1. Chaidez V, Hansen RL, Hertz-Picciotto I. {{Gastrointestinal Problems in Children with Autism, Developmental Delays or Typical Development}}. {J Autism Dev Disord};2013 (Nov 6)
To compare gastrointestinal (GI) problems among children with: (1) autism spectrum disorder (ASD), (2) developmental delay (DD) and (3) typical development (TD), GI symptom frequencies were obtained for 960 children from the CHildhood Autism Risks from Genetics and Environment (CHARGE) study. We also examined scores on five Aberrant Behavior Checklist (ABC) subscales comparing ASD children with high versus low frequency GI symptoms. Compared to TD children, those with ASD [aOR 7.92 (4.89-12.85)] and DD [aOR 4.55 (2.51-8.24)] were more likely to have at least one frequent GI symptom. Restricting to ASD children, those with frequent abdominal pain, gaseousness, diarrhea, constipation or pain on stooling scored worse on irritability, social withdrawal, stereotypy, and hyperactivity compared with children having no frequent GI symptoms. Frequent GI problems affect young children with ASD and DD more commonly than those with TD. Maladaptive behaviors correlate with GI problems, suggesting these comorbidities require attention.
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2. Elmose M, Trillingsgaard A, Jorgensen M, Nielsen A, Bruhn SS, Sorensen EU. {{Follow-up at mid-school age (9-13 years) of children assessed for autism spectrum disorder before the age of four}}. {Nord J Psychiatry};2013 (Nov 7)
Background: Studies of diagnosis and outcome in mid-school age children (9-13 years) referred early in life for a suspected autism spectrum disorder (ASD) are scarce. Aims: This study aimed to describe outcome, developmental change and the stability of the early diagnosis in mid-school age. Methods: Children consecutively referred to a specialized autism unit at a regional psychiatric diagnostic centre in Denmark before the age of 4 were contacted in mid-school age (9-13 years). 14 children with ASD and 9 children diagnosed outside the spectrum were included. Current clinical diagnosis, autism characteristics, intellectual abilities and adaptive functioning were assessed at follow-up, and investigated in relation to early measures of intellectual abilities and difficulties in social and communicative situations. Results: The stability of an early ASD diagnosis was confirmed. However, a high degree of change into the autism spectrum was found for children who were initially diagnosed with another developmental disorder. A positive change with regard to IQ level was evident at the individual level. At group level, there was a tendency for lower functioning in the children diagnosed early with ASD. Early measures of intellectual abilities, and of social and communicative difficulties, predicted between 16% and 50% of the variance in intellectual abilities and adaptive functioning. Conclusions: The findings are in line with follow-up studies in preschool and early school age but highlight the need to monitor early diagnostic decisions, and the need for more nuanced baseline and outcome measures that may help increase our prognostic understanding.
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3. Grainger C, Williams DM, Lind SE. {{Online Action Monitoring and Memory for Self-Performed Actions in Autism Spectrum Disorder}}. {J Autism Dev Disord};2013 (Nov 6)
This study explored whether individuals with autism spectrum disorder (ASD) experience difficulties with action monitoring. Two experimental tasks examined whether adults with ASD are able to monitor their own actions online, and whether they also show a typical enactment effects in memory (enhanced memory for actions they have performed compared to actions they have observed being performed). Individuals with ASD and comparison participants showed a similar pattern of performance on both tasks. In a task which required individuals to distinguish person-caused from computer-caused changes in phenomenology both groups found it easier to monitor their own actions compared to those of an experimenter. Both groups also showed typical enactment effects. Despite recent suggestions to the contrary, these results support suggestions that action monitoring is unimpaired in ASD.
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4. Moy SS, Riddick NV, Nikolova VD, Teng BL, Agster KL, Nonneman RJ, Young NB, Baker LK, Nadler JJ, Bodfish JW. {{Repetitive behavior profile and supersensitivity to amphetamine in the C58/J mouse model of autism}}. {Behav Brain Res};2013 (Nov 7)
Restricted repetitive behaviors are core symptoms of autism spectrum disorders (ASDs). The range of symptoms encompassed by the repetitive behavior domain includes lower-order stereotypy and self-injury, and higher-order indices of circumscribed interests and cognitive rigidity. Heterogeneity in clinical ASD profiles suggests that specific manifestations of repetitive behavior reflect differential neuropathology. The present studies utilized a set of phenotyping tasks to determine a repetitive behavior profile for the C58/J mouse strain, a model of ASD core symptoms. In an observational screen, C58/J demonstrated overt motor stereotypy, but not over-grooming, a commonly-used measure for mouse repetitive behavior. Amphetamine did not exacerbate motor stereotypy, but had enhanced stimulant effects on locomotion and rearing in C58/J, compared to C57BL/6J. Both C58/J and Grin1 knockdown mice, another model of ASD-like behavior, had marked deficits in marble-burying. In a nose poke task for higher-order repetitive behavior, C58/J had reduced holeboard exploration and preference for non-social, versus social, olfactory stimuli, but did not demonstrate cognitive rigidity following familiarization to an appetitive stimulus. Analysis of available high-density genotype data indicated specific regions of divergence between C58/J and two highly-sociable strains with common genetic lineage. Strain genome comparisons identified autism candidate genes, including Cntnap2 and Slc6a4, located within regions divergent in C58/J. However, Grin1, Nlgn1, Sapap3, and Slitrk5, genes linked to repetitive over-grooming, were not in regions of divergence. These studies suggest that specific repetitive phenotypes can be used to distinguish ASD mouse models, with implications for divergent underlying mechanisms for different repetitive behavior profiles.
