ASD children, where diagnosis is solely based on behavioral signs and symptoms, which are difficult to evaluate in very young children. Although it is advisable that specific psychotherapeutic and pedagogic interventions are initiated as early as possible, early diagnosis is hampered by the lack of nongenetic specific biological markers. In the past ten years, the scientific literature has reported dozens of neurophysiological and biochemical alterations in ASD children; however no real biomarker has emerged. Such literature is here reviewed in the light of Receiver Operating Characteristic (ROC) analysis, a very valuable statistical tool, which evaluates the sensitivity and the specificity of biomarkers to be used in diagnostic decision making. We also apply ROC analysis to some of our previously published data and discuss the increased diagnostic value of combining more variables in one ROC curve analysis. We also discuss the use of biomarkers as a tool for advancing our understanding of nonsyndromic ASD.
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2. Benevides TW, Carretta HJ, Lane SJ. {{Unmet Need for Therapy Among Children with Autism Spectrum Disorder: Results from the 2005-2006 and 2009-2010 National Survey of Children with Special Health Care Needs}}. {Matern Child Health J};2015 (Dec 10)
Objectives We examined population-based trends in unmet need for therapy service in children with autism spectrum disorder (ASD) compared to other children with special health care needs (CSHCN), and identified factors associated with unmet need for therapy. Methods A pooled cross-sectional comparison of the 2005-2006 and 2009-2010 waves of the National Survey for Children with Special Health Care Needs (NS-CSHCN) was used. Weighted bivariate analyses were used to compare children ages 3-17 years with ASD (n = 5113) to other CSHCN (n = 71,294) on unmet need for therapy services. Survey weighted multivariate models were used to examine child, family, and contextual characteristics associated with unmet need. Results A greater percentage of children with ASD across both surveys were reported to need therapy than other children with CSHCN. Among children with a reported need, children with ASD were 1.4 times more likely to report an unmet need for therapy compared to other CSHCN (OR 1.42, 95 % CI 1.18-1.71). Variables significantly associated with unmet need for therapy services included not receiving a well-child visit in the past year (OR 5.81, CI 3.83-8.81), surveyed in 2009 (OR 1.42, CI 1.18-1.71), child being female (OR 1.27, CI 1.05-1.53), uninsured (OR 1.72, CI 1.15-2.56), and having greater functional limitation (OR 2.44, CI 1.80-3.34). Conclusions for Practice Children with ASD require supportive services such as occupational, physical, and speech therapy but are less likely to receive such services than other CSHCN. Receiving a well-child visit in the past year was strongly associated with receipt of needed therapy services.
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3. Brown K, Selfridge J, Lagger S, Connelly J, De Sousa D, Kerr A, Webb S, Guy J, Merusi C, Koerner MV, Bird A. {{The molecular basis of variable phenotypic severity among common missense mutations causing Rett syndrome}}. {Hum Mol Genet};2015 (Dec 8)
Rett syndrome is caused by mutations in the X-linked MECP2 gene, which encodes a chromosomal protein that binds to methylated DNA. Mouse models mirror the human disorder and therefore allow investigation of phenotypes at a molecular level. We describe an Mecp2 allelic series representing the three most common missense RTT mutations, including first reports of Mecp2[R133C] and Mecp2[T158M] knock-in mice, in addition to Mecp2[R306C] mutant mice. Together these three alleles comprise approximately 25% of all RTT mutations in humans, but they vary significantly in average severity. This spectrum is mimicked in the mouse models; R133C being least severe, T158M most severe and R306C of intermediate severity. Both R133C and T158M mutations cause compound phenotypes at the molecular level, combining compromised DNA binding with reduced stability, the destabilising effect of T158M being more severe. Our findings contradict the hypothesis that the R133C mutation exclusively abolishes binding to hydroxymethylated DNA, as interactions with DNA containing methyl-CG, methyl-CA and hydroxymethyl-CA are all reduced in vivo. We find that MeCP2[T158M] is significantly less stable than MeCP2[R133C], which may account the divergent clinical impact of the mutations. Overall this allelic series recapitulates human RTT severity, reveals compound molecular aetiologies, and provides a valuable resource in the search for personalised therapeutic interventions.
