1. {{Autism trainer manual – autism awareness training covering a level 2 qualification unit autism trainer manual – autism awareness training covering a level 2 qualification unit}}. {Nurs Stand}. 2013; 28(3): 28.
Autism probably has more trees lost to the cause of explaining its nature than any other genetic condition. It is a fascinating and tantalising subject, and this suite of training materials captures those aspects well and without using up too much paper.
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2. {{Abstracts of the European Academy of Childhood Disability 25th Annual Meeting. October 1-12, 2013. Newcastle-Gateshead, United Kingdom}}. {Dev Med Child Neurol}. 2013; 55 Suppl 2: 1-66.
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3. Angkustsiri K, Goodlin-Jones B, Deprey L, Brahmbhatt K, Harris S, Simon TJ. {{Social Impairments in Chromosome 22q11.2 Deletion Syndrome (22q11.2DS): Autism Spectrum Disorder or a Different Endophenotype?}}. {J Autism Dev Disord}. 2013.
High prevalence of autism spectrum disorders (ASD) has been reported in 22q11.2DS, although this has been based solely on parent report measures. This study describes the presence of ASD using a procedure more similar to that used in clinical practice by incorporating history (Social Communication Questionnaire) AND a standardized observation measure (Autism Diagnostic Observation Schedule) and suggests that ASD is not as common as previously reported in 22q11.2DS. Differences in methodology, along with comorbid conditions such as anxiety, likely contribute to false elevations in ASD prevalence and information from multiple sources should be included in the evaluation of ASD.
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4. Bagga JS, LA DA. {{Role of conserved cis-regulatory elements in the post-transcriptional regulation of the human MECP2 gene involved in autism}}. {Hum Genomics}. 2013; 7(1): 19.
BACKGROUND: The MECP2 gene codes for methyl CpG binding protein 2 which regulates activities of other genes in the early development of the brain. Mutations in this gene have been associated with Rett syndrome, a form of autism. The purpose of this study was to investigate the role of evolutionarily conserved cis-elements in regulating the post-transcriptional expression of the MECP2 gene and to explore their possible correlations with a mutation that is known to cause mental retardation. RESULTS: A bioinformatics approach was used to map evolutionarily conserved cis-regulatory elements in the transcribed regions of the human MECP2 gene and its mammalian orthologs. Cis-regulatory motifs including G-quadruplexes, microRNA target sites, and AU-rich elements have gained significant importance because of their role in key biological processes and as therapeutic targets. We discovered in the 5[prime]-UTR (untranslated region) of MECP2 mRNA a highly conserved G-quadruplex which overlapped a known deletion in Rett syndrome patients with decreased levels of MeCP2 protein. We believe that this 5[prime]-UTR G-quadruplex could be involved in regulating MECP2 translation. We mapped additional evolutionarily conserved G-quadruplexes, microRNA target sites, and AU-rich elements in the key sections of both untranslated regions. Our studies suggest the regulation of translation, mRNA turnover, and development-related alternative MECP2 polyadenylation, putatively involving interactions of conserved cis-regulatory elements with their respective trans factors and complex interactions among the trans factors themselves. We discovered highly conserved G-quadruplex motifs that were more prevalent near alternative splice sites as compared to the constitutive sites of the MECP2 gene. We also identified a pair of overlapping G-quadruplexes at an alternative 5[prime] splice site that could potentially regulate alternative splicing in a negative as well as a positive way in the MECP2 pre-mRNAs. CONCLUSIONS: A Rett syndrome mutation with decreased protein expression was found to be associated with a conserved G-quadruplex. Our studies suggest that MECP2 post-transcriptional gene expression could be regulated by several evolutionarily conserved cis-elements like G-quadruplex motifs, microRNA target sites, and AU-rich elements. This phylogenetic analysis has provided some interesting and valuable insights into the regulation of the MECP2 gene involved in autism.
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5. Berry-Kravis E, Hessl D, Abbeduto L, Reiss AL, Beckel-Mitchener A, Urv TK. {{Outcome Measures for Clinical Trials in Fragile X Syndrome}}. {J Dev Behav Pediatr}. 2013; 34(7): 508-22.
