1. {{Correction for Chen et al., MeCP2 binds to non-CG methylated DNA as neurons mature, influencing transcription and the timing of onset for Rett syndrome}}. {Proc Natl Acad Sci U S A};2015 (Apr 27)
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2. {{International society for autism research news}}. {Autism Res};2015 (Apr);8(2):240.
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3. Basuta K, Schneider A, Gane L, Polussa J, Woodruff B, Pretto D, Hagerman R, Tassone F. {{High functioning male with fragile X syndrome and fragile x-associated tremor/ataxia syndrome}}. {Am J Med Genet A};2015 (Apr 29)
Fragile X syndrome (FXS) affects individuals with more than 200 CGG repeats (full mutation) in the fragile X mental retardation 1 (FMR1) gene. Those born with FXS experience cognitive and social impairments, developmental delays, and some features of autism spectrum disorders. Carriers of a premutation (55-200 CGG repeats) are generally not severely affected early in life; however, are at high risk of developing the late onset neurodegenerative disorder, Fragile X-associated Tremor/Ataxia Syndrome (FXTAS), or Fragile X-associated Primary Ovarian Insufficiency (FXPOI), and may have other medical conditions such as developmental delay, autism spectrum disorders, hypertension, anxiety, and immune-mediated disorders. Here we present a case of a 58-year-old man with a borderline IQ, average memory skills, and executive function deficits. He met criteria for multiple psychiatric diagnoses and presented with tremor and ataxia, meeting criteria for FXTAS. Molecular testing unveiled a completely unmethylated FMR1 full mutation in peripheral blood mononucleated cells with elevated FMR1 mRNA and premutation alleles of different sizes in two other tissues (primary fibroblasts and sperm), indicating the presence of allele instability based on both inter- and intra-tissue mosaicism. The observation of FXTAS in this case of a full mutation mosaic man suggests that the pathogenic mechanism underlying this disorder is not observed exclusively in premutation carriers as it was originally thought. The concomitant presence of features of FXS and late onset neurological deterioration with probable FXTAS likely result from a combined molecular pathology of elevated FMR1 mRNA levels, a molecular hallmark of FXTAS and low FMRP expression that leads to FXS. (c) 2015 Wiley Periodicals, Inc.
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4. Biyani S, Morgan PS, Hotchkiss K, Cecchini M, Derkay CS. {{Autism spectrum disorder 101: A primer for pediatric otolaryngologists}}. {Int J Pediatr Otorhinolaryngol};2015 (Apr 11)
Based on a comprehensive review of the literature as well as personal experiences at a tertiary children’s hospital, we present an encompassing guide of the management of children with autism spectrum disorder (ASD) in the otolaryngology practice. ASD is a disorder involving persistent deficits in social communication and interaction across multiple contexts with restricted and repetitive patterns of behavior, which presents early in age and causes significant impairment in function. With the increasing prevalence of autism, the otolaryngologist’s understanding of the disease and how it affects the management of patients is of paramount importance in order to provide a safe medical and surgical environment. Special considerations in the outpatient visit and peri-operative setting in the management of ASD patients can enhance the patient-provider relationship and improve the quality of care delivered. We discuss several strategies, such as utilization of communication devices and use of pre-medication prior to surgery, to facilitate the clinical experience.
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5. Cochran DM, Sikoglu EM, Hodge SM, Edden RA, Foley A, Kennedy DN, Moore CM, Frazier JA. {{Relationship Among Glutamine, gamma-Aminobutyric Acid, and Social Cognition In Autism Spectrum Disorders}}. {J Child Adolesc Psychopharmacol};2015 (Apr 28)
OBJECTIVE: An imbalance of excitatory and inhibitory neurotransmission in autism spectrum disorder (ASD) has been proposed. We compared glutamate (Glu), glutamine (Gln), and gamma-aminobutyric acid (GABA) levels in the anterior cingulate cortex (ACC) of 13 males with ASD and 14 typically developing (TD) males (ages 13-17), and correlated these levels with intelligence quotient (IQ) and measures of social cognition. METHODS: Social cognition was evaluated by administration of the Social Responsiveness Scale (SRS) and the Reading the Mind in the Eyes Test (RMET). We acquired proton magnetic resonance spectroscopy (1H-MRS) data from the bilateral ACC using the single voxel point resolved spectroscopy sequence (PRESS) to quantify Glu and Gln, and Mescher-Garwood point-resolved spectroscopy sequence (MEGA-PRESS) to quantify GABA levels referenced to creatine (Cr). RESULTS: There were higher Gln levels (p=0.04), and lower GABA/Cre levels (p=0.09) in the ASD group than in the TD group. There was no difference in Glu levels between groups. Gln was negatively correlated with RMET score (rho=-0.62, p=0.001) and IQ (rho=-0.56, p=0.003), and positively correlated with SRS scores (rho=0.53, p=0.007). GABA/Cre levels were positively correlated with RMET score (rho=0.34, p=0.09) and IQ (rho=0.36, p=0.07), and negatively correlated with SRS score (rho=-0.34, p=0.09). CONCLUSIONS: These data suggest an imbalance between glutamatergic neurotransmission and GABA-ergic neurotransmission in ASD. Higher Gln levels and lower GABA/Cre levels were associated with lower IQ and greater impairments in social cognition across groups.
