1. Al-Farsi YM, Waly MI, Deth RC, Al-Sharbati MM, Al-Shafaee M, Al-Farsi O, Al-Khaduri MM, Al-Adawi S, Hodgson NW, Gupta I, Ouhtit A. {{Impact of nutrition on serum levels of docosahexaenoic acid among Omani children with autism}}. {Nutrition};2013 (Jun 22)
OBJECTIVES: Autism is a lifelong neurodevelopmental disorder of early childhood. Dietary supplementation of the omega-3 fatty acid (docosahexaenoic acid [DHA]) during prenatal and postnatal life is considered a protective dietary intervention strategy to minimize the risk for autism spectrum disorder (ASD). To our knowledge, no relevant studies have been conducted in the Middle East investigating the status of DHA among children with autism during early childhood. The aim of this study was to investigate the serum levels and dietary intake status of DHA among Omani children recently diagnosed with ASD. METHODS: The present case-control study involved 80 Omani children (<5 y), 40 cases and 40 controls matched for age and sex. A semi-quantitative food frequency questionnaire was used to assess dietary intake of all the participants, while serum levels of DHA were measured using high-performance liquid chromatography. RESULTS: Our results showed that children with ASD had lower dietary consumption of foodstuff containing DHA, as well as lower serum levels of DHA than controls. CONCLUSION: The present finding from Oman supports the view of other studies that there are low serum levels of DHA among children with ASD.
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2. Ghanizadeh A, Sahraeizadeh A, Berk M. {{A Head-to-Head Comparison of Aripiprazole and Risperidone for Safety and Treating Autistic Disorders, a Randomized Double Blind Clinical Trial}}. {Child Psychiatry Hum Dev};2013 (Jun 26)
Aripiprazole and risperidone are the only FDA approved medications for treating irritability in autistic disorder, however there are no head-to-head data comparing these agents. This is the first prospective randomized clinical trial comparing the safety and efficacy of these two medications in patients with autism spectrum disorders. Fifty nine children and adolescents with autism spectrum disorders were randomized to receive either aripiprazole or risperidone for 2 months. The primary outcome measure was change in Aberrant Behavior Checklist (ABC) scores. Adverse events were assessed. Aripiprazole as well as risperidone lowered ABC scores during 2 months. The rates of adverse effects were not significantly different between the two groups. The safety and efficacy of aripiprazole (mean dose 5.5 mg/day) and risperidone (mean dose 1.12 mg/day) were comparable. The choice between these two medications should be on the basis of clinical equipoise considering the patient’s preference and clinical profile.
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3. Griesi-Oliveira K, Sunaga DY, Alvizi L, Vadasz E, Passos-Bueno MR. {{Stem Cells as a Good Tool to Investigate Dysregulated Biological Systems in Autism Spectrum Disorders}}. {Autism Res};2013 (Jun 25)
Identification of the causes of autism spectrum disorders (ASDs) is hampered by their genetic heterogeneity; however, the different genetic alterations leading to ASD seem to be implicated in the disturbance of common molecular pathways or biological processes. In this scenario, the search for differentially expressed genes (DEGs) between ASD patients and controls is a good alternative to identify the molecular etiology of such disorders. Here, we employed genome-wide expression analysis to compare the transcriptome of stem cells of human exfoliated deciduous teeth (SHEDs) of idiopathic autistic patients (n = 7) and control samples (n = 6). Nearly half of the 683 identified DEGs are expressed in the brain (P = 0.003), and a significant number of them are involved in mechanisms previously associated with ASD such as protein synthesis, cytoskeleton regulation, cellular adhesion and alternative splicing, which validate the use of SHEDs to disentangle the causes of autism. Autistic patients also presented overexpression of genes regulated by androgen receptor (AR), and AR itself, which in turn interacts with CHD8 (chromodomain helicase DNA binding protein 8), a gene recently shown to be associated with the cause of autism and found to be upregulated in some patients tested here. These data provide a rationale for the mechanisms through which CHD8 leads to these diseases. In summary, our results suggest that ASD share deregulated pathways and revealed that SHEDs represent an alternative cell source to be used in the understanding of the biological mechanisms involved in the etiology of ASD. Autism Res 2013, : -. (c) 2013 International Society for Autism Research, Wiley Periodicals, Inc.
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4. Komeda H, Kosaka H, Saito DN, Inohara K, Munesue T, Ishitobi M, Sato M, Okazawa H. {{Episodic memory retrieval for story characters in high-functioning autism}}. {Mol Autism};2013 (Jun 24);4(1):20.
