1. {{Partnership Working with Family Carers of People with a Learning Disability and People with AutismPartnership Working with Family Carers of People with a Learning Disability and People with Autism}}. {Nurs Stand}. 2013; 27(52): 28.
Establishing sound working relationships between service users, family carers and paid staff is one of the most crucial aspects to delivering good support.
2. Ajamian M, Rajadhyaksha AM, Alaedini A. {{Autism and Lyme disease–reply}}. {JAMA}. 2013; 310(8): 857.
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3. Bransfield RC, Kuhn M. {{Autism and Lyme disease}}. {JAMA}. 2013; 310(8): 856-7.
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4. Bruno JL, Shelly EW, Quintin EM, Rostami M, Patnaik S, Spielman D, Mayer D, Gu M, Lightbody AA, Reiss AL. {{Aberrant basal ganglia metabolism in fragile X syndrome: a magnetic resonance spectroscopy study}}. {J Neurodev Disord}. 2013; 5(1): 20.
BACKGROUND: The profile of cognitive and behavioral variation observed in individuals with fragile X syndrome (FXS), the most common known cause of inherited intellectual impairment, suggests aberrant functioning of specific brain systems. Research investigating animal models of FXS, characterized by limited or lack of fragile X mental retardation protein, (FMRP), has linked brain dysfunction to deficits in the cholinergic and glutamatergic systems. Thus, we sought to examine in vivo levels of neurometabolites related to cholinergic and glutamatergic functioning in males and females with FXS. METHODS: The study participants included 18 adolescents and young adults with FXS, and a comparison group of 18 individuals without FXS matched for age, sex and general intellectual functioning. Proton magnetic resonance spectroscopy (MRS) was used to assess neurometabolite levels in the caudate nucleus, a region known to be greatly enlarged and involved in abnormal brain circuitry in individuals with FXS. A general linear model framework was used to compare group differences in metabolite concentration. RESULTS: We observed a decrease in choline (P = 0.027) and in glutamate + glutamine (P = 0.032) in the caudate nucleus of individuals with FXS, relative to individuals in the comparison group. CONCLUSIONS: This study provides evidence of metabolite differences in the caudate nucleus, a brain region of potential importance to our understanding of the neural deficits underlying FXS. These metabolic differences may be related to aberrant receptor signaling seen in animal models. Furthermore, identification of the specific neurometabolites involved in FXS dysfunction could provide critical biomarkers for the design and efficacy tracking of disease-specific pharmacological treatments.
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5. Buchovecky CM, Turley SD, Brown HM, Kyle SM, McDonald JG, Liu B, Pieper AA, Huang W, Katz DM, Russell DW, Shendure J, Justice MJ. {{A suppressor screen in Mecp2 mutant mice implicates cholesterol metabolism in Rett syndrome}}. {Nat Genet}. 2013; 45(9): 1013-20.
Mutations in MECP2, encoding methyl CpG-binding protein 2, cause Rett syndrome, the most severe autism spectrum disorder. Re-expressing Mecp2 in symptomatic Mecp2-null mice markedly improves function and longevity, providing hope that therapeutic intervention is possible in humans. To identify pathways in disease pathology for therapeutic intervention, we carried out a dominant N-ethyl-N-nitrosourea (ENU) mutagenesis suppressor screen in Mecp2-null mice and isolated five suppressors that ameliorate the symptoms of Mecp2 loss. We show that a stop codon mutation in Sqle, encoding squalene epoxidase, a rate-limiting enzyme in cholesterol biosynthesis, underlies suppression in one line. Subsequently, we also show that lipid metabolism is perturbed in the brains and livers of Mecp2-null male mice. Consistently, statin drugs improve systemic perturbations of lipid metabolism, alleviate motor symptoms and confer increased longevity in Mecp2 mutant mice. Our genetic screen therefore points to cholesterol homeostasis as a potential target for the treatment of patients with Rett syndrome.
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6. Duffield TC, Trontel HG, Bigler ED, Froehlich A, Prigge MB, Travers B, Green RR, Cariello AN, Cooperrider J, Nielsen J, Alexander A, Anderson J, Fletcher PT, Lange N, Zielinski B, Lainhart J. {{Neuropsychological investigation of motor impairments in autism}}. {J Clin Exp Neuropsychol}. 2013.
