1. Ahn Y, Narous M, Tobias R, Rho JM, Mychasiuk R. {{The Ketogenic Diet Modifies Social and Metabolic Alterations Identified in the Prenatal Valproic Acid Model of Autism Spectrum Disorder}}. {Developmental neuroscience}. 2014 Jul 8.
Autism spectrum disorder (ASD) is a highly prevalent neurodevelopmental disorder characterized by abnormal social interactions, communication deficits and stereotyped or repetitive behaviors. Although the etiology of ASD remains elusive, converging lines of research indicate that mitochondrial dysfunction may play a substantive role in disease pathophysiology. Without an established causal link, the generation of therapeutic targets for ASD has been relatively unsuccessful and has focused solely on individual symptoms. The ketogenic diet (KD) is a high-fat low-carbohydrate diet that has previously been used for the treatment of intractable epilepsy and is known to enhance mitochondrial function. The purpose of this study was to determine if the KD could reverse the social deficits and mitochondrial dysfunction identified in the prenatal valproic acid (VPA) rodent model of ASD. Sprague-Dawley dams were administered VPA or saline on gestational day 12.5. The pups were treated with the KD or their standard diet (SD) for 10 days beginning on postnatal day 21 (PD21). On PD35 juvenile play behavior was tested with the play-fighting paradigm and rats were then sacrificed for mitochondrial bioenergetic analysis. The offspring exposed to VPA prenatally demonstrated a significant decrease in the number of play initiations/attacks and this was reversed with the KD. Prenatal VPA exposure also disrupted the pattern of play responses; VPA/SD animals used complete rotations more often than saline control animals. Treatment with the KD did not affect the number of complete rotations. In addition, while prenatal exposure to VPA altered mitochondrial respiration, the KD was able to restore aspects of bioenergetic dysfunction. As the KD was able to modify complex social behaviors and mitochondrial respiration, it may be a useful treatment option for ASD. Future studies will need to examine the effectiveness of the KD to reverse the two additional core deficits of ASD and to explore various treatment regimens to determine optimal treatment duration and formulation. (c) 2014 S. Karger AG, Basel.
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2. Besterman AD, Wilke SA, Mulligan TE, Allison SC, Hagerman R, Seritan AL, Bourgeois JA. {{Towards an Understanding of Neuropsychiatric Manifestations in Fragile X Premutation Carriers}}. {Future neurology}. 2014 Mar;9(2):227-39.
Fragile X-associated disorders (FXD) are a group of disorders caused by expansion of non-coding CGG repeat elements in the fragile X (FMR1) gene. One of these disorders, fragile X syndrome (FXS), is the most common heritable cause of intellectual disability, and is caused by large CGG repeat expansions (>200) resulting in silencing of the FMR1 gene. An increasingly recognized number of neuropsychiatric FXD have recently been identified that are caused by ‘premutation’ range expansions (55-200). These disorders are characterized by a spectrum of neuropsychiatric manifestations ranging from an increased risk of neurodevelopmental, mood and anxiety disorders to neurodegenerative phenotypes such as the fragile X-associated tremor ataxia syndrome (FXTAS). Here, we review advances in the clinical understanding of neuropsychiatric disorders in premutation carriers across the lifespan and offer guidance for the detection of such disorders by practicing psychiatrists and neurologists.
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3. Caffarelli C, Hayek J, Pitinca MD, Nuti R, Gonnelli S. {{A Comparative Study of Dual-X-ray Absorptiometry and Quantitative Ultrasonography for the Evaluating Bone Status in Subjects with Rett Syndrome}}. {Calcified tissue international}. 2014 Jul 11.
