1. Alonso Canal L, Isasi Zaragoza C, Colmenero Blanco I, Martinez Gomez MJ, Arcas Martinez J. {{[Clinical features suggesting autism spectrum disorder as a manifestation of non-celiac gluten sensitivity.]}}. {An Pediatr (Barc)}. 2014.
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2. Ben-David E, Shohat S, Shifman S. {{Allelic expression analysis in the brain suggests a role for heterogeneous insults affecting epigenetic processes in autism spectrum disorders}}. {Hum Mol Genet}. 2014.
Monoallelic expression, including genomic imprinting, X-chromosome inactivation and random monoallelic expression of autosomal genes are epigenetic phenomena. Genes that are expressed in a monoallelic way may be more vulnerable to genetic or epigenetic mutations. Thus, comprehensive exploration of monoallelic expression in human brains may shed light on complex brain disorders. Autism-related disorders are known to be associated with imprinted genes on chromosome 15. However, it is not clear if other imprinted regions or other types of monoallelic expression are associated with autism spectrum disorder (ASD). Here, we performed a genome-wide survey of allele expression imbalance (AEI) in the human brain using single nucleotide polymorphisms (SNPs), in 18 individuals with ASD and 15 controls. Individuals with ASD had the most extreme number of monoallelic expressed SNPs in both the autosomes and the X chromosome. In two cases that were studied in detail the monoallelic expression was confined to specific brain region or cell type. Using these data we were also able to define the allelic expression status of known imprinted genes in the human brain, and to identify abnormal imprinting in an individual with ASD. Lastly, we developed an analysis of individual level expression, focusing on the difference of each individual from the mean. We found that individuals with ASD had more genes that were up or down-regulated in an individual-specific manner. We also identified pathways perturbed in specific individuals. These results underline the heterogeneity in gene regulation in ASD, at the level of both allelic and total expression.
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3. Bottema-Beutel K, Yoder PJ, Hochman JM, Watson LR. {{The Role of Supported Joint Engagement and Parent Utterances in Language and Social Communication Development in Children with Autism Spectrum Disorder}}. {J Autism Dev Disord}. 2014.
This study examined associations between three parent-child engagement states and social communication, expressive language, and receptive language at 8 month follow-up, in 63 preschool-age children with autism spectrum disorder. We extend the literature on supported joint engagement by dividing this state into higher order (HSJE) and lower order types, with HSJE involving greater reciprocity in toy play. We also examined parents’ follow-in utterances that co-occurred with each state. We found that only HSJE predicts later social communication and expressive language, while object engagement predicts receptive language. HSJE combined with follow-in utterances (HSJE+FI) predicts all three outcomes when controlling for HSJE+FI in other engagement states. When controlling for total HSJE, HSJE+FI is predictive of receptive language.
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4. Brown-Lavoie SM, Viecili MA, Weiss JA. {{Sexual Knowledge and Victimization in Adults with Autism Spectrum Disorders}}. {J Autism Dev Disord}. 2014.
There is a significant gap in understanding the risk of sexual victimization in individuals with autism spectrum disorders (ASD) and the variables that contribute to risk. Age appropriate sexual interest, limited sexual knowledge and experiences, and social deficits, may place adults with ASD at increased risk. Ninety-five adults with ASD and 117 adults without ASD completed questionnaires regarding sexual knowledge sources, actual knowledge, perceived knowledge, and sexual victimization. Individuals with ASD obtained less of their sexual knowledge from social sources, more sexual knowledge from non-social sources, had less perceived and actual knowledge, and experienced more sexual victimization than controls. The increased risk of victimization by individuals with ASD was partially mediated by their actual knowledge. The link between knowledge and victimization has important clinical implications for interventions.
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5. Greydanus DE, Truba N, Pratt HD. {{Asperger syndrome in young adulthood: the physician as supportive coach and medical advisor}}. {Adolesc Med State Art Rev}. 2013; 24(3): 629-42.
6. Han S, Tai C, Jones CJ, Scheuer T, Catterall WA. {{Enhancement of Inhibitory Neurotransmission by GABAA Receptors Having alpha2,3-Subunits Ameliorates Behavioral Deficits in a Mouse Model of Autism}}. {Neuron}. 2014; 81(6): 1282-9.
