Healthy cortical development depends on precise regulation of transcription and translation. However, the dynamics of how proteins are expressed, function and interact across postnatal human cortical development remain poorly understood. We surveyed the proteomic landscape of 69 dorsolateral prefrontal cortex samples across seven stages of postnatal life and integrated these data with paired transcriptome data. We detected 911 proteins by liquid chromatography-mass spectrometry, and 83 were significantly associated with postnatal age (FDR < 5%). Network analysis identified three modules of co-regulated proteins correlated with age, including two modules with increasing expression involved in gliogenesis and NADH metabolism and one neurogenesis-related module with decreasing expression throughout development. Integration with paired transcriptome data revealed that these age-related protein modules overlapped with RNA modules and displayed collinear developmental trajectories. Importantly, RNA expression profiles that are dynamically regulated throughout cortical development display tighter correlations with their respective translated protein expression compared to those RNA profiles that are not. Moreover, the correspondence between RNA and protein expression significantly decreases as a function of cortical aging, especially for genes involved in myelination and cytoskeleton organization. Finally, we used this data resource to elucidate the functional impact of genetic risk loci for intellectual disability, converging on gliogenesis, myelination and ATP-metabolism modules in the proteome and transcriptome. We share all data in an interactive, searchable companion website. Collectively, our findings reveal dynamic aspects of protein regulation and provide new insights into brain development, maturation, and disease.
Temporal proteomic profiling of postnatal human cortical development
Access to early intensive behavioral intervention for children with autism spectrum disorder is commonly recommended. Intervention programs may include high rates of instructional trials, which may evoke escape-maintained problem behavior. Recent research on “pairing” or “rapport-building” interventions have sought to reduce the likelihood that problem behavior occurs during instruction using antecedent manipulations. The current study evaluated a structured intervention that included differential reinforcement and demand fading to increase participants’ response allocation to instructional settings without the use of physical guidance. Nine minimally verbal girls under the age of 6 years with autism spectrum disorder enrolled in the study. The protocol was effective for seven of the nine participants. One participant did not complete the protocol due to competing behavior and an additional participant did not require the intervention. Our findings suggest that the structured intervention was effective in increasing appropriate behavioral repertoires that are necessary for children with autism spectrum disorder to effectively benefit from early educational programs.
The aim of this study is to holistically synthesise the extent and range of literature relating to the employment of individuals with autism spectrum disorder. Database searches of Medline, CINAHL, PsychINFO, Scopus, ERIC, Web of Science and EMBASE were conducted. Studies describing adults with autism spectrum disorder employed in competitive, supported or sheltered employment were included. Content analysis was used to identify the strengths and abilities in the workplace of employees with autism spectrum disorder. Finally, meaningful concepts relating to employment interventions were extracted and linked to the International Classification of Functioning, Disability and Health Core Sets for autism spectrum disorder. The search identified 134 studies for inclusion with methodological quality ranging from limited to strong. Of these studies, only 36 evaluated employment interventions that were coded and linked to the International Classification of Functioning, Disability and Health, primarily focusing on modifying autism spectrum disorder characteristics for improved job performance, with little consideration of the impact of contextual factors on work participation. The International Classification of Functioning, Disability and Health Core Sets for autism spectrum disorder are a useful tool in holistically examining the employment literature for individuals with autism spectrum disorder. This review highlighted the key role that environmental factors play as barriers and facilitators in the employment of people with autism spectrum disorder and the critical need for interventions which target contextual factors if employment outcomes are to be improved.
Keywords: adult; intervention; strengths-based; vocational rehabilitation; work environment.
BACKGROUND:
The problem of persistently low rates of employment and earnings for people with autism is well established. In the U.S., the 2014 Workforce Innovation and Opportunity Act (WIOA) updated the legal framework for the federal Vocational Rehabilitation (VR) program which assists people with disabilities to find and maintain employment.
OBJECTIVE:
This study examined whether and how the needs of transition-age youth and adults with autism are addressed in state WIOA plans.
METHODS:
We analyzed WIOA documents for all states plus the District of Columbia using content analysis.
RESULTS:
Of the 51 state plans, 44 contained references to autism, and 19 explicitly identified autism as a disability group that is underserved by the state VR agency. Even among states that clearly defined autism as underserved, only 10 provided comprehensive plans which defined goals and strategies to address the vocational needs of this group. We discuss major themes related to VR service delivery for people with autism identified within the state plans.
CONCLUSIONS:
This study identifies state policy aimed at facilitating employment for people with autism and contributes to efforts to discover why individuals with autism in some states have better employment outcomes than in others.
Despite efforts to improve employment outcomes for autistic individuals, internationally their employment rates remain low. There is a need to better understand the factors influencing successful employment for autistic adults in the labor market from the perspectives of multiple key stakeholders. This study represents the second in a series of papers conducted as part of an International Society for Autism Research policy brief aimed at improving employment outcomes for autistic individuals. A community consultation methodology using focus groups, forums, and interviews was applied with autistic individuals (n = 19), family members (n = 18), service providers (n = 21), employers (n = 11), researchers (n = 5), and advocacy group representatives (n = 5) in Australia, Sweden, and the United States, aiming to identify the factors perceived to determine gaining and maintaining employment for autistic individuals. Directed content analysis, guided by the International Classification of Functioning, Disability and Health (ICF), was conducted to investigate the key factors influencing employment outcomes for autistic individuals. Meaningful verbal concepts, or units of text with common themes, were also derived from the qualitative data and then linked and compared to the ICF Autism Spectrum Disorder (ASD) Core-sets. Across countries, activity and participation and environmental factor categories of the ICF were the most associated with employment outcomes. Results suggest that removal of environmental barriers and enhancing environmental facilitators may assist to remediate ASD-related difficulties in the workplace. Autism Res 2019, © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: This study sought to understand the perspectives of autistic individuals and key stakeholders on factors influencing if autistic adults get and keep jobs. Across Australia, Sweden, and the United States, focus groups and interviews were conducted to understand international perspectives on what helps and hinders getting and keeping a job for autistic individuals. The environment, including supports, relationships, attitudes, and services, were perceived to be the most important for workplace success. Intervention targeting barriers and facilitators in the workplace environment may support autistic adults to be successful in the labor market.
Keywords: ICF; autism; cross-cultural; employment.
Despite evidence suggesting differences in early event-related potential (ERP) responses to social emotional stimuli, little is known about later stage ERP contributions to social emotional processing in individuals with autism spectrum disorder (ASD). Adults with and without ASD completed a facial emotion recognition task involving stimuli that varied by emotional intensity while electroencephalograms were recorded. Principal components analysis was used to examine P300 and late positive potential (LPP) modulation by emotional intensity. Results indicated that greater ASD symptomatology evinced heightened P300 to high relative to low intensity faces, then heightened LPP to low relative to high intensity faces. Findings suggest that adults with greater ASD symptomatology may demonstrate a lag in engagement in elaborative processing of low intensity faces.
Keywords: Autism spectrum disorder; ERP; Emotion processing; LPP; P300; Social cognition