1. Gerdts JA, Bernier R, Dawson G, Estes A. {{The Broader Autism Phenotype in Simplex and Multiplex Families}}. {J Autism Dev Disord};2012 (Nov 2)
Mothers, fathers, and siblings from 87 multiplex (M-mothers, M-fathers, and M-siblings) and 41 simplex (S-mothers, S-fathers, and S-siblings) Autism spectrum disorder families were assessed using the Broader Phenotype Autism Symptom Scale. S-mothers, S-fathers, and S-siblings showed more social interest and were more expressive in their use of nonverbal communication compared to M-mothers, M-fathers, and M-siblings. Conversational skills were also improved in S-fathers and S-siblings compared to M-fathers and M-siblings. S-siblings showed significantly lower rigidity and intense interests compared to M-siblings. The decreased number and intensity of broader autism phenotype traits observed in parents and siblings within simplex families provide behavioral evidence consistent with findings of increased de novo genetic events in simplex families.
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2. Hoffman K, Kalkbrenner AE, Vieira VM, Daniels JL. {{The spatial distribution of known predictors of autism spectrum disorders impacts geographic variability in prevalence in central North Carolina}}. {Environ Health};2012 (Oct 31);11(1):80.
ABSTRACT: BACKGROUND: The causes of autism spectrum disorders (ASD) remain largely unknown and widely debated; however, evidence increasingly points to the importance of environmental exposures. A growing number of studies use geographic variability in ASD prevalence or exposure patterns to investigate the association between environmental factors and ASD. However, differences in the geographic distribution of established risk and predictive factors for ASD, such as maternal education or age, can interfere with investigations of ASD etiology. We evaluated geographic variability in the prevalence of ASD in central North Carolina and the impact of spatial confounding by known risk and predictive factors. METHODS: Children meeting a standardized case definition for ASD at 8 years of age were identified through records-based surveillance for 8 counties biennially from 2002 to 2008 (n=532). Vital records were used to identify the underlying cohort (15% random sample of children born in the same years as children with an ASD, n=11,034), and to obtain birth addresses. We used generalized additive models (GAMs) to estimate the prevalence of ASD across the region by smoothing latitude and longitude. GAMs, unlike methods used in previous spatial analyses of ASD, allow for extensive adjustment of individual-level risk factors (e.g. maternal age and education) when evaluating spatial variability of disease prevalence. RESULTS: Unadjusted maps revealed geographic variation in surveillance-recognized ASD. Children born in certain regions of the study area were up to 1.27 times as likely to be recognized as having ASD compared to children born in the study area as a whole (prevalence ratio (PR) range across the study area 0.57-1.27; global P=0.003). However, geographic gradients of ASD prevalence were attenuated after adjusting for spatial confounders (adjusted PR range 0.72-1.12 across the study area; global P=0.052). CONCLUSIONS: In these data, spatial variation of ASD in central NC can be explained largely by factors impacting diagnosis, such as maternal education, emphasizing the importance of adjusting for differences in the geographic distribution of known individual-level predictors in spatial analyses of ASD. These results underscore the critical importance of accounting for such factors in studies of environmental exposures that vary across regions.
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3. Katz DM, Berger-Sweeney JE, Eubanks JH, Justice MJ, Neul JL, Pozzo-Miller L, Blue ME, Christian D, Crawley JN, Giustetto M, Guy J, Howell CJ, Kron M, Nelson SB, Samaco RC, Schaevitz LR, St Hillaire-Clarke C, Young JL, Zoghbi HY, Mamounas LA. {{Preclinical research in Rett syndrome: setting the foundation for translational success}}. {Dis Model Mech};2012 (Nov);5(6):733-745.
In September of 2011, the National Institute of Neurological Disorders and Stroke (NINDS), the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the International Rett Syndrome Foundation (IRSF) and the Rett Syndrome Research Trust (RSRT) convened a workshop involving a broad cross-section of basic scientists, clinicians and representatives from the National Institutes of Health (NIH), the US Food and Drug Administration (FDA), the pharmaceutical industry and private foundations to assess the state of the art in animal studies of Rett syndrome (RTT). The aim of the workshop was to identify crucial knowledge gaps and to suggest scientific priorities and best practices for the use of animal models in preclinical evaluation of potential new RTT therapeutics. This review summarizes outcomes from the workshop and extensive follow-up discussions among participants, and includes: (1) a comprehensive summary of the physiological and behavioral phenotypes of RTT mouse models to date, and areas in which further phenotypic analyses are required to enhance the utility of these models for translational studies; (2) discussion of the impact of genetic differences among mouse models, and methodological differences among laboratories, on the expression and analysis, respectively, of phenotypic traits; and (3) definitions of the standards that the community of RTT researchers can implement for rigorous preclinical study design and transparent reporting to ensure that decisions to initiate costly clinical trials are grounded in reliable preclinical data.
