1. Castro K, Baronio D, Perry IS, Riesgo RD, Gottfried C. {{The effect of ketogenic diet in an animal model of autism induced by prenatal exposure to valproic acid}}. {Nutr Neurosci};2016 (Feb 9)
OBJECTIVES: Autism spectrum disorder (ASD) is characterized by impairments in social interaction and communication, and by restricted repetitive behaviors and interests. Its etiology is still unknown, but different environmental factors during pregnancy, such as exposure to valproic acid (VPA), are associated with high incidence of ASD in children. In this context, prenatal exposure to VPA in rodents has been used as a reliable model of ASD. Ketogenic diet (KD) is an alternative therapeutic option for refractory epilepsy; however, the effects of this approach in ASD-like behavior need to be evaluated. We conducted a behavioral assessment of the effects of KD in the VPA model of autism. METHODS: Pregnant animals received a single-intraperitoneal injection of 600 mg/kg VPA, and their offspring were separated into four groups: (1) control group with standard diet (C-SD), (2) control group with ketogenic diet (C-KD), (3) VPA group with standard diet (VPA-SD), and (4) VPA group with ketogenic diet (VPA-KD). RESULTS: When compared with the control group, VPA animals presented increased social impairment, repetitive behavior and higher nociceptive threshold. Interestingly, the VPA group fed with KD presented improvements in social behavior. These mice displayed higher scores in sociability index and social novelty index when compared with the SD-fed VPA mice. DISCUSSION: VPA mice chronically exposed to a KD presented behavioral improvements; however, the mechanism by which KD improves ASD-like features needs to be further investigated. In conclusion, the present study reinforces the potential use of KD as a treatment for the core deficits of ASD.
Lien vers le texte intégral (Open Access ou abonnement)
2. Davenport MH, Schaefer TL, Friedmann KJ, Fitzpatrick SE, Erickson CA. {{Pharmacotherapy for Fragile X Syndrome: Progress to Date}}. {Drugs};2016 (Feb 8)
To date, no drug is approved for the treatment of Fragile X Syndrome (FXS) although many drugs are used to manage challenging behaviors from a symptomatic perspective in this population. While our understanding of FXS pathophysiology is expanding, efforts to devise targeted FXS-specific treatments have had limited success in placebo-controlled trials. Compounds aimed at rectifying excessive glutamate and deficient gamma-aminobutyric acid (GABA) neurotransmission, as well as other signaling pathways known to be affected by Fragile X Mental Retardation Protein (FMRP) are under various phases of development in FXS. With the failure of several metabotropic glutamate receptor subtype 5 (mGlur5) selective antagonists under clinical investigation, no clear single treatment appears to be greatly effective. These recent challenges call into question various aspects of clinical study design in FXS. More objective outcome measures are under development and validation. Future trials will likely be aimed at correcting multiple pathways known to be disrupted by the loss of FMRP. This review offers a brief summary of the prevalence, phenotypic characteristics, genetic causes and molecular functions of FMRP in the brain (as these have been extensively reviewed elsewhere), discusses the most recent finding in FXS drug development, and summarizes FXS trials utilizing symptomatic treatment.
Lien vers le texte intégral (Open Access ou abonnement)
3. Derguy C, M’Bailara K, Michel G, Roux S, Bouvard M. {{The Need for an Ecological Approach to Parental Stress in Autism Spectrum Disorders: The Combined Role of Individual and Environmental Factors}}. {J Autism Dev Disord};2016 (Feb 8)
This study aimed to identify parental stress predictors in ASD by considering individual and environmental factors in an ecological approach. Participants were 115 parents of children with ASD aged from 3 to 10 years. Multiple regression analyses were conducted to determine the best predictors of parental stress among child-related, parent-related and environmental factors. Poor quality interactions within the extended family, high levels of expressed emotion and absence of children’s schooling were associated with higher stress, regardless of the child’s age and developmental quotient [F (3) = 37.051; p < 0.001; Adj. R2 = 0.457]. This study highlights the importance of considering environmental factors, specifically family variables, to understand parental stress. These key findings should be considered when designing support programs.
Lien vers le texte intégral (Open Access ou abonnement)
4. Duda M, Ma R, Haber N, Wall DP. {{Use of machine learning for behavioral distinction of autism and ADHD}}. {Transl Psychiatry};2016;6:e732.