Autism spectrum disorder (ASD) may arise from increased ratio of excitatory to inhibitory neurotransmission in the brain. Many pharmacological treatments have been tested in ASD, but only limited success has been achieved. Here we report that BTBR T(+)Itpr3(tf)/J (BTBR) mice, a model of idiopathic autism, have reduced spontaneous GABAergic neurotransmission. Treatment with low nonsedating/nonanxiolytic doses of benzodiazepines, which increase inhibitory neurotransmission through positive allosteric modulation of postsynaptic GABAA receptors, improved deficits in social interaction, repetitive behavior, and spatial learning. Moreover, negative allosteric modulation of GABAA receptors impaired social behavior in C57BL/6J and 129SvJ wild-type mice, suggesting that reduced inhibitory neurotransmission may contribute to social and cognitive deficits. The dramatic behavioral improvement after low-dose benzodiazepine treatment was subunit specific-the alpha2,3-subunit-selective positive allosteric modulator L-838,417 was effective, but the alpha1-subunit-selective drug zolpidem exacerbated social deficits. Impaired GABAergic neurotransmission may contribute to ASD, and alpha2,3-subunit-selective positive GABAA receptor modulation may be an effective treatment.
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7. Johnson CR, Turner K, Stewart PA, Schmidt B, Shui A, Macklin E, Reynolds A, James J, Johnson SL, Manning Courtney P, Hyman SL. {{Relationships Between Feeding Problems, Behavioral Characteristics and Nutritional Quality in Children with ASD}}. {J Autism Dev Disord}. 2014.
Many children with autism spectrum disorders (ASD) have co-occurring feeding problems. However, there is limited knowledge about how these feeding habits are related to other behavioral characteristics ubiqitious in ASD. In a relatively large sample of 256 children with ASD, ages 2-11, we examined the relationships between feeding and mealtime behaviors and social, communication, and cognitive levels as well repetitive and ritualistic behaviors, sensory behaviors, and externalizing and internalizing behaviors. Finally, we examined whether feeding habits were predictive of nutritional adequacy. In this sample, we found strong associations between parent reported feeding habits and (1) repetitive and ritualistic behaviors, (2) sensory features, and (3) externalizing and internalizing behavior. There was a lack of association between feeding behaviors and the social and communication deficits of ASD and cognitive levels. Increases in the degree of problematic feeding behaviors predicted decrements in nutritional adequacy.
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8. Lee J, Spratling R. {{Care of Gastrostomy Feeding Tube in Children With Developmental Disabilities}}. {Rehabil Nurs}. 2014.
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9. Lerna A, Esposito D, Conson M, Massagli A. {{Long-term effects of PECS on social-communicative skills of children with autism spectrum disorders: a follow-up study}}. {Int J Lang Commun Disord}. 2014.
BACKGROUND: The Picture Exchange Communication System (PECS) is a popular augmentative communication system frequently used with ‘nonverbal’ children with autism. Several studies suggested that PECS could represent an effective tool for promoting improvement of several social-communicative skills. Only sparse evidence is instead available on the long-term effectiveness of this treatment system. AIMS: To test the long-term effects of PECS, for which a follow-up study was conducted by assessing social-communicative skills in nonverbal preschool children with autism after 12 months from treatment completion. METHODS & PROCEDURES: Two groups of children (N = 14) were assessed; one group had completed the PECS training and the other conventional language therapy (CLT). At follow-up all children received the same pre- and post-treatment assessment. Outcome measures were the following: Communication and Social domains of Autism Diagnostic Observation Schedule (ADOS); Language and Personal-Social subscales of the Griffiths’ Mental Developmental Scales (GMDS); Communication and Social Abilities domains of the Vineland Adaptive Behavior Scales (VABS); and several social-communicative variables coded in an unstructured setting. OUTCOMES & RESULTS: The PECS group showed significant improvements compared with the CLT group on ADOS severity scores (Communication, Social and Total), on GMDS Social domain and on VABS Communication and Social domains. PECS-related gains on the VABS Social domain and on specific social-communicative measures coded during free-play, i.e. frequency of joint attention and initiation, and duration of cooperative play, were stable after 1-year follow-up. Cooperative play continued to improve on follow-up with respect to both post- and pre-treatment assessment. CONCLUSIONS & IMPLICATIONS: These findings demonstrated that PECS training can promote long-term enhancement of specific socio-communicative skills in children with autism.
