1. Anagnostou E, Jones N, Huerta M, Halladay AK, Wang P, Scahill L, Horrigan JP, Kasari C, Lord C, Choi D, Sullivan K, Dawson G. {{Measuring social communication behaviors as a treatment endpoint in individuals with autism spectrum disorder}}. {Autism};2014 (Aug 5)
Social communication impairments are a core deficit in autism spectrum disorder. Social communication deficit is also an early indicator of autism spectrum disorder and a factor in long-term outcomes. Thus, this symptom domain represents a critical treatment target. Identifying reliable and valid outcome measures for social communication across a range of treatment approaches is essential. Autism Speaks engaged a panel of experts to evaluate the readiness of available measures of social communication for use as outcome measures in clinical trials. The panel held monthly conference calls and two face-to-face meetings over 14 months. Key criteria used to evaluate measures included the relevance to the clinical target, coverage of the symptom domain, and psychometric properties (validity and reliability, as well as evidence of sensitivity to change). In all, 38 measures were evaluated and 6 measures were considered appropriate for use, with some limitations. This report discusses the relative strengths and weaknesses of existing social communication measures for use in clinical trials and identifies specific areas in need of further development.
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2. Bedford R, Pickles A, Gliga T, Elsabbagh M, Charman T, Johnson MH. {{Additive effects of social and non-social attention during infancy relate to later autism spectrum disorder}}. {Dev Sci};2014 (Jul);17(4):612-620.
Emerging findings from studies with infants at familial high risk for autism spectrum disorder (ASD), owing to an older sibling with a diagnosis, suggest that those who go on to develop ASD show early impairments in the processing of stimuli with both social and non-social content. Although ASD is defined by social-communication impairments and restricted and repetitive behaviours, the majority of cognitive theories of ASD posit a single underlying factor, which over development has secondary effects across domains. This is the first high-risk study to statistically differentiate theoretical models of the development of ASD in high-risk siblings using multiple risk factors. We examined the prediction of ASD outcome by attention to social and non-social stimuli: gaze following and attentional disengagement assessed at 13 months in low-risk controls and high-risk ASD infants (who were subsequently diagnosed with ASD at 3 years). When included in the same regression model, these 13-month measures independently predicted ASD outcome at 3 years of age. The data were best described by an additive model, suggesting that non-social attention, disengagement, and social attention as evidenced by gaze following, have a cumulative impact on ASD risk. These data argue against cognitive theories of ASD which propose that a single underlying factor has cascading effects across early development leading to an ASD outcome, and support multiple impairment models of ASD that are more consistent with recent genetic and neurobiological evidence.
3. Castro K, Klein LD, Baronio D, Gottfried C, Riesgo R, Perry IS. {{Folic acid and autism: What do we know?}}. {Nutr Neurosci};2014 (Aug 2)
Autism spectrum disorders (ASD) consist in a range of neurodevelopmental conditions that share common features with autism, such as impairments in communication and social interaction, repetitive behaviors, stereotypies, and a limited repertoire of interests and activities. Some studies have reported that folic acid supplementation could be associated with a higher incidence of autism, and therefore, we aimed to conduct a systematic review of studies involving relationships between this molecule and ASD. The MEDLINE database was searched for studies written in English which evaluated the relationship between autism and folate. The initial search yielded 60 potentially relevant articles, of which 11 met the inclusion criteria. The agreement between reviewers was kappa = 0.808. The articles included in the present study addressed topics related to the prescription of vitamins, the association between folic acid intake/supplementation during pregnancy and the incidence of autism, food intake, and/or nutrient supplementation in children/adolescents with autism, the evaluation of serum nutrient levels, and nutritional interventions targeting ASD. Regarding our main issue, namely the effect of folic acid supplementation, especially in pregnancy, the few and contradictory studies present inconsistent conclusions. Epidemiological associations are not reproduced in most of the other types of studies. Although some studies have reported lower folate levels in patients with ASD, the effects of folate-enhancing interventions on the clinical symptoms have yet to be confirmed.