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6. Dubin AH, Lieberman-Betz R, Michele Lease A. {{Investigation of Individual Factors Associated with Anxiety in Youth with Autism Spectrum Disorders}}. {J Autism Dev Disord};2015 (Apr 28)
As youth with autism spectrum disorder (ASD) are more likely to experience anxiety than youth in the general population, investigation of associated factors is important for diagnosis and treatment. The present study extended prior research by examining factors associated with caregiver-reported anxiety in 2662 youth (mean age = 8.82 years) with ASD. Logistic regression analyses indicated increases in age, social problems, and cognitive functioning predicted high anxiety group membership. Cognitive functioning moderated the relation of adaptive social behaviors and anxiety. Results from the present study provide support for previously identified factors associated with anxiety; however, further investigation is necessary to uncover additional factors and to explore their relation to anxiety across individuals with ASD with varying levels of cognitive functioning.
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7. Duda M, Kosmicki JA, Wall DP. {{Testing the accuracy of an observation-based classifier for rapid detection of autism risk}}. {Transl Psychiatry};2015;5:e556.
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8. Gengoux GW, Berquist KL, Salzman E, Schapp S, Phillips JM, Frazier TW, Minjarez MB, Hardan AY. {{Pivotal Response Treatment Parent Training for Autism: Findings from a 3-Month Follow-Up Evaluation}}. {J Autism Dev Disord};2015 (Apr 26)
This study’s objective was to assess maintenance of treatment effects 3 months after completion of a 12-week Pivotal Response Treatment (PRT) parent education group. Families who completed the active treatment (N = 23) were followed for an additional 12 weeks to measure changes in language and cognitive skills. Results indicated a significant improvement in frequency of functional utterances, with maintenance at 3-month follow-up [F(2, 21): 5.9, p = .009]. Children also made significant gains on the Vineland Communication Domain Standard Score [F(2, 12):11.74, p = .001] and the Mullen Scales of Early Learning Composite score [F(1, 20) = 5.43, p = .03]. These results suggest that a brief PRT parent group intervention can lead to improvements in language and cognitive functioning that are maintained 12 weeks post treatment.
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9. Hagen E, Shprung D, Minakova E, Washington J, 3rd, Kumar U, Shin D, Sankar R, Mazarati A. {{Autism-Like Behavior in BTBR Mice Is Improved by Electroconvulsive Therapy}}. {Neurotherapeutics};2015 (Apr 28)
Autism is a developmental disorder characterized by impairments in social and communication abilities, as well as by restricted and repetitive behaviors. Incidence of autism is higher than earlier estimates, and treatments have limited efficacy and are costly. Limited clinical and experimental evidence suggest that patients with autism may benefit from electroconvulsive therapy (ECT). We examined the therapeutic potential of ECT in BTBR T+ tf/j mice, which represent a validated model of autism. A series of 13 electroconvulsive shocks (ECS) delivered twice a day over 7 days reversed core autism-like behavioral abnormalities-impaired sociability, social novelty, and repetitive behavior-when the animals were tested 24 h after the last ECS. The effect lasted up to 2 weeks after ECT. Neither single ECS nor a series of 6 ECS modified animals’ behavior. Chronic infusion into the lateral brain ventricle of a preferential oxytocin receptor blocker (2S)-2-Amino-N-[(1S,2S,4R)-7,7-dimethyl-1-[[[4-(2-methylphenyl)-1-piperazinyl]sul fonyl]methyl]bicyclo[2.2.1]hept-2-yl]-4-(methylsulfonyl)butanamide hydrochloride abolished ECT-induced improvement of sociability and mitigated improvement of social novelty but did not affect ECT-induced reversal of repetitive behavior. These proof-of-principle experiments suggest that ECT may, indeed, be useful in the treatment of autism, and that its therapeutic effects may be mediated, in part, by central oxytocin signaling.
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10. Harfterkamp M, van der Meer D, van der Loo-Neus G, Buitelaar JK, Minderaa RB, Hoekstra PJ. {{No Evidence for Predictors of Response to Atomoxetine Treatment of Attention-Deficit/Hyperactivity Disorder Symptoms in Children and Adolescents with Autism Spectrum Disorder}}. {J Child Adolesc Psychopharmacol};2015 (Apr 28)
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11. Heberling C, Dhurjati P. {{Novel systems modeling methodology in comparative microbial metabolomics: identifying key enzymes and metabolites implicated in autism spectrum disorders}}. {Int J Mol Sci};2015;16(4):8949-8967.