OBJECTIVE:: Progress in basic neuroscience has led to identification of molecular targets for treatment in fragile X syndrome (FXS) and other neurodevelopmental disorders; however, there is a gap in translation to targeted therapies in humans. One major obstacle to the demonstration of efficacy in human trials has been the lack of generally accepted endpoints to assess improvement in function in individuals with FXS. To address this problem, the National Institutes of Health convened a meeting of leading scientists and clinicians with the goal of identifying and standardizing outcome measures for use as potential endpoints in clinical trials in FXS. METHODS:: Participants in the meeting included FXS experts, experts in the design and implementation of clinical trials and measure development, and representatives from advocacy groups, industry, and federal agencies. RESULTS:: The group generated recommendations for optimal outcome measures in cognitive, behavioral, and biomarker/medical domains, including additional testing and validation of existing measures and development of new measures in areas of need. Although no one endpoint or set of endpoints could be identified that met all criteria as an optimal measure, recommendations are presented in this report. CONCLUSION:: The report is expected to guide the selection of measures in clinical trials and lead to the use of a more consistent battery of measures across trials. Furthermore, this will help to direct research toward gaps in the development of validated FXS-specific outcome measures and to assist with interpretation of clinical trial data by creating templates for measurement of treatment efficacy.
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6. Coury DL. {{DSM-5 and Autism Spectrum Disorders: Implications for Families and Clinicians}}. {J Dev Behav Pediatr}. 2013; 34(7): 494-6.
: Changes in the criteria for autism spectrum disorders in the new Diagnostic and Statistical Manual, fifth edition (DSM-5), have raised concerns among both professionals and the public. This commentary reviews these changes and their implications for families and clinicians.
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7. Franklin AV, King MK, Palomo V, Martinez A, McMahon LL, Jope RS. {{Glycogen Synthase Kinase-3 Inhibitors Reverse Deficits in Long-term Potentiation and Cognition in Fragile X Mice}}. {Biol Psychiatry}. 2013.
BACKGROUND: Identifying feasible therapeutic interventions is crucial for ameliorating the intellectual disability and other afflictions of fragile X syndrome (FXS), the most common inherited cause of intellectual disability and autism. Hippocampal glycogen synthase kinase-3 (GSK3) is hyperactive in the mouse model of FXS (FX mice), and hyperactive GSK3 promotes locomotor hyperactivity and audiogenic seizure susceptibility in FX mice, raising the possibility that specific GSK3 inhibitors may improve cognitive processes. METHODS: We tested if specific GSK3 inhibitors improve deficits in N-methyl-D-aspartate receptor-dependent long-term potentiation at medial perforant path synapses onto dentate granule cells and dentate gyrus-dependent cognitive behavioral tasks. RESULTS: GSK3 inhibitors completely rescued deficits in long-term potentiation at medial perforant path-dentate granule cells synapses in FX mice. Furthermore, synaptosomes from the dentate gyrus of FX mice displayed decreased inhibitory serine-phosphorylation of GSK3beta compared with wild-type littermates. The potential therapeutic utility of GSK3 inhibitors was further tested on dentate gyrus-dependent cognitive behaviors. In vivo administration of GSK3 inhibitors completely reversed impairments in several cognitive tasks in FX mice, including novel object detection, coordinate and categorical spatial processing, and temporal ordering for visual objects. CONCLUSIONS: These findings establish that synaptic plasticity and cognitive deficits in FX mice can be improved by intervention with inhibitors of GSK3, which may prove therapeutically beneficial in FXS.
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8. Galligan MG, Feinstein C, Sulkes SS, Bisagno JM, Stein MT. {{Asperger Syndrome and DSM-5: A Dilemma for a College Freshman}}. {J Dev Behav Pediatr}. 2013; 34(7): 529-32.