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4. De la Marche W, Noens I, Kuppens S, Spilt JL, Boets B, Steyaert J. {{Measuring quantitative autism traits in families: informant effect or intergenerational transmission?}}. {Eur Child Adolesc Psychiatry};2014 (Aug 3)
Autism spectrum disorders (ASD) have a high degree of heritability, but there is still much debate about specific causal genes and pathways. To gain insight into patterns of transmission, research has focused on the relatedness of quantitative autism traits (QAT) between family members, mostly using questionnaires. Yet, different kinds of bias may influence research results. In this paper, we focus on possible informant effects and, taking these into account, on possible intergenerational transmission of QAT. This study used multiple informant data retrieved via the Social Responsiveness Scale from 170 families with at least one member with ASD. Using intraclass correlations (ICCs) and mixed model analyses, we investigated inter-informant agreement and differences between parent and teacher reports on children and between self- and other-reports on adults. Using structural equation modelling (SEM), we investigated the relatedness of QAT between family members in ASD families. Parent-teacher agreement about social responsiveness was poor, especially for children with ASD, though agreement between parents was moderate to strong for affected and unaffected children. Agreement between self- and other-report in adult men was good, but only moderate in women. Agreement did not differ between adults with and without ASD. While accounting for informant effects, our SEM results corroborated the assortative mating theory and the intergenerational transmission of QAT from both fathers and mothers to their offspring.
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5. Donaldson AL, Stahmer AC. {{Team Collaboration: The Use of Behavior Principles for Serving Students with ASD}}. {Lang Speech Hear Serv Sch};2014 (Aug 5)
Purpose: SLPs and behavior analysts are key members of school-based teams that serve children with autism spectrum disorders (ASD). Behavior analysts approach assessment and intervention through the lens of applied behavior analysis (ABA). ABA-based interventions have been found effective for targeting skills across multiple domains for children with ASD. However, some SLPs may be unfamiliar with the breadth of ABA-based interventions. The intent of this tutorial is to briefly introduce key ABA principles, provide examples of ABA-based interventions used within schools, and identify strategies for successful collaboration between behavior analysts and SLPs. Method: This tutorial draws from empirical studies of ABA-based interventions for children with ASD within school settings, as well as discussions in the extant literature about the use of behavior principles by SLPs, and strategies for interdisciplinary collaboration. Conclusion: Given the prevalence of ASD at 1 in 68 children (CDC, 2014) and the high cost of serving these children within schools (an average cost of 286% over regular education; Chambers, Shkolnik & Perez, 2003), the need for effective, comprehensive service provision and efficiency within interdisciplinary teams is paramount. Communication, mutual understanding, and recognition of common ground between SLPs and behavior analysts can lead to successful collaboration.
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6. Groskreutz NC, Groskreutz MP, Bloom SE, Slocum TA. {{Generalization of negatively reinforced mands in children with autism}}. {J Appl Behav Anal};2014 (Aug 4)
Each day, people encounter stimuli they find unpleasant. Some children with autism may require systematic instruction to acquire the communication skills necessary to request the termination of such aversive stimuli. We taught 2 school-aged boys with autism a mand (e.g., signing « stop ») that could be used to escape a variety of aversive stimuli. First, we employed a systematic assessment to identify aversive stimuli to use during training. We then conducted mand training sequentially across those stimuli until sufficient exemplars were trained for generalization to occur to untrained stimuli. For both participants, cross-stimulus generalization was observed after training with 2 stimuli. Participants manded for escape in the presence of aversive stimuli, but almost never manded in the presence of preferred stimuli or when the programmed stimuli were absent. In addition, we found an inverse relation between acquisition of the mand and engagement in problem behavior and evidence of generalization to nontraining contexts.
