1. Baron-Cohen S, Johnson D, Asher J, Wheelwright S, Fisher SE, Gregersen PK, Allison C. {{Is synaesthesia more common in autism?}}. {Mol Autism};2013 (Nov 20);4(1):40.
BACKGROUND: Synaesthesia is a neurodevelopmental condition in which a sensation in one modality triggers a perception in a second modality. Autism (shorthand for Autism Spectrum Conditions) is a neurodevelopmental condition involving social-communication disability alongside resistance to change and unusually narrow interests or activities. Whilst on the surface they appear distinct, they have been suggested to share common atypical neural connectivity. METHODS: In the present study, we carried out the first prevalence study of synaesthesia in autism to formally test whether these conditions are independent. After exclusions, 164 adults with autism and 97 controls completed a synaesthesia questionnaire, autism spectrum quotient, and test of genuineness-revised (ToG-R) online. RESULTS: The rate of synaesthesia in adults with autism was 18.9% (31 out of 164), almost three times greater than in controls (7.22%, 7 out of 97, P <0.05). ToG-R proved unsuitable for synaesthetes with autism. CONCLUSIONS: The significant increase in synaesthesia prevalence in autism suggests that the two conditions may share some common underlying mechanisms. Future research is needed to develop more feasible validation methods of synaesthesia in autism.
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2. Bergeron JD, Deslauriers J, Grignon S, Fortier LC, Lepage M, Stroh T, Poyart C, Sebire G. {{White Matter Injury and Autistic-Like Behavior Predominantly Affecting Male Rat Offspring Exposed to Group B Streptococcal Maternal Inflammation}}. {Dev Neurosci};2013 (Nov 12):504-515.
The impact of the group B streptococcus (GBS)-induced maternal inflammation on offspring’s brain has not yet been investigated despite GBS being one of the most frequent bacteria colonizing or infecting pregnant women. According to our hypothesis GBS-induced maternal immune activation plays a role in offspring perinatal brain damage and subsequent neurodisabilities such as autism. Using a new preclinical rat model of maternal inflammation triggered by inactivated GBS, we demonstrated placental, neuropathological and behavioral impacts on offspring. GBS-exposed placentas presented cystic lesions and polymorphonuclear infiltration located within the decidual/maternal side of the placenta, contrasting with macrophagic infiltration and necrotic areas located in the labyrinth/fetal compartment of the placenta after lipopolysaccharide-induced maternal inflammation. Brain damage featured lateral ventricles widening, predominately in the male, reduction of periventricular external capsules thickness, oligodendrocyte loss, and disorganization of frontoparietal subcortical tissue with no glial proliferation. Autistic hallmarks were found in offspring exposed to GBS, namely deficits in motor behavior, social and communicative impairments, i.e. profound defects in the integration and response to both acoustic and chemical signals that are predominant modes of communication in rats. Surprisingly, only male offspring were affected by these combined autistic-like traits. Our results show for the first time that materno-fetal inflammatory response to GBS plays a role in the induction of placental and cerebral insults, remarkably recapitulating cardinal features of human autism such as gender dichotomy and neurobehavioral traits. Unlike other models of prenatal inflammatory brain damage (induced by viral/toll-like receptor 3 (TLR3) or Gram-negative/TLR4), maternal inflammation resulting from GBS/TLR2 interactions induced a distinctive pattern of chorioamnionitis and cerebral injuries. These results also provide important evidence that beyond genetic influences, modifiable environmental factors play a role in both the occurrence of autism and its gender imbalance. (c) 2013 S. Karger AG, Basel.
