Cognitive, behavioral and socio-communication skills as predictors of response to Early Start Denver Model: a prospective study in 32 young children with Autism Spectrum Disorder.

Introduction: The effectiveness of early interventions in young autistic children is well established, but there is great interindividual variability in treatment response. Predictors of response to naturalistic developmental behavioral interventions (NDBI), like the Early Start Denver Model (ESDM), are needed. Methods: We conducted an exploratory study to prospectively seek predictors of response in 32 young children treated with ESDM after receiving an ASD diagnosis. All children were less than 39 months old (mean age: 29.7 mo), and received individualized ESDM for nine months. Tests were administered at the beginning, after 4 months, and at the end of treatment. Results: Four children (12.5%) were "strong responders", 8 children (25.0%) were "moderate responders", and 20 children (62.5%) were "poor responders". A more favorable response to ESDM was significantly predicted by higher PEP-3 Expressive Language, Receptive Language, Cognitive Verbal/Preverbal, Visuo-Motor Imitation scores, higher GMDS-ER Personal/Social, and VABS-II Communication scores, by lower ADI-R C restricted/stereotypic behaviors, and by joint attention level. Discussion: Most predictors showed a linear association with increasing response to ESDM, but GMDS-ER Personal-Social and joint attention level predicted strong response, while PEP-3 receptive language equally predicted moderate or strong response. Although larger samples will be necessary to reach definitive conclusions, in conjunction with prior reports our findings begin providing information able to assist clinicians in choosing the most appropriate treatment program for young autistic children.

High-Risk Siblings without Autism: Insights from a Clinical and Eye-Tracking Study.

Joint attention (JA)-the human ability to coordinate our attention with that of other people-is impaired in the early stage of Autism Spectrum Disorder (ASD). However, little is known about the JA skills in the younger siblings of children with ASD who do not develop ASD at 36 months of age [high-risk (HR)-noASD]. In order to advance our understanding of this topic, a prospective multicenter observational study was conducted with three groups of toddlers (age range: 18-33 months): 17 with ASD, 19 with HR-noASD and 16 with typical development (TD). All subjects underwent a comprehensive clinical assessment and an eye-tracking experiment with pre-recorded stimuli in which the visual patterns during two tasks eliciting initiating joint attention (IJA) were measured. Specifically, fixations, transitions and alternating gaze were analyzed. Clinical evaluation revealed that HR-noASD subjects had lower non-verbal cognitive skills than TD children, while similar levels of restricted and repetitive behaviors and better social communication skills were detected in comparison with ASD children. Eye-tracking paradigms indicated that HR-noASD toddlers had visual patterns resembling TD in terms of target-object-to-face gaze alternations, while their looking behaviors were similar to ASD toddlers regarding not-target-object-to-face gaze alternations. This study indicated that high-risk, unaffected siblings displayed a shared profile of IJA-eye-tracking measures with both ASD patients and TD controls, providing new insights into the characterization of social attention in this group of toddlers.

Gut mobilization improves behavioral symptoms and modulates urinary p-cresol in chronically constipated autistic children: A prospective study.

Chronic constipation is common among children with ASD and is associated with more severe hyperactivity, anxiety, irritability, and repetitive behaviors. Young autistic children with chronic constipation display higher urinary, and foecal concentrations of p-cresol, an aromatic compound produced by gut bacteria, known to negatively affect brain function. Acute p-cresol administration to BTBR mice enhances anxiety, hyperactivity and stereotypic behaviors, while blunting social interaction. This study was undertaken to prospectively assess the behavioral effects of gut mobilization in young autistic children with chronic constipation, and to verify their possible correlation with urinary p-cresol. To this aim, 21 chronically constipated autistic children 2-8 years old were evaluated before (T0), 1 month (T1), and 6 months (T2) after intestinal mobilization, recording Bristol stool scale scores, urinary p-cresol concentrations, and behavioral scores for social interaction deficits, stereotypic behaviors, anxiety, and hyperactivity. Gut mobilization yielded a progressive and highly significant decrease in all behavioral symptoms over the 6-month study period. Urinary p-cresol levels displayed variable trends not significantly correlated with changes in behavioral parameters, mainly increasing at T1 and decreasing at T2. These results support gut mobilization as a simple strategy to ameliorate ASD symptoms, as well as comorbid anxiety and hyperactivity, in chronically constipated children. Variation in p-cresol absorption seemingly provides limited contributions, if any, to these behavioral changes. Further research will be needed to address the relative role of reduced abdominal discomfort following mobilization, as compared to specific modifications in microbiome composition and in gut bacteria-derived neuroactive compounds.

FARP-1 deletion is associated with lack of response to autism treatment by early start denver model in a multiplex family.

BACKGROUND: Children with autism spectrum disorder (ASD) display impressive clinical heterogeneity, also involving treatment response. Genetic variants can contribute to explain this large interindividual phenotypic variability. METHODS: Array-CGH (a-CGH) and whole genome sequencing (WGS) were performed on a multiplex family with two small children diagnosed with ASD at 17 and 18 months of age. Both brothers received the same naturalistic intervention for one year according to the Early Start Denver Model (ESDM), applied by the same therapists, yielding dramatically different treatment outcomes. RESULTS: The older sibling came out of the autism spectrum, while the younger sibling displayed very little, in any, improvement. This boy was subsequently treated applying a structured Early Intensive Behavioral Intervention paired with Augmentative Alternative Communication, which yielded a partial response within another year. The ESDM nonresponsive child carries a novel maternally inherited 65 Kb deletion at chr. 13q32.2 spanning FARP1. Farp1 is a synaptic scaffolding protein, which plays a significant role in neural plasticity. CONCLUSION: These results represent a paradigmatic example of the heuristic potential of genetic markers in predicting treatment response and possibly in supporting the targeted prescription of specific early intervention approaches.

How Attention to Faces and Objects Changes Over Time in Toddlers with Autism Spectrum Disorders: Preliminary Evidence from An Eye Tracking Study.

Further understanding of the longitudinal changes in visual pattern of toddlers with autism spectrum disorders (ASDs) is needed. We examined twelve 19 to 33-month-old toddlers at their first diagnosis (mean age: 25.1 months) and after six months (mean age: 31.7 months) during two initiating joint attention (IJA) tasks using eye tracking. Results were compared with the performance of age-matched typically developing (TD) toddlers evaluated at a single time-point. Autistic toddlers showed longitudinal changes in the visual sensory processing of the IJA tasks, approaching TD performance with an improvement in the ability to disengage and to explore the global space. Findings suggest the use of eye tracking technology as an objective, non-intrusive, adjunctive tool to measure outcomes in toddlers with ASD.

A Comparison between Children with ADHD and Children with Epilepsy in Self-Esteem and Parental Stress Level.

Attention-deficit/hyperactivity disorder (ADHD) is frequently associated with negative psychological outcomes. This study explores the relationship between self-esteem, ADHD symptoms and parental stress. It compares children with ADHD, children with epilepsy (E) and typical developmental controls (TD). Participants included 65 children (aged 9-12 yrs) and their parents. The assessment was conducted by Multidimensional Self-Concept Scale (MSCS), Parent Stress Index (PSI) and Conners' Parent Rating Scales-Revised. Significant differences were found in Social, Competence and Academic areas of self-esteem between children with ADHD, with E and TD. Moreover, parents of children with ADHD showed a higher overall stress than both other groups. In conclusion, it seems important to evaluate the psychological aspects of ADHD con-dition, both in children and in parents, in order to suggest an individual multimodal treatment.