BACKGROUND: The objective of this study was to examine differences in episodic memory retrieval between individuals with autism spectrum disorder (ASD) and typically developing (TD) individuals. Previous studies have shown that personality similarities between readers and characters facilitated reading comprehension. Highly extraverted participants read stories featuring extraverted protagonists more easily and judged the outcomes of such stories more rapidly than did less extraverted participants. Similarly, highly neurotic participants judged the outcomes of stories with neurotic protagonists more rapidly than did participants with low levels of neuroticism. However, the impact of the similarity effect on memory retrieval remains unclear. This study tested our ‘similarity hypothesis’, namely that memory retrieval is enhanced when readers with ASD and TD readers read stories featuring protagonists with ASD and with characteristics associated with TD individuals, respectively. METHODS: Eighteen Japanese individuals (one female) with high-functioning ASD (aged 17 to 40 years) and 17 age- and intelligence quotient (IQ)-matched Japanese (one female) TD participants (aged 22 to 40 years) read 24 stories; 12 stories featured protagonists with ASD characteristics, and the other 12 featured TD protagonists. Participants read a single sentence at a time and pressed a spacebar to advance to the next sentence. After reading all 24 stories, they were asked to complete a recognition task about the target sentence in each story. RESULTS: To investigate episodic memory in ASD, we analyzed encoding based on the reading times for and readability of the stories and retrieval processes based on the accuracy of and response times for sentence recognition. Although the results showed no differences between ASD and TD groups in encoding processes, they did reveal inter-group differences in memory retrieval. Although individuals with ASD demonstrated the same level of accuracy as did TD individuals, their patterns of memory retrieval differed with respect to response times. CONCLUSIONS: Individuals with ASD more effectively retrieved ASD-congruent than ASD-incongruent sentences, and TD individuals retrieved stories with TD more effectively than stories with ASD protagonists. Thus, similarity between reader and story character had different effects on memory retrieval in the ASD and TD groups.
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5. Lahiri DK, Sokol DK, Erickson C, Ray B, Ho CY, Maloney B. {{Autism as early neurodevelopmental disorder: evidence for an sAPPalpha-mediated anabolic pathway}}. {Front Cell Neurosci};2013;7:94.
Autism is a neurodevelopmental disorder marked by social skills and communication deficits and interfering repetitive behavior. Intellectual disability often accompanies autism. In addition to behavioral deficits, autism is characterized by neuropathology and brain overgrowth. Increased intracranial volume often accompanies this brain growth. We have found that the Alzheimer’s disease (AD) associated amyloid-beta precursor protein (APP), especially its neuroprotective processing product, secreted APP alpha, is elevated in persons with autism. This has led to the « anabolic hypothesis » of autism etiology, in which neuronal overgrowth in the brain results in interneuronal misconnections that may underlie multiple autism symptoms. We review the contribution of research in brain volume and of APP to the anabolic hypothesis, and relate APP to other proteins and pathways that have already been directly associated with autism, such as fragile X mental retardation protein, Ras small GTPase/extracellular signal-regulated kinase, and phosphoinositide 3 kinase/protein kinase B/mammalian target of rapamycin. We also present additional evidence of magnetic resonance imaging intracranial measurements in favor of the anabolic hypothesis. Finally, since it appears that APP’s involvement in autism is part of a multi-partner network, we extend this concept into the inherently interactive realm of epigenetics. We speculate that the underlying molecular abnormalities that influence APP’s contribution to autism are epigenetic markers overlaid onto potentially vulnerable gene sequences due to environmental influence.
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6. Mathersul D, McDonald S, Rushby JA. {{Understanding advanced theory of mind and empathy in high-functioning adults with autism spectrum disorder}}. {J Clin Exp Neuropsychol};2013 (Jun 25)
It has been argued that higher functioning individuals with autism spectrum disorders (ASDs) have specific deficits in advanced but not simple theory of mind (ToM), yet the questionable ecological validity of some tasks reduces the strength of this assumption. The present study employed The Awareness of Social Inference Test (TASIT), which uses video vignettes to assess comprehension of subtle conversational inferences (sarcasm, lies/deception). Given the proposed relationships between advanced ToM and cognitive and affective empathy, these associations were also investigated. As expected, the high-functioning adults with ASDs demonstrated specific deficits in comprehending the beliefs, intentions, and meaning of nonliteral expressions. They also had significantly lower cognitive and affective empathy. Cognitive empathy was related to ToM and group membership whereas affective empathy was only related to group membership.
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7. Mazefsky CA, Herrington J, Siegel M, Scarpa A, Maddox BB, Scahill L, White SW. {{The role of emotion regulation in autism spectrum disorder}}. {J Am Acad Child Adolesc Psychiatry};2013 (Jul);52(7):679-688.