It is unclear how standardized neuropsychological measures of motor function relate to brain volumes of motor regions in autism spectrum disorder (ASD). An all-male sample composed of 59 ASD and 30 controls (ages 5-33 years) completed three measures of motor function: strength of grip (SOG), finger tapping test (FTT), and grooved pegboard test (GPT). Likewise, all participants underwent magnetic resonance imaging with region of interest (ROI) volumes obtained to include the following regions: motor cortex (precentral gyrus), somatosensory cortex (postcentral gyrus), thalamus, basal ganglia, cerebellum, and caudal middle frontal gyrus. These traditional neuropsychological measures of motor function are assumed to differ in motor complexity, with GPT requiring the most followed by FTT and SOG. Performance by ASD participants on the GPT and FTT differed significantly from that of controls, with the largest effect size differences observed on the more complex GPT task. Differences on the SOG task between the two groups were nonsignificant. Since more complex motor tasks tap more complex networks, poorer GPT performance by those with ASD may reflect less efficient motor networks. There was no gross pathology observed in classic motor areas of the brain in ASD, as ROI volumes did not differ, but FTT was negatively related to motor cortex volume in ASD. The results suggest a hierarchical motor disruption in ASD, with difficulties evident only in more complex tasks as well as a potential anomalous size-function relation in motor cortex in ASD.
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7. Foxe JJ, Molholm S, Del Bene VA, Frey HP, Russo NN, Blanco D, Saint-Amour D, Ross LA. {{Severe Multisensory Speech Integration Deficits in High-Functioning School-Aged Children with Autism Spectrum Disorder (ASD) and Their Resolution During Early Adolescence}}. {Cereb Cortex}. 2013.
Under noisy listening conditions, visualizing a speaker’s articulations substantially improves speech intelligibility. This multisensory speech integration ability is crucial to effective communication, and the appropriate development of this capacity greatly impacts a child’s ability to successfully navigate educational and social settings. Research shows that multisensory integration abilities continue developing late into childhood. The primary aim here was to track the development of these abilities in children with autism, since multisensory deficits are increasingly recognized as a component of the autism spectrum disorder (ASD) phenotype. The abilities of high-functioning ASD children (n = 84) to integrate seen and heard speech were assessed cross-sectionally, while environmental noise levels were systematically manipulated, comparing them with age-matched neurotypical children (n = 142). Severe integration deficits were uncovered in ASD, which were increasingly pronounced as background noise increased. These deficits were evident in school-aged ASD children (5-12 year olds), but were fully ameliorated in ASD children entering adolescence (13-15 year olds). The severity of multisensory deficits uncovered has important implications for educators and clinicians working in ASD. We consider the observation that the multisensory speech system recovers substantially in adolescence as an indication that it is likely amenable to intervention during earlier childhood, with potentially profound implications for the development of social communication abilities in ASD children.
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8. Gliga T, Senju A, Pettinato M, Charman T, Johnson MH. {{Spontaneous Belief Attribution in Younger Siblings of Children on the Autism Spectrum}}. {Dev Psychol}. 2013.
The recent development in the measurements of spontaneous mental state understanding, employing eye-movements instead of verbal responses, has opened new opportunities for understanding the developmental origin of « mind-reading » impairments frequently described in autism spectrum disorders (ASDs). Our main aim was to characterize the relationship between mental state understanding and the broader autism phenotype, early in childhood. An eye-tracker was used to capture anticipatory looking as a measure of false beliefs attribution in 3-year-old children with a family history of autism (at-risk participants, n = 47) and controls (control participants, n = 39). Unlike controls, the at-risk group, independent of their clinical outcome (ASD, broader autism phenotype or typically developing), performed at chance. Performance was not related to children’s verbal or general IQ, nor was it explained by children « missing out » on crucial information, as shown by an analysis of visual scanning during the task. We conclude that difficulties with using mental state understanding for action prediction may be an endophenotype of autism spectrum disorders. (PsycINFO Database Record (c) 2013 APA, all rights reserved).