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5. Ro M, Won S, Kang H, Kim SY, Lee SK, Nam M, Bang HJ, Yang JW, Choi KS, Kim SK, Chung JH, Kwack K. {{Association of the FGA and SLC6A4 Genes with Autistic Spectrum Disorder in a Korean Population}}. {Neuropsychobiology};2013 (Nov 1);68(4):212-220.
Background: Autism spectrum disorder (ASD) is a neurobiological disorder characterized by distinctive impairments in cognitive function, language, and behavior. Linkage and population studies suggest a genetic association between solute carrier family 6 member 4 (SLC6A4) variants and ASD. Method: Logistic regression was used to identify associations between single-nucleotide polymorphisms (SNPs) and ASD with 3 alternative models (additive, dominant, and recessive). Linear regression analysis was performed to determine the influence of SNPs on Childhood Autism Rating Scale (CARS) scores as a quantitative phenotype. Results: In the present study, we examined the associations of SNPs in the SLC6A4 gene and the fibrinogen alpha chain (FGA) gene. Logistic regression analysis showed a significant association between the risk of ASD and rs2070025 and rs2070011 in the FGA gene. The gene-gene interaction between SLC6A4 and FGA was not significantly associated with ASD susceptibility. However, polymorphisms in both SLC6A4 and the FGA gene significantly affected the symptoms of ASD. Conclusion: Our findings indicate that FGA and SLC6A4 gene interactions may contribute to the phenotypes of ASD rather than the incidence of ASD. (c) 2013 S. Karger AG, Basel.
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6. Russell-Smith SN, Comerford BJ, Maybery MT, Whitehouse AJ. {{Brief Report: Further Evidence for a Link Between Inner Speech Limitations and Executive Function in High-Functioning Children with Autism Spectrum Disorders}}. {J Autism Dev Disord};2013 (Nov 7)
This study investigated the involvement of inner speech limitations in the executive dysfunction associated with autism spectrum disorders (ASDs). Seventeen children with ASD and 18 controls, statistically-matched in age and IQ, performed a computer-based card sorting test (CST) to assess cognitive flexibility under four conditions: baseline, with articulatory suppression, with a concurrent mouthing task, and while verbalizing their strategies aloud. Articulatory suppression adversely affected CST performance for the control group but not the ASD group. The results additionally showed that overtly verbalizing strategies did not benefit the ASD children as it did the typically developing children. The findings thus provide further evidence that ASD children do not use inner speech to the same extent, or with the same effectiveness, as typically developing children when performing executive tasks.
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7. Steinberg J, Webber C. {{The Roles of FMRP-Regulated Genes in Autism Spectrum Disorder: Single- and Multiple-Hit Genetic Etiologies}}. {Am J Hum Genet};2013 (Nov 7);93(5):825-839.
Autism spectrum disorder (ASD) is a highly heritable complex neurodevelopmental condition characterized by impairments in social interaction and communication and restricted and repetitive behaviors. Although roles for both de novo and familial genetic variation have been documented, the underlying disease mechanisms remain poorly elucidated. In this study, we defined and explored distinct etiologies of genetic variants that affect genes regulated by Fragile-X mental retardation protein (FMRP), thought to play a key role in neuroplasticity and neuronal translation, in ASD-affected individuals. In particular, we developed the Trend test, a pathway-association test that is able to robustly detect multiple-hit etiologies and is more powerful than existing approaches. Exploiting detailed spatiotemporal maps of gene expression within the human brain, we identified four discrete FMRP-target subpopulations that exhibit distinct functional biases and contribute to ASD via different types of genetic variation. We also demonstrated that FMRP target genes are more likely than other genes with similar expression patterns to contribute to disease. We developed the hypothesis that FMRP targets contribute to ASD via two distinct etiologies: (1) ultra-rare and highly penetrant single disruptions of embryonically upregulated FMRP targets (« single-hit etiology ») or (2) the combination of multiple less penetrant disruptions of nonembryonic, synaptic FMRP targets (« multiple-hit etiology »). The Trend test provides rigorous support for a multiple-hit genetic etiology in a subset of autism cases and is easily extendible to combining information from multiple types of genetic variation (i.e., copy-number and exome variants), increasing its value to next-generation sequencing approaches.
