1. Arons MH, Thynne CJ, Grabrucker AM, Li D, Schoen M, Cheyne JE, Boeckers TM, Montgomery JM, Garner CC. {{Autism-Associated Mutations in ProSAP2/Shank3 Impair Synaptic Transmission and Neurexin-Neuroligin-Mediated Transsynaptic Signaling}}. {J Neurosci};2012 (Oct 24);32(43):14966-14978.
Mutations in several postsynaptic proteins have recently been implicated in the molecular pathogenesis of autism and autism spectrum disorders (ASDs), including Neuroligins, Neurexins, and members of the ProSAP/Shank family, thereby suggesting that these genetic forms of autism may share common synaptic mechanisms. Initial studies of ASD-associated mutations in ProSAP2/Shank3 support a role for this protein in glutamate receptor function and spine morphology, but these synaptic phenotypes are not universally penetrant, indicating that other core facets of ProSAP2/Shank3 function must underlie synaptic deficits in patients with ASDs. In the present study, we have examined whether the ability of ProSAP2/Shank3 to interact with the cytoplasmic tail of Neuroligins functions to coordinate pre/postsynaptic signaling through the Neurexin-Neuroligin signaling complex in hippocampal neurons of Rattus norvegicus. Indeed, we find that synaptic levels of ProSAP2/Shank3 regulate AMPA and NMDA receptor-mediated synaptic transmission and induce widespread changes in the levels of presynaptic and postsynaptic proteins via Neurexin-Neuroligin transsynaptic signaling. ASD-associated mutations in ProSAP2/Shank3 disrupt not only postsynaptic AMPA and NMDA receptor signaling but also interfere with the ability of ProSAP2/Shank3 to signal across the synapse to alter presynaptic structure and function. These data indicate that ASD-associated mutations in a subset of synaptic proteins may target core cellular pathways that coordinate the functional matching and maturation of excitatory synapses in the CNS.
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2. Bailey DB, Jr., Bann C, Bishop E, Guarda S, Barnum L, Roche M. {{Can a decision aid enable informed decisions in neonatal nursery recruitment for a fragile X newborn screening study?}}. {Genet Med};2012 (Oct 25)
Purpose:To determine whether a brochure based on principles of informed decision making improved attention to study materials or altered decisions made by parents invited to participate in a fragile X syndrome newborn screening study.Methods:A total of 1,323 families were invited to participate in a newborn screening study to identify infants with fragile X syndrome as well as premutation carrier infants. Of these families, 716 received the original project brochure and 607 were given a new decision aid brochure.Results:Families were more likely to look at the new decision aid and mothers were more likely to read it completely, but the proportion of mothers who read the entire decision aid was only 14%. Families were more likely to rate the decision aid as very helpful. Consistent with informed decision making theory and research, participants receiving the decision aid brochure were less likely to agree to participate.Conclusion:The decision aid increased attention to and perceived helpfulness of educational information about the study, but most families did not read it completely. The study suggests that even well-designed study materials are not fully reviewed in the context of in-hospital postpartum study recruitment and may need to be accompanied by a research recruiter to obtain informed consent.Genet Med advance online publication 25 October 2012.Genetics in Medicine (2012); doi:10.1038/gim.2012.135.
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3. Benson PR. {{Erratum to: Network Characteristics, Perceived Social Support, and Psychological Adjustment in Mothers of Children with Autism Spectrum Disorder}}. {J Autism Dev Disord};2012 (Oct 26)
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4. Bowling FG, Heussler HS, McWhinney A, Dawson PA. {{Plasma and Urinary Sulfate Determination in a Cohort with Autism}}. {Biochem Genet};2012 (Oct 27)
Sulfate is important for mammalian development but is not routinely measured in clinical settings. The renal NaS1 sulfate transporter maintains circulating sulfate levels and is linked to renal sulfate wasting in mice. Some autistic individuals exhibit renal sulfate wasting, but the etiology is yet unknown. We measured plasma and urinary sulfate levels, calculated the fractional excretion index (FEI) of sulfate, and screened for two loss-of-function NaS1 sequence variants (R12X and N174S) in 23 autistic individuals. The FEI sulfate values ranged from 0.13 to 0.50. NaS1 variants were detected in 18 of the 23 individuals (11 heterozygous N174S, four homozygous N174S, two heterozygous R12X, and one individual carried both R12X and N174S). Those individuals with neither sequence variant had FEI sulfate </= 0.34, whereas FEI sulfate >/= 0.35 was found in about 60 % (11 of 18) of individuals that had R12X and/or N174S. This study links renal sulfate wasting with loss-of-function NaS1 sequence variants in humans.