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4. Cheng XP, Zhao J, Chen Y, Meng FK, Xu B, Yu HW, Meng QH, Liu YM, Zhang SB, Meng S, Zhang JY, Duan ZP, Zheng SJ. {{Comparison of the ability of the PDD-ICG clearance test, CTP, MELD, and MELD-Na to predict short-term and medium-term mortality in patients with decompensated hepatitis B cirrhosis}}. {Eur J Gastroenterol Hepatol};2015 (Dec 8)
OBJECTIVE: Various methods, including the indocyanine green (ICG) clearance test, the Child-Turcotte-Pugh score (CTP), model for end-stage liver disease (MELD), and MELD combined with serum sodium concentration (MELD-Na), have been used widely in liver function evaluation in patients with end-stage liver disease. In this study, we compared the ability of these methods to predict mortality in patients with decompensated hepatitis B cirrhosis. METHODS: A total of 98 patients with decompensated hepatitis B cirrhosis were included in this study and followed up for 12 months. The ICG-derived measurements (ICG-PDR, ICG-R15, EHBF), CTP, MELD, and MELD-Na were obtained within 2 days after patients’ admission and patients’ survival at 1, 3, 6, and 12 months was recorded. Receiver operating curve was used to evaluate the ability of these methods to predict mortality in these patients with decompensated hepatitis B cirrhosis. RESULTS: At 1 month, 3 months, 6 months and 12 months, the cumulative number of deaths and liver transplant recipients was 12 (12.2%), 17 (17.3%), 21 (21.4%) and 25 (25.5%), respectively. The ICG-derived measurements, CTP, MELD, and MELD-Na of nonsurvivors were significantly different compared with that in survivors. All methods yielded viable values in predicting short-term and medium-term prognosis for patients with decompensated hepatitis B cirrhosis, with most area under the curve exceeding 0.8. Moreover, the ICG-derived measurements showed a significant correlation with that of CTP, MELD, and MELD-Na. CONCLUSION: All four methods, ICG clearance test, CTP, MELD, and MELD-Na, provided reliable prediction of mortality in patients with decompensated hepatitis B cirrhosis for both short-term and medium-term prognosis.
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5. Christensen DL, Bilder DA, Zahorodny W, Pettygrove S, Durkin MS, Fitzgerald RT, Rice C, Kurzius-Spencer M, Baio J, Yeargin-Allsopp M. {{Prevalence and Characteristics of Autism Spectrum Disorder Among 4-Year-Old Children in the Autism and Developmental Disabilities Monitoring Network}}. {J Dev Behav Pediatr};2015 (Dec 9)
OBJECTIVE: Early identification of children with autism spectrum disorder (ASD) facilitates timely access to intervention services. Yet, few population-based data exist on ASD identification among preschool-aged children. The authors aimed to describe ASD prevalence and characteristics among 4-year-old children in 5 of 11 sites participating in the 2010 Autism and Developmental Disabilities Monitoring Network. METHOD: Children with ASD were identified through screening of health and education records for ASD indicators, data abstraction and compilation for each child, and clinician review of records. ASD prevalence estimates, ages at first evaluation and ASD diagnosis, cognitive test scores, and demographics were compared for 4-year-old children and 8-year-old children living in the same areas. RESULTS: Among 58,467 children in these 5 sites, 4-year-old ASD prevalence was 13.4 per 1000, which was 30% lower than 8-year-old ASD prevalence. Prevalence of ASD without cognitive impairment was 40% lower among 4-year-olds compared with 8-year-olds, but prevalence of ASD with cognitive impairment was 20% higher among 4-year-olds compared with 8-year-olds. Among 4-year-olds with ASD, female and non-Hispanic white children were more likely to receive their first comprehensive evaluation by age 36 months compared with male and non-Hispanic black children, respectively. Among children diagnosed with ASD by age 48 months, median age at first comprehensive evaluation was 27 months for 4-year-olds compared with 32 months for 8-year-olds. CONCLUSION: Population-based ASD surveillance among 4-year-old children provides valuable information about the early identification of children with ASD and suggests progression toward lowering the age of first ASD evaluation within participating Autism and Developmental Disabilities Monitoring communities.