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4. Kaufmann L, Zotter S, Pixner S, Starke M, Haberlandt E, Steinmayr-Gensluckner M, Egger K, Schocke M, Weiss EM, Marksteiner J. {{Brief Report: CANTAB Performance and Brain Structure in Pediatric Patients with Asperger Syndrome}}. {J Autism Dev Disord};2012 (Nov 2)
By merging neuropsychological (CANTAB/Cambridge Neuropsychological Test Automated Battery) and structural brain imaging data (voxel-based-morphometry) the present study sought to identify the neurocognitive correlates of executive functions in individuals with Asperger syndrome (AS) compared to healthy controls. Results disclosed subtle group differences regarding response speed on only one CANTAB subtest that is thought to tap fronto-executive network functions (SWM/spatial working memory). Across all participants, SWM performance was significantly associated with two brain regions (precentral gyrus white matter, precuneus grey matter), thus suggesting a close link between fronto-executive functions (SWM) and circumscribed fronto-parietal brain structures. Finally, symptom severity (ADOS total score) was best predicted by response speed on a set-shifting task (IES) thought to tap fronto-striatal functions (corrected R(2) 56 %).
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5. Kim SH, Thurm A, Shumway S, Lord C. {{Multisite Study of New Autism Diagnostic Interview-Revised (ADI-R) Algorithms for Toddlers and Young Preschoolers}}. {J Autism Dev Disord};2012 (Nov 1)
Using two independent datasets provided by National Institute of Health funded consortia, the Collaborative Programs for Excellence in Autism and Studies to Advance Autism Research and Treatment (n = 641) and the National Institute of Mental Health (n = 167), diagnostic validity and factor structure of the new Autism Diagnostic Interview (ADI-R) algorithms for toddlers and young preschoolers were examined as a replication of results with the 2011 Michigan sample (Kim and Lord in J Autism Dev Disord 42(1): 82-93, 2012). Sensitivities and specificities and a three-factor solution were replicated. Results suggest that the new ADI-R algorithms can be appropriately applied to existing research databases with children from 12 to 47 months and down to nonverbal mental ages of 10 months for diagnostic grouping.
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6. Mori K, Toda Y, Ito H, Mori T, Goji A, Fujii E, Miyazaki M, Harada M, Kagami S. {{A proton magnetic resonance spectroscopic study in autism spectrum disorders: Amygdala and orbito-frontal cortex}}. {Brain Dev};2012 (Oct 29)
We previously reported neural dysfunction in the anterior cingulate cortex and dorsolateral prefrontal cortex in autistic patients using proton magnetic resonance spectroscopy ((1)H-MRS). In this investigation, we measured chemical metabolites in the left amygdala and the bilateral orbito-frontal cortex (OFC), which are the main components of the social brain. We also examined the association between these metabolic findings and social abilities in subjects with autism. The study group included 77 autistic patients (3-6years old; mean age 4.1; 57 boys and 20 girls). The control subjects were 31 children (3-6years old; mean age 4.0; 23 boys and 8 girls). Conventional proton MR spectra were obtained using the STEAM sequence with parameters of TR=5 sec and TE=15 msec by a 1.5-tesla clinical MRI system. We analyzed the concentrations of N-acetylaspartate (NAA), creatine/phosphocreatine (Cr), and choline-containing compounds (Cho) using LCModel (Ver. 6.1). The concentrations of NAA in the left amygdala and the bilateral OFC in autistic patients were significantly decreased compared to those in the control group. In the autistic patients, the NAA concentrations in these regions correlated with their social quotient. These findings suggest the presence of neuronal dysfunction in the amygdala and OFC in autism. Dysfunction in the amygdala and OFC may contribute to the pathogenesis of autism.