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9. Hamilton PJ, Campbell NG, Sharma S, Erreger K, Herborg Hansen F, Saunders C, Belovich AN, Sahai MA, Cook EH, Gether U, McHaourab HS, Matthies HJ, Sutcliffe JS, Galli A. {{De novo mutation in the dopamine transporter gene associates dopamine dysfunction with autism spectrum disorder}}. {Mol Psychiatry}. 2013.
De novo genetic variation is an important class of risk factors for autism spectrum disorder (ASD). Recently, whole-exome sequencing of ASD families has identified a novel de novo missense mutation in the human dopamine (DA) transporter (hDAT) gene, which results in a Thr to Met substitution at site 356 (hDAT T356M). The dopamine transporter (DAT) is a presynaptic membrane protein that regulates dopaminergic tone in the central nervous system by mediating the high-affinity reuptake of synaptically released DA, making it a crucial regulator of DA homeostasis. Here, we report the first functional, structural and behavioral characterization of an ASD-associated de novo mutation in the hDAT. We demonstrate that the hDAT T356M displays anomalous function, characterized as a persistent reverse transport of DA (substrate efflux). Importantly, in the bacterial homolog leucine transporter, substitution of A289 (the homologous site to T356) with a Met promotes an outward-facing conformation upon substrate binding. In the substrate-bound state, an outward-facing transporter conformation is required for substrate efflux. In Drosophila melanogaster, the expression of hDAT T356M in DA neurons-lacking Drosophila DAT leads to hyperlocomotion, a trait associated with DA dysfunction and ASD. Taken together, our findings demonstrate that alterations in DA homeostasis, mediated by aberrant DAT function, may confer risk for ASD and related neuropsychiatric conditions.Molecular Psychiatry advance online publication, 27 August 2013; doi:10.1038/mp.2013.102.
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10. Kendall T, Megnin-Viggars O, Gould N, Taylor C, Burt LR, Baird G. {{Management of autism in children and young people: summary of NICE and SCIE guidance}}. {BMJ}. 2013; 347: f4865.
11. Kotte A, Joshi G, Fried R, Uchida M, Spencer A, Woodworth KY, Kenworthy T, Faraone SV, Biederman J. {{Autistic Traits in Children With and Without ADHD}}. {Pediatrics}. 2013.
OBJECTIVE:To assess the implications of autistic traits (ATs) in youth with attention-deficit/hyperactivity disorder (ADHD) without a diagnosis of autism.METHODS:Participants were youth with (n = 242) and without (n = 227) ADHD and controls without ADHD in whom a diagnosis of autism was exclusionary. Assessment included measures of psychiatric, psychosocial, educational, and cognitive functioning. ATs were operationalized by using the withdrawn + social + thought problems T scores from the Child Behavior Checklist.RESULTS:A positive AT profile was significantly overrepresented among ADHD children versus controls (18% vs 0.87%; P < .001). ADHD children with the AT profile were significantly more impaired than control subjects in psychopathology, interpersonal, school, family, and cognitive domains.CONCLUSIONS:A substantial minority of ADHD children manifests ATs, and those exhibiting ATs have greater severity of illness and dysfunction.
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12. Lv YT, Zhang Y, Liu M, Qiuwaxi JN, Ashwood P, Cho SC, Huan Y, Ge RC, Chen XW, Wang ZJ, Kim BJ, Hu X. {{Transplantation of human cord blood mononuclear cells and umbilical cord-derived mesenchymal stem cells in autism}}. {J Transl Med}. 2013; 11(1): 196.