Autism spectrum disorders are a group of mental illnesses highly correlated with gastrointestinal dysfunction. Recent studies have shown that there may be one or more microbial « fingerprints » in terms of the composition characterizing individuals with autism, which could be used for diagnostic purposes. This paper proposes a computational approach whereby metagenomes characteristic of « healthy » and autistic individuals are artificially constructed via genomic information, analyzed for the enzymes coded within, and then these enzymes are compared in detail. This is a text mining application. A custom-designed online application was built and used for the comparative metabolomics study and made publically available. Several of the enzyme-catalyzing reactions involved with the amino acid glutamate were curiously missing from the « autism » microbiome and were coded within almost every organism included in the « control » microbiome. Interestingly, there exists a leading hypothesis regarding autism and glutamate involving a neurological excitation/inhibition imbalance; but the association with this study is unclear. The results included data on the transsulfuration and transmethylation pathways, involved with oxidative stress, also of importance to autism. The results from this study are in alignment with leading hypotheses in the field, which is impressive, considering the purely in silico nature of this study. The present study provides new insight into the complex metabolic interactions underlying autism, and this novel methodology has potential to be useful for developing new hypotheses. However, limitations include sparse genome data availability and conflicting literature experimental data. We believe our software tool and methodology has potential for having great utility as data become more available, comprehensive and reliable.
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12. Hull MM, Madhavan D, Zaroff CM. {{Autistic spectrum disorder, epilepsy, and vagus nerve stimulation}}. {Childs Nerv Syst};2015 (Apr 29)
PURPOSE: In individuals with a comorbid autistic spectrum disorder and medically refractory epilepsy, vagus nerve stimulation may offer the potential of seizure control and a positive behavioral side effect profile. We aimed to examine the behavioral side effect profile using longitudinal and quantitative data and review the potential mechanisms behind behavioral changes. METHODS: We present a case report of a 10-year-old boy with autistic spectrum disorder and epilepsy, who underwent vagus nerve stimulation subsequent to unsuccessful treatment with antiepileptic medication. RESULTS: Following vagus nerve stimulation implantation, initial, if temporary, improvement was observed in seizure control. Modest improvements were also observed in behavior and development, improvements which were observed independent of seizure control. CONCLUSIONS: Vagus nerve stimulation in autistic spectrum disorder is associated with modest behavioral improvement, with unidentified etiology, although several candidates for this improvement are evident.
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13. Kihara H, Nakamura T. {{Early standard development assessment characteristics in very low birth weight infants later classified with autism spectrum disorder}}. {Early Hum Dev};2015 (Apr 23);91(6):357-359.
BACKGROUND: The prevalence of autism spectrum disorder (ASD) symptoms is high among very low birth weight infants (VLBWIs). Early diagnosis of ASD is crucial, because early intervention for ASD is effective. OBJECTIVE: To evaluate early standard development assessment characteristics in VLBWIs later classified with ASD. METHODS: Thirty-five VLBWIs later diagnosed with ASD were compared with 169 children with typical development who were admitted to the neonatal intensive care unit at Nagano Children’s Hospital between 2001 and 2005. We retrospectively evaluated developmental quotient (DQ) using the Kyoto Scale of Psychological Development (KSPD) at 6 and 18months post-term age (PTA) and 3year chronological age. RESULTS: KSPD DQ was significantly lower in ASD infants than in typical development infants at all ages. Postural-motor DQs of ASD infants at 18months PTA and 3year chronological age showed some increase compared to that at 6months PTA. CONCLUSION: Early recognition of ASD using standardized development assessment tools in VLBWIs might be possible.
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14. Liu J, Yang A, Zhang Q, Yang G, Yang W, Lei H, Quan J, Qu F, Wang M, Zhang Z, Yu K. {{Association between genetic variants in SLC25A12 and risk of autism spectrum disorders: An integrated meta-analysis}}. {Am J Med Genet B Neuropsychiatr Genet};2015 (Apr 29)
The solute carrier family 25 (aspartate/glutamate carrier), member 12 gene (SLC25A12) has been strongly posed as a candidate gene for autism spectrum disorder (ASD) given its important role in mitochondrial function and adenosine triphosphate (ATP) synthesis. Evidence is mounting for the association between SLC25A12 variants (rs2056202 and rs2292813) and ASD risk, but the results are inconsistent. To clarify the effect of these two variants on ASD, a meta-analysis integrating case-control and transmission disequilibrium test (TDT) studies was performed. The PubMed, Embase, Cochrane Library, Web of Science, Chinese BioMedical Literature (CBM), Wanfang, and Chinese National Knowledge Infrastructure (CNKI) databases were systematically searched to identify relevant studies published up to May 2014. Odds ratios (ORs) and 95% confidence intervals (95%CIs) were calculated to assess the strength of association. A total of 775 cases, 922 controls, and 1289 families available from 8 studies concerning rs2056202, and 465 cases, 450 controls, and 1516 families available from 7 studies concerning rs2292813 were finally included. In the overall meta-analysis, the rs2056202 T allele and rs2292813 T allele were both significantly associated with a decreased risk of ASD (rs2056202: OR = 0.809, P = 0.001, 95%CI: 0.713-0.917, I2 = 0.0%, and Pheterogeneity = 0.526; rs2292813: OR = 0.752, P < 0.001, 95%CI: 0.649-0.871, I2 = 0.0%, Pheterogeneity = 0.486). Besides, subjects with T-T haplotype of rs2056202-rs2292813 had a significantly reduced risk of ASD (OR = 0.672, P < 0.001, 95%CI: 0.564-0.801, I2 = 0.0%, Pheterogeneity = 0.631). Sensitivity analysis, cumulative meta-analysis, and publication bias diagnostics confirmed the reliability and stability of our results. Our meta-analysis suggests that rs2056202 and rs2292813 in SLC25A12 may contribute significantly to ASD risk. (c) 2015 Wiley Periodicals, Inc.