Rett syndrome, an X-linked neurodevelopmental disorder primarily affecting girls, is frequently characterized by a reduced bone mineral density (BMD) with an increased risk of fragility fractures. The aim of the study was to assess bone status by DXA technique and by quantitative ultrasound (QUS) in subjects with Rett syndrome and to evaluate which DXA or QUS parameters better correlate with clinical features. In 156 Rett subjects (mean age 13.6 +/- 8.2 years) and in 62 controls, we measured BMD at femoral neck (BMD-FN) and at total femur (BMD-TF). Apparent volumetric bone mineral density (vBMAD) was also calculated. In all subjects, QUS parameters at phalanges by Bone Profiler-IGEA (amplitude-dependent speed of sound: AD-SoS and bone transmission time: BTT) were evaluated. We found that both DXA parameters and QUS parameters were significantly lower in Rett subjects than in controls. All clinical characteristics were positively correlated to BMD-FN, BMD-TF, AD-SoS, and BTT (p < 0.001) but not with vBMAD-FN. All ultrasonographic parameters were significantly correlated to BMD-FN and BMD-TF, whereas vBMAD-FN showed only positive significant correlation with densitometric parameters (p < 001). In Rett subjects BMD-FN was predicted primarily by weight and movement capacity, whereas vBMAD-FN was predicted by weight, height, and calcium intake. Moreover, AD-SoS was predicted by weight, height, and age, while BTT was predicted only by height. In conclusion, in our study the performance of QUS at phalanges was similar to those of BMD at femur, therefore, both areal BMD at femur and QUS at phalanges (AD-SoS and BTT) may be equally useful in the evaluation of skeletal status in Rett patients.
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4. Carnerero JJ, Perez-Gonzalez LA. {{Induction of naming after observing visual stimuli and their names in children with autism}}. {Research in developmental disabilities}. 2014 Jul 8;35(10):2514-26.
A novel procedure to induce pairing naming, considered the emergence of tacts and selection of pictures after observing names and its corresponding pictures without specific consequences, was probed in 4 persons with autism who lacked this capability with a multiple probe design across participants. Five pictures were selected per set. The participants observed the pictures on a computer screen while the experimenter said the name of the picture. Then, the emission of untaught uninstructed tacts of the pictures was tested without reinforcement. The cycle was repeated until a criterion of 90% correct responses was achieved. Thereafter, in probes without reinforcement, the participants tacted the pictures without specific instructions and also when asked to name them, and selected the correct picture upon hearing their names. The procedure was repeated with two additional stimulus sets and the probed relations emerged always. Two children showed the emergence with fewer trials across sets, which indicate emergence induction. Thus, the procedure served to test whether the pairing naming capability was missing and induced the capability. The results may have important utility in teaching persons diagnosed with autism and other learning difficulties and for accelerating learning in all children.
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5. Hernandez LM, Rudie JD, Green SA, Bookheimer S, Dapretto M. {{Neural Signatures of Autism Spectrum Disorders: Insights into Brain Network Dynamics}}. {Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology}. 2014 Jul 11.
Neuroimaging investigations of Autism Spectrum Disorders (ASDs) have advanced our understanding of atypical brain function and structure, and have recently converged on a model of altered network-level connectivity. Traditional task-based functional magnetic resonance imaging (MRI) and volume-based structural MRI studies have identified widespread atypicalities in brain regions involved in social behavior and other core ASD-related behavioral deficits. More recent advances in MR-neuroimaging methods allow for quantification of brain connectivity using diffusion tensor imaging, functional connectivity, and graph theoretic methods. These newer techniques have moved the field toward a systems-level understanding of ASD etiology, integrating functional and structural measures across distal brain regions. Neuroimaging findings in ASD as a whole have been mixed and at times contradictory, likely due to the vast genetic and phenotypic heterogeneity characteristic of the disorder. Future longitudinal studies of brain development will be crucial to yield insights into mechanisms of disease etiology in ASD subpopulations. Advances in neuroimaging methods and large-scale collaborations will also allow for an integrated approach linking neuroimaging, genetics, and phenotypic data.Neuropsychopharmacology Reviews accepted article preview online, 11 July 2014; doi:10.1038/npp.2014.172.
