1. Austerweil JL. {{Contradictory « heuristic » theories of autism spectrum disorders: The case for theoretical precision using computational models}}. {Autism}. 2014.
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2. Chanson JB, Boehm N, Samama B, Echaniz-Laguna A, Anheim M. {{Small fiber neuropathy in a woman with fragile X-associated tremor/ataxia syndrome (FXTAS)}}. {J Neurol}. 2014.
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3. Dudova I, Markova D, Kasparova M, Zemankova J, Beranova S, Urbanek T, Hrdlicka M. {{Comparison of three screening tests for autism in preterm children with birth weights less than 1,500 grams}}. {Neuropsychiatr Dis Treat}. 2014; 10: 2201-8.
BACKGROUND: Preterm children seem to be at increased risk for autism spectrum disorders (ASD). METHODS: Parents of 157 children with birth weights less than 1,500 g (age 2 years, corrected for prematurity; 88 boys, 69 girls) completed screening questionnaires. The screening battery included the Modified Checklist for Autism in Toddlers (M-CHAT), Communication and Symbolic Behavior Scales Developmental Profile Infant-Toddler Checklist (CSBS-DP-ITC), and the Infant/Toddler Sensory Profile (ITSP). Children with disabilities were excluded. All children who screened positive on any of the screening tools were subsequently assessed by clinical examination including the Autism Diagnostic Observation Schedule. RESULTS: Fifty-six children (35.7%) screened positive on at least one of the parental screening questionnaires. Of the 56 children who tested positive, 33 participated in the detailed clinical follow-up assessment. A diagnosis of ASD was confirmed in 13 of the 33 children. The ASD prevalence was 9.7% of the sample. Analysis of children with and without an ASD diagnosis found significant differences relative to gestational age (26.9 weeks vs 28.3 weeks, P=0.033) and length of the stay in hospital (89.5 days vs 75.4 days, P=0.042). The screening tool with the most positive results was CSBS-DP-ITC (42 positive screens [PS]), followed by M-CHAT (28 PS), and ITSP (22 PS). Differences in the frequency of PS among the tests were significant (P=0.008). CSBS-DP-ITC had the highest sensitivity (0.846), followed by M-CHAT (0.692) and ITSP (0.462). CONCLUSION: Our results indicate a higher prevalence of autism in children with birth weights <1,500 g at 2 years of age compared to the general population prevalence. The ASD diagnosis was associated with shorter gestation times and longer hospital stays. Our findings support the simultaneous use of more than one screening tests in order to increase screening sensitivity.
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4. Halevy T, Czech C, Benvenisty N. {{Molecular Mechanisms Regulating the Defects in Fragile X Syndrome Neurons Derived from Human Pluripotent Stem Cells}}. {Stem Cell Reports}. 2014.
Fragile X syndrome (FXS) is caused by the absence of the fragile X mental retardation protein (FMRP). We have previously generated FXS-induced pluripotent stem cells (iPSCs) from patients’ fibroblasts. In this study, we aimed at unraveling the molecular phenotype of the disease. Our data revealed aberrant regulation of neural differentiation and axon guidance genes in FXS-derived neurons, which are regulated by the RE-1 silencing transcription factor (REST). Moreover, we found REST to be elevated in FXS-derived neurons. As FMRP is involved in the microRNA (miRNA) pathway, we employed miRNA-array analyses and uncovered several miRNAs dysregulated in FXS-derived neurons. We found hsa-mir-382 to be downregulated in FXS-derived neurons, and introduction of mimic-mir-382 into these neurons was sufficient to repress REST and upregulate its axon guidance target genes. Our data link FMRP and REST through the miRNA pathway and show a new aspect in the development of FXS.
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5. Hartley SL, Mihaila I, Otalora-Fadner HS, Bussanich PM. {{Division of Labor in Families of Children and Adolescents with Autism Spectrum Disorder}}. {Fam Relat}. 2014; 63(5): 627-38.