OBJECTIVE: Autism spectrum disorder (ASD) is associated with amplified emotional responses and poor emotional control, but little is known about the underlying mechanisms. This article provides a conceptual and methodologic framework for understanding compromised emotion regulation (ER) in ASD. METHOD: After defining ER and related constructs, methods to study ER were reviewed with special consideration on how to apply these approaches to ASD. Against the backdrop of cognitive characteristics in ASD and existing ER theories, available research was examined to identify likely contributors to emotional dysregulation in ASD. RESULTS: Little is currently known about ER in youth with ASD. Some mechanisms that contribute to poor ER in ASD may be shared with other clinical populations (e.g., physiologic arousal, degree of negative and positive affect, alterations in the amygdala and prefrontal cortex), whereas other mechanisms may be more unique to ASD (e.g., differences in information processing/perception, cognitive factors [e.g., rigidity], less goal-directed behavior and more disorganized emotion in ASD). CONCLUSIONS: Although assignment of concomitant psychiatric diagnoses is warranted in some cases, poor ER may be inherent in ASD and may provide a more parsimonious conceptualization for the many associated socioemotional and behavioral problems in this population. Further study of ER in youth with ASD may identify meaningful subgroups of patients and lead to more effective individualized treatments.
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8. Nurmi EL, Spilman SL, Whelan F, Scahill LL, Aman MG, McDougle CJ, Arnold LE, Handen B, Johnson C, Sukhodolsky DG, Posey DJ, Lecavalier L, Stigler KA, Ritz L, Tierney E, Vitiello B, McCracken JT. {{Moderation of antipsychotic-induced weight gain by energy balance gene variants in the RUPP autism network risperidone studies}}. {Transl Psychiatry};2013;3:e274.
Second-generation antipsychotic exposure, in both children and adults, carries significant risk for excessive weight gain that varies widely across individuals. We queried common variation in key energy balance genes (FTO, MC4R, LEP, CNR1, FAAH) for their association with weight gain during the initial 8 weeks in the two NIMH Research Units on Pediatric Psychopharmacology Autism Network trials (N=225) of risperidone for treatment of irritability in children/adolescents aged 4-17 years with autism spectrum disorders. Variants in the cannabinoid receptor (CNR)-1 promoter (P=1.0 x 10-6), CNR1 (P=9.6 x 10-5) and the leptin (LEP) promoter (P=1.4 x 10-4) conferred robust-independent risks for weight gain. A model combining these three variants was highly significant (P=1.3 x 10-9) with a 0.85 effect size between lowest and highest risk groups. All results survived correction for multiple testing and were not dependent on dose, plasma level or ethnicity. We found no evidence for association with a reported functional variant in the endocannabinoid metabolic enzyme, fatty acid amide hydrolase, whereas body mass index-associated single-nucleotide polymorphisms in FTO and MC4R showed only trend associations. These data suggest a substantial genetic contribution of common variants in energy balance regulatory genes to individual antipsychotic-associated weight gain in children and adolescents, which supersedes findings from prior adult studies. The effects are robust enough to be detected after only 8 weeks and are more prominent in this largely treatment naive population. This study highlights compelling directions for further exploration of the pharmacogenetic basis of this concerning multifactorial adverse event.
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9. Parsons S, Kasari C. {{Schools at the centre of educational research in autism: possibilities, practices and promises}}. {Autism};2013 (May);17(3):251-253.
10. Wong CS. {{A play and joint attention intervention for teachers of young children with autism: a randomized controlled pilot study}}. {Autism};2013 (May);17(3):340-357.
The aim of this study was to pilot test a classroom-based intervention focused on facilitating play and joint attention for young children with autism in self-contained special education classrooms. Thirty-three children with autism between the ages of 3 and 6 years participated in the study with their classroom teachers (n = 14). The 14 preschool special education teachers were randomly assigned to one of three groups: (1) symbolic play then joint attention intervention, (2) joint attention then symbolic intervention, and (3) wait-list control period then further randomized to either group 1 or group 2. In the intervention, teachers participated in eight weekly individualized 1-h sessions with a researcher that emphasized embedding strategies targeting symbolic play and joint attention into their everyday classroom routines and activities. The main child outcome variables of interest were collected through direct classroom observations. Findings indicate that teachers can implement an intervention to significantly improve joint engagement of young children with autism in their classrooms. Furthermore, multilevel analyses showed significant increases in joint attention and symbolic play skills. Thus, these pilot data emphasize the need for further research and implementation of classroom-based interventions targeting play and joint attention skills for young children with autism.