Although autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) continue to rise in prevalence, together affecting >10% of today’s pediatric population, the methods of diagnosis remain subjective, cumbersome and time intensive. With gaps upward of a year between initial suspicion and diagnosis, valuable time where treatments and behavioral interventions could be applied is lost as these disorders remain undetected. Methods to quickly and accurately assess risk for these, and other, developmental disorders are necessary to streamline the process of diagnosis and provide families access to much-needed therapies sooner. Using forward feature selection, as well as undersampling and 10-fold cross-validation, we trained and tested six machine learning models on complete 65-item Social Responsiveness Scale score sheets from 2925 individuals with either ASD (n=2775) or ADHD (n=150). We found that five of the 65 behaviors measured by this screening tool were sufficient to distinguish ASD from ADHD with high accuracy (area under the curve=0.965). These results support the hypotheses that (1) machine learning can be used to discern between autism and ADHD with high accuracy and (2) this distinction can be made using a small number of commonly measured behaviors. Our findings show promise for use as an electronically administered, caregiver-directed resource for preliminary risk evaluation and/or pre-clinical screening and triage that could help to speed the diagnosis of these disorders.
Lien vers le texte intégral (Open Access ou abonnement)
5. Fabio RA, Billeci L, Crifaci G, Troise E, Tortorella G, Pioggia G. {{Cognitive training modifies frequency EEG bands and neuropsychological measures in Rett syndrome}}. {Res Dev Disabil};2016 (Feb 6);53-54:73-85.
Rett syndrome (RS) is a childhood neurodevelopmental disorder characterized by a primary disturbance in neuronal development. Neurological abnormalities in RS are reflected in several behavioral and cognitive impairments such as stereotypies, loss of speech and hand skills, gait apraxia, irregular breathing with hyperventilation while awake, and frequent seizures. Cognitive training can enhance both neuropsychological and neurophysiological parameters. The aim of this study was to investigate whether behaviors and brain activity were modified by training in RS. The modifications were assessed in two phases: (a) after a short-term training (STT) session, i.e., after 30min of training and (b) after long-term training (LTT), i.e., after 5 days of training. Thirty-four girls with RS were divided into two groups: a training group (21 girls) who underwent the LTT and a control group (13 girls) that did not undergo LTT. The gaze and quantitative EEG (QEEG) data were recorded during the administration of the tasks. A gold-standard eye-tracker and a wearable EEG equipment were used. Results suggest that the participants in the STT task showed a habituation effect, decreased beta activity and increased right asymmetry. The participants in the LTT task looked faster and longer at the target, and show increased beta activity and decreased theta activity, while a leftward asymmetry was re-established. The overall result of this study indicates a positive effect of long-term cognitive training on brain and behavioral parameters in subject with RS.
Lien vers le texte intégral (Open Access ou abonnement)
6. Odom SL. {{Steve Silberman: NeuroTribes: The Legacy of Autism and the Future of Neurodiversity}}. {J Autism Dev Disord};2016 (Feb 8)
Lien vers le texte intégral (Open Access ou abonnement)
7. Pietropaolo S, Crusio WE, D’Amato F R. {{Treatment Approaches in Rodent Models for Autism Spectrum Disorder}}. {Curr Top Behav Neurosci};2016 (Feb 9)
Recent years have seen an impressive amount of research devoted to the developing of therapies to treat autism spectrum disorder (ASD). This work has been largely based on rodent models, employing a multitude of genetic and environmental manipulations. Unfortunately, the task of identifying suitable treatments for ASD is extremely challenging, due to a variety of problems specific to the research in this field. Here, we first discuss these problems, including (I) the presence of a large variety of rodent models (often without universal consensus on their validity), (II) the difficulties in choosing the most appropriate behavioural markers to assess the efficacy of possible treatments, (III) the limited knowledge we still have of the neurobiological bases of ASD pathology and of its aetiology, and (IV) the complexity of ASD itself, including a highly heterogeneous group of disorders sometimes with markedly different symptoms (therefore unlikely to be treated with the same approaches). Second, we give a critical overview of the most relevant advances in designing treatments for ASD, focusing on the most commonly used animal model, the laboratory mouse. We include pharmacological and non-pharmacological approaches, underlining their specific advantages, but also their current limitations especially in relation to the problems discussed before. Finally, we highlight the theoretical (e.g. the combination of multiple rather than single treatments) and methodological (e.g. use of single-gene mouse models) approaches that seem more promising to us, suggesting various strategies that can be adopted to simplify the complex field of research on treatments for ASD.
Lien vers le texte intégral (Open Access ou abonnement)
8. Quick VB, Davis JM, Olincy A, Sikela JM. {{DUF1220 copy number is associated with schizophrenia risk and severity: implications for understanding autism and schizophrenia as related diseases}}. {Transl Psychiatry};2016;6:e735.