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15. Liu Y, Zhang Y, Zhao D, Dong R, Yang X, Tammimies K, Uddin M, Scherer SW, Gai Z. {{Rare de novo deletion of metabotropic glutamate receptor 7 (GRM7) gene in a patient with autism spectrum disorder}}. {Am J Med Genet B Neuropsychiatr Genet};2015 (Apr 29)
GRM7, the gene encoding metabotropic glutamate receptor 7 (mGluR7), have been implicated in multiple neuropsychiatric disorders and shown to mediate excitatory synaptic neurotransmitter signaling and plasticity in the mammalian brain. Here we report a 303 kb de novo deletion at band 3q26.1, disrupting five coding exons of GRM7 in a proband with autism spectrum disorder, and hyperactivity. Our exon transcriptome-mutation contingency index method shows that three of the exons within the breakpoint boundaries are under purifying selection and highly expressed in prenatal brain regions. Based on our results and a thorough review of the literature, we propose that haploinsufficiency of the GRM7 product (mGluR7) contributes to autism spectrum disorders and hyperactivity phenotype as seen in the patient described here. (c) 2015 Wiley Periodicals, Inc.
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16. Logan SL, Carpenter L, Leslie RS, Garrett-Mayer E, Hunt KJ, Charles J, Nicholas JS. {{Aberrant Behaviors and Co-occurring Conditions as Predictors of Psychotropic Polypharmacy among Children with Autism Spectrum Disorders}}. {J Child Adolesc Psychopharmacol};2015 (Apr 28)
OBJECTIVES: The purpose of this study was to identify rates and predictors of psychotropic medication polypharmacy among Medicaid-eligible children in South Carolina with autism spectrum disorder (ASD) from 2000 to 2008. METHODS: Population-based surveillance data were linked with state Medicaid records to obtain a detailed demographic, behavioral, educational, clinical, and diagnostic data set for all Medicaid-eligible 8-year-old children (n=629) who were identified and diagnosed with ASD using standardized criteria. Polypharmacy was defined as having interclass psychotropic medication claims overlapping for >/=30 consecutive days at any time during the 2-year study period. Multivariable logistic regression was used to model predictors of any polypharmacy, and for the three most common combinations. RESULTS: Overall, 60% (n=377) used any psychotropic medication, and 41% (n=153) of those had interclass polypharmacy. Common combinations were attention-deficit/hyperactivity disorder (ADHD) medications with an antidepressant (A/AD), antipsychotic (A/AP) or a mood stabilizer (A/MS). Black children had lower odds of any polypharmacy, as did those eligible for Medicaid because of income or being foster care versus those eligible because of disability. There were no significant associations between polypharmacy and social deficits in ASD for any combination, although children with communication deficits diagnostic of ASD had lower odds of any polypharmacy and A/AP polypharmacy. Children with argumentative, aggressive, hyperactive/impulsive, or self-injurious aberrant behaviors had higher odds of polypharmacy, as did children with diagnosed co-occurring ADHD, anxiety or mood disorders, or conduct/oppositional defiant disorder (ODD) in Medicaid records. CONCLUSIONS: Future research is warranted to investigate how child-level factors impact combination psychotropic medication prescribing practices and outcomes in ASD.
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17. Ma L, Fu C, Liu H, Jin S, Gu B, Yan S, Wang P, Xu Y, Xue S, Li W, Sun A, Wu D. {{[Retrospective study of the efficacy and safety of treatment with PDD vs PAD in de novo patients with multiple myiloma]}}. {Zhonghua Xue Ye Xue Za Zhi};2015 (Apr 14);36(4):340-343.
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18. Magiati I, Ong C, Lim XY, Tan JW, Ong AY, Patrycia F, Fung DS, Sung M, Poon KK, Howlin P. {{Anxiety symptoms in young people with autism spectrum disorder attending special schools: Associations with gender, adaptive functioning and autism symptomatology}}. {Autism};2015 (Apr 27)
Anxiety-related problems are among the most frequently reported mental health difficulties in autism spectrum disorder. As most research has focused on clinical samples or high-functioning children with autism spectrum disorder, less is known about the factors associated with anxiety in community samples across the ability range. This cross-sectional study examined the association of gender, age, adaptive functioning and autism symptom severity with different caregiver-reported anxiety symptoms. Participants were caregivers of 241 children (6-18 years old) with autism spectrum disorder attending special schools in Singapore. Measures included the Spence Children’s Anxiety Scale and assessments of overall emotional, behavioural and adaptive functioning. Caregivers reported more anxiety symptoms in total, but fewer social anxiety symptoms, than Spence Children’s Anxiety Scale Australian/Dutch norms. There were no gender differences. Variance in total anxiety scores was best explained by severity of repetitive speech/stereotyped behaviour symptoms, followed by adaptive functioning. Severity of repetitive speech/behaviour symptoms was a significant predictor of separation anxiety, generalized anxiety, panic/agoraphobia and obsessive-compulsive subscale symptoms, but not of social phobia and physical injury fears. Adaptive functioning and chronological age predicted social phobia and generalized anxiety symptoms only. Severity of social/communication autism symptoms did not explain any anxiety symptoms, when the other variables were controlled for. Findings are discussed in relation to the existing literature. Limitations and possible implications for prevention, assessment and intervention are also discussed.