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10. Marrale M, Albanese NN, Cali F, Romano V. {{Assessing the Impact of Copy Number Variants on miRNA Genes in Autism by Monte Carlo Simulation}}. {PLoS One}. 2014; 9(3): e90947.
Autism Spectrum Disorders (ASDs) are childhood neurodevelopmental disorders with complex genetic origins. Previous studies have investigated the role of de novo Copy Number Variants (CNVs) and microRNAs as important but distinct etiological factors in ASD. We developed a novel computational procedure to assess the potential pathogenic role of microRNA genes overlapping de novo CNVs in ASD patients. Here we show that for chromosomes # 1, 2 and 22 the actual number of miRNA loci affected by de novo CNVs in patients was found significantly higher than that estimated by Monte Carlo simulation of random CNV events. Out of 24 miRNA genes over-represented in CNVs from these three chromosomes only hsa-mir-4436b-1 and hsa-mir-4436b-2 have not been detected in CNVs from non-autistic subjects as reported in the Database of Genomic Variants. Altogether the results reported in this study represent a first step towards a full understanding of how a dysregulated expression of the 24 miRNAs genes affect neurodevelopment in autism. We also propose that the procedure used in this study can be effectively applied to CNVs/miRNA genes association data in other genomic disorders beyond autism.
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11. Nah YH, Young RL, Brewer N. {{Using the Autism Detection in Early Childhood (ADEC) and Childhood Autism Rating Scales (CARS) to Predict Long Term Outcomes in Children with Autism Spectrum Disorders}}. {J Autism Dev Disord}. 2014.
This study evaluated the predictive validity of the Autism Detection in Early Childhood (ADEC; Young, Autism detection in early childhood: ADEC. Australian Council of Educational Research, Camberwell, VIC 2007) and a well-established screening tool, the Childhood Autism Rating Scale (CARS; Schopler et al. The childhood autism rating scale (CARS). Western Psychological Services, Los Angeles 1988), for long term outcomes of children with ASD engaged in an early intervention program. Participants were 55 children (44 male, 11 female) aged 19-42 months (M = 33.5, SD = 5.6) at initial assessment who were followed up 2 and 6 years after their initial assessment. The ADEC and the CARS performed similarly when predicting long term outcomes such as clinical diagnostic outcome and overall adaptive functioning level. However, only the ADEC score was significantly correlated with ASD symptom severity at the 6-year follow up. Although these findings need to be replicated with additional and larger samples, this study extends our understanding of the psychometric properties of both the ADEC and the CARS.
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12. Olli J, Vehkakoski T, Salantera S. {{The habilitation nursing of children with developmental disabilities-Beyond traditional nursing practices and principles?}}. {Int J Qual Stud Health Well-being}. 2014; 9: 23106.
Research-based descriptions of the contents of the habilitation nursing of children with developmental disabilities are lacking. The objective of this qualitative study was to describe the habilitation nursing of children with developmental disabilities in a Finnish children’s neurological ward. In addition, the purpose was to outline the principles that directed the nursing functions (which consisted of various nursing interventions). The data collection included observation, a retrospective think-aloud method with video-taped nursing situations, the nursing records, and an open-ended questionnaire. The data were analysed with a qualitative content analysis of the manifest and latent content. The findings show that habilitation nursing in a children’s neurological ward consists of assessing the child’s skills, supporting the child’s development, and collaborating with the child’s immediate adults. When implementing those functions with nursing interventions, the nurses demonstrated four principles: client-originated and professional-originated principles, and individual-centred and community-centred principles. Becoming conscious of these principles and the theoretical frameworks behind them enables the development of a nursing science-based model for habilitation nursing.
