1. Becerra TA, von Ehrenstein OS, Heck JE, Olsen J, Arah OA, Jeste SS, Rodriguez M, Ritz B. {{Autism Spectrum Disorders and Race, Ethnicity, and Nativity: A Population-Based Study}}. {Pediatrics};2014 (Jun 23)
OBJECTIVE: Our understanding of the influence of maternal race/ethnicity and nativity and childhood autistic disorder (AD) in African Americans/blacks, Asians, and Hispanics in the United States is limited. Phenotypic differences in the presentation of childhood AD in minority groups may indicate etiologic heterogeneity or different thresholds for diagnosis. We investigated whether the risk of developing AD and AD phenotypes differed according to maternal race/ethnicity and nativity.METHODS: Children born in Los Angeles County with a primary AD diagnosis at ages 3 to 5 years during 1998-2009 were identified and linked to 1995-2006 California birth certificates (7540 children with AD from a cohort of 1 626 354 births). We identified a subgroup of children with AD and a secondary diagnosis of mental retardation and investigated heterogeneity in language and behavior.RESULTS: We found increased risks of being diagnosed with AD overall and specifically with comorbid mental retardation in children of foreign-born mothers who were black, Central/South American, Filipino, and Vietnamese, as well as among US-born Hispanic and African American/black mothers, compared with US-born whites. Children of US African American/black and foreign-born black, foreign-born Central/South American, and US-born Hispanic mothers were at higher risk of exhibiting an AD phenotype with both severe emotional outbursts and impaired expressive language than children of US-born whites.CONCLUSIONS: Maternal race/ethnicity and nativity are associated with offspring’s AD diagnosis and severity. Future studies need to examine factors related to nativity and migration that may play a role in the etiology as well as identification and diagnosis of AD in children.
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2. Castro J, Garcia RI, Kwok S, Banerjee A, Petravicz J, Woodson J, Mellios N, Tropea D, Sur M. {{Functional recovery with recombinant human IGF1 treatment in a mouse model of Rett Syndrome}}. {Proc Natl Acad Sci U S A};2014 (Jun 23)
Rett Syndrome is a neurodevelopmental disorder that arises from mutations in the X-linked gene methyl-CpG binding protein 2 (MeCP2). MeCP2 has a large number of targets and a wide range of functions, suggesting the hypothesis that functional signaling mechanisms upstream of synaptic and circuit maturation may contribute to our understanding of the disorder and provide insight into potential treatment. Here, we show that insulin-like growth factor-1 (IGF1) levels are reduced in young male Mecp2-null (Mecp2-/y) mice, and systemic treatment with recombinant human IGF1 (rhIGF1) improves lifespan, locomotor activity, heart rate, respiration patterns, and social and anxiety behavior. Furthermore, Mecp2-null mice treated with rhIGF1 show increased synaptic and activated signaling pathway proteins, enhanced cortical excitatory synaptic transmission, and restored dendritic spine densities. IGF1 levels are also reduced in older, fully symptomatic heterozygous (Mecp2-/+) female mice, and short-term treatment with rhIGF1 in these animals improves respiratory patterns, reduces anxiety levels, and increases exploratory behavior. In addition, rhIGF1 treatment normalizes abnormally prolonged plasticity in visual cortex circuits of adult Mecp2-/+ female mice. Our results provide characterization of the phenotypic development of Rett Syndrome in a mouse model at the molecular, circuit, and organismal levels and demonstrate a mechanism-based therapeutic role for rhIGF1 in treating Rett Syndrome.
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3. Funahashi Y, Karashima C, Hoshiyama M. {{Compensatory Postural Sway While Seated Posture During Tasks in Children with Autism Spectrum Disorder}}. {Occup Ther Int};2014 (Jun 23)
Postural stability while seated was investigated in 16 children with autism spectrum disorder (ASD) and 16 typically developed (TD) children, aged 7-8 years. The lateral and antero-posterior (A-P) deviations of the centre of pressure (COP) were serially measured during sequential, upper limb, desk-top tasks, including nine subtests. The average COP deviation was larger, especially in the lateral direction, in the group of children with ASD compared with TD children. However, the larger COP deviation in the children with ASD was not generalized across tasks. Analyses of subtests revealed that deviations were different on three and four (of eight) subtests in the lateral and A-P directions, respectively. The time needed to complete each subtest was not correlated with the lateral COP deviation but with A-P deviation during the subtest in the children with ASD. Preserved task performance with marked body sway in the children with ASD suggested that the body sway was not a functionally abnormal movement that disturbed performance but could be a compensatory movement to actually facilitate performance. A new approach with occupational therapy to support such compensatory movement of ASD children could be considered in their school life. Further studies, including those in the classroom, to clarify the relationship between daily task performance and body instability are necessary. Copyright (c) 2014 John Wiley & Sons, Ltd.