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19. Must A, Phillips S, Curtin C, Bandini LG. {{Barriers to Physical Activity in Children With Autism Spectrum Disorders: Relationship to Physical Activity and Screen Time}}. {J Phys Act Health};2015 (Apr 28)
BACKGROUND: Individual, social, and community barriers to physical activity (PA) experienced by children with autism spectrum disorder (ASD) make PA participation more difficult and may contribute to increased screen time. METHODS: We compared the prevalence of parent-reported barriers to PA among 58 typically developing (TD) children and 53 children with an ASD, 3-11 years, and assessed the association between barriers and PA participation and screen time among children with ASD. RESULTS: Parents of children with ASD reported significantly more barriers than parents of TD children. Based on parent-report, 60% of children with ASD required too much supervision compared to no TD children (p<0.001). Parents of children with ASD were more likely to report that adults lack skills needed to include their child (58%), that their child has few friends (45%), and that other children exclude their child (23%). The number of parent-reported barriers to PA was inversely correlated with the hours spent in PA per year (r=-0.27, p=0.05) and positively related to total screen time (r=0.32, p<0.03). CONCLUSIONS: These findings underscore the need for community-based PA programs designed to meet the special requirements of this population and policies that compel schools and other government-supported organizations for inclusion and/or targeted programming.
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20. O’Haire ME, McKenzie SJ, Beck AM, Slaughter V. {{Animals may act as social buffers: Skin conductance arousal in children with autism spectrum disorder in a social context}}. {Dev Psychobiol};2015 (Apr 27)
Children with autism spectrum disorder (ASD) experience high rates of social stress and anxious arousal. Preliminary evidence suggests that companion animals can act as buffers against the adverse effects of social stress in adults. We measured continuous physiological arousal in children with ASD and typically developing (TD) children in a social context during four conditions: (a) a baseline of reading silently, (b) a scripted classroom activity involving reading aloud, (c) free play with peers and toys, and (d) free play with peers and animals (guinea pigs). Our results confirmed heightened arousal among children with ASD compared to TD children in all conditions, except when the animals were present. Children with ASD showed a 43% decrease in skin conductance responses during free play with peers in the presence of animals, compared to toys. Thus, animals may act as social buffers for children with ASD, conferring unique anxiolytic effects. (c) 2015 Wiley Periodicals, Inc. Dev Psychobiol.
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21. Olson HE, Tambunan D, LaCoursiere C, Goldenberg M, Pinsky R, Martin E, Ho E, Khwaja O, Kaufmann WE, Poduri A. {{Mutations in epilepsy and intellectual disability genes in patients with features of Rett syndrome}}. {Am J Med Genet A};2015 (Apr 25)
Rett syndrome and neurodevelopmental disorders with features overlapping this syndrome frequently remain unexplained in patients without clinically identified MECP2 mutations. We recruited a cohort of 11 patients with features of Rett syndrome and negative initial clinical testing for mutations in MECP2. We analyzed their phenotypes to determine whether patients met formal criteria for Rett syndrome, reviewed repeat clinical genetic testing, and performed exome sequencing of the probands. Using 2010 diagnostic criteria, three patients had classical Rett syndrome, including two for whom repeat MECP2 gene testing had identified mutations. In a patient with neonatal onset epilepsy with atypical Rett syndrome, we identified a frameshift deletion in STXBP1. Among seven patients with features of Rett syndrome not fulfilling formal diagnostic criteria, four had suspected pathogenic mutations, one each in MECP2, FOXG1, SCN8A, and IQSEC2. MECP2 mutations are highly correlated with classical Rett syndrome. Genes associated with atypical Rett syndrome, epilepsy, or intellectual disability should be considered in patients with features overlapping with Rett syndrome and negative MECP2 testing. While most of the identified mutations were apparently de novo, the SCN8A variant was inherited from an unaffected parent mosaic for the mutation, which is important to note for counseling regarding recurrence risks. (c) 2015 Wiley Periodicals, Inc.