13. Ozonoff S, Young GS, Belding A, Hill M, Hill A, Hutman T, Johnson S, Miller M, Rogers SJ, Schwichtenberg AJ, Steinfeld M, Iosif AM. {{The broader autism phenotype in infancy: when does it emerge?}}. {J Am Acad Child Adolesc Psychiatry}. 2014; 53(4): 398-407 e2.
OBJECTIVE: This study had 3 goals, which were to examine the following: the frequency of atypical development, consistent with the broader autism phenotype, in high-risk infant siblings of children with autism spectrum disorder (ASD); the age at which atypical development is first evident; and which developmental domains are affected. METHOD: A prospective longitudinal design was used to compare 294 high-risk infants and 116 low-risk infants. Participants were tested at 6, 12, 18, 24, and 36 months of age. At the final visit, outcome was classified as ASD, Typical Development (TD), or Non-TD (defined as elevated Autism Diagnostic Observation Schedule [ADOS] score, low Mullen Scale scores, or both). RESULTS: Of the high-risk group, 28% were classified as Non-TD at 36 months of age. Growth curve models demonstrated that the Non-TD group could not be distinguished from the other groups at 6 months of age, but differed significantly from the Low-Risk TD group by 12 months on multiple measures. The Non-TD group demonstrated atypical development in cognitive, motor, language, and social domains, with differences particularly prominent in the social-communication domain. CONCLUSIONS: These results demonstrate that features of atypical development, consistent with the broader autism phenotype, are detectable by the first birthday and affect development in multiple domains. This highlights the necessity for close developmental surveillance of infant siblings of children with ASD, along with implementation of appropriate interventions as needed.
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14. Pathania M, Davenport EC, Muir J, Sheehan DF, Lopez-Domenech G, Kittler JT. {{The autism and schizophrenia associated gene CYFIP1 is critical for the maintenance of dendritic complexity and the stabilization of mature spines}}. {Transl Psychiatry}. 2014; 4: e374.
Copy number variation (CNV) at the 15q11.2 region has been identified as a significant risk locus for neurological and neuropsychiatric conditions such as schizophrenia (SCZ) and autism spectrum disorder (ASD). However, the individual roles for genes at this locus in nervous system development, function and connectivity remain poorly understood. Haploinsufficiency of one gene in this region, Cyfip1, may provide a model for 15q11.2 CNV-associated neuropsychiatric phenotypes. Here we show that altering CYFIP1 expression levels in neurons both in vitro and in vivo influences dendritic complexity, spine morphology, spine actin dynamics and synaptic alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor lateral diffusion. CYFIP1 is highly enriched at synapses and its overexpression in vitro leads to increased dendritic complexity. Neurons derived from Cyfip1 heterozygous animals on the other hand, possess reduced dendritic complexity, increased mobile F-actin and enhanced GluA2-containing AMPA receptor mobility at synapses. Interestingly, Cyfip1 overexpression or haploinsufficiency increased immature spine number, whereas activity-dependent changes in spine volume were occluded in Cyfip1 haploinsufficient neurons. In vivo, Cyfip1 heterozygous animals exhibited deficits in dendritic complexity as well as an altered ratio of immature-to-mature spines in hippocampal CA1 neurons. In summary, we provide evidence that dysregulation of CYFIP1 expression levels leads to pathological changes in CNS maturation and neuronal connectivity, both of which may contribute to the development of the neurological symptoms seen in ASD and SCZ.
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15. Pearson A, Marsh L, Hamilton A, Ropar D. {{Spatial Transformations of Bodies and Objects in Adults with Autism Spectrum Disorder}}. {J Autism Dev Disord}. 2014.
Previous research into autism spectrum disorder (ASD) has shown people with autism to be impaired at visual perspective taking. However it is still unclear to what extent the spatial mechanisms underlying this ability contribute to these difficulties. In the current experiment we examine spatial transformations in adults with ASD and typical adults. Participants performed egocentric transformations and mental rotation of bodies and cars. Results indicated that participants with ASD had general perceptual differences impacting on response times across tasks. However, they also showed more specific differences in the egocentric task suggesting particular difficulty with using the self as a reference frame. These findings suggest that impaired perspective taking could be grounded in difficulty with the spatial transformation used to imagine the self in someone else’s place.
