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The article presents an abstract of the study "Cocaine Inhibition of Neuronal Differentiation in NGF-Induced PC12 Cells is Independent of RAS Signaling." The study reports that, cocaine and dopamine affect the NGF signaling downstream or independent of Ras. The research paper for the study would be presented in the 30th Annual Meeting of the American Society for Neurochemistry, on March 14-17, 1999, in New Orleans, Louisiana.

Lay Abstract: Today, children with autism spectrum disorder (ASD) are placed in mainstream or special education settings somewhat arbitrarily with no clear clinical recommendations. Here, we compared changes in core ASD symptoms, as measured by the Autism Diagnostic Observation Schedule, 2nd edition (ADOS-2) clinical assessment, across ASD preschool children placed in special or mainstream education. Longitudinal changes in ADOS-2 scores did not differ significantly across settings over a 1- to 2-year period. While some children improved in core ASD symptoms, others deteriorated in both settings. This highlights the need to identify specific criteria for establishing meaningful placement recommendations.

Lay Abstract: Early intensive applied behaviour analysis-based interventions are designed to support young autistic children's learning and development. Unfortunately, the available evidence about the effectiveness of these interventions remains unclear. Several reviews have focused on the published findings rather than contacting the authors to collect and analyse data about the individual participants in the original studies. Also, most of the studies were carried out by groups involved in delivering the interventions leading to the potential bias in interpreting the results. Our research team (supported by an international advisory group) carried out an independent individual patient data review by collecting the original participant data from the authors of the studies, to examine the effectiveness of these interventions. The results suggested that early intensive applied behaviour analysis-based interventions might lead to some changes in children's cognitive ability (intelligence quotient) and everyday life skills after 2 years, compared with standard treatments. However, all the studies had problems with the way they were designed. Also, few of the studies looked at outcomes that have been described as most important to autistic people or followed children beyond 2 years. We think that further systematic reviews of the existing evidence are unlikely to add to the findings of our review. Furthermore, we recommend that future research should investigate which types of supports and interventions are most effective for children and families, prioritising outcomes measures that are meaningful for the autism community and include, wherever possible, longer-term follow-up.

Internal action models (IAMs) are brain templates for sensory-motor coordination underlying diverse behaviors. An emerging theory suggests that impaired IAMs are a common theme in autism spectrum disorder (ASD). However, whether impaired IAMs occur across sensory systems and how they relate to the major phenotype of ASD, namely impaired social communication, remains unclear. Olfaction relies on an IAM known as the sniff response, where sniff magnitude is automatically modulated to account for odor valence. To test the failed IAM theory in olfaction, we precisely measured the non-verbal non-task-dependent sniff response concurrent with pleasant and unpleasant odors in 36 children--18 with ASD and 18 matched typically developing (TD) controls. We found that whereas TD children generated a typical adult-like sniff response within 305 ms of odor onset, ASD children had a profoundly altered sniff response, sniffing equally regardless of odor valance. This difference persisted despite equal reported odor perception and allowed for 81% correct ASD classification based on the sniff response alone (binomial, p < 0.001). Moreover, increasingly aberrant sniffing was associated with increasingly severe ASD (r = -0.75, p < 0.001), specifically with social (r = -0.72, p < 0.001), but not motor (r < -0.38, p > 0.18), impairment. These results uncover a novel ASD marker implying a mechanistic link between the underpinnings of olfaction and ASD and directly linking an impaired IAM with impaired social abilities., (Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Several studies have suggested that iron deficiency may be related to the pathophysiology of attention deficit hyperactivity disorder (ADHD) due to the role of iron in the production of dopamine and noradrenaline., Objectives: To evaluate the status of iron deficiency in ADHD children, using ferritin levels, a reliable measure of iron storage in body tissue, as an iron status marker, and to investigate a possible correlation between ferritin levels and the diagnosis of ADHD., Methods: The study group included 113 newly referred ADHD children aged 5-15 years (mean age 8.8 +/- 2.7)., Results: Ferritin levels were below 20 ng/ml in 67 children (59%) and above 20 ng/ml in 46 (41%). There was a very low inverse statistical correlation between scores on Conners' Rating Scale and ferritin levels, probably without clinical significance., Conclusions: Our findings suggest that low iron stores may be related to ADHD pathophysiology; therefore, ferritin should be included in the overall evaluation of children with ADHD.

Objective: To examine the relationship between culture and symptoms of comorbid psychopathology in those with autism spectrum disorders (ASD)., Design: Multivariate analyses of variance (MANOVAs) for each country and each sub-scale of the Autism Spectrum Disorders-Comorbid for Children (ASD-CC). Follow-up independent univariate analyses and post-hoc tests as needed., Methods: Separate samples from South Korea, the UK and Israel were compared to a sample from the US in order to examine cultural contributions, using the ASD-CC., Results: Overall, few differences were found. Significantly, the US had significantly higher scores than South Korea on the avoidant sub-scale. Additionally, the US had significantly higher scores than Israel on the over-eating and tantrum sub-scales. No significant differences were found between the US and the UK., Conclusion: Cultural factors, such as views of typical behaviour, should be taken into account when examining symptoms of comorbidity in children with ASD.

In utero cocaine exposure can affect CNS development. Previous studies showed that cocaine inhibits neuronal differentiation in a dose-dependent fashion, in nerve growth factor (NGF)-stimulated PC12 cells, without affecting cell viability. NGF activates intracellular signaling proteins, specific immediate-early genes (IEG) including a transient peak of c-fos expression, and induction of late genes expression, leading to the neuronal phenotype. We hypothesized that cocaine interferes with NGF signaling. Therefore, we examined the pattern of c-fos expression in our cellular model. Time course of c-fos expression up to 72 h was determined in cells treated with NGF 20 ng/ml and cocaine 10 microgram/ml (a moderately toxic level) by RT-PCR analysis. Total RNA was isolated from cells, and levels of c-fos mRNA were estimated using gene-specific primers. In both control and experimental conditions, c-fos level was maximal at 0.5 h. In the control cells, c-fos expression declined rapidly to less than 5% of the 0.5h value, while in the cocaine-treated cells, c-fos level persisted through the 72-h exposure. Adding c-fos antisense to cells treated with NGF and cocaine resulted in significant improvement of neurite out-growth, from 28% (NGF + cocaine) to 89% (NGF + cocaine + c-fos antisense) of control differentiation after 72 h of exposure (Dunnet's T < 3.24). Inhibitory effects of cocaine on NGF-induced PC12 differentiation may be attributed to alteration of c-fos expression. Further studies will be required to examine the role of D1 receptor activation in mediating c-fos expression and to explore the effects of cocaine on other IEGs.