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22. Ozonoff S, Young GS, Landa RJ, Brian J, Bryson S, Charman T, Chawarska K, Macari SL, Messinger D, Stone WL, Zwaigenbaum L, Iosif AM. {{Diagnostic stability in young children at risk for autism spectrum disorder: a baby siblings research consortium study}}. {J Child Psychol Psychiatry};2015 (Apr 29)
BACKGROUND: The diagnosis of autism spectrum disorder (ASD) made before age 3 has been found to be remarkably stable in clinic- and community-ascertained samples. The stability of an ASD diagnosis in prospectively ascertained samples of infants at risk for ASD due to familial factors has not yet been studied, however. The American Academy of Pediatrics recommends intensive surveillance and screening for this high-risk group, which may afford earlier identification. Therefore, it is critical to understand the stability of an ASD diagnosis made before age 3 in young children at familial risk. METHODS: Data were pooled across seven sites of the Baby Siblings Research Consortium. Evaluations of 418 later-born siblings of children with ASD were conducted at 18, 24, and 36 months of age and a clinical diagnosis of ASD or Not ASD was made at each age. RESULTS: The stability of an ASD diagnosis at 18 months was 93% and at 24 months was 82%. There were relatively few children diagnosed with ASD at 18 or 24 months whose diagnosis was not confirmed at 36 months. There were, however, many children with ASD outcomes at 36 months who had not yet been diagnosed at 18 months (63%) or 24 months (41%). CONCLUSIONS: The stability of an ASD diagnosis in this familial-risk sample was high at both 18 and 24 months of age and comparable with previous data from clinic- and community-ascertained samples. However, almost half of the children with ASD outcomes were not identified as being on the spectrum at 24 months and did not receive an ASD diagnosis until 36 months. Thus, longitudinal follow-up is critical for children with early signs of social-communication difficulties, even if they do not meet diagnostic criteria at initial assessment. A public health implication of these data is that screening for ASD may need to be repeated multiple times in the first years of life. These data also suggest that there is a period of early development in which ASD features unfold and emerge but have not yet reached levels supportive of a diagnosis.
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23. Patel N, Crider A, Pandya CD, Ahmed AO, Pillai A. {{Altered mRNA Levels of Glucocorticoid Receptor, Mineralocorticoid Receptor, and Co-Chaperones (FKBP5 and PTGES3) in the Middle Frontal Gyrus of Autism Spectrum Disorder Subjects}}. {Mol Neurobiol};2015 (Apr 26)
Although stress has been implicated in the pathophysiology of autistic spectrum disorder (ASD), it is not known whether glucocorticoid receptor (GR) levels are altered in the brain of subjects with ASD. The messenger RNA (mRNA) levels of GR isoforms (GRalpha, GRbeta, GRgamma, and GRP), mineralocorticoid receptor (MR), GR co-chaperones (FKBP5, PTGES3, and BAG1), and inflammatory cytokines (IL-6, IL-1beta, and IFN-gamma) were examined in the postmortem middle frontal gyrus tissues of 13 ASD and 13 age-matched controls by qRT-PCR. The protein levels were examined by Western blotting. We found significant decreases in GRalpha (64 %), GRgamma (48 %), GRP (20 %) and MR (46 %) mRNA levels in ASD subjects as compared to controls. However, significant increases in FKBP5 (42 %) and PTGES3 (35 %) mRNA levels were observed in ASD subjects. There were no differences in the mRNA levels of GRbeta and BAG1 in ASD subjects as compared to controls. MR mRNA was found to be negatively correlated with the diagnostic score for abnormality of development. On the protein level, significant reductions in GR and MR, but no change in FKBP5 and PTGES3 were found in ASD subjects as compared to controls. Moreover, we observed significant increases in IL-1beta and IFN-gamma mRNA levels in ASD subjects, and these cytokines were negatively associated with GR levels. Our data, for the first time, reports dysregulation of GR, MR, FKBP5, and PTGES3 in ASD and suggest a possible role of inflammation in altered GR function in ASD.
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24. Pehrs C, Samson AC, Gross JJ. {{The quartet theory: Implications for autism spectrum disorder: Comment on « The quartet theory of human emotions: An integrative and neurofunctional model » by S. Koelsch et al}}. {Phys Life Rev};2015 (Apr 20)
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25. Romero-Martinez A, Gonzalez-Bono E, Salvador A, Moya-Albiol L. {{Declarative verbal memory impairments in middle-aged women who are caregivers of offspring with autism spectrum disorders: The role of negative affect and testosterone}}. {Memory};2015 (Apr 27):1-10.
Caring for offspring diagnosed with a chronic psychological disorder such as autism spectrum disorder (ASD) is used in research as a model of chronic stress. This chronic stress has been reported to have deleterious effects on caregivers’ cognition, particularly in verbal declarative memory. Moreover, such cognitive decline may be mediated by testosterone (T) levels and negative affect, understood as depressive mood together with high anxiety and anger. This study aimed to compare declarative memory function in middle-aged women who were caregivers for individuals with ASD (n = 24; mean age = 45) and female controls (n = 22; mean age = 45), using a standardised memory test (Rey’s Auditory Verbal Learning Test). It also sought to examine the role of care recipient characteristics, negative mood and T levels in memory impairments. ASD caregivers were highly sensitive to proactive interference and verbal forgetting. In addition, they had higher negative affect and T levels, both of which have been associated with poorer verbal memory performance. Moreover, the number of years of caregiving affected memory performance and negative affect, especially, in terms of anger feelings. On the other hand, T levels in caregivers had a curvilinear relationship with verbal memory performance; that is, increases in T were associated with improvements in verbal memory performance up to a certain point, but subsequently, memory performance decreased with increasing T. Chronic stress may produce disturbances in mood and hormonal levels, which in turn might increase the likelihood of developing declarative memory impairments although caregivers do not show a generalised decline in memory. These findings should be taken into account for understanding the impact of cognitive impairments on the ability to provide optimal caregiving.