Lien vers le texte intégral (Open Access ou abonnement)
9. Snow M, Donnelly J. {{Factors Mediating Dysphoric Moods and Help Seeking Behaviour Among Australian Parents of Children with Autism}}. {J Autism Dev Disord};2016 (Feb 8)
This study compared levels of state affect, dysphoric mood, and parenting sense of competence in Australian parents of children with or without autism. The effects of personality and location on the parents’ experience were also examined, while controlling for current affect. Possible relationships among personality, location factors and help-seeking behavior were also explored in parents of children with autism. Prior findings of higher dysphoric mood levels in parents of children with autism were supported, as was the positive correlation between dysphoric moods and Neuroticism levels. Parenting Sense of Competence did not differ across locations, and there were no parent type by location interactions. Access to services among parents of a child with autism did not moderate dysphoria levels.
Lien vers le texte intégral (Open Access ou abonnement)
10. Stewart E, Cancilliere MK, Freeman J, Wellen B, Garcia A, Sapyta J, Franklin M. {{Elevated Autism Spectrum Disorder Traits in Young Children with OCD}}. {Child Psychiatry Hum Dev};2016 (Feb 8)
Studies have shown a high prevalence of autistic spectrum traits in both children and adults with psychiatric disorders; however the prevalence rate has not yet been investigated in young children with OCD. The aim of the current study was to (1) determine whether ASD traits indicated by the Social Communication Questionnaire (SCQ) and the Social Responsiveness Scale (SRS) were elevated in young children with OCD who do not have a specific ASD diagnosis and (2) determine if ASD traits were associated with OCD severity. Participants (N = 127) were children ages 5-8 years enrolled in the pediatric obsessive-compulsive disorder treatment study for young children (POTS Jr.). Results indicated that the SRS showed elevated autistic traits in the sample and was associated with OCD severity whereas the SCQ did not indicate heightened ASD symptoms. Implications of these results are discussed.
Lien vers le texte intégral (Open Access ou abonnement)
11. Takahashi T, Yoshimura Y, Hiraishi H, Hasegawa C, Munesue T, Higashida H, Minabe Y, Kikuchi M. {{Enhanced brain signal variability in children with autism spectrum disorder during early childhood}}. {Hum Brain Mapp};2016 (Mar);37(3):1038-1050.
Extensive evidence shows that a core neurobiological mechanism of autism spectrum disorder (ASD) involves aberrant neural connectivity. Recent advances in the investigation of brain signal variability have yielded important information about neural network mechanisms. That information has been applied fruitfully to the assessment of aging and mental disorders. Multiscale entropy (MSE) analysis can characterize the complexity inherent in brain signal dynamics over multiple temporal scales in the dynamics of neural networks. For this investigation, we sought to characterize the magnetoencephalography (MEG) signal variability during free watching of videos without sound using MSE in 43 children with ASD and 72 typically developing controls (TD), emphasizing early childhood to older childhood: a critical period of neural network maturation. Results revealed an age-related increase of brain signal variability in a specific timescale in TD children, whereas atypical age-related alteration was observed in the ASD group. Additionally, enhanced brain signal variability was observed in children with ASD, and was confirmed particularly for younger children. In the ASD group, symptom severity was associated region-specifically and timescale-specifically with reduced brain signal variability. These results agree well with a recently reported theory of increased brain signal variability during development and aberrant neural connectivity in ASD, especially during early childhood. Results of this study suggest that MSE analytic method might serve as a useful approach for characterizing neurophysiological mechanisms of typical-developing and its alterations in ASD through the detection of MEG signal variability at multiple timescales. Hum Brain Mapp 37:1038-1050, 2016. (c) 2015 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.
Lien vers le texte intégral (Open Access ou abonnement)
12. Yoganathan S, Arunachal G, Sudhakar SV, Rajaraman V, Thomas M, Danda S. {{Beta Propellar Protein-Associated Neurodegeneration: A Rare Cause of Infantile Autistic Regression and Intracranial Calcification}}. {Neuropediatrics};2016 (Feb 9)
Neurodegeneration with brain iron accumulation (NBIA) is a heterogeneous group of single gene disorders with distinguished clinical phenotypes and definitive imaging findings. Beta propeller protein-associated neurodegeneration (BPAN) is a subentity of NBIA with X linked dominant inheritance. In this report, we describe a girl with autistic regression, seizures, intracranial calcification, iron accumulation in substantia nigra, and globi pallidi, and diagnosis of BPAN was established based on the identification of previously described disease causing variant in WD repeat domain 45 (WDR45) gene encoding for beta propeller protein. This is the first genetically proven case from India. BPAN is an underrecognized disorder and must be considered as a differential diagnosis in children with atypical Rett features and should be enlisted among the causes for autistic regression and intracranial calcification. Pediatricians must be aware of this rare entity for establishing early diagnosis, prognostication, and genetic counseling. Treatment is usually supportive. More research is needed to explore drugs in the management of BPAN that can facilitate the autophagy and promotes cytoprotection.