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6. Fluegge K. {{A reply to Wang T, Shan L, Du L, Feng J, Xu Z, Staal WG, Jia F. Serum concentration of 25-hydroxyvitamin D in autism spectrum disorder: a systematic review and meta-analysis. Eur Child Adolesc Psychiatry. 2015; doi: 10.1007/s00787-015-0786-1}}. {Eur Child Adolesc Psychiatry};2015 (Dec 10)
The author of this correspondence has recently published findings of an ecological investigation wherein herbicide use was proposed as an instrumental variable that predicts healthcare utilization among subjects with severe ADHD impairment via individual exposure to nitrous oxide (N2O) emissions. Vitamin D deficiency, a possible risk factor for autism spectrum disorders (ASD) as discussed by Wang et al., may be a homeostatic response to increasing chronic environmental N2O exposures. The author explains how deficient and insufficient states of vitamin D may promote vagal withdrawal and tolerance to increasing opioid exposures in the environment and how these characteristics are particularly relevant in neurodevelopmental disorders, like ASD and ADHD.
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7. Howlin P, Taylor JL. {{Addressing the need for high quality research on autism in adulthood}}. {Autism};2015 (Oct);19(7):771-773.
8. Kirchgessner MA, Chuang AZ, Patel SS, Sereno AB. {{Intact Reflexive but Deficient Voluntary Social Orienting in Autism Spectrum Disorder}}. {Front Neurosci};2015;9:453.
Impairment in social interactions is a primary characteristic of people diagnosed with autism spectrum disorder (ASD). Although these individuals tend to orient less to naturalistic social cues than do typically developing (TD) individuals, laboratory experiments testing social orienting in ASD have been inconclusive, possibly because of a failure to fully isolate reflexive (stimulus-driven) and voluntary (goal-directed) social orienting processes. The purpose of the present study was to separately examine potential reflexive and/or voluntary social orienting differences in individuals with ASD relative to TD controls. Subjects (ages 7-14) with high-functioning ASD and a matched control group completed three gaze cueing tasks on an iPad in which individuals briefly saw a face with averted gaze followed by a target after a variable delay. Two tasks were 100% predictive with either all congruent (target appears in gaze direction) or all incongruent (target appears opposite from gaze direction) trials, respectively. Another task was non-predictive with these same trials (half congruent and half incongruent) intermixed randomly. Response times (RTs) to the target were used to calculate reflexive (incongruent condition RT-congruent condition RT) and voluntary (non-predictive condition RT-predictive condition RT) gaze cueing effects. Subjects also completed two additional non-social orienting tasks (ProPoint and AntiPoint). Subjects with ASD demonstrate intact reflexive but deficient voluntary gaze following. Similar results were found in a separate test of non-social orienting. This suggests problems with using social cues, but only in a goal-directed fashion, in our sample of high-functioning individuals with ASD. Such findings may not only explain inconclusive previous findings but more importantly be critical for understanding social dysfunctions in ASD and for developing future interventions.
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9. Knutsen J, Mandell DS, Frye D. {{Children with autism are impaired in the understanding of teaching}}. {Dev Sci};2015 (Dec 8)
Children learn novel information using various methods, and one of the most common is human pedagogical communication or teaching – the purposeful imparting of information from one person to another. Neuro-typically developing (TD) children gain the ability to recognize and understand teaching as a core method for acquiring knowledge from others. However, it is not known when children with Autism Spectrum Disorder (ASD) acquire the ability to recognize and understand teaching. This study (total N = 70) examined whether children with ASD recognize the two central elements that define teaching: (1) that teaching is an intentional activity; and (2) that teaching requires a knowledge difference between teacher and learner. Theory of mind understanding was also tested. Compared to individually matched TD children, high cognitively functioning children with ASD were impaired in their comprehension of both components of teaching understanding, and their performance was correlated with theory of mind understanding. These findings could have broad implications for explaining learning in children with autism, and could help in designing more effective interventions, which could ultimately lead to improved learning outcomes for everyday life skills, school performance, health, and overall well-being.