Couples who have a child or adolescent with autism spectrum disorder (ASD) are faced with the difficult decision of how to divide childcare responsibilities and paid employment. We examined the division of labor and its relation to parenting stress and marital adjustment in 73 married couples who have a child or adolescent with ASD. Mothers and fathers independently reported on their global level of parenting stress and marital adjustment and then completed a 7-day online daily diary of time spent in childcare, time spent in paid employment, and satisfaction with the time that one’s spouse spent in childcare. Overall, couples demonstrated a pattern of partial role specialization in which mothers engaged in more childcare and fathers engaged in more paid employment. Child age was negatively related and degree of disability was positively related to role specialization. Time spent in paid employment and satisfaction with the time that one’s spouse spent in childcare had important associations with parenting stress and marital adjustment.
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6. Huddleston LB, Visootsak J, Sherman SL. {{Cognitive Aspects of Fragile X syndrome}}. {Wiley Interdiscip Rev Cogn Sci}. 2014; 5(4): 501-8.
Fragile X syndrome (FXS) is the leading inherited cause of intellectual disability. It is primarily caused by the expansion of a CGG trinucleodide repeat located in the 5′ untranslated region of the X-linked FMR1 gene. Individuals with FXS present with variable intellectual quotients (IQs) ranging from the average to the severe intellectual disability level. A range of neurocognitive strengths and challenges are observed in individuals with FXS. This article provides an overview of our current understanding related to cognition and FXS. Cognitive functioning levels, profiles, and IQ trajectories are discussed. Limitations of existing neuropsychological measures are described.
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7. Kim YS, Leventhal BL. {{Genetic Epidemiology and Insights into Interactive Genetic and Environmental Effects in Autism Spectrum Disorders}}. {Biol Psychiatry}. 2015; 77(1): 66-74.
Understanding the pathogenesis of neurodevelopmental disorders has proven to be challenging. Using autism spectrum disorder (ASD) as a paradigmatic neurodevelopmental disorder, this article reviews the existing literature on the etiological substrates of ASD and explores how genetic epidemiology approaches including gene-environment interactions (GxE) can play a role in identifying factors associated with ASD etiology. New genetic and bioinformatics strategies have yielded important clues to ASD genetic substrates. The next steps for understanding ASD pathogenesis require significant effort to focus on how genes and environment interact with one another in typical development and its perturbations. Along with larger sample sizes, future study designs should include sample ascertainment that is epidemiologic and population-based to capture the entire ASD spectrum with both categorical and dimensional phenotypic characterization; environmental measurements with accuracy, validity, and biomarkers; statistical methods to address population stratification, multiple comparisons, and GxE of rare variants; animal models to test hypotheses; and new methods to broaden the capacity to search for GxE, including genome-wide and environment-wide association studies, precise estimation of heritability using dense genetic markers, and consideration of GxE both as the disease cause and a disease course modifier. Although examination of GxE appears to be a daunting task, tremendous recent progress in gene discovery has opened new horizons for advancing our understanding of the role of GxE in the pathogenesis of ASD and ultimately identifying the causes, treatments, and even preventive measures for ASD and other neurodevelopmental disorders.
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8. Lukose R, Beebe K, Kulesza RJ. {{Organization of the human superior olivary complex in 15q duplication syndromes and autism spectrum disorders}}. {Neuroscience}. 2014.
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by a number of behavioral and social features. Although the etiology of most cases of ASD is idiopathic, a significant number of cases can be attributed to genetic causes, such as chromosome 15q duplications [dup(15q)]. Recent neuropathological investigations have provided evidence for distinct patterns of heterotopias and dysplasias in ASD and subjects with both ASD and dup(15q). Individuals with ASD characteristically have hearing difficulties and we have previously demonstrated significant and consistent hypoplasia in a number of auditory brainstem nuclei in subjects with ASD. Herein, we compare results from a morphometric investigation of auditory brainstem nuclei in subjects with ASD, dup(15q) and controls. Our observations in subjects with ASD support our previous reports. However, in subjects with dup(15q), we find significantly fewer neurons and in many nuclei, neurons were significantly smaller than in ASD subjects. Finally, we find a notably higher incidence of ectopic neurons in dup(15q). These results suggest that in the brainstem, these neuropathological conditions may evolve from some of the same developmental errors but are distinguished on microscopic features.