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7. Guastella AJ, Gray KM, Rinehart NJ, Alvares GA, Tonge BJ, Hickie IB, Keating CM, Cacciotti-Saija C, Einfeld SL. {{The effects of a course of intranasal oxytocin on social behaviors in youth diagnosed with autism spectrum disorders: a randomized controlled trial}}. {J Child Psychol Psychiatry};2014 (Aug 2)
BACKGROUND: There is increasing interest in oxytocin as a therapeutic to treat social deficits in autism spectrum disorders (ASD). The aim of this study was to investigate the efficacy of a course of oxytocin nasal spray to improve social behavior in youth with ASD. METHODS: In a double-blind, placebo-controlled trial across two Australian university sites between February 2009 and January 2012, 50 male participants aged between 12 and 18 years, with Autistic or Asperger’s Disorder, were randomized to receive either oxytocin (n = 26) or placebo (n = 24) nasal sprays (either 18 or 24 International Units), administered twice-daily for 8 weeks. Participants were assessed at baseline, after 4- and 8-weeks of treatment, and at 3-month follow-up. Primary outcomes were change in total scores on the caregiver-completed Social Responsiveness Scale and clinician-ratings on the Clinical Global Impressions-Improvement scale. Secondary assessments included caregiver reports of repetitive and other developmental behaviors and social cognition. Clinical trial registration: Australian New Zealand Clinical Trials Registry www.anzctr.org.au ACTRN12609000513213. RESULTS: Participants who received oxytocin showed no benefit following treatment on primary or secondary outcomes. However, caregivers who believed their children received oxytocin reported greater improvements compared to caregivers who believed their child received placebo. Nasal sprays were well tolerated and there was no evidence of increased side effects resulting from oxytocin administration. CONCLUSIONS: This is the first evaluation of the efficacy for a course of oxytocin treatment for youth with ASD. Although results did not suggest clinical efficacy, further research is needed to explore alternative delivery methods, earlier age of intervention, and the influence of caregiver expectation on treatment response.
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8. Kover ST, Davidson MM, Sindberg HA, Weismer SE. {{Use of the ADOS for Assessing Spontaneous Expressive Language in Young Children with ASD: A Comparison of Sampling Contexts}}. {J Speech Lang Hear Res};2014 (Aug 5)
Purpose: The current study compared the spontaneous expressive language of children with autism spectrum disorder (ASD) across multiple language sampling contexts: the Autism Diagnostic Observation Schedule (ADOS) and play with an examiner or parent. Method: Participants were children with ASD (n = 63; 55 males) with a mean age of 45 months (SD = 3.94; Range = 37-53). The number of utterances produced, percent intelligibility, number of different words, mean length of utterance, and the number of requests, comments, and instances of turn-taking were calculated for the ADOS, examiner-child play, and parent-child play. Children were categorized into Tager-Flusberg et al.’s (2009) developmental language phases for each context. Result: Effects of sampling context were identified for all variables examined. The ADOS resulted in fewer utterances and lower structural and pragmatic language performance than examiner- and/or parent-child play. Categorization of children into language phases differed across contexts. Conclusion: Use of the ADOS as a language sampling context may lead to underestimating the abilities of young children with ASD relative to play with an examiner or parent. Researchers and clinicians should be aware of context effects, particularly for assessments designed to observe autism symptoms.
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9. LoParo D, Waldman ID. {{The oxytocin receptor gene (OXTR) is associated with autism spectrum disorder: a meta-analysis}}. {Mol Psychiatry};2014 (Aug 5)
The oxytocin receptor gene (OXTR) has been studied as a risk factor for autism spectrum disorder (ASD) owing to converging evidence from multiple levels of analysis that oxytocin (OXT) has an important role in the regulation of affiliative behavior and social bonding in both nonhuman mammals and humans. Inconsistency in the effect sizes of the OXTR variants included in association studies render it unclear whether OXTR is truly associated with ASD, and, if so, which OXTR single-nucleotide polymorphisms (SNPs) are associated. Thus, a meta-analytic review of extant studies is needed to determine whether OXTR shows association with ASD, and to elucidate which specific SNPs have a significant effect on ASD. The current meta-analysis of 16 OXTR SNPs included 3941 individuals with ASD from 11 independent samples, although analyses of each individual SNP included a subset of this total. We found significant associations between ASD and the SNPs rs7632287, rs237887, rs2268491 and rs2254298. OXTR was also significantly associated with ASD in a gene-based test. The current meta-analysis is the largest and most comprehensive investigation of the association of OXTR with ASD and the findings suggest directions for future studies of the etiology of ASD.Molecular Psychiatry advance online publication, 5 August 2014; doi:10.1038/mp.2014.77.
