Articles 1278 An Inflammatory Biomarker as a Differential Predictor of Outcome of Depression Treatment With Escitalopram and Nortriptyline Rudolf Uher et. al 1287 Identification and Replication of a Combined Epigenetic and Genetic Biomarker Predicting Suicide and Suicidal Behaviors Jerry Guintivano et. al 1297 Clinical Outcomes and Genome-Wide Association for a Brain Methylation Site in an Antidepressant Pharmacogenetics Study in Mexican Americans Ma-Li Wong et. al

The american journal of psychiatry

BACKGROUND: The needs of children with autism spectrum disorder (ASD) are complex and this is reflected in the number and diversity of outcomes assessed and measurement tools used to collect evidence about children's progress. Relevant outcomes include improvement in core ASD impairments, such as communication, social awareness, sensory sensitivities and repetitiveness; skills such as social functioning and play; participation outcomes such as social inclusion; and parent and family impact. OBJECTIVES: To examine the measurement properties of tools used to measure progress and outcomes in children with ASD up to the age of 6 years. To identify outcome areas regarded as important by people with ASD and parents. METHODS: The MeASURe (Measurement in Autism Spectrum disorder Under Review) research collaboration included ASD experts and review methodologists. We undertook systematic review of tools used in ASD early intervention and observational studies from 1992 to 2013; systematic review, using the COSMIN checklist (Consensus-based Standards for the selection of health Measurement Instruments) of papers addressing the measurement properties of identified tools in children with ASD; and synthesis of evidence and gaps. The review design and process was informed throughout by consultation with stakeholders including parents, young people with ASD, clinicians and researchers. RESULTS: The conceptual framework developed for the review was drawn from the International Classification of Functioning, Disability and Health, including the domains 'Impairments', 'Activity Level Indicators', 'Participation', and 'Family Measures'. In review 1, 10,154 papers were sifted - 3091 by full text - and data extracted from 184; in total, 131 tools were identified, excluding observational coding, study-specific measures and those not in English. In review 2, 2665 papers were sifted and data concerning measurement properties of 57 (43%) tools were extracted from 128 papers. Evidence for the measurement properties of the reviewed tools was combined with information about their accessibility and presentation. Twelve tools were identified as having the strongest supporting evidence, the majority measuring autism characteristics and problem behaviour. The patchy evidence and limited scope of outcomes measured mean these tools do not constitute a 'recommended battery' for use. In particular, there is little evidence that the identified tools would be good at detecting change in intervention studies. The obvious gaps in available outcome measurement include well-being and participation outcomes for children, and family quality-of-life outcomes, domains particularly valued by our informants (young people with ASD and parents). CONCLUSIONS: This is the first systematic review of the quality and appropriateness of tools designed to monitor progress and outcomes of young children with ASD. Although it was not possible to recommend fully robust tools at this stage, the review consolidates what is known about the field and will act as a benchmark for future developments. With input from parents and other stakeholders, recommendations are made about priority targets for research. FUTURE WORK: Priorities include development of a tool to measure child quality of life in ASD, and validation of a potential primary outcome tool for trials of early social communication intervention. STUDY REGISTRATION: This study is registered as PROSPERO CRD42012002223. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

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Systematic review of tools to measure outcomes for young children with autism spectrum disorder

Autism spectrum disorder (ASD) is a neurodevelopmental condition of heterogeneous etiology. While it is widely recognized that genetic and environmental factors and their interactions contribute to autism phenotypes, their precise causal mechanisms remain poorly understood. This article reviews our current understanding of environmental risk factors of ASD and their presumed adverse physiological mechanisms. It comprehensively maps the significance of parental age, teratogenic compounds, perinatal risks, medication, smoking and alcohol use, nutrition, vaccination, toxic exposures, as well as the role of extreme psychosocial factors. Further, we consider the role of potential protective factors such as folate and fatty acid intake. Evidence indicates an increased offspring vulnerability to ASD through advanced maternal and paternal age, valproate intake, toxic chemical exposure, maternal diabetes, enhanced steroidogenic activity, immune activation, and possibly altered zinc–copper cycles and treatment with selective serotonin reuptake inhibitors. Epidemiological studies demonstrate no evidence for vaccination posing an autism risk. It is concluded that future research needs to consider categorical autism, broader autism phenotypes, as well as autistic traits, and examine more homogenous autism variants by subgroup stratification. Our understanding of autism etiology could be advanced by research aimed at disentangling the causal and non-causal environmental effects, both founding and moderating, and gene–environment interplay using twin studies, longitudinal and experimental designs. The specificity of many environmental risks for ASD remains unknown and control of multiple confounders has been limited. Further understanding of the critical windows of neurodevelopmental vulnerability and investigating the fit of multiple hit and cumulative risk models are likely promising approaches in enhancing the understanding of role of environmental factors in the etiology of ASD.

https://link.springer.com/content/pdf/10.1007/s00018-018-2988-4.pdf

The contribution of environmental exposure to the etiology of autism spectrum disorder.