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10. Luisier AC, Petitpierre G, Ferdenzi C, Clerc Berod A, Giboreau A, Rouby C, Bensafi M. {{Odor Perception in Children with Autism Spectrum Disorder and its Relationship to Food Neophobia}}. {Front Psychol};2015;6:1830.
Atypical sensory functioning in Autism Spectrum Disorder (ASD) has been well documented in the last decade for the visual, tactile and auditory systems, but olfaction in ASD is still understudied. The aim of the present study was to examine whether children with ASD and neuro-typically (NT) developed children differed in odor perception, at the cognitive (familiarity and identification ability), sensorimotor (olfactory exploration) and affective levels (hedonic evaluation). Because an important function of the sense of smell is its involvement in eating, from food selection to appreciation and recognition, a potential link between odor perception and food neophobia was also investigated. To these ends, 10 children between 6 and 13 years old diagnosed with ASD and 10 NT control children were tested. To compare performance, 16 stimuli were used and food neophobia was assessed by the parents on a short food neophobia scale. Results revealed that (i) significant hedonic discrimination between attractive and aversive odors was observed in NT (p = 0.005; d = 2.378) and ASD children (p = 0.042; d = 0.941), and (ii) hedonic discrimination level was negatively correlated with food neophobia scores in ASD (p = 0.007) but not NT children. In conclusion, this study offers new insights into odor perception in ASD children, highlighting a relationship between odor hedonic reactivity and eating behavior. This opens up new perspectives on both (i) the role of olfaction in the construction of eating behavior in ASD children, and (ii) the measurement and meaning of food neophobia in this population.
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11. Markowitz LA, Reyes C, Embacher RA, Speer LL, Roizen N, Frazier TW. {{Development and psychometric evaluation of a psychosocial quality-of-life questionnaire for individuals with autism and related developmental disorders}}. {Autism};2015 (Dec 10)
This study investigated the psychometric properties of the Child and Family Quality of Life scale, a measure of psychosocial quality of life in those with autism and related developmental disorders. Parents of 212 children suspected of autism spectrum disorder completed the Child and Family Quality of Life prior to a diagnostic evaluation. Results indicated that the Child and Family Quality of Life measured six unique quality-of-life constructs (child, family/caregiver, financial, external support, partner relationship, and coping), had good reliability across score ranges and exhibited expected patterns of convergent validity. Caregivers of autism spectrum disorder-affected children reported reduced family quality of life prior to the time of diagnosis relative to caregivers of children with other developmental disabilities. The Child and Family Quality of Life is a brief, reliable measure for assessing psychosocial quality of life in families affected by developmental disability. This study is the first to demonstrate impairments in family quality of life early in the developmental course of autism spectrum disorder, prior to formal diagnosis. In addition to traditional child-focused intervention strategies, families with autism spectrum disorder-affected children require early, broad intervention strategies that positively impact the whole family.
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12. Monteiro SA, Dempsey J, Broton S, Berry L, Goin-Kochel RP, Voigt RG. {{Early Intervention Before Autism Diagnosis in Children Referred to a Regional Autism Clinic}}. {J Dev Behav Pediatr};2015 (Dec 1)
OBJECTIVE: To determine the prevalence of receipt of early intervention and therapeutic services in children suspected of having possible autism spectrum disorder (ASD) before their diagnostic ASD evaluations. METHODS: The electronic medical records of all children Lien vers le texte intégral (Open Access ou abonnement)
13. Ouyang M, Cheng H, Mishra V, Gong G, Mosconi MW, Sweeney J, Peng Y, Huang H. {{Atypical age-dependent effects of autism on white matter microstructure in children of 2-7 years}}. {Hum Brain Mapp};2015 (Dec 10)
Atypical age-dependent changes of white matter (WM) microstructure play a central role in abnormal brain maturation of the children with autism spectrum disorder (ASD), but their early manifestations have not been systematically characterized. The entire brain core WM voxels were surveyed to detect differences in WM microstructural development between 31 children with ASD of 2-7 years and 19 age-matched children with typical development (TD), using measurements of fractional anisotropy (FA) and radial diffusivity (RD) from diffusion tensor imaging (DTI). The anatomical locations, distribution, and extent of the core WM voxels with atypical age-dependent changes in a specific tract or tract group were delineated and evaluated by integrating the skeletonized WM with a digital atlas. Exclusively, unidirectional FA increases and RD decreases in widespread WM tracts were revealed in children with ASD before 4 years, with bi-directional changes found for children with ASD of 2-7 years. Compared to progressive development that raised FA and lowered RD during 2-7 years in the TD group, flattened curves of WM maturation were found in multiple major WM tracts of all five tract groups, particularly associational and limbic tracts, in the ASD group with trend lines of ASD and TD crossed around 4 years. We found atypical age-dependent changes of FA and RD widely and heterogeneously distributed in WM tracts of children with ASD. The early higher WM microstructural integrity before 4 years reflects abnormal neural patterning, connectivity, and pruning that may contribute to aberrant behavioral and cognitive development in ASD. Hum Brain Mapp, 2015. (c) 2015 Wiley Periodicals, Inc.