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16. Pruett JR, Jr. {{BAP: Not-Quite-Autism in Infants}}. {J Am Acad Child Adolesc Psychiatry}. 2014; 53(4): 392-4.
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17. Renoux AJ, Sala-Hamrick KJ, Carducci NM, Frazer M, Halsey KE, Sutton MA, Dolan DF, Murphy GG, Todd PK. {{Impaired sensorimotor gating in Fmr1 knock out and Fragile X premutation model mice}}. {Behav Brain Res}. 2014.
Fragile X syndrome (FXS) is a common inherited cause of intellectual disability that results from a CGG repeat expansion in the FMR1 gene. Large repeat expansions trigger both transcriptional and translational suppression of Fragile X protein (FMRP) production. Fragile X-associated Tremor/Ataxia Syndrome (FXTAS) is an allelic neurodegenerative disease caused by smaller « pre-mutation » CGG repeat expansions that enhance FMR1 transcription but lead to translational inefficiency and reduced FMRP expression in animal models. Sensorimotor gating as measured by pre-pulse inhibition (PPI) is altered in both FXS patients and Fmr1 knock out (KO) mice. Similarly, FXTAS patients have demonstrated PPI deficits. Recent work suggests there may be overlapping synaptic defects between Fmr1 KO and CGG knock-in premutation mouse models (CGG KI). We therefore sought to interrogate PPI in CGG KI mice. Using a quiet PPI protocol more akin to human testing conditions, we find that Fmr1 KO animals have significantly impaired PPI. Using this same protocol, we find CGG KI mice demonstrate an age-dependent impairment in PPI compared to wild type (WT) controls. This study describes a novel phenotype in CGG KI mice that can be used in future therapeutic development targeting premutation associated symptoms.
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18. Sokolov O, Kost N, Andreeva O, Korneeva E, Meshavkin V, Tarakanova Y, Dadayan A, Zolotarev Y, Grachev S, Mikheeva I, Varlamov O, Zozulya A. {{Autistic children display elevated urine levels of bovine casomorphin-7 immunoreactivity}}. {Peptides}. 2014.
Elevated concentrations of circulating casomorphins (CM), the exogenous opioid peptides from milk casein, may contribute to the pathogenesis of autism in children. Because several mass spectrometry studies failed to detect casomorphins in autistic children, it was questioned whether these peptides can be detected in body fluids by mass spec. Here we demonstrated, using a novel high sensitivity ELISA method, that autistic children have significantly higher levels of urine CM-7 than control children. The severity of autistic symptoms correlated with concentrations of CM-7 in the urine. Because CMs interact with opioid and serotonin receptors, the known modulators of synaptogenesis, we suggest that chronic exposure to elevated levels of bovine CMs may impair early child development, setting the stage for autistic disorders.
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19. Sun MK, Hongpaisan J, Lim C, Alkon DL. {{Bryostatin-1 restores hippocampal synapses and spatial learning and memory in adult fragile X mice}}. {J Pharmacol Exp Ther}. 2014.
Fragile X syndrome (FXS) is caused by transcriptional silencing in neurons of the FMR1 gene product, fragile X mental retardation protein (FMRP), a repressor of dendritic mRNA translation. The lack of FMRP leads to dysregulation of synaptically driven protein synthesis and impairments of intellect, cognition, and behavior, a disorder which currently has no effective therapeutics. Fragile X mice were treated with chronic bryostatin-1, a relatively selective PKCepsilon activator with pharmacological profiles of a rapid mGluR desensitization, synaptogenesis, and synaptic maturation/repairing. Differences in the major FXS phenotypes, synapses, and cognitive functions were evaluated and compared among the age-matched groups. Chronic treatment with bryostatin-1 rescues adult fragile X mice from the disorder phenotypes, including normalization of most FXS abnormalities in hippocampal brain-derived neurotrophic factor (BDNF) expression and secretion, PSD-95 levels, GSK-3beta phosphorylation, transformation of immature dendritic spines to mature synapses, densities of the presynaptic and postsynaptic membranes, and spatial learning and memory. Our results show that synaptic and cognitive function of adult FXS mice can be normalized through pharmacological treatment and that bryostatin-1-like agents may represent a novel class of drugs to treat fragile X mental retardation even after postpartum brain development has largely completed.