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3. Blice-Baum AC, Mihailescu MR. {{Biophysical characterization of G-quadruplex forming FMR1 mRNA and of its interactions with different fragile X mental retardation protein isoforms}}. {RNA};2013 (Nov 18)
Fragile X syndrome, the most common form of inherited mental impairment in humans, is caused by the absence of the fragile X mental retardation protein (FMRP) due to a CGG trinucleotide repeat expansion in the 5′-untranslated region (UTR) and subsequent translational silencing of the fragile x mental retardation-1 (FMR1) gene. FMRP, which is proposed to be involved in the translational regulation of specific neuronal messenger RNA (mRNA) targets, contains an arginine-glycine-glycine (RGG) box RNA binding domain that has been shown to bind with high affinity to G-quadruplex forming mRNA structures. FMRP undergoes alternative splicing, and the binding of FMRP to a proposed G-quadruplex structure in the coding region of its mRNA (named FBS) has been proposed to affect the mRNA splicing events at exon 15. In this study, we used biophysical methods to directly demonstrate the folding of FMR1 FBS into a secondary structure that contains two specific G-quadruplexes and analyze its interactions with several FMRP isoforms. Our results show that minor splice isoforms, ISO2 and ISO3, created by the usage of the second and third acceptor sites at exon 15, bind with higher affinity to FBS than FMRP ISO1, which is created by the usage of the first acceptor site. FMRP ISO2 and ISO3 cannot undergo phosphorylation, an FMRP post-translational modification shown to modulate the protein translation regulation. Thus, their expression has to be tightly regulated, and this might be accomplished by a feedback mechanism involving the FMRP interactions with the G-quadruplex structures formed within FMR1 mRNA.
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4. Eisinger BE, Saul MC, Driessen TM, Gammie SC. {{Development of a versatile enrichment analysis tool reveals associations between the maternal brain and mental health disorders, including autism}}. {BMC Neurosci};2013 (Nov 19);14(1):147.
: A recent study of lateral septum (LS) suggested a large number of autism-related genes with altered expression in the postpartum state. However, formally testing the findings for enrichment of autism-associated genes proved to be problematic with existing software. Many gene-disease association databases have been curated which are not currently incorporated in popular, full-featured enrichment tools, and the use of custom gene lists in these programs can be difficult to perform and interpret. As a simple alternative, we have developed the Modular Single-set Enrichment Test (MSET), a minimal tool that enables one to easily evaluate expression data for enrichment of any conceivable gene list of interest. RESULTS: The MSET approach was validated by testing several publicly available expression data sets for expected enrichment in areas of autism, attention deficit hyperactivity disorder (ADHD), and arthritis. Using nine independent, unique autism gene lists extracted from association databases and two recent publications, a striking consensus of enrichment was detected within gene expression changes in LS of postpartum mice. A network of 160 autism-related genes was identified, representing developmental processes such as synaptic plasticity, neuronal morphogenesis, and differentiation. Additionally, maternal LS displayed enrichment for genes associated with bipolar disorder, schizophrenia, ADHD, and depression. CONCLUSIONS: The transition to motherhood includes the most fundamental social bonding event in mammals and features naturally occurring changes in sociability. Some individuals with autism, schizophrenia, or other mental health disorders exhibit impaired social traits. Genes involved in these deficits may also contribute to elevated sociability in the maternal brain. To date, this is the first study to show a significant, quantitative link between the maternal brain and mental health disorders using large scale gene expression data. Thus, the postpartum brain may provide a novel and promising platform for understanding the complex genetics of improved sociability that may have direct relevance for multiple psychiatric illnesses. This study also provides an important new tool that fills a critical analysis gap and makes evaluation of enrichment using any database of interest possible with an emphasis on ease of use and methodological transparency.