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14. Quintin EM, Jo B, Hall SS, Bruno JL, Chromik LC, Raman MM, Lightbody AA, Martin A, Reiss AL. {{The cognitive developmental profile associated with fragile X syndrome: A longitudinal investigation of cognitive strengths and weaknesses through childhood and adolescence}}. {Dev Psychopathol};2015 (Dec 9):1-13.
Few studies have investigated developmental strengths and weaknesses within the cognitive profile of children and adolescents with fragile X syndrome (FXS), a single-gene cause of inherited intellectual impairment. With a prospective longitudinal design and using normalized raw scores (Z scores) to circumvent floor effects, we measured cognitive functioning of 184 children and adolescents with FXS (ages 6 to 16) using the Wechsler Scale of Intelligence for Children on one to three occasions for each participant. Participants with FXS received lower raw scores relative to the Wechsler Scale of Intelligence for Children normative sample across the developmental period. Verbal comprehension, perceptual organization, and processing speed Z scores were marked by a widening gap from the normative sample, while freedom from distractibility Z scores showed a narrowing gap. Key findings include a relative strength for verbal skills in comparison with visuospatial-constructive skills arising in adolescence and a discrepancy between working memory (weakness) and processing speed (strength) in childhood that diminishes in adolescence. Results suggest that the cognitive profile associated with FXS develops dynamically from childhood to adolescence. Findings are discussed within the context of aberrant brain morphology in childhood and maturation in adolescence. We argue that assessing disorder-specific cognitive developmental profiles will benefit future disorder-specific treatment research.
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15. Robins DL. {{Prevalence Counts: Commentary on « Prevalence and Characteristics of Autism Spectrum Disorder Among 4-Year-Old Children in the Autism and Developmental Disabilities Monitoring Network »}}. {J Dev Behav Pediatr};2015 (Dec 9)
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16. Roux AM, Shattuck PT, Rast JE, Rava JA, Edwards AD, Wei X, McCracken M, Yu JW. {{Characteristics of Two-Year College Students on the Autism Spectrum and Their Support Services Experiences}}. {Autism Res Treat};2015;2015:391693.
Approximately 80% of college-going youth with autism in the US attend a 2-year college at some point. These community-based, universally accessible institutions offer both academic and vocational courses and have experience in teaching diverse learners. This study used nationally representative survey data from the National Longitudinal Transition Study-2 to describe the characteristics and services experiences of adults with autism who attended postsecondary education after high school, focusing on those who attended a 2-year college. Over 60% of those who attended 2-year colleges had little to no trouble conversing or performing functional skills like counting change during high school, and extracurricular participation was common (93.8%). Most 2-year college attenders (85.7%) were able to navigate to places outside the home versus 43.9% of those with no postsecondary education. Over half took vocational courses at 2-year colleges, while one-quarter pursued academic study. Less than half (48.6%) of those who disclosed their disability to the school reported receiving services, accommodations, or other help. Most (87.3%) felt they received enough help, but fewer (68.0%) felt the services they received were useful. Future research should delineate specific needs of students with autism in 2-year college settings and identify what supports are needed to improve persistence and completion rates.