BACKGROUND: Autism is a pervasive neurodevelopmental disorder. At present there are no defined mechanisms of pathogenesis and therapy is mostly limited to behavioral interventions. Stem cell transplantation may offer a unique treatment strategy for autism due to immune and neural dysregulation observed in this disease. This non-randomized, open-label, single center phase I/II trial investigated the safety and efficacy of combined transplantation of human cord blood mononuclear cells (CBMNCs) and umbilical cord-derived mesenchymal stem cells (UCMSCs) in treating children with autism. METHODS: 37 subjects diagnosed with autism were enrolled into this study and divided into three groups: CBMNC group (14 subjects, received CBMNC transplantation and rehabilitation therapy), Combination group (9 subjects, received both CBMNC and UCMSC transplantation and rehabilitation therapy), and Control group (14 subjects, received only rehabilitation therapy). Transplantations included four stem cell infusions through intravenous and intrathecal injections once a week. Treatment safety was evaluated with laboratory examinations and clinical assessment of adverse effects. The Childhood Autism Rating Scale (CARS), Clinical Global Impression (CGI) scale and Aberrant Behavior Checklist (ABC) were adopted to assess the therapeutic efficacy at baseline (pre-treatment) and following treatment. RESULTS: There were no significant safety issues related to the treatment and no observed severe adverse effects. Statistically significant differences were shown on CARS, ABC scores and CGI evaluation in the two treatment groups compared to the control at 24 weeks post-treatment (p < 0.05). CONCLUSIONS: Transplantation of CBMNCs demonstrated efficacy compared to the control group; however, the combination of CBMNCs and UCMSCs showed larger therapeutic effects than the CBMNC transplantation alone. There were no safety issues noted during infusion and the whole monitoring period.Trial registration: ClinicalTrials.gov: NCT01343511, Title « Safety and Efficacy of Stem Cell Therapy in Patients with Autism ».
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13. Nagy G, Ackerman SL. {{Cholesterol metabolism and Rett syndrome pathogenesis}}. {Nat Genet}. 2013; 45(9): 965-7.
Rett syndrome is caused by mutations in the gene encoding the transcriptional regulator MECP2. A new study demonstrates that cholesterol homeostasis is disrupted in Mecp2 mutant mice and suggests new therapeutic options for this disease.
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14. Neuhaus E, Bernier R, Beauchaine TP. {{Brief Report: Social Skills, Internalizing and Externalizing Symptoms, and Respiratory Sinus Arrhythmia in Autism}}. {J Autism Dev Disord}. 2013.
Theoretical and empirical models describe respiratory sinus arrhythmia (RSA) as a peripheral biomarker of emotion regulation and social competence. Recent findings also link RSA to individual differences in social functioning within autism spectrum disorder (ASD). However, associations between RSA and symptoms of internalizing/externalizing psychopathology in ASD have not been explored. We assessed RSA, social functioning, and internalizing/externalizing symptoms among boys with and without ASD. Compared with controls, participants with ASD evidenced reduced parasympathetic cardiac control, which correlated with social behavior. Symptoms were associated with deficiencies in RSA, over-and-above the contribution of social functioning. These findings yield a more nuanced understanding of parasympathetic function in ASD, and suggest a role for integrative intervention strategies that address socioemotional difficulties.
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15. Sipes M, Matson JL. {{Factor Structure for Autism Spectrum Disorders with Toddlers Using DSM-IV and DSM-5 Criteria}}. {J Autism Dev Disord}. 2013.
With the publication of the Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition, autism spectrum disorders are defined by two symptom clusters (social communication and restricted/repetitive behaviors) instead of the current three clusters. The current study examined the structure of the Baby and Infant Screen for Children with aUtIsm Traits (BISCUIT). First, an exploratory factor analysis was replicated whose results were largely comparable to the previous findings. Then, confirmatory factor analyses compared a two and three factor structure for the BISCUIT. Measures of model fit supported both the two and three factor models relatively well. When directly compared, the three factor model was found to be preferred over the two factor model. Implications are discussed.
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16. Tyson K, Kelley E, Fein D, Orinstein A, Troyb E, Barton M, Eigsti IM, Naigles L, Schultz RT, Stevens M, Helt M, Rosenthal M. {{Language and Verbal Memory in Individuals with a History of Autism Spectrum Disorders Who Have Achieved Optimal Outcomes}}. {J Autism Dev Disord}. 2013.
Some individuals who lose their autism spectrum disorder diagnosis may continue to display subtle weaknesses in language. We examined language and verbal memory in 44 individuals with high-functioning autism (HFA), 34 individuals with « optimal outcomes » (OO) and 34 individuals with typical development (TD). The OO group scored in the average range or above on all measures and showed few differences from the TD group. The HFA group performed within the average range but showed significantly lower mean performance than the other groups on multiple language measures, even when controlling for verbal IQ. Results also indicate that OO individuals show strong language abilities in all areas tested, but that their language may show greater reliance on verbal memory.