Diagnosis, intervention and support for people with autism can be assisted by research into the aetiology of the condition. Twin and family studies indicate that autism spectrum conditions are highly heritable; genetic relatives of people with autism often show milder expression of traits characteristic for autism, referred to as the Broader Autism Phenotype (BAP). In the past decade, advances in the biological and behavioural sciences have facilitated a more thorough examination of the BAP from multiple levels of analysis. Here, the candidate phenotypic traits delineating the BAP are summarised, including key findings from neuroimaging studies examining the neural substrates of the BAP. We conclude by reviewing the value of further research into the BAP, with an emphasis on deriving heritable endophenotypes which will reliably index autism susceptibility and offer neurodevelopmental mechanisms that bridge the gap between genes and a clinical autism diagnosis.

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Autistic traits below the clinical threshold: re-examining the broader autism phenotype in the 21st century.

Eighty-seven preschoolers with autism spectrum disorders who were initially nonverbal (under 6 words in language sample and under 21 parent-reported words said) were assessed at five time points over 16 months. Statistical models that accounted for the intercorrelation among nine theoretically- and empirically-motivated predictors, as well as two background variables (i.e., cognitive impairment level, autism severity), were applied to identify value-added predictors of expressive and receptive spoken language growth and outcome. The results indicate that responding to joint attention, intentional communication, and parent linguistic responses were value-added predictors of both expressive and receptive spoken language growth. In addition, consonant inventory was a value-added predictor of expressive growth; early receptive vocabulary and autism severity were value-added predictors of receptive growth.

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Value-Added Predictors of Expressive and Receptive Language Growth in Initially Nonverbal Preschoolers with Autism Spectrum Disorders.

Factors influencing adjustment in siblings of children with autism spectrum disorders

This study examined the relationship between the broader autism phenotype (BAP) and depressed mood in mothers of children with and without autism spectrum disorders (ASD). One hundred and sixty-five mothers (71 with an ASD child and 94 with a non-ASD child) completed a survey of child autism severity (ASD mothers only), parenting stress, BAP, and depression. Mothers of children with ASD reported greater depressed mood, higher parenting stress, and more characteristics associated with the BAP than mothers of children without ASD. For mothers of children with ASD, the BAP uniquely predicted number of depressive symptoms after controlling for child autism severity and parenting stress. In the full sample, the relationship between group status and depressed mood was no longer significant after controlling for parenting stress and maternal BAP. These findings suggest that the higher rate of depression found in mothers of children with ASD may be attributed both to the increased stress of raising a child with ASD, as well as a greater number of autistic features in the mothers that may place them at higher risk for developing depression.

Increased rates of depressed mood in mothers of children with ASD associated with the presence of the broader autism phenotype

Examination of correlates of different imitative functions in young children with autism spectrum disorders

Purpose Developmental social–pragmatic and naturalistic behavioral interventions share a number of features, but they differ in their use of facilitative strategies and direct elicitation of child ...

A Comparison of Developmental Social–Pragmatic and Naturalistic Behavioral Interventions on Language Use and Social Engagement in Children With Autism

Children with autism exhibit significant deficits in imitation. Previous research has suggested that object and gesture imitation are independent in autism, and that object imitation may be related to play skills, while gesture imitation may be related to expressive language. However, this finding has not been replicated in the literature. This study examined the concurrent relationship between imitation and language and play in 27 young children with autism. After controlling for developmental age, total imitation was related to child expressive vocabulary. Object imitation had a unique relationship with symbolic play; however, gesture imitation was not uniquely correlated with language. Object and gesture imitation skills were highly correlated, questioning the true independence of these skills in children with autism. Different types of imitation skills in children with autism may be better described as involving a general imitative capacity along with other more specific skills.

Katherine Meyer

Papers

Factors influencing adjustment in siblings of children with autism spectrum disorders

Increased rates of depressed mood in mothers of children with ASD associated with the presence of the broader autism phenotype

Examination of correlates of different imitative functions in young children with autism spectrum disorders

A Comparison of Developmental Social–Pragmatic and Naturalistic Behavioral Interventions on Language Use and Social Engagement in Children With Autism

Do Object and Gesture Imitation Skills Represent Independent Dimensions in Autism