CASE: Angela is an 18-year-old college freshman who made an appointment with her pediatrician because of academic and social difficulties at college. She was diagnosed with Asperger disorder at age 6 based on difficulties relating to adults and peers, perseverative patterns of interest, and normal language development.She received special education services in middle school to help follow directions and complete assignments. She reports feeling very isolated during this time. In freshman year of high school, she insisted on discontinuing special education and managed with weekly private individual psychotherapy.In sophomore year, Angela learned strategies to get additional help from her teachers about assignments, and her grades improved. Socially, she formed a close friendship with a classmate who was also on the autistic spectrum, and she found a group of friends through this individual. As a senior with an upward grade trajectory and good SAT scores, she was admitted to a competitive 4-year college. In a precollege consult 6 months ago, she was anxious about fitting in.Angela began college classes without accommodations, but she now describes a challenging semester. She has not made many friends. She finds her courses difficult and does not fully understand assignments. She believes her peers dislike her. She thinks she would benefit from receiving note-taking and other services and asks you to document her disability for the college so that she might obtain accommodations.You point out that the DSM-5 eliminates the Asperger category. Angela is concerned. She does not believe that her profile is consistent with autism spectrum disorder, and she fears that being labeled as autistic will be prejudicial at school. Yet she is worried about retaining eligibility for services on the basis of a disability. How do you counsel her?
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9. Graf-Myles J, Farmer C, Thurm A, Royster C, Kahn P, Soskey L, Rothschild L, Swedo S. {{Dietary adequacy of children with autism compared with controls and the impact of restricted diet}}. {J Dev Behav Pediatr}. 2013; 34(7): 449-59.
OBJECTIVE: Children with autism (AUT) may consume a restricted diet relative to typical peers, whether due to therapeutic measures or sensory sensitivities. The objective of this study was to compare children with AUT with both typically developing (TYP) and developmentally delayed children on nutrient and food group intake and overall diet quality and to evaluate the impact of diet restriction. METHODS: Three-day food records and interview information were analyzed from 69 children with AUT, 14 children with developmental delay, and 37 TYP children, drawn from a larger longitudinal study. RESULTS: Children with AUT did not differ significantly from children with other developmental delays on any dietary measures. Although there were differences in the average intake of some nutrients between AUT and typical controls, only calcium and dairy were also less likely to be consumed in adequate amounts by the AUT group. Intentional diet restriction accounted for most of the differences between AUT and typical controls. On average, all groups had inadequate fiber, vitamin D, and vegetable intake. Inadequate intake of folate, grains, and dairy was noted for the AUT subgroup with intentional diet restrictions. Children in the AUT group not following a restricted diet received significantly worse Healthy Eating Index-2005 scores than those following a restricted diet and typical controls. These differences were not nutritionally significant. CONCLUSIONS: When evaluating nutritional adequacy of children with AUT, special consideration should be given to calcium, folate, dairy, and grains. Diets of all children with AUT should be evaluated for idiosyncratic deficiencies because of unique dietary patterns.
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10. Liu B, Li L, Chen J, Wang Z, Li Z, Wan Q. {{Regulation of GABAA receptors by fragile X mental retardation protein}}. {Int J Physiol Pathophysiol Pharmacol}. 2013; 5(3): 169-76.
Fragile X syndrome (FXS) is caused by the loss of fragile X mental retardation protein (FMRP). The deficiency of GABAA receptors (GABAARs) is implicated in FXS. However, the underlying mechanisms remain unclear. To investigate the effect of FMRP on GABAARs, we transfected FMRP cDNAs in rat cortical neurons. We measured the protein expression of GABAARs and phosphatase PTEN, and recorded GABAAR-mediated whole-cell currents in the transfected neurons. We show that the transfection of FMRP cDNAs causes increased protein expression of GABAARs in cortical neurons, but GABAAR-mediated whole-cell currents are not potentiated by FMRP transfection. These results suggest the possibility that intracellular signaling antagonizing GABAAR activity may play a role in inhibiting GABAAR function in FMRP-transfected neurons. We further show that FMRP transfection results in an enhanced protein expression of PTEN, which contributes to the inhibition of GABAAR function in FMRP-transfected neurons. These results indicate that GABAARs are regulated by FMRP through both an up-regulation of GABAAR expression and a PTEN enhancement-induced inhibition of GABAAR function, suggesting that an abnormal regulation of GABAAR and PTEN by the loss of FMRP underlies the pathogenesis of FXS.