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17. Sasson NJ, Pinkham AE, Weittenhiller LP, Faso DJ, Simpson C. {{Context Effects on Facial Affect Recognition in Schizophrenia and Autism: Behavioral and Eye-tracking Evidence}}. {Schizophr Bull};2015 (Dec 7)
Although Schizophrenia (SCZ) and Autism Spectrum Disorder (ASD) share impairments in emotion recognition, the mechanisms underlying these impairments may differ. The current study used the novel « Emotions in Context » task to examine how the interpretation and visual inspection of facial affect is modulated by congruent and incongruent emotional contexts in SCZ and ASD. Both adults with SCZ (n = 44) and those with ASD (n = 21) exhibited reduced affect recognition relative to typically-developing (TD) controls (n = 39) when faces were integrated within broader emotional scenes but not when they were presented in isolation, underscoring the importance of using stimuli that better approximate real-world contexts. Additionally, viewing faces within congruent emotional scenes improved accuracy and visual attention to the face for controls more so than the clinical groups, suggesting that individuals with SCZ and ASD may not benefit from the presence of complementary emotional information as readily as controls. Despite these similarities, important distinctions between SCZ and ASD were found. In every condition, IQ was related to emotion-recognition accuracy for the SCZ group but not for the ASD or TD groups. Further, only the ASD group failed to increase their visual attention to faces in incongruent emotional scenes, suggesting a lower reliance on facial information within ambiguous emotional contexts relative to congruent ones. Collectively, these findings highlight both shared and distinct social cognitive processes in SCZ and ASD that may contribute to their characteristic social disabilities.
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18. Sheppard DP, Kvavilashvili L, Ryder N. {{Event-based prospective memory in mildly and severely autistic children}}. {Res Dev Disabil};2015 (Nov 29);49-50:22-33.
BACKGROUND: There is a growing body of research into the development of prospective memory (PM) in typically developing children but research is limited in autistic children (Aut) and rarely includes children with more severe symptoms. AIMS: This study is the first to specifically compare event-based PM in severely autistic children to mildly autistic and typically developing children. METHODS AND PROCEDURES: Fourteen mildly autistic children and 14 severely autistic children, aged 5-13 years, were matched for educational attainment with 26 typically developing children aged 5-6 years. Three PM tasks and a retrospective memory task were administered. OUTCOMES AND RESULTS: Results showed that severely autistic children performed less well than typically developing children on two PM tasks but mildly autistic children did not differ from either group. No group differences were found on the most motivating (a toy reward) task. CONCLUSIONS AND IMPLICATIONS: The findings suggest naturalistic tasks and motivation are important factors in PM success in severely autistic children and highlights the need to consider the heterogeneity of autism and symptom severity in relation to performance on event-based PM tasks.
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19. Situ M, Hu X, Cai J, Guo K, Huang Y. {{[Behavioral phenotypes of autism spectrum disorder patients and their parents]}}. {Zhonghua Yi Xue Yi Chuan Xue Za Zhi};2015 (Dec 10);32(6):797-800.
OBJECTIVE: To explore the relationship between the behavior phenotypes of patients with autism spectrum disorder (ASD) and their parents through family study. METHODS: Forty-five core families with ASD and 30 control families from Chengdu area were examined using Autism Spectrum Quotient (AQ). Descriptive statistical analysis, correlation analysis, and Logistic regression analysis were used to investigate the effect of various factors, especially genetic factors that may affect the pathogenesis of ASD. RESULTS: The social skills factor and communication factor of the father’s AQ scale, as well as the mother’s age of childbearing and AQ social skills factor are related to whether children with ASD (R were 0.46, 0.39, 0.39 and 0.36, P<0.05). The communication factor of the parents' AQ and mother's attention to detail factor are related to whether children will show developmental anomaly before the age of 36 months (R were 0.55, 0.51 and 0.54, P<0.05). The social skill problems of parents and father's communication problems are risk factors for children with autism. CONCLUSION: ASD may be influenced by both genetic and environmental factors. The autistic behavior phenotype of parents is a risk factor for ASD and is associated with developmental anomalies of early childhood. Lien vers le texte intégral (Open Access ou abonnement)
