1. 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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2. Gaugler T, Klei L, Sanders SJ, Bodea CA, Goldberg AP, Lee AB, Mahajan M, Manaa D, Pawitan Y, Reichert J, Ripke S, Sandin S, Sklar P, Svantesson O, Reichenberg A, Hultman CM, Devlin B, Roeder K, Buxbaum JD. {{Most genetic risk for autism resides with common variation}}. {Nat Genet};2014 (Jul 20)
A key component of genetic architecture is the allelic spectrum influencing trait variability. For autism spectrum disorder (herein termed autism), the nature of the allelic spectrum is uncertain. Individual risk-associated genes have been identified from rare variation, especially de novo mutations. From this evidence, one might conclude that rare variation dominates the allelic spectrum in autism, yet recent studies show that common variation, individually of small effect, has substantial impact en masse. At issue is how much of an impact relative to rare variation this common variation has. Using a unique epidemiological sample from Sweden, new methods that distinguish total narrow-sense heritability from that due to common variation and synthesis of results from other studies, we reach several conclusions about autism’s genetic architecture: its narrow-sense heritability is approximately 52.4%, with most due to common variation, and rare de novo mutations contribute substantially to individual liability, yet their contribution to variance in liability, 2.6%, is modest compared to that for heritable variation.
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3. Naganathan AN, Munoz V. {{Thermodynamics of Downhill Folding: Multi-Probe Analysis of PDD, a Protein that Folds Over a Marginal Free Energy Barrier}}. {J Phys Chem B};2014 (Jul 21)
Downhill folding proteins fold in microseconds by crossing a very low or no free energy barrier (<3 RT), and exhibit a complex unfolding behavior in equilibrium. Such unfolding complexity is due to the weak thermodynamic coupling that exists between the various structural segments of these proteins, and it is manifested in unfolding curves that differ depending on the structural probe employed to monitor the process. Probe-dependent unfolding has important practical implications because it permits one to investigate the folding energy landscape in detail using multiprobe thermodynamic experiments. This type of thermodynamic behavior has been investigated in depth on the protein BBL, an example of extreme (one-state) downhill folding in which there is no free energy barrier at any condition, including the denaturation midpoint. However, an open question is, to what extent is such thermodynamic behavior observed on less extreme downhill folders? Here we perform a multiprobe spectroscopic characterization of the microsecond folder PDD, a structural and functional homologue of BBL that folds within the downhill regime, but is not an example of one-state downhill folding; rather at the denaturation midpoint PDD folds by crossing an incipient free energy barrier. Model-free analysis of the unfolding curves from four different spectroscopic probes together with differential scanning calorimetry reveals a dispersion of approximately 9 K in the apparent melting temperature and also marked differences in unfolding broadness (from approximately 50 to approximately 130 kJ mol-1 when analyzed with a two-state model), confirming that such properties are also observed on less extreme downhill folders. We subsequently perform a global quantitative analysis of the unfolding data of PDD using the same ME statistical mechanical model that was used before for the BBL domain. The analysis shows that this simple model captures all of the features observed on the unfolding of PDD (i.e., the intensity and temperature dependence of the different spectroscopic signals). From the model we estimate a free energy landscape for PDD in which the maximal thermodynamic barrier (i.e., at the denaturation midpoint) is only approximately 0.5 RT, consistent with previous independent estimates. Our results highlight that multiprobe unfolding experiments in equilibrium combined with statistical mechanical modeling provide important insights into the structural events that take place during the unfolding process of downhill proteins, and thus effectively probe the free energy landscape of these proteins.
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4. 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.