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26. Salomone E, Beranova S, Bonnet-Brilhault F, Briciet Lauritsen M, Budisteanu M, Buitelaar J, Canal-Bedia R, Felhosi G, Fletcher-Watson S, Freitag C, Fuentes J, Gallagher L, Garcia Primo P, Gliga F, Gomot M, Green J, Heimann M, Jonsdottir SL, Kaale A, Kawa R, Kylliainen A, Lemcke S, Markovska-Simoska S, Marschik PB, McConachie H, Moilanen I, Muratori F, Narzisi A, Noterdaeme M, Oliveira G, Oosterling I, Pijl M, Pop-Jordanova N, Poustka L, Roeyers H, Roge B, Sinzig J, Vicente A, Warreyn P, Charman T. {{Use of early intervention for young children with autism spectrum disorder across Europe}}. {Autism};2015 (Apr 27)
Little is known about use of early interventions for autism spectrum disorder in Europe. Parents of children with autism spectrum disorder aged 7 years or younger (N = 1680) were recruited through parent organisations in 18 European countries and completed an online survey about the interventions their child received. There was considerable variation in use of interventions, and in some countries more than 20% of children received no intervention at all. The most frequently reported interventions were speech and language therapy (64%) and behavioural, developmental and relationship-based interventions (55%). In some parts of Europe, use of behavioural, developmental and relationship-based interventions was associated with higher parental educational level and time passed since diagnosis, rather than with child characteristics. These findings highlight the need to monitor use of intervention for children with autism spectrum disorder in Europe in order to contrast inequalities.
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27. Samadi SA, McConkey R. {{Screening for Autism in Iranian Preschoolers: Contrasting M-CHAT and a Scale Developed in Iran}}. {J Autism Dev Disord};2015 (Apr 26)
Suitable screening instruments for the early diagnosis of autism are not readily available for use with preschoolers in non-Western countries. This study evaluated two tools: M-CHAT which is widely used internationally and one developed in Iran called Hiva. A population sample was recruited of nearly 3000 preschoolers in one Iranian city. Parents self-completed the two tools and children who screened positive were invited for a follow-up interview followed by a diagnostic assessment. The Hiva scale proved to be more efficacious in identifying children with ASD and the resulting prevalence rate was higher than that previously reported for Iranian 5 year olds. The study confirms the need to attune screening tools to the cultural contexts in which they are used.
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28. Schilit Nitenson A, Stackpole EE, Truszkowski TL, Midroit M, Fallon JR, Bath KG. {{Fragile X Mental Retardation Protein Regulates Olfactory Sensitivity But Not Odorant Discrimination}}. {Chem Senses};2015 (Apr 27)
Fragile X syndrome (FXS) is the most common cause of inherited intellectual disability and is characterized by cognitive impairments and altered sensory function. It is caused by absence of fragile X mental retardation protein (FMRP), an RNA-binding protein essential for normal synaptic plasticity and function. Animal models have provided important insights into mechanisms through which loss of FMRP impacts cognitive and sensory development and function. While FMRP is highly enriched in the developing and adult olfactory bulb (OB), its role in olfactory sensory function remains poorly understood. Here, we used a mouse model of FXS, the fmr1 -/y mouse, to test whether loss of FMRP impacts olfactory discrimination, habituation, or sensitivity using a spontaneous olfactory cross-habituation task at a range of odorant concentrations. We demonstrated that fmr1 -/y mice have a significant decrease in olfactory sensitivity compared with wild type controls. When we controlled for differences in sensitivity, we found no effect of loss of FMRP on the ability to habituate to or spontaneously discriminate between odorants. These data indicate that loss of FMRP significantly alters olfactory sensitivity, but not other facets of basal olfactory function. These findings have important implications for future studies aimed at understanding the role of FMRP on sensory functioning.
