1. {{Neurodevelopmental disorders: No evidence for efficiency of weighted blankets in improving sleep in children with autism spectrum disorder}}. {Nat Rev Neurol};2014 (Jul 22)
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2. Bacchelli E, Ceroni F, Pinto D, Lomartire S, Giannandrea M, D’Adamo P, Bonora E, Parchi P, Tancredi R, Battaglia A, Maestrini E. {{A CTNNA3 compound heterozygous deletion implicates a role for alphaT-catenin in susceptibility to autism spectrum disorder}}. {J Neurodev Disord};2014;6(1):17.
BACKGROUND: Autism spectrum disorder (ASD) is a highly heritable, neurodevelopmental condition showing extreme genetic heterogeneity. While it is well established that rare genetic variation, both de novo and inherited, plays an important role in ASD risk, recent studies also support a rare recessive contribution. METHODS: We identified a compound heterozygous deletion intersecting the CTNNA3 gene, encoding alphaT-catenin, in a proband with ASD and moderate intellectual disability. The deletion breakpoints were mapped at base-pair resolution, and segregation analysis was performed. We compared the frequency of CTNNA3 exonic deletions in 2,147 ASD cases from the Autism Genome Project (AGP) study versus the frequency in 6,639 controls. Western blot analysis was performed to get a quantitative characterisation of Ctnna3 expression during early brain development in mouse. RESULTS: The CTNNA3 compound heterozygous deletion includes a coding exon, leading to a putative frameshift and premature stop codon. Segregation analysis in the family showed that the unaffected sister is heterozygote for the deletion, having only inherited the paternal deletion. While the frequency of CTNNA3 exonic deletions is not significantly different between ASD cases and controls, no homozygous or compound heterozygous exonic deletions were found in a sample of over 6,000 controls. Expression analysis of Ctnna3 in the mouse cortex and hippocampus (P0-P90) provided support for its role in the early stage of brain development. CONCLUSION: The finding of a rare compound heterozygous CTNNA3 exonic deletion segregating with ASD, the absence of CTNNA3 homozygous exonic deletions in controls and the high expression of Ctnna3 in both brain areas analysed implicate CTNNA3 in ASD susceptibility.
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3. Dykens EM, Fisher MH, Taylor JL, Lambert W, Miodrag N. {{Reducing Distress in Mothers of Children With Autism and Other Disabilities: A Randomized Trial}}. {Pediatrics};2014 (Jul 21)
BACKGROUND: Compared with other parents, mothers of children with autism spectrum disorder or other neurodevelopmental disabilities experience more stress, illness, and psychiatric problems. Although the cumulative stress and disease burden of these mothers is exceptionally high, and associated with poorer outcomes in children, policies and practices primarily serve the identified child with disabilities.METHODS: A total of 243 mothers of children with disabilities were consented and randomized into either Mindfulness-Based Stress Reduction (mindfulness practice) or Positive Adult Development (positive psychology practice). Well-trained, supervised peer mentors led 6 weeks of group treatments in 1.5-hour weekly sessions, assessing mothers 6 times before, during, and up to 6 months after treatment. Mothers had children with autism (65%) or other disabilities (35%). At baseline, 85% of this community sample had significantly elevated stress, 48% were clinically depressed, and 41% had anxiety disorders.RESULTS: Using slopes-as-outcomes, mixed random effects models, both treatments led to significant reductions in stress, depression, and anxiety, and improved sleep and life satisfaction, with large effects in depression and anxiety. Mothers in Mindfulness-Based Stress Reduction versus Positive Adult Development had greater improvements in anxiety, depression, sleep, and well-being. Mothers of children with autism spectrum disorder improved less in anxiety, but did not otherwise differ from their counterparts.CONCLUSIONS: Future studies are warranted on how trained mentors and professionals can address the unmet mental health needs of mothers of children with developmental disabilities. Doing so improves maternal well-being and furthers their long-term caregiving of children with complex developmental, physical, and behavioral needs.
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4. Oberman LM, Pascual-Leone A. {{Hyperplasticity in Autism Spectrum Disorder confers protection from Alzheimer’s disease}}. {Med Hypotheses};2014 (Jun 17)
Autism Spectrum Disorders (ASD) currently affects approximately 1% of the population causing grave disability and necessitating a better understanding of the currently enigmatic etiology of these disorders. Recent data suggest that some patients with ASD may have a dysfunction in brain plasticity (specifically data from animal models and human studies suggest a propensity toward excessive amount of plasticity). Plasticity is essential to the establishment and maintenance of brain circuitry; however, too much plasticity may lead to instability of structural connections and compromise of functional systems necessary for cognition and behavior. Multiple lines of evidence suggest that plasticity declines throughout the age-span and may underlie age-related cognitive decline. We hypothesize that individuals whose cortex begins as relatively « hyperplastic » (such as may be seen in ASD) should then be relatively protected from age-related cognitive decline (which we suggest is related to a reduction in plasticity). In the current study, we conducted a multiple linear regression using age and diagnosis as predictor variables in order to evaluate strength of the relationship between age, diagnosis or an interaction of the two factors and the degree of modulation in cortical excitability by transcranial magnetic stimulation as an index of cortical plasticity. Results indicate that across the age-span individuals with ASD show a consistently increased modulation of cortical excitability as compared to typically developing individuals, such that the general slope of decline across the age span is matched across both groups. We have argued that an individual’s risk of age-related cognitive decline (and risk for manifesting symptoms of dementia) depends on the individual’s starting point and slopes of change in plasticity efficiency over the lifespan. Therefore, our results suggest that individuals with ASD might be relatively protected from age-related cognitive decline and the risk of dementia.
