1. Anwar A, Abruzzo PM, Pasha S, Rajpoot K, Bolotta A, Ghezzo A, Marini M, Posar A, Visconti P, Thornalley PJ, Rabbani N. {{Advanced glycation endproducts, dityrosine and arginine transporter dysfunction in autism – a source of biomarkers for clinical diagnosis}}. {Mol Autism}. 2018; 9: 3.
Background: Clinical chemistry tests for autism spectrum disorder (ASD) are currently unavailable. The aim of this study was to explore the diagnostic utility of proteotoxic biomarkers in plasma and urine, plasma protein glycation, oxidation, and nitration adducts, and related glycated, oxidized, and nitrated amino acids (free adducts), for the clinical diagnosis of ASD. Methods: Thirty-eight children with ASD (29 male, 9 female; age 7.6 +/- 2.0 years) and 31 age-matched healthy controls (23 males, 8 females; 8.6 +/- 2.0 years) were recruited for this study. Plasma protein glycation, oxidation, and nitration adducts and amino acid metabolome in plasma and urine were determined by stable isotopic dilution analysis liquid chromatography-tandem mass spectrometry. Machine learning methods were then employed to explore and optimize combinations of analyte data for ASD diagnosis. Results: We found that children with ASD had increased advanced glycation endproducts (AGEs), Nepsilon-carboxymethyl-lysine (CML) and Nomega-carboxymethylarginine (CMA), and increased oxidation damage marker, dityrosine (DT), in plasma protein, with respect to healthy controls. We also found that children with ASD had increased CMA free adduct in plasma ultrafiltrate and increased urinary excretion of oxidation free adducts, alpha-aminoadipic semialdehyde and glutamic semialdehyde. From study of renal handling of amino acids, we found that children with ASD had decreased renal clearance of arginine and CMA with respect to healthy controls. Algorithms to discriminate between ASD and healthy controls gave strong diagnostic performance with features: plasma protein AGEs-CML, CMA-and 3-deoxyglucosone-derived hydroimidazolone, and oxidative damage marker, DT. The sensitivity, specificity, and receiver operating characteristic area-under-the-curve were 92%, 84%, and 0.94, respectively. Conclusions: Changes in plasma AGEs were likely indicative of dysfunctional metabolism of dicarbonyl metabolite precursors of AGEs, glyoxal and 3-deoxyglucosone. DT is formed enzymatically by dual oxidase (DUOX); selective increase of DT as an oxidative damage marker implicates increased DUOX activity in ASD possibly linked to impaired gut mucosal immunity. Decreased renal clearance of arginine and CMA in ASD is indicative of increased arginine transporter activity which may be a surrogate marker of disturbance of neuronal availability of amino acids. Data driven combination of these biomarkers perturbed by proteotoxic stress, plasma protein AGEs and DT, gave diagnostic algorithms of high sensitivity and specificity for ASD.
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2. Frank R, Schulze L, Hellweg R, Koehne S, Roepke S. {{Impaired detection and differentiation of briefly presented facial emotions in adults with high-functioning autism and asperger syndrome}}. {Behaviour research and therapy}. 2018; 104: 7-13.
Although deficits in the recognition of emotional facial expressions are considered a hallmark of autism spectrum disorder (ASD), characterization of abnormalities in the differentiation of emotional expressions (e.g., sad vs. angry) has been rather inconsistent, especially in adults without intellectual impairments who may compensate for their deficits. In addition, previous research neglected the ability to detect emotional expressions (e.g., angry vs. neutral). The present study used a backward masking paradigm to investigate, a) the detection of emotional expressions, and b) the differentiation of emotional expressions in adults diagnosed with high functioning autism or Asperger syndrome (n=23) compared to neurotypical controls (n=25). Compensatory strategies were prevented by shortening the stimulus presentation time (33, 67, and 100ms). In general, participants with ASD were significantly less accurate in detecting and differentiating emotional expressions compared to the control group. In the emotion differentiation task, individuals with ASD profited significantly less from an increase in presentation time. These results reinforce theoretical models that individuals with ASD have deficits in emotion recognition under time constraints. Furthermore, first evidence was provided that emotion detection and emotion differentiation are impaired in ASD.
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3. Krutt H, Dyer L, Arora A, Rollman J, Jozkowski AC. {{PhotoVoice is a feasible method of program evaluation at a center serving adults with autism}}. {Evaluation and program planning}. 2018; 68: 74-80.