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10. Pathania M, Davenport EC, Muir J, Sheehan DF, Lopez-Domenech G, Kittler JT. {{The autism and schizophrenia associated gene CYFIP1 is critical for the maintenance of dendritic complexity and the stabilization of mature spines}}. {Transl Psychiatry};2014;4:e423.
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11. Rahbar MH, Samms-Vaughan M, Dickerson AS, Loveland KA, Ardjomand-Hessabi M, Bressler J, Lee M, Shakespeare-Pellington S, Grove ML, Pearson DA, Boerwinkle E. {{Role of fruits, grains, and seafood consumption in blood cadmium concentrations of Jamaican children with and without Autism Spectrum Disorder}}. {Res Autism Spectr Disord};2014 (Sep 1);8(9):1134-1145.
Human exposure to cadmium has adverse effects on the nervous system. Utilizing data from 110 age- and sex-matched case-control pairs (220 children) ages 2-8 years in Kingston, Jamaica, we compared the 75th percentile of blood cadmium concentrations in children with and without Autism Spectrum Disorder (ASD). In both univariable and multivariable Quantile Regression Models that controlled for potential confounding factors, we did not find any significant differences between ASD cases and typically developing (TD) controls with respect to the 75th percentile of blood cadmium concentrations, (P > 0.22). However, we found a significantly higher 75th percentile of blood cadmium concentrations in TD Jamaican children who consumed shellfish (lobsters, crabs) (P <0.05), fried plantain (P <0.01), and boiled dumpling (P <0.01). We also observed that children living in Jamaica have an arithmetic mean blood cadmium concentration of 0.16mug/L which is similar to that of the children in developed countries and much lower than that of children in developing countries. Although our results do not support an association between blood cadmium concentrations and ASD, to our knowledge, this study is the first to report levels of blood cadmium in TD children as well as those with ASD in Jamaica.
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12. Ranjbar A, Rashedi V, Rezaei M. {{Comparison of urinary oxidative biomarkers in Iranian children with autism}}. {Res Dev Disabil};2014 (Jul 31);35(11):2751-2755.
Autism is a complex neurodevelopmental disorder usually presents in early childhood and thought to be influenced by genetic and environmental factors. Individuals with autism vary widely in abilities, intelligence, and behaviors. It is common for children with autism to exhibit eating disorders and some have preferences for soft and sweetened food making them susceptible to caries. Furthermore, a wide spectrum of medical and behavioral symptoms exhibited by children with autism makes routine dental care very difficult. Intellectual disability is evident in approximately 70% of individuals with autism and most psychiatric disorders, including autism, are associated with increased oxidative stress. 29 subjects diagnosed with autism, in the age group of 6 to 12 years, were a part of the study. Furturemore, 24 normal healthy siblings of same age group were taken as the control group. The present study aimed to evaluate oxidative stress biomarkers such as urinary total antioxidant concentration (TAC), catalase activity (CAT) and total thiol molecules (TTM). The results showed the autism group have significantly higher CAT activity and concomitant lower TAC and TTM concentration in comparison with control group. The results are discussed in relation to an increased vulnerability to oxidative damage, which may contribute to the development and clinical manifestation of symptoms of autism.