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20. Taha MS, Nouri K, Milroy LG, Moll JM, Herrmann C, Brunsveld L, Piekorz RP, Ahmadian MR. {{Subcellular Fractionation and Localization Studies Reveal a Direct Interaction of the Fragile X Mental Retardation Protein (FMRP) with Nucleolin}}. {PLoS One}. 2014; 9(3): e91465.
Fragile X mental Retardation Protein (FMRP) is a well-known regulator of local translation of its mRNA targets in neurons. However, despite its ubiquitous expression, the role of FMRP remains ill-defined in other cell types. In this study we investigated the subcellular distribution of FMRP and its protein complexes in HeLa cells using confocal imaging as well as detergent-free fractionation and size exclusion protocols. We found FMRP localized exclusively to solid compartments, including cytosolic heavy and light membranes, mitochondria, nuclear membrane and nucleoli. Interestingly, FMRP was associated with nucleolin in both a high molecular weight ribosomal and translation-associated complex (>/=6 MDa) in the cytosol, and a low molecular weight complex ( approximately 200 kDa) in the nucleoli. Consistently, we identified two functional nucleolar localization signals (NoLSs) in FMRP that are responsible for a strong nucleolar colocalization of the C-terminus of FMRP with nucleolin, and a direct interaction of the N-terminus of FMRP with the arginine-glycine-glycine (RGG) domain of nucleolin. Taken together, we propose a novel mechanism by which a transient nucleolar localization of FMRP underlies a strong nucleocytoplasmic translocation, most likely in a complex with nucleolin and possibly ribosomes, in order to regulate translation of its target mRNAs.
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21. Tureck K, Matson JL, Cervantes P, Konst MJ. {{An examination of the relationship between autism spectrum disorder, intellectual functioning, and comorbid symptoms in children}}. {Res Dev Disabil}. 2014.
There is a deficiency of research looking at how rates of comorbid psychopathology are effected by autism spectrum disorder (ASD) and intellectual functioning level. The present study aimed to extend the literature in this area by evaluating how ASD and IQ scores are related to ratings on a measure of comorbid symptoms. Twenty-three children with ASD and 87 children without ASD participated in this study. Rates of tantrum behavior, avoidant behavior, worry/depressed, repetitive behavior, under-eating, over-eating, and conduct behavior were examined utilizing the Autism Spectrum Disorders-Comorbidity for Children (ASD-CC). Correlational and multiple regression analyses were then conducted. ASD diagnosis significantly predicted rates of tantrum behavior, avoidant behavior, and repetitive behavior. Children with ASD tended to have higher rates of all three of these comorbid symptoms than children without ASD. Although not statistically significant, there was a negative correlation between IQ and rates of comorbid symptoms, such that children with higher IQ scores tended to have lower rates of comorbid symptoms. The implications of these findings on assessment and intervention are discussed.
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22. van Rijn S, Stockmann L, Van Buggenhout G, van Ravenswaaij-Arts C, Swaab H. {{Social cognition and underlying cognitive mechanisms in children with an extra X chromosome: a comparison with autism spectrum disorder}}. {Genes Brain Behav}. 2014.
Individuals with an extra X chromosome are at increased risk for autism symptoms. This study is the first to assess Theory of Mind and facial affect labeling in children with an extra X chromosome. Forty-six children with an extra X chromosome (29 boys with Klinefelter syndrome and 17 girls with Trisomy X), 56 children with ASD, and 88 non-clinical controls, aged 9 to 18 years, were included. Similar to children with ASD, children with an extra X chromosome showed significant impairments in social cognition. Regression analyses showed that different cognitive functions predicted social cognitive skills in the extra X and ASD groups. The social cognitive deficits were similar for boys and girls with an extra X chromosome, and not specific for a subgroup with high (ADI-R) autism scores. Thus, children with an extra X chromosome show social cognitive deficits, which may contribute to social dysfunction, not only in children showing a developmental pattern that is ‘typical’ for autism, but also in those showing mild or late presenting autism symptoms. Our findings may also help explain variance in type of social deficit: Children may show similar social difficulties, but these may arise as a consequence of different underlying information processing deficits.