The purpose of this small-scale pilot study, was to assess the feasibility of PhotoVoice as a participatory method of program evaluation for the Hussman Center for Adults with Autism (HCAA), a community-based center in greater Baltimore, MD. PhotoVoice is a data collection method that uses photography to give informants, in this case three adults with autism spectrum disorder (ASD), the opportunity to voice their opinions, concerns, and ideas for programs they participate in. This participatory approach serves to empower individuals and communities, and increases the likelihood that the generated information will be used and recommendations will be implemented. Although some challenges to implementation have been described in the literature, PhotoVoice has also been shown to improve the quality and validity of findings. This benefit is especially relevant when targeting feedback from individuals such as those with ASD, whose voices have to date been underrepresented in the literature. In conducting a PhotoVoice pilot study, the researchers sought to determine its effectiveness as a data collection method and to identify potential roadblocks that may affect applicability to a larger study. Collected photographs and feedback allowed for rich analysis and interpretation. Researchers determined that PhotoVoice was a feasible participatory method of program evaluation that highlighted the strengths and capabilities of the community, and could enable informants to have a collaborative role in shaping a program designed to address their needs. Based on the outcomes of this pilot study, it is recommended that PhotoVoice be used in a larger population of adults with ASD.
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4. Lai X, Wu X, Hou N, Liu S, Li Q, Yang T, Miao J, Dong Z, Chen J, Li T. {{Vitamin A Deficiency Induces Autistic-Like Behaviors in Rats by Regulating the RARbeta-CD38-Oxytocin Axis in the Hypothalamus}}. {Molecular nutrition & food research}. 2018; 62(5).
SCOPE: Vitamin A (VA) is an essential nutrient for the development of the brain. We previously found that children with autism spectrum disorder (ASD) have a significant rate of VA deficiency (VAD). In the current study, we aim to determine whether VAD is a risk factor for the generation of autistic-like behaviors via the transcription factor retinoic acid receptor beta (RARbeta)-regulated cluster of differentiation 38 (CD38)-oxytocin (OXT) axis. METHODS AND RESULTS: Gestational VAD or VA supplementation (VAS) rat models are established, and the autistic-like behaviors in the offspring rats are investigated. The different expression levels of RARbeta and CD38 in hypothalamic tissue and serum retinol and OXT concentration are tested. Primary cultured rat hypothalamic neurons are treated with all-trans retinoic acid (atRA), and recombinant adenoviruses carrying the rat RARbeta (AdRARbeta) or RNA interference virus RARbeta-siRNA (siRARbeta) are used to infect neurons to change RARbeta signal. Western blotting, chromatin immunoprecipitation (ChIP), and intracellular Ca(2+) detections are used to investigate the primary regulatory mechanism of RARbeta in the CD38-OXT signaling pathway. We found that gestational VAD increases autistic-like behaviors and decreases the expression levels of hypothalamic RARbeta and CD38 and serum OXT levels in the offspring. VAS ameliorates these autistic-like behaviors and increases the expression levels of RARbeta, CD38, and OXT in the gestational VAD pups. In vitro, atRA increases the Ca(2+) excitability of neurons, which might further promote the release of OXT. Different CD38 levels are induced in the neurons by infection with different RARbeta adenoviruses. Furthermore, atRA enhances the binding of RARbeta to the proximal promoter of CD38, indicating a potential upregulation of CD38 transcriptional activity by RARbeta. CONCLUSIONS: Gestational VAD might be a risk factor for autistic-like behaviors due to the RARbeta signal suppression of CD38 expression in the hypothalamus of the offspring, which improves with VAS during the early-life period. The nutritional status during pregnancy and the early-life period is important in rats.
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5. Neely L, Garcia E, Bankston B, Green A. {{Generalization and maintenance of functional communication training for individuals with developmental disabilities: A systematic and quality review}}. {Res Dev Disabil}. 2018.
BACKGROUND: Functional communication training (FCT) is considered an evidence-based practice for treating problem behavior in individuals with developmental disabilities (e.g. autism, intellectual disabilities, down syndrome, etc.). However, there is little known on how to sustain behavioral change following FCT interventions. This systematic and quality review synthesizes the current literature base evaluating the maintenance and generalization of behavioral effects following FCT. METHOD: A systematic review identified 37 studies that met the pre-set inclusion criteria. Those studies were summarized in terms of: (a) generalization dimension, (b) generalization assessment design, (c) maintenance assessment design, (d) maintenance and generalization teaching strategy, and (e) latency to maintenance probes. All studies employed single-case research designs and were evaluated using the What Works Clearinghouse pilot single-case research standards (Kratochwill et al., 2013) as adapted by Maggin, Briesch, and Chafouleas (2013). Maintenance and generalization data were evaluated using a researcher-developed rubric based on the WWC standards. RESULTS AND DISCUSSION: Results indicate that 30 studies met standards or met standards with reservations while only six studies also met all of the maintenance and generalization standards. Of the six studies, five did not implement any additional strategies beyond the contacting natural contingencies that is inherent in the FCT intervention. Implications for future research and practice are discussed.