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29. Tilot AK, Frazier TW, 2nd, Eng C. {{Balancing Proliferation and Connectivity in PTEN-associated Autism Spectrum Disorder}}. {Neurotherapeutics};2015 (Apr 28)
Germline mutations in PTEN, which encodes a widely expressed phosphatase, was mapped to 10q23 and identified as the susceptibility gene for Cowden syndrome, characterized by macrocephaly and high risks of breast, thyroid, and other cancers. The phenotypic spectrum of PTEN mutations expanded to include autism with macrocephaly only 10 years ago. Neurological studies of patients with PTEN-associated autism spectrum disorder (ASD) show increases in cortical white matter and a distinctive cognitive profile, including delayed language development with poor working memory and processing speed. Once a germline PTEN mutation is found, and a diagnosis of phosphatase and tensin homolog (PTEN) hamartoma tumor syndrome made, the clinical outlook broadens to include higher lifetime risks for multiple cancers, beginning in childhood with thyroid cancer. First described as a tumor suppressor, PTEN is a major negative regulator of the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (mTOR) signaling pathway-controlling growth, protein synthesis, and proliferation. This canonical function combines with less well-understood mechanisms to influence synaptic plasticity and neuronal cytoarchitecture. Several excellent mouse models of Pten loss or dysfunction link these neural functions to autism-like behavioral abnormalities, such as altered sociability, repetitive behaviors, and phenotypes like anxiety that are often associated with ASD in humans. These models also show the promise of mTOR inhibitors as therapeutic agents capable of reversing phenotypes ranging from overgrowth to low social behavior. Based on these findings, therapeutic options for patients with PTEN hamartoma tumor syndrome and ASD are coming into view, even as new discoveries in PTEN biology add complexity to our understanding of this master regulator.
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30. van der Helm PA. {{A cognitive architecture account of the visual local advantage phenomenon in autism spectrum disorders}}. {Vision Res};2015 (Apr 24)
Ideally, a cognitive architecture is a neurally plausible model that unifies mental representations and cognitive processes. Here, I apply such a model to re-evaluate the local advantage phenomenon in autism spectrum disorders (ASD), that is, the better than typical performance on visual tasks in which local stimulus features are to be discerned. The model takes (a) perceptual organization as a predominantly stimulus-driven process yielding hierarchical stimulus organizations, and (b) attention as predominantly scrutinizing the hierarchical structure of established percepts in a task-driven top-down fashion. This accounts for a dominance of wholes over parts and implies that perceived global structures mask incompatible local features. The model also substantiates that impairments in neuronal synchronization – as found in ASD – reduce the emergence of global structures and, thereby, their masking effect on incompatible features. I argue that this explains the local advantage phenomenon and I discuss implications and suggestions for future research.
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31. Van Naarden Braun K, Christensen D, Doernberg N, Schieve L, Rice C, Wiggins L, Schendel D, Yeargin-Allsopp M. {{Trends in the prevalence of autism spectrum disorder, cerebral palsy, hearing loss, intellectual disability, and vision impairment, metropolitan atlanta, 1991-2010}}. {PLoS One};2015;10(4):e0124120.
This study examined the prevalence and characteristics of autism spectrum disorder (ASD), cerebral palsy (CP), hearing loss (HL), intellectual disability (ID), and vision impairment (VI) over a 15-20 year time period, with specific focus on concurrent changes in ASD and ID prevalence. We used data from a population-based developmental disabilities surveillance program for 8-year-olds in metropolitan Atlanta. From 1991-2010, prevalence estimates of ID and HL were stable with slight increases in VI prevalence. CP prevalence was constant from 1993-2010. The average annual increase in ASD prevalence was 9.3% per year from 1996-2010, with a 269% increase from 4.2 per 1,000 in 1996 to 15.5 per 1,000 in 2010. From 2000-2010, the prevalence of ID without ASD was stable; during the same time, the prevalence of ASD with and without co-occurring ID increased by an average of 6.6% and 9.6% per year, respectively. ASD prevalence increases were found among both males and females, and among nearly all racial/ethnic subgroups and levels of intellectual ability. Average annual prevalence estimates from 1991-2010 underscore the significant community resources needed to provide early intervention and ongoing supports for children with ID (13.0 per 1,000), CP, (3.5 per 1,000), HL (1.4 per 1,000) and VI (1.3 in 1,000), with a growing urgency for children with ASD.
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32. Zhao G, Gao J, Liang S, Wang X, Sun C, Xia W, Hao Y, Li X, Cao Y, Wu L. {{Study of the serum levels of polyunsaturated fatty acids and the expression of related liver metabolic enzymes in a rat valproate-induced autism model}}. {Int J Dev Neurosci};2015 (Apr 24)
To investigate whether the decreased level of serum polyunsaturated fatty acids (PUFAs) in patients with autism is associated with the expression of related liver metabolic enzymes, we selected rats that were exposed to valproic acid (VPA) on embryonic day 12.5 (E12.5) as a model of autism. We observed the serum levels of PUFAs and the expression of related liver metabolic enzymes, including Delta5-desaturase, Delta6-desaturase and elongase (Elovl2), in VPA-exposed and control rats on postnatal day 35 (PND35) and conducted sex dimorphic analysis. We found that the levels of serum PUFAs and related liver metabolic enzymes in the VPA rats were significantly reduced, in association with autism-like behavioral changes, the abnormal expression of apoptosis-related proteins and hippocampal neuronal injury, compared to the control rats and showed sex difference in VPA group. This finding indicated that rats exposed to VPA at the embryonic stage may exhibit reduced synthesis of serum PUFAs due to the down-regulation of liver metabolic enzymes, thereby inducing nervous system injury and behavioral changes, which is affected by sex in the meantime.