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7. Strid K, Heimann M, Tjus T. {{Pretend play, deferred imitation and parent-child interaction in speaking and non-speaking children with autism}}. {Scand J Psychol};2012 (Nov 2)
Strid, K., Heimann, M. & Tjus T. (2012). Pretend play, deferred imitation and parent-child interaction in speaking and non-speaking children with autism. Scandinavian Journal of Psychology. This study investigates spontaneous pretend play during a parent-child free play observation, and deferred imitation observed in an experimental setting in speaking and non-speaking children with autism in comparison to children with typical development. Both groups of children with autism showed a reduced level of deferred imitation compared to the typically developing group, but only the non-speaking children with autism spent significantly less time in pretend play compared to children with typical development. Deferred imitation was related to parents’ verbal interaction in both groups. An analysis of the parent-child interaction revealed that parents of children with autism used less synchronized comments compared to parents of typically developing children. Parents of the speaking group with autism used more synchronized than unsynchronized comments, while parents of the non-speaking group used the same amount of synchronized and unsynchronized comments. These findings are discussed in terms of how the developmental level affects behavior and interaction in autism.
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8. Uljarevic M, Hamilton A. {{Recognition of Emotions in Autism: A Formal Meta-Analysis}}. {J Autism Dev Disord};2012 (Nov 1)
Determining the integrity of emotion recognition in autistic spectrum disorder is important to our theoretical understanding of autism and to teaching social skills. Previous studies have reported both positive and negative results. Here, we take a formal meta-analytic approach, bringing together data from 48 papers testing over 980 participants with autism. Results show there is an emotion recognition difficulty in autism, with a mean effect size of 0.80 which reduces to 0.41 when a correction for publication bias is applied. Recognition of happiness was only marginally impaired in autism, but recognition of fear was marginally worse than recognition of happiness. This meta-analysis provides an opportunity to survey the state of emotion recognition research in autism and to outline potential future directions.
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9. Wei X, Yu JW, Shattuck P, McCracken M, Blackorby J. {{Science, Technology, Engineering, and Mathematics (STEM) Participation Among College Students with an Autism Spectrum Disorder}}. {J Autism Dev Disord};2012 (Nov 1)
Little research has examined the popular belief that individuals with an autism spectrum disorder (ASD) are more likely than the general population to gravitate toward science, technology, engineering, and mathematics (STEM) fields. This study analyzed data from the National Longitudinal Transition Study-2, a nationally representative sample of students with an ASD in special education. Findings suggest that students with an ASD had the highest STEM participation rates although their college enrollment rate was the third lowest among 11 disability categories and students in the general population. Disproportionate postsecondary enrollment and STEM participation by gender, family income, and mental functioning skills were found for young adults with an ASD. Educational policy implications are discussed.
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10. Zhang Y, Brown MR, Hyland C, Chen Y, Kronengold J, Fleming MR, Kohn AB, Moroz LL, Kaczmarek LK. {{Regulation of neuronal excitability by interaction of fragile x mental retardation protein with slack potassium channels}}. {J Neurosci};2012 (Oct 31);32(44):15318-15327.
Loss of the RNA-binding protein fragile X mental retardation protein (FMRP) represents the most common form of inherited intellectual disability. Studies with heterologous expression systems indicate that FMRP interacts directly with Slack Na(+)-activated K(+) channels (K(Na)), producing an enhancement of channel activity. We have now used Aplysia bag cell (BC) neurons, which regulate reproductive behaviors, to examine the effects of Slack and FMRP on excitability. FMRP and Slack immunoreactivity were colocalized at the periphery of isolated BC neurons, and the two proteins could be reciprocally coimmunoprecipitated. Intracellular injection of FMRP lacking its mRNA binding domain rapidly induced a biphasic outward current, with an early transient tetrodotoxin-sensitive component followed by a slowly activating sustained component. The properties of this current matched that of the native Slack potassium current, which was identified using an siRNA approach. Addition of FMRP to inside-out patches containing native Aplysia Slack channels increased channel opening and, in current-clamp recordings, produced narrowing of action potentials. Suppression of Slack expression did not alter the ability of BC neurons to undergo a characteristic prolonged discharge in response to synaptic stimulation, but prevented recovery from a prolonged inhibitory period that normally follows the discharge. Recovery from the inhibited period was also inhibited by the protein synthesis inhibitor anisomycin. Our studies indicate that, in BC neurons, Slack channels are required for prolonged changes in neuronal excitability that require new protein synthesis, and raise the possibility that channel-FMRP interactions may link changes in neuronal firing to changes in protein translation.