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6. Nyp SS, Nadler CB, Call CR, Little VC. {{Driven by evidence: diagnosis and treatment for children with autism spectrum disorders}}. {Missouri medicine}. 2014 May-Jun;111(3):195-8.
As the prevalence of autism spectrum disorders increases, practitioners across the state of Missouri face an increasing need to understand and provide evidence-based clinical care for these children and families. We describe the breadth of diagnosis and treatment services offered at Children’s Mercy Hospital (Kansas City, Missouri), one of the designated Missouri Autism Centers, to demonstrate a model of implementation for evidence-based practice. Finally, we discuss relevant clinical considerations and provide resources for physicians to assist in the care and education of their patients.
7. Poliakov E, Koonin EV, Rogozin IB. {{Impairment of translation in neurons as a putative causative factor for autism}}. {Biology direct}. 2014 Jul 10;9(1):16.
BACKGROUND: A dramatic increase in the prevalence of autism and Autistic Spectrum Disorders (ASD) has been observed over the last two decades in USA, Europe and Asia. Given the accumulating data on the possible role of translation in the etiology of ASD, we analyzed potential effects of rare synonymous substitutions associated with ASD on mRNA stability, splicing enhancers and silencers, and codon usage. PRESENTATION OF THE HYPOTHESIS: We hypothesize that subtle impairment of translation, resulting in dosage imbalance of neuron-specific proteins, contributes to the etiology of ASD synergistically with environmental neurotoxins. TESTING THE HYPOTHESIS: A statistically significant shift from optimal to suboptimal codons caused by rare synonymous substitutions associated with ASD was detected whereas no effect on other analyzed characteristics of transcripts was identified. This result suggests that the impact of rare codons on the translation of genes involved in neuron development, even if slight in magnitude, could contribute to the pathogenesis of ASD in the presence of an aggressive chemical background. This hypothesis could be tested by further analysis of ASD-associated mutations, direct biochemical characterization of their effects, and assessment of in vivo effects on animal models. IMPLICATIONS OF THE HYPOTHESIS: It seems likely that the synergistic action of environmental hazards with genetic variations that in themselves have limited or no deleterious effects but are potentiated by the environmental factors is a general principle that underlies the alarming increase in the ASD prevalence.Reviewers: This article was reviewed by Andrey Rzhetsky, Neil R. Smalheiser, and Shamil R. Sunyaev.
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8. Pozo P, Sarria E. {{Prediction of stress in mothers of children with autism spectrum disorders}}. {The Spanish journal of psychology}. 2014 Jan;17:E6.
Raising a child with autism spectrum disorders presents families with exceptional caregiving challenges. Consequently, parents, particularly mothers, evidence unusually high stress levels. Previous research has identified relevant variables that help explain maternal stress: the child’s behavior problems, social support and the sense of coherence (SOC) as a perception of problem. However, there are few longitudinal studies demonstrating how these variables correlate over time. We present a longitudinal study of 21 Spanish mothers of children with autism spectrum disorders (ASD) at two measurement time points over an interval of 4.5 years. Our aims are to examine the predictive relationships of these variables (behavior problems, social support and SOC) to stress and to analyse their changes over time. Data were collected through questionnaires. The results of the regression analysis (multiple adjusted R 2= .45, f2 = .82) highlight the predictive values of SOC (adjusted R 2 = .31) and the initial stress levels (Delta adjusted R 2 = .14) for stress levels 4.5-years later. Our study used t-tests to compare measurements at the two time points; results demonstrate the permanence of stress levels and behavior problems and the effects of reduced social support and increased SOC levels (t(20) = 2.48, p = .02, Cohen’s d = .63; t(20) = -4.22, p < .001, Cohen’ d = .58). Implications for interventions are discussed.
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9. Rivera NR. {{Early childhood music therapy and autism spectrum disorders: Developing potential in young children and their families}}. {Journal of music therapy}. 2014 Spring;51(1):126-9.