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5. Engelhardt CR, Mazurek MO, Sohl K. {{Media Use and Sleep Among Boys With Autism Spectrum Disorder, ADHD, or Typical Development}}. {Pediatrics};2013 (Nov 18)
OBJECTIVE:The current study examined the relationships between media use (television, computer, and video games) and sleep among boys with autism spectrum disorder (ASD) compared with those with attention-deficit/hyperactivity disorder (ADHD) or with typical development (TD).METHODS:Participants included parents of boys with ASD (n = 49), ADHD (n = 38), or TD (n = 41) (ages 8-17 years). Questionnaires assessed daily hours of media use, bedroom access to media, and average sleep hours per night.RESULTS:Bedroom media access was associated with less time spent sleeping per night, irrespective of diagnostic group. Bedroom access to a television or a computer was more strongly associated with reduced sleep among boys with ASD compared with boys with ADHD or TD. Multivariate models showed that, in addition to bedroom access, the amount of time spent playing video games was uniquely associated with less sleep among boys with ASD. In the ASD group only, the relationship between bedroom access to video games and reduced sleep was mediated by hours of video game play.CONCLUSIONS:The current results suggest that media-related variables may be an important consideration in understanding sleep disturbances in children with ASD. Further research is needed to better characterize the processes by which media use may affect sleep among individuals with ASD. Overall, the current findings suggest that screen-based media time and bedroom media access should be routinely assessed and may be important intervention targets when addressing sleep problems in children with ASD.
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6. Feng L. {{Autism in children born after in vitro fertilization}}. {JAMA};2013 (Nov 20);310(19):2100-2101.
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7. Gomez-Mancilla B, Berry-Kravis E, Hagerman R, von Raison F, Apostol G, Ufer M, Gasparini F, Jacquemont S. {{Development of mavoglurant and its potential for the treatment of fragile X syndrome}}. {Expert Opin Investig Drugs};2013 (Nov 20)
Introduction: Fragile X syndrome (FXS) is the most common inherited cause of intellectual disability. With no curative treatment available, current therapeutic approaches are aimed at symptom management. FXS is caused by silencing the FMR1 gene, which encodes FMRP; as loss of FMRP leads to the development of symptoms associated with FXS. Areas covered: In this evaluation, the authors examine the role of the metabotropic glutamate receptor 5 (mGluR5) in the pathophysiology of FXS, and its suitability as a target for rescuing the disease state. Furthermore, the authors review the evidence from preclinical studies of pharmacological interventions targeting mGluR5 in FXS. Lastly, the authors assess the findings from clinical studies in FXS, in particular the use of the Aberrant Behavior Checklist-Community Edition (ABC-C) and the recently developed ABC-C for FXS scale, as clinical endpoints to assess disease modification in this patient population. Expert opinion: There is cautious optimism for the successful treatment of the core behavioral and cognitive symptoms of FXS based on preclinical data in animal models and early studies in humans. However, the association between mGluR5-heightened responsiveness and the clinical phenotype in humans remains to be demonstrated. Many questions regarding the optimal treatment and outcome measures of FXS remain unanswered.
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8. Maister L, Simons JS, Plaisted-Grant K. {{Executive functions are employed to process episodic and relational memories in children with autism spectrum disorders}}. {Neuropsychology};2013 (Nov);27(6):615-627.
Objective: Long-term memory functioning in autism spectrum disorders (ASDs) is marked by a characteristic pattern of impairments and strengths. Individuals with ASD show impairment in memory tasks that require the processing of relational and contextual information, but spared performance on tasks requiring more item-based, acontextual processing. Two experiments investigated the cognitive mechanisms underlying this memory profile. Method: A sample of 14 children with a diagnosis of high-functioning ASD (age: M = 12.2 years), and a matched control group of 14 typically developing (TD) children (age: M = 12.1 years), participated in a range of behavioral memory tasks in which we measured both relational and item-based memory abilities. They also completed a battery of executive function measures. Results: The ASD group showed specific deficits in relational memory, but spared or superior performance in item-based memory, across all tasks. Importantly, for ASD children, executive ability was significantly correlated with relational memory but not with item-based memory. No such relationship was present in the control group. This suggests that children with ASD atypically employed effortful, executive strategies to retrieve relational (but not item-specific) information, whereas TD children appeared to use more automatic processes. Conclusions: The relational memory impairment in ASD may result from a specific impairment in automatic associative retrieval processes with an increased reliance on effortful and strategic retrieval processes. Our findings allow specific neural predictions to be made regarding the interactive functioning of the hippocampus, prefrontal cortex, and posterior parietal cortex in ASD as a neural network supporting relational memory processing. (PsycINFO Database Record (c) 2013 APA, all rights reserved).
