1. Bader PL, Faizi M, Kim LH, Owen SF, Tadross MR, Alfa RW, Bett GC, Tsien RW, Rasmusson RL, Shamloo M. {{Mouse model of Timothy syndrome recapitulates triad of autistic traits}}. {Proc Natl Acad Sci U S A};2011 (Aug 30)
Autism and autism spectrum disorder (ASD) typically arise from a mixture of environmental influences and multiple genetic alterations. In some rare cases, such as Timothy syndrome (TS), a specific mutation in a single gene can be sufficient to generate autism or ASD in most patients, potentially offering insights into the etiology of autism in general. Both variants of TS (the milder TS1 and the more severe TS2) arise from missense mutations in alternatively spliced exons that cause the same G406R replacement in the Ca(V)1.2 L-type calcium channel. We generated a TS2-like mouse but found that heterozygous (and homozygous) animals were not viable. However, heterozygous TS2 mice that were allowed to keep an inverted neomycin cassette (TS2-neo) survived through adulthood. We attribute the survival to lowering of expression of the G406R L-type channel via transcriptional interference, blunting deleterious effects of mutant L-type channel overactivity, and addressed potential effects of altered gene dosage by studying Ca(V)1.2 knockout heterozygotes. Here we present a thorough behavioral phenotyping of the TS2-neo mouse, capitalizing on this unique opportunity to use the TS mutation to model ASD in mice. Along with normal general health, activity, and anxiety level, TS2-neo mice showed markedly restricted, repetitive, and perseverative behavior, altered social behavior, altered ultrasonic vocalization, and enhanced tone-cued and contextual memory following fear conditioning. Our results suggest that when TS mutant channels are expressed at levels low enough to avoid fatality, they are sufficient to cause multiple, distinct behavioral abnormalities, in line with the core aspects of ASD.
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2. Croen LA, Connors SL, Matevia M, Qian Y, Newschaffer C, Zimmerman AW. {{Prenatal exposure to beta2-adrenergic receptor agonists and risk of autism spectrum disorders}}. {J Neurodev Disord};2011 (Aug 27)
This study aims to investigate the association between prenatal exposure to terbutaline and other beta2 adrenergic receptor (B2AR) agonists and autism spectrum disorders (ASDs). The methodology used is a case-control study among children born from 1995 to 1999 at Kaiser Permanente Northern California hospitals. Cases (n = 291) were children with an ASD diagnosis; controls (n = 284) were children without ASDs, randomly sampled and frequency-matched to cases on sex, birth year, and delivery hospital. Exposure to B2AR agonists during 30 days prior to conception and each trimester of pregnancy was ascertained from prenatal medical records and health plan databases. The frequency of exposure to any B2AR agonist during pregnancy was similar for mothers of children with ASD and mothers of controls (18.9% vs. 14.8%, P = 0.19). Exposure to B2AR agonists other than terbutaline was not associated with an increased risk for ASDs. However, terbutaline exposure for >2 days during the third trimester was associated with more than a fourfold increased risk for ASDs independent of indication although the limited sample size resulted in an imprecise and nonsignificant effect estimate (OR(adj) = 4.4; 95% confidence interval, 0.8-24.6). This analysis does not offer evidence linking B2AR exposure in pregnancy with autism risk. However, exposure to terbutaline during the third trimester for >2 days may be associated with an increased risk of autism. Should this result be confirmed in larger samples, it would point to late pregnancy as an etiologic window of interest in autism risk factor research.
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3. Curran MP. {{Aripiprazole in the treatment of irritability associated with autistic disorder in paediatric patientsdagger: profile report}}. {CNS Drugs};2011 (Sep 1);25(9):801-802.
dagger Adapted and reproduced from the original article published in Pediatric Drugs 2011; 13 (3): 197-204.
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4. Feliciano P. {{Fragile X protein stalls ribosomes}}. {Nat Genet};2011;43(9):824.
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5. Reiersen AM. {{Links between autism spectrum disorder and ADHD symptom trajectories: important findings and unanswered questions}}. {J Am Acad Child Adolesc Psychiatry};2011 (Sep);50(9):857-859.
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6. Reiersen AM, Handen B. {{Commentary on ‘Selective serotonin reuptake inhibitors (SSRIs) for autism spectrum disorders (ASD)’}}. {Evid Based Child Health};2011 (Jul);6(4):1082-1085.
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7. Sipes M, Matson JL, Horovitz M. {{Autism spectrum disorders and motor skills: The effect on socialization as measured by the Baby and Infant Screen for Children with aUtIsm Traits (BISCUIT)}}. {Dev Neurorehabil};2011;14(5):290-296.
Purpose: To examine the effects of ASD diagnosis and motor skills on socialization in young children. Methods: Two samples were used: gross motor skills sample (n = 408) and fine motor skills sample (n = 402). The Battelle Developmental Inventory-Second Edition assessed motor skills, while the Baby and Infant Screen for Children with aUtIsm Traits, Part 1 assessed socialization. Results: A main effect of diagnosis was found for both samples on socialization such that those with autism exhibited the most severe deficits followed by those with PDD-NOS and then atypically developing children. There was a main effect for gross motor skills, with high gross motor skills showing less social impairment. The interaction term was only significant in regards to fine motor skills. Conclusions: The individual effects of ASD diagnosis and motor impairment as well as the interaction have implications for the assessment and treatment in these individuals.
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8. Sipes M, Matson JL, Turygin N. {{The use of the Battelle Developmental Inventory-Second Edition (BDI-2) as an early screener for autism spectrum disorders}}. {Dev Neurorehabil};2011;14(5):310-314.
Purpose: The purpose was to develop cut-off scores for a measure of developmental level (Battelle Developmental Inventory-Second Edition; BDI-2) which could be used as a screening tool to differentiate young children with possible autism spectrum disorders (ASD). Methods: Infants and toddlers with ASD (n = 604) and atypically-developing infants and toddlers (n = 1064) were administered the BDI-2. Cut-off scores were determined based on standard deviations from the mean of the ASD group. Results: Using 1.5 standard deviations from the mean of the ASD group, a cut-off score of 96 was determined which had a sensitivity of 0.94 and a specificity of 0.31. Conclusions: With high sensitivity, these cut-off scores can be used to identify children who require further assessment. In addition, the measure can be used to determine treatment targets.
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9. White SW, Schry AR, Maddox BB. {{Brief Report: The Assessment of Anxiety in High-Functioning Adolescents with Autism Spectrum Disorder}}. {J Autism Dev Disord};2011 (Aug 27)
Anxiety may exacerbate interpersonal difficulties and contribute to secondary behavioral problems in adolescents with High-Functioning Autism Spectrum Disorder (HFASD). This study was conducted to assess the psychometric properties and construct validity of measures of anxiety with a sample (n = 30) of adolescents with HFASD and comorbid anxiety disorders. Results indicate that the measures (CASI-Anxiety Scale; Sukhodolsky et al. 2008; MASC; March 1998) possess acceptable internal consistency, and there is evidence of discriminant validity. Most of the adolescents, however, under-reported problems with anxiety, compared to parent-reported and clinician-derived reports and given they were seeking treatment for anxiety problems. Findings highlight the importance of using multiple raters in clinical practice and consideration of rater discrepancies in clinical research.