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4. Grainger C, Williams DM, Lind SE. {{Metacognition, Metamemory, and Mindreading in High-Functioning Adults With Autism Spectrum Disorder}}. {J Abnorm Psychol};2014 (Jun 23)
Metacognition refers to cognition about cognition and encompasses both knowledge of cognitive processes and the ability to monitor and control one’s own cognitions. The current study aimed to establish whether metacognition is impaired in autism spectrum disorder (ASD). According to some theories, the ability to represent one’s own mental states (an aspect of metacognition) relies on the same mechanism as the ability to represent others’ mental states (« mindreading »). Given numerous studies have shown mindreading is impaired in ASD, there is good reason to predict concurrent impairments in metacognition. Metacognition is most commonly explored in the context of memory, often by assessing people’s ability to monitor their memory processes. The current study addressed the question of whether people with ASD have difficulty monitoring the contents of their memory (alongside impaired mindreading). Eighteen intellectually high-functioning adults with ASD and 18 IQ- and age-matched neurotypical adults participated. Metamemory monitoring ability and mindreading ability were assessed by using a feeling-of-knowing task and the « animations » task, respectively. Participants also completed a self-report measure of metacognitive ability. In addition to showing impaired mindreading, participants with ASD made significantly less accurate feeling-of-knowing judgments than neurotypical adults, suggesting that metamemory monitoring (an aspect of metacognition) was impaired. Conversely, participants with ASD self-reported superior metacognitive abilities compared with those reported by neurotypical participants. This study provides evidence that individuals with ASD have metamemory monitoring impairments. The theoretical and practical implications of these findings for our current understanding of metacognition in ASD and typical development are discussed. (PsycINFO Database Record (c) 2014 APA, all rights reserved).
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5. Kasari C, Lawton K, Shih W, Barker TV, Landa R, Lord C, Orlich F, King B, Wetherby A, Senturk D. {{Caregiver-Mediated Intervention for Low-Resourced Preschoolers With Autism: An RCT}}. {Pediatrics};2014 (Jun 23)
OBJECTIVES: To compare 2 short-term, community caregiver training interventions for preschool-aged children with Autism Spectrum Disorder who had low resources. Low resource was defined by the US Department of Housing and Urban Development low-income index or 1 « indicator, » (eg, Medicaid eligibility). Child outcomes focused on joint engagement, joint attention, and play.METHODS: Participants included 112 families of a child who had Autism Spectrum Disorder who met criteria for being low-resourced and who were randomly assigned to 1 of 2 3-month interventions, group caregiver education or individualized caregiver-mediated intervention (CMM). Children were assessed for social communication skills pre- and post-treatment, and followed up at 3 months.RESULTS: All children improved in joint engagement and initiating joint attention, with significantly greater improvement by the CMM group. Outcomes on play skills were mixed, with improvement of symbolic play for the CMM group and no change in functional play skills. Joint engagement maintained over time for the CMM group, and initiating joint attention maintained for both groups over time.CONCLUSIONS: This study is among the first randomized trials comparing 2 active interventions with a large sample of low-resourced families. Results suggest improvements in core autism deficits of joint engagement, joint attention, and symbolic play with relatively brief, caregiver-mediated interventions, but additional support is necessary to maintain and generalize these gains over time.
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6. Luo S, Huang W, Xia Q, Du Q, Wu L, Duan R. {{Mutational Analyses of the FMR1 Gene in Chinese Pediatric Population of Fragile X Suspects: Low Tolerance for Point Mutation}}. {J Child Neurol};2014 (Jun 23)
CGG repeat expansion is the most common cause of fragile X syndrome. Numerous efforts have been made to identify novel mutations in patients with intellectual disability, developmental delay, and/or autism. To evaluate the mutational spectrum in the at-risk Chinese population, 60 pediatric patients presenting fragile X traits but normal-sized CGG repeats were sequenced for all 17 exons and regulatory regions in FMR1. A c.879A>C mutation, reported to alter a neighboring splicing, was detected in a severely retarded male and his normal mother. However, the exon junction appears unaffected. A 237-kb deletion covering the entire FMR1 was identified to cause moderate intellectual disability and marked hyperactivity in an 8-year-old boy. The 5′ and 3′ breakpoints were buried in the surrounding long interspersed and short interspersed elements, respectively. In general, missense mutations do not commonly cause fragile X syndrome, whereas deletions should be considered with caution in patient referrals presenting with developmental delay and/or ordinary retardation.
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7. Mellios N, Woodson J, Garcia RI, Crawford B, Sharma J, Sheridan SD, Haggarty SJ, Sur M. {{beta2-Adrenergic receptor agonist ameliorates phenotypes and corrects microRNA-mediated IGF1 deficits in a mouse model of Rett syndrome}}. {Proc Natl Acad Sci U S A};2014 (Jun 23)
Rett syndrome is a severe childhood onset neurodevelopmental disorder caused by mutations in methyl-CpG-binding protein 2 (MECP2), with known disturbances in catecholamine synthesis. Here, we show that treatment with the beta2-adrenergic receptor agonist clenbuterol increases survival, rescues abnormalities in respiratory function and social recognition, and improves motor coordination in young male Mecp2-null (Mecp2-/y) mice. Importantly, we demonstrate that short-term treatment with clenbuterol in older symptomatic female heterozygous (Mecp2-/+) mice rescues respiratory, cognitive, and motor coordination deficits, and induces an anxiolytic effect. In addition, we reveal abnormalities in a microRNA-mediated pathway, downstream of brain-derived neurotrophic factor that affects insulin-like growth factor 1 (IGF1) expression in Mecp2-/y mice, and show that treatment with clenbuterol restores the observed molecular alterations. Finally, cotreatment with clenbuterol and recombinant human IGF1 results in additional increases in survival in male null mice. Collectively, our data support a role for IGF1 and other growth factor deficits as an underlying mechanism of Rett syndrome and introduce beta2-adrenergic receptor agonists as potential therapeutic agents for the treatment of the disorder.