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13. Siegel M, Beresford CA, Bunker M, Verdi M, Vishnevetsky D, Karlsson C, Teer O, Stedman A, Smith KA. {{Preliminary Investigation of Lithium for Mood Disorder Symptoms in Children and Adolescents with Autism Spectrum Disorder}}. {J Child Adolesc Psychopharmacol};2014 (Aug 5)
Abstract Objective: Children with autism spectrum disorder (ASD) have higher rates of comorbid psychiatric disorders, including mood disorders, than the general child population. Although children with ASD may experience irritability (aggression, self-injury, and tantrums), a portion also experience symptoms that are typical of a mood disorder, such as euphoria/elevated mood, mania, hypersexuality, paranoia, or decreased need for sleep. Despite lithium’s established efficacy in controlling mood disorder symptoms in the neurotypical population, lithium has been rarely studied in children with ASD. Methods: We performed a retrospective chart review of 30 children and adolescents diagnosed with ASD by the, Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text Revision (DSM-IV-TR) criteria who were prescribed lithium in order to assess target symptoms, safety, and tolerability. Clinical Global Impressions – Improvement (CGI-I) ratings were performed by two board-certified child psychiatrists with expertise in ASD. CGI-I scores were dichotomized into « improved » (CGI-I score of 1 or 2) or « not improved » (CGI-I score >/=3). Results: Forty-three percent of patients who received lithium were rated as « improved » on the CGI-I. Seventy-one percent of patients who had two or more pretreatment mood disorder symptoms were rated as « improved. » The presence of mania (p=0.033) or euphoria/elevated mood (p=0.041) were the pretreatment symptoms significantly associated with an « improved » rating. The mean lithium blood level was 0.70 mEq/L (SD=0.26), and the average length of lithium treatment was 29.7 days (SD=23.9). Forty-seven percent of patients were reported to have at least one side effect, most commonly vomiting (13%), tremor (10%), fatigue (10%), irritability (7%), and enuresis (7%). Conclusions: This preliminary assessment of lithium in children and adolescents with ASD suggests that lithium may be a medication of interest for those who exhibit two or more mood disorder symptoms, particularly mania or euphoria/elevated mood. A relatively high side effect rate merits caution, and these results are limited by the retrospective, uncontrolled study design. Future study of lithium in a prospective trial with treatment-sensitive outcome measures may be indicated.
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14. Taylor MJ, Charman T, Robinson EB, Hayiou-Thomas ME, Happe F, Dale PS, Ronald A. {{Language and traits of autism spectrum conditions: Evidence of limited phenotypic and etiological overlap}}. {Am J Med Genet B Neuropsychiatr Genet};2014 (Aug 2)
Language difficulties have historically been viewed as integral to autism spectrum conditions (ASC), leading molecular genetic studies to consider whether ASC and language difficulties have overlapping genetic bases. The extent of genetic, and also environmental, overlap between ASC and language is, however, unclear. We hence conducted a twin study of the concurrent association between autistic traits and receptive language abilities. Internet-based language tests were completed by approximately 3,000 pairs of twins, while autistic traits were assessed via parent ratings. Twin model fitting explored the association between these measures in the full sample, while DeFries-Fulker analysis tested these associations at the extremes of the sample. Phenotypic associations between language ability and autistic traits were modest and negative. The degree of genetic overlap was also negative, indicating that genetic influences on autistic traits lowered language scores in the full sample (mean genetic correlation = -0.13). Genetic overlap was also low at the extremes of the sample (mean genetic correlation = 0.14), indicating that genetic influences on quantitatively defined language difficulties were largely distinct from those on extreme autistic traits. Variation in language ability and autistic traits were also associated with largely different nonshared environmental influences. Language and autistic traits are influenced by largely distinct etiological factors. This has implications for molecular genetic studies of ASC and understanding the etiology of ASC. Additionally, these findings lend support to forthcoming DSM-5 changes to ASC diagnostic criteria that will see language difficulties separated from the core ASC communication symptoms, and instead listed as a clinical specifier. (c) 2014 Wiley Periodicals, Inc.