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5. Good P. {{Does infectious fever relieve autistic behavior by releasing glutamine from skeletal muscles as provisional fuel?}}. {Med Hypotheses};2012 (Oct 23)
First reported formally in 1980, the frequent ability of infectious fever to relieve autistic behavior, often dramatically (and rarely aggravate), has long tantalized parents, practitioners, and researchers – yet its physiology and biochemistry have never been investigated, to judge from the literature. Fever is a complex interplay of immune, metabolic, and stress responses, yet its benefit in autistic disorders (ASD) may derive largely from a single response – release of the amino acid glutamine from skeletal muscles as provisional fuel. This proposal is based on evidence of low blood and brain glutamine in ASD children and adults, notable lack of autistic behavior in children with high brain glutamine from urea cycle disorders, and other events that elicit dramatic improvements – fasting, panic, pain, and the corticosteroid prednisone – that release or synthesize glutamine. Glutamine released from muscles is metabolized by the intestines like ingested glutamine. If glutamine released by fever rarely aggravates autistic behavior, why would supplemental glutamine?
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6. Jones KL, Will MJ, Hecht PM, Parker CL, Beversdorf DQ. {{Maternal Diet Rich in Omega-6 Polyunsaturated Fatty Acids during Gestation and Lactation Produces Autistic-Like Sociability Deficits in Adult Offspring}}. {Behav Brain Res};2012 (Oct 22)
Multiple studies have reported prenatal stress as a potential risk factor for the development of autism spectrum disorder (ASD). In rodents, a significant reduction in sociability is seen in prenatally stressed offspring of genetically stress-susceptible dams. Certain dietary factors that contribute to stress reactivity may, therefore, exacerbate prenatal stress-mediated behavioral changes in adult offspring. Adults with a diet rich in omega-6 polyunsaturated fatty acids (PUFAs) display increased stress reactivity. In the current study, the effects of prenatal diet and prenatal stress on social behavior in adult offspring mice were examined. Pregnant C57BL/6J dams received either chronic variable stress or no stress, and were also placed on a control diet or a diet rich in omega-6 PUFAs, in a 2×2 design. We subsequently tested the adult offspring for sociability, anxiety, and locomotor behaviors using a 3-chambered social approach task, an elevated-plus maze, an open field task and a rotarod task. Results indicated that a maternal diet rich in omega-6 PUFAs during gestation and lactation produce changes in sociability consistent with those observed in ASD. Additionally, offspring exposed to a diet rich in omega-6 PUFAs during gestation and lactation had increased levels of anxiety in the elevated-plus maze. Prenatal stress had no effect on offspring behavior. These findings provide evidence for a possible environmental risk factor that contributes to the production of autistic-like behavior in mice.
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7. Koldewyn K, Weigelt S, Kanwisher N, Jiang Y. {{Multiple Object Tracking in Autism Spectrum Disorders}}. {J Autism Dev Disord};2012 (Oct 27)
Difficulties in visual attention are often implicated in autism spectrum disorders (ASD) but it remains unclear which aspects of attention are affected. Here, we used a multiple object tracking (MOT) task to quantitatively characterize dynamic attentional function in children with ASD aged 5-12. While the ASD group performed significantly worse overall, the group difference did not increase with increased object speed. This finding suggests that decreased MOT performance is not due to deficits in dynamic attention but instead to a diminished capacity to select and maintain attention on multiple targets. Further, MOT performance improved from 5 to 10 years in both typical and ASD groups with similar developmental trajectories. These results argue against a specific deficit in dynamic attention in ASD.
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8. Mitterauer BJ. {{Astrocyte mega-domain hypothesis of the autistic savantism}}. {Med Hypotheses};2012 (Oct 22)
Individuals with autism who show high abilities are called savants. Whereas in their brains a disconnection in and between neural networks has been identified, savantism is yet poorly understood. Focusing on astrocyte domain organization, it is hypothesized that local astrocyte mega-organizations may be responsible for exerting high capabilities in brains of autistic savants. Astrocytes, the dominant glial cell type, modulate synaptic information transmission. Each astrocyte is organized in non-overlapping domains. Formally, each astrocyte contacting n-neurons with m-synapses via its processes generates dynamic domains of synaptic interactions based on qualitative computation criteria, and hereby it structures neuronal information processing. If the number of processes is genetically significantly increased, these astrocytes operate in a mega-domain with a higher complexitiy of computation. From this model savant abilities are deduced.