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5. Tebartz van Elst L, Maier S, Fangmeier T, Endres D, Mueller GT, Nickel K, Ebert D, Lange T, Hennig J, Biscaldi M, Riedel A, Perlov E. {{Disturbed cingulate glutamate metabolism in adults with high-functioning autism spectrum disorder: evidence in support of the excitatory/inhibitory imbalance hypothesis}}. {Mol Psychiatry};2014 (Jul 22)
Over the last few years, awareness of autism spectrum disorder (ASD) in adults has increased. The precise etiology of ASD is still unresolved. Animal research, genetic and postmortem studies suggest that the glutamate (Glu) system has an important role, possibly related to a cybernetic imbalance between neuronal excitation and inhibition. To clarify the possible disruption of Glu metabolism in adults with high-functioning autism, we performed a magnetic resonance spectroscopy (MRS) study investigating the anterior cingulate cortex (ACC) and the cerebellum in adults with high-functioning ASD. Twenty-nine adult patients with high-functioning ASD and 29 carefully matched healthy volunteers underwent MRS scanning of the pregenual ACC and the left cerebellar hemisphere. Metabolic data were compared between groups and were correlated with psychometric measures of autistic features. We found a significant decrease in the cingulate N-acetyl-aspartate (NAA) and the combined Glu and glutamine (Glx) signals in adults with ASD, whereas we did not find other metabolic abnormalities in the ACC or the cerebellum. The Glx signal correlated significantly with psychometric measures of autism, particularly with communication deficits. Our data support the hypothesis that there is a link between disturbances of the cingulate NAA and Glx metabolism, and autism. The findings are discussed in the context of the hypothesis of excitatory/inhibitory imbalance in autism. Further research should clarify the specificity and dynamics of these findings regarding other neuropsychiatric disorders and other brain areas.Molecular Psychiatry advance online publication, 22 July 2014; doi:10.1038/mp.2014.62.
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6. von Ehrenstein OS, Aralis H, Cockburn M, Ritz B. {{In Utero Exposure to Toxic Air Pollutants and Risk of Childhood Autism}}. {Epidemiology};2014 (Jul 22)
BACKGROUND:: Genetic and environmental factors are believed to contribute to the development of autism, but relatively few studies have considered potential environmental risks. Here, we examine risks for autism in children related to in utero exposure to monitored ambient air toxics from urban emissions. METHODS:: Among the cohort of children born in Los Angeles County, California, 1995-2006, those whose mothers resided during pregnancy in a 5-km buffer around air toxics monitoring stations were included (n = 148,722). To identify autism cases in this cohort, birth records were linked to records of children diagnosed with primary autistic disorder at the California Department of Developmental Services between 1998 and 2009 (n = 768). We calculated monthly average exposures during pregnancy for 24 air toxics selected based on suspected or known neurotoxicity or neurodevelopmental toxicity. Factor analysis helped us identify the correlational structure among air toxics, and we estimated odds ratios (ORs) for autism from logistic regression analyses. RESULTS:: Autism risks were increased per interquartile range increase in average concentrations during pregnancy of several correlated toxics mostly loading on 1 factor, including 1,3-butadiene (OR = 1.59 [95% confidence interval = 1.18-2.15]), meta/para-xylene (1.51 [1.26-1.82]), other aromatic solvents, lead (1.49 [1.23-1.81]), perchloroethylene (1.40 [1.09-1.80]), and formaldehyde (1.34 [1.17-1.52]), adjusting for maternal age, race/ethnicity, nativity, education, insurance type, parity, child sex, and birth year. CONCLUSIONS:: Risks for autism in children may increase following in utero exposure to ambient air toxics from urban traffic and industry emissions, as measured by community-based air-monitoring stations.
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7. Wee CY, Wang L, Shi F, Yap PT, Shen D. {{Diagnosis of autism spectrum disorders using regional and interregional morphological features}}. {Hum Brain Mapp};2014 (Jul);35(7):3414-3430.
This article describes a novel approach to identify autism spectrum disorder (ASD) utilizing regional and interregional morphological patterns extracted from structural magnetic resonance images. Two types of features are extracted to characterize the morphological patterns: (1) Regional features, which includes the cortical thickness, volumes of cortical gray matter, and cortical-associated white matter regions, and several subcortical structures extracted from different regions-of-interest (ROIs); (2) Interregional features, which convey the morphological change pattern between pairs of ROIs. We demonstrate that the integration of regional and interregional features via multi-kernel learning technique can significantly improve the classification performance of ASD, compared with using either regional or interregional features alone. Specifically, the proposed framework achieves an accuracy of 96.27% and an area of 0.9952 under the receiver operating characteristic curve, indicating excellent diagnostic power and generalizability. The best performance is achieved when both feature types are weighted approximately equal, indicating complementary between these two feature types. Regions that contributed the most to classification are in line with those reported in the previous studies, particularly the subcortical structures that are highly associated with human emotional modulation and memory formation. The autistic brains demonstrate a significant rightward asymmetry pattern particularly in the auditory language areas. These findings are in agreement with the fact that ASD is a behavioral- and language-related neurodevelopmental disorder. By concurrent consideration of both regional and interregional features, the current work presents an effective means for better characterization of neurobiological underpinnings of ASD that facilitates its identification from typically developing children.