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9. Manning C, Baker DH. {{Response to Davis and Plaisted-Grant: Psychophysical data do not support the low-noise account of autism}}. {Autism}. 2014.
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10. Walker CK, Krakowiak P, Baker A, Hansen RL, Ozonoff S, Hertz-Picciotto I. {{Preeclampsia, Placental Insufficiency, and Autism Spectrum Disorder or Developmental Delay}}. {JAMA Pediatr}. 2014.
Importance: Increasing evidence suggests that autism spectrum disorder (ASD) and many forms of developmental delay (DD) originate during fetal development. Preeclampsia may trigger aberrant neurodevelopment through placental, maternal, and fetal physiologic mechanisms. Objective: To determine whether preeclampsia is associated with ASD and/or DD. Design, Setting, and Participants: The Childhood Autism Risks from Genetics and the Environment (CHARGE) study is a population-based, case-control investigation of ASD and/or DD origins. Children from 20 California counties aged 24 to 60 months at the time of recruitment and living in catchment areas with a biological parent fluent in English or Spanish were enrolled from January 29, 2003, through April 7, 2011. Children with ASD (n = 517) and DD (n = 194) were recruited through the California Department of Developmental Services, the Medical Investigation of Neurodevelopmental Disorders (MIND) Institute, and referrals. Controls with typical development (TD) (n = 350) were randomly selected from birth records and frequency matched on age, sex, and broad geographic region. Physicians diagnosing preeclampsia were masked to neurodevelopmental outcome, and those assessing neurodevelopmental function were masked to preeclampsia status. Exposures: Preeclampsia and placental insufficiency were self-reported and abstracted from medical records. Main Outcomes and Measures: The Autism Diagnostic Observation Schedule and Autism Diagnostic Interview-Revised were used to confirm ASD, whereas children with DD and TD were confirmed by Mullen Scales of Early Learning and Vineland Adaptive Behavior Scales and were free of autistic symptoms. Hypotheses were formulated before data collection. Results: Children with ASD were twice as likely to have been exposed in utero to preeclampsia as controls with TD after adjustment for maternal educational level, parity, and prepregnancy obesity (adjusted odds ratio, 2.36; 95% CI, 1.18-4.68); risk increased with greater preeclampsia severity (test for trend, P = .02). Placental insufficiency appeared responsible for the increase in DD risk associated with severe preeclampsia (adjusted odds ratio, 5.49; 95% CI, 2.06-14.64). Conclusions and Relevance: Preeclampsia, particularly severe disease, is associated with ASD and DD. Faulty placentation manifests in the mother as preeclampsia with vascular damage, enhanced systemic inflammation, and insulin resistance; in the placenta as oxygen and nutrient transfer restriction and oxidative stress; and in the fetus as growth restriction and progressive hypoxemia. All are potential mechanisms for neurodevelopmental compromise.
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11. Zalla T, Miele D, Leboyer M, Metcalfe J. {{Metacognition of agency and theory of mind in adults with high functioning autism}}. {Conscious Cogn}. 2014; 31C: 126-38.
We investigated metacognition of agency in adults with high functioning autism or Asperger Syndrome (HFA/AS) using a computer task in which participants moved the mouse to get the cursor to touch the downward moving X’s and avoid the O’s. They were then asked to make judgments of performance and judgments of agency. Objective control was either undistorted, or distorted by adding turbulence (i.e., random noise) or a time Lag between the mouse and cursor movements. Participants with HFA/AS used sensorimotor cues available in the turbulence and lag conditions to a lesser extent than control participants in making their judgments of agency. Furthermore, the failure to use these internal diagnostic cues to their own agency was correlated with decrements in a theory of mind task. These findings suggest that a reduced sensitivity to veridical internal cues about the sense of agency is related to mentalizing impairments in autism.