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9. Papadopoulos N, Rinehart N, Bradshaw JL, McGinley JL. {{Brief Report: Children with ADHD Without Co-morbid Autism do not have Impaired Motor Proficiency on the Movement Assessment Battery for Children}}. {J Autism Dev Disord};2012 (Oct 26)
Motor proficiency was investigated in a sample of children with Attention Deficit Hyperactivity Disorder-Combined type (ADHD-CT) without autism. Accounting for the influence of co-morbid autistic symptoms in ADHD motor studies is vital given that motor impairment has been linked to social-communication symptoms in children who have co-morbid ADHD and autistic-like symptoms. Two groups of children aged between 7-14 years were recruited; children with ADHD-CT (n = 16; mean age 10 years, 7 months [SD = 1 year, 10 months]) and a typically developing (n = 16; mean age 10 years, 6 months [SD = 2 years, 6 months]) group. Motor proficiency was measured using the Movement Assessment Battery for Children-2nd Edition, ADHD symptoms were measured using the Conner’s Parent Rating Scale. Children with ADHD-CT who had been screened for co-morbid autism did not display motor difficulties on the MABC-2. Higher levels of inattention, but not hyperactivity or impulsivity were associated with poorer motor performance. These findings provide indirect evidence that the motor problems that children with ADHD experience may be related to co-occurring social responsiveness impairments.
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10. Reinvall O, Voutilainen A, Kujala T, Korkman M. {{Neurocognitive Functioning in Adolescents with Autism Spectrum Disorder}}. {J Autism Dev Disord};2012 (Oct 27)
There is a paucity of research studying comprehensive neurocognitive profiles of adolescents with higher functioning autism spectrum disorders (ASD). This study compared the neurocognitive profiles of higher functioning adolescents with ASD (n = 30, mean age 13.5) with that of typically developing adolescents (n = 30; mean age 13.7). Adolescents with ASD demonstrated a significantly higher mean Verbal Intelligence Quotient compared to the standardized mean. However, the ASD group had significantly lower scores than the control group on the subtests Auditory Attention and Response Set, Memory for Faces, Visuomotor Precision, and Design Copying. Thus, particular strengths were seen in verbal reasoning, while weaknesses were observed in auditory attention, facial recognition memory, and visuomotor functions in adolescents with ASD.
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11. Scahill L, Hallett V, Aman MG, McDougle CJ, Eugene Arnold L, McCracken JT, Tierney E, Deng Y, Dziura J, Vitiello B. {{Brief Report: Social Disability in Autism Spectrum Disorder: Results from Research Units on Pediatric Psychopharmacology (RUPP) Autism Network Trials}}. {J Autism Dev Disord};2012 (Oct 27)
There is growing interest in measuring social disability as a core element of autism spectrum disorders in medication trials. We conducted a secondary analysis on the Aberrant Behavior Checklist Social Withdrawal subscale using data from two federally-funded, multi-site, randomized trials with risperidone. Study 1 included 52 subjects assigned to placebo and 49 subjects to risperidone under double-blind conditions. Study 2 included 49 subjects assigned to risperidone only and 75 subjects assigned to risperidone plus parent training. After 8 weeks of treatment, all active treatments were superior to placebo (effect sizes ranging from 0.42 to 0.65). The findings suggest that the Social Withdrawal subscale may be a useful measure of social disability in acute treatment trials.
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12. van Rijn S, de Sonneville L, Lahuis B, Pieterse J, van Engeland H, Swaab H. {{Executive Function in MCDD and PDD-NOS: A Study of Inhibitory Control, Attention Regulation and Behavioral Adaptivity}}. {J Autism Dev Disord};2012 (Oct 27)
A proportion of children within the autism spectrum is at risk for severe deregulation of thought, emotion and behaviour resulting in (symptoms of) psychotic disorders over the course of development. In an attempt to identify this subgroup, children with PDD-NOS, subtype MCDD (n = 24) were compared to children with PDD-NOS (n = 23) on executive function (EF) skills. Significant differences emerged, always to the disadvantage of the children with PDD-NOS, subtype MCDD on various EF measures. The findings suggest compromised attention regulation and impaired inhibitory control in children with MCDD, which may help explain high levels of thought problems which are frequently observed in these children. Our findings provide evidence for recognizing a PDD subcategory of MCDD that is of specific interest with regard to long-term developmental risks involved.
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13. Zablotsky B, Bradshaw CP, Stuart EA. {{The Association Between Mental Health, Stress, and Coping Supports in Mothers of Children with Autism Spectrum Disorders}}. {J Autism Dev Disord};2012 (Oct 26)
Raising a child with an autism spectrum disorder (ASD) can be a stressful experience for parents. When left unmanaged, high stress levels can lead to the development of depressive symptomatology, highlighting the importance of coping supports. The current paper examined the stress level and psychological wellbeing of mothers with a child with ASD in a national survey. After adjusting for child, mother and family level characteristics, it was determined that mothers of children with ASDs were at greater risk for poor mental health and high stress levels compared to mothers of children without ASDs. The presence of maternal coping strategies, in the form of emotional and neighborhood social supports, as well as strong coping skills, reduced these risks between models.