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23. Wong CT, Ahmad E, Li H, Crawford DA. {{Prostaglandin E2 alters Wnt-dependent migration and proliferation in neuroectodermal stem cells: implications for autism spectrum disorders}}. {Cell Commun Signal}. 2014; 12(1): 19.
Prostaglandin E2 (PGE2) is a natural lipid-derived molecule that is involved in important physiological functions. Abnormal PGE2 signalling has been associated with pathologies of the nervous system. Previous studies provide evidence for the interaction of PGE2 and canonical Wnt signalling pathways in non-neuronal cells. Since the Wnt pathway is crucial in the development and organization of the brain, the main goal of this study is to determine whether collaboration between these pathways exists in neuronal cell types. We report that PGE2 interacts with canonical Wnt signalling through PKA and PI-3K in neuroectodermal (NE-4C) stem cells. We used time-lapse microscopy to determine that PGE2 increases the final distance from origin, path length travelled, and the average speed of migration in Wnt-activated cells. Furthermore, PGE2 alters distinct cellular phenotypes that are characteristic of Wnt-induced NE-4C cells, which corresponds to the modified splitting behaviour of the cells. We also found that in Wnt-induced cells the level of beta-catenin protein was increased and the expression levels of Wnt-target genes (Ctnnb1, Ptgs2, Ccnd1, Mmp9) was significantly upregulated in response to PGE2 treatment. This confirms that PGE2 activated the canonical Wnt signalling pathway. Furthermore, the upregulated genes have been previously associated with ASD. Our findings show, for the first time, evidence for cross-talk between PGE2 and Wnt signalling in neuronal cells, where PKA and PI-3K might act as mediators between the two pathways. Given the importance of PGE2 and Wnt signalling in prenatal development of the nervous system, our study provides insight into how interaction between these two pathways may influence neurodevelopment.
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24. Xu JP, Yi HL, Li M, Shi ZC, Li JF, Zhao YC, Lin GB, Wang HY, Shen F. {{[Clinical application of Wallis interspinous dynamic stabilization in treating adjacent segment degeneration (ASD) after lumbar spinal fusion]}}. {Zhongguo Gu Shang}. 2013; 26(12): 1005-9.
OBJECTIVE: To evaluate therapeutic effects of Wallis interspinous dynamic stabilization in treating ASD after lumbar spinal fusion. METHODS: Totally 40 patients (included 16 males and 24 females, aged 25 to 60 years old) with degenerative disc disease were treated with posterior interbody fusion. Among them, 20 cases (treatment group) were treated with posterior interbody fusion combined with Wallis interspinous dynamic stabilization, while other 20 cases (control group) only treated with posterior interbody fusion. JOA score and VAS score were compared after inserted Wallis interspinous dynamic stabilization at 1 month and 3 years, and changes of intervertebral disc height of adjacent segment and cross-sectional area of the canal were tested and compared. RESULTS: All patients were followed up from 3 to 5 years with an average of 3.6 years. All injuries were healed at stage I and the pain were released after treatment. There were no significant meaning in JOA score and VAS score at 1 month after treatment between two groups (P>0.05), while had meaning at 3 years (P<0.05). There were no statistical significane in intervertebral disc height of adjacent segment and cross-sectional area of the canal at 1 month after treatment (P>0.05), while had statistical meaning at 3 years (P<0.05). CONCLUSION: There is no difference in immediate effects between two groups. Both of them can obtain good results for effective decompression. Medial-term effectiveness of treatment group is obviously better than control group, which depends on Wallis interspinous dynamic stabilization to plays good biology effects and effective accelerate adjacent degeneration caused by lumbar fusion.