11. Majewska MD, Hill M, Urbanowicz E, Rok-Bujko P, Bienkowski P, Namyslowska I, Mierzejewski P. {{Marked elevation of adrenal steroids, especially androgens, in saliva of prepubertal autistic children}}. {Eur Child Adolesc Psychiatry}. 2013.
Autism is diagnosed on the basis of behavioral manifestations, but its biomarkers are not well defined. A strong gender bias typifying autism (it is 4-5 times more prevalent in males) suggests involvement of steroid hormones in autism pathobiology. In order to evaluate the potential roles of such hormones in autism, we compared the salivary levels of 22 steroids in prepubertal autistic male and female children from two age groups (3-4 and 7-9 years old) with those in healthy controls. The steroids were analyzed using gas chromatography-mass spectrometry and radioimmunoassay. Statistical analysis (ANOVA) revealed that autistic children had significantly higher salivary concentrations of many steroid hormones (both C21 and C19) than control children. These anomalies were more prominent in older autistic children and in boys. The levels of androgens (androstenediol, dehydroepiandrosterone, androsterone and their polar conjugates) were especially increased, indicative of precocious adrenarche and predictive of early puberty. The concentrations of the steroid precursor, pregnenolone, and of several pregnanolones were also higher in autistic than in healthy children, but cortisol levels were not different. Some steroids, whose levels are raised in autism (allopregnanolone, androsterone, pregnenolone, dehydroepiandrosterone and their sulfate conjugates) are neuroactive and modulate GABA, glutamate, and opioid neurotransmission, affecting brain development and functioning. These steroids may contribute to autism pathobiology and symptoms such as elevated anxiety, sleep disturbances, sensory deficits, and stereotypies among others. We suggest that salivary levels of selected steroids may serve as biomarkers of autism pathology useful for monitoring the progress of therapy.
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12. Rattaz C, Dubois A, Michelon C, Viellard M, Poinso F, Baghdadli A. {{How do children with autism spectrum disorders express pain? A comparison with developmentally delayed and typically developing children}}. {Pain}. 2013; 154(10): 2007-13.
There is a lack of knowledge about pain reactions in children with autism spectrum disorders (ASD), who have often been considered as insensitive to pain. The objective of this study was to describe the facial, behavioral and physiological reactions of children with ASD during venipuncture and to compare them to the reactions of children with an intellectual disability and nonimpaired control children. We also examined the relation between developmental age and pain reactions. The sample included 35 children with ASD, 32 children with an intellectual disability, and 36 nonimpaired children. The children were videotaped during venipuncture and their heart rate was recorded. Facial reactions were assessed using the Child Facial Coding System (CFCS) and behavioral reactions were scored using the Noncommunicating Children’s Pain Checklist (NCCPC). A linear mixed-effects model showed that children’s reactions increased between baseline and venipuncture and decreased between the end of venipuncture and the recovery period. There was no significant difference between groups regarding the amount of facial, behavioral and physiological reactions. However, behavioral reactions seemed to remain high in children with ASD after the end of the venipuncture, in contrast with children in the 2 other groups. Moreover, we observed a significant decrease in pain expression with age in nonimpaired children, but no such effect was found regarding children with ASD. The data reveal that children with ASD displayed a significant pain reaction in this situation and tend to recover more slowly after the painful experience. Improvement in pain assessment and management in this population is necessary.
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13. Wang J, Barstein J, Ethridge LE, Mosconi MW, Takarae Y, Sweeney JA. {{Resting state EEG abnormalities in autism spectrum disorders}}. {J Neurodev Disord}. 2013; 5(1): 24.
Autism spectrum disorders (ASD) are a group of complex and heterogeneous developmental disorders involving multiple neural system dysfunctions. In an effort to understand neurophysiological substrates, identify etiopathophysiologically distinct subgroups of patients, and track outcomes of novel treatments with translational biomarkers, EEG (electroencephalography) studies offer a promising research strategy in ASD. Resting-state EEG studies of ASD suggest a U-shaped profile of electrophysiological power alterations, with excessive power in low-frequency and high-frequency bands, abnormal functional connectivity, and enhanced power in the left hemisphere of the brain. In this review, we provide a summary of recent findings, discuss limitations in available research that may contribute to inconsistencies in the literature, and offer suggestions for future research in this area for advancing the understanding of ASD.