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9. Sandin S, Hultman C, Reichenberg A. {{Autism in children born after in vitro fertilization-reply}}. {JAMA};2013 (Nov 20);310(19):2101.
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10. Scahill L, Aman MG, Lecavalier L, Halladay AK, Bishop SL, Bodfish JW, Grondhuis S, Jones N, Horrigan JP, Cook EH, Handen BL, King BH, Pearson DA, McCracken JT, Sullivan KA, Dawson G. {{Measuring repetitive behaviors as a treatment endpoint in youth with autism spectrum disorder}}. {Autism};2013 (Nov 20)
Restricted interests and repetitive behaviors vary widely in type, frequency, and intensity among children and adolescents with autism spectrum disorder. They can be stigmatizing and interfere with more constructive activities. Accordingly, restricted interests and repetitive behaviors may be a target of intervention. Several standardized instruments have been developed to assess restricted interests and repetitive behaviors in the autism spectrum disorder population, but the rigor of psychometric assessment is variable. This article evaluated the readiness of available measures for use as outcome measures in clinical trials. The Autism Speaks Foundation assembled a panel of experts to examine available instruments used to measure restricted interests and repetitive behaviors in youth with autism spectrum disorder. The panel held monthly conference calls and two face-to-face meetings over 14 months to develop and apply evaluative criteria for available instruments. Twenty-four instruments were evaluated and five were considered « appropriate with conditions » for use as outcome measures in clinical trials. Ideally, primary outcome measures should be relevant to the clinical target, be reliable and valid, and cover the symptom domain without being burdensome to subjects. The goal of the report was to promote consensus across funding agencies, pharmaceutical companies, and clinical investigators about advantages and disadvantages of existing outcome measures.
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11. Sesarini CV, Costa L, Naymark M, Granana N, Cajal AR, Garcia Coto M, Pallia RC, Argibay PF. {{Evidence for Interaction Between Markers in GABA(A) Receptor Subunit Genes in an Argentinean Autism Spectrum Disorder Population}}. {Autism Res};2013 (Nov 18)
Autism spectrum disorders (ASD) can be conceptualized as a genetic dysfunction that disrupts development and function of brain circuits mediating social cognition and language. At least some forms of ASD may be associated with high level of excitation in neural circuits, and gamma-aminobutyric acid (GABA) has been implicated in its etiology. Single-nucleotide polymorphisms (SNP) located within the GABA receptor (GABAR) subunit genes GABRA1, GABRG2, GABRB3, and GABRD were screened. A hundred and thirty-six Argentinean ASD patients and 150 controls were studied, and the contribution of the SNPs in the etiology of ASD was evaluated independently and/or through gene-gene interaction using multifactor dimensionality reduction (MDR) method. From the 18 SNP studied, 11 were not present in our Argentinean population (patients and controls) and 1 SNP had minor allele frequency < 0.1%. For the remaining six SNPs, none provided statistical significant association with ASD when considering allelic or genotypic frequencies. Non-significant association with ASD was found for the haplotype analysis. MDR identified evidence for synergy between markers in GABRB3 (chromosome 15) and GABRD (chromosome 1), suggesting potential gene-gene interaction across chromosomes associated with increased risk for autism (testing balanced accuracy: 0.6081 and cross-validation consistency: 10/10, P < 0.001). Considering our Argentinean ASD sample, it can be inferred that GABRB3 would be involved in the etiology of autism through interaction with GABRD. These results support the hypothesis that GABAR subunit genes are involved in autism, most likely via complex gene-gene interactions. Autism Res 2013, : -. (c) 2013 International Society for Autism Research, Wiley Periodicals, Inc.
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12. Smith AL, Romski M, Sevcik RA. {{Examining the role of communication on sibling relationship quality and interaction for sibling pairs with and without a developmental disability}}. {Am J Intellect Dev Disabil};2013 (Sep);118(5):394-409.
Abstract This study examined communication interaction patterns when one sibling had a developmental disability as well as the role of communication skills in sibling relationship quality. Thirty sibling dyads were categorized into one of three communication status groups: emerging, context-dependent, and independent communicators. Independent communicators and their siblings did not differ in terms of syntactic complexity but typically developing siblings dominated the interaction and exhibited greater lexical diversity regardless of communication status. Communication status did not impact the warmth/closeness, rivalry, or conflict in the sibling relationship, but siblings of independent communicators engaged in the greatest amount of helping and managing behaviors. These results represent a first step in understanding the role of communication skills in the sibling relationship for families of children with disabilities.
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13. Utine GE, Akpinar B, Arslan U, Kiper PO, Volkan-Salanci B, Alanay Y, Aktas D, Haliloglu G, Oguz KK, Boduroglu K, Alikasifoglu M. {{Neurochemical evaluation of brain function with H magnetic resonance spectroscopy in patients with fragile X syndrome}}. {Am J Med Genet A};2013 (Nov 20)
Fragile X syndrome (FXS) is the most common hereditary disorder of intellectual disability. Cognitive deficits involve executive function, attention, learning and memory. Advanced neuroimaging techniques are available, and 1 H magnetic resonance spectroscopy (MRS) can be used as a complementary method to MR imaging to understand disease processes in brain, by in vivo demonstration of brain metabolites. MRS was performed in 13 male patients with FXS full mutation, and 13 age- and sex-matched healthy controls. FXS diagnosis was based on clinical evaluation, followed by detection of FMR1 full mutation. Axial T2 TSE, sagittal T1 SE and coronal 3D MPRAGE images were obtained for both morphological imaging and voxel localization. Following evaluation of conventional images, multivoxel MRS (CSI) through supraventricular white matter and single voxel MRS (svs) with an intermediate echo time (TE:135 ms) from the cerebellar vermis were performed. Choline/Creatine (Cho/Cr), N-acetyl aspartate/Creatine (NAA/Cr), and Choline/N-acetyl aspartate (Cho/NAA) ratios were examined at right frontal (RF), left frontal (LF), right parietal (RP), left parietal (LP), and cerebellar vermian (C) white matter. Statistical analyses were done using t-test and Mann-Whitney U tests. A statistically significant difference was observed in RP Cho/NAA ratio (cell membrane marker/neuroaxonal marker), FXS patients having lower levels than controls (P = 0.016). The results should be evaluated cautiously in parallel to consequences in brain metabolism leading to alterations in neurotransmitter levels, osmoregulation, energy metabolism and oxidative stress response described in animal models. MRS may serve to define a metabolic signature and biomarkers associated with FXS. (c) 2013 Wiley Periodicals, Inc.
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14. Wilkinson KM, McIlvane WJ. {{Perceptual factors influence visual search for meaningful symbols in individuals with intellectual disabilities and down syndrome or autism spectrum disorders}}. {Am J Intellect Dev Disabil};2013 (Sep);118(5):353-364.
Abstract Augmentative and alternative communication (AAC) systems often supplement oral communication for individuals with intellectual and communication disabilities. Research with preschoolers without disabilities has demonstrated that two visual-perceptual factors influence speed and/or accuracy of finding a target: the internal color and spatial organization of symbols. Twelve participants with Down syndrome and 12 with autism spectrum disorders (ASDs) completed two search tasks. In one, the symbols were clustered by internal color; in the other, the identical symbols had no arrangement cue. Visual search was superior in participants with ASDs compared to those with Down syndrome. In both groups, responses were significantly faster when the symbols were clustered by internal color. Construction of aided AAC displays may benefit from attention to their physical and perceptual features.
