Pubmed du 28/06/16

Pubmed du jour

2016-06-28 12:03:50

1. Ahmad SF, Zoheir KM, Ansari MA, Nadeem A, Bakheet SA, Al-Ayadhi LY, Alzahrani MZ, Al-Shabanah OA, Al-Harbi MM, Attia SM. {{Dysregulation of Th1, Th2, Th17, and T regulatory cell-related transcription factor signaling in children with autism}}. {Mol Neurobiol}. 2016.

Autism is a neurodevelopmental disorder characterized by stereotypic repetitive behaviors, impaired social interactions, and communication deficits. Numerous immune system abnormalities have been described in individuals with autism including abnormalities in the ratio of Th1/Th2/Th17 cells; however, the expression of the transcription factors responsible for the regulation and differentiation of Th1/Th2/Th17/Treg cells has not previously been evaluated. Peripheral blood mononuclear cells (PBMCs) from children with autism (AU) or typically developing (TD) control children were stimulated with phorbol-12-myristate 13-acetate (PMA) and ionomycin in the presence of brefeldin A. The expressions of Foxp3, RORgammat, STAT-3, T-bet, and GATA-3 mRNAs and proteins were then assessed. Our study shows that children with AU displayed altered immune profiles and function, characterized by a systemic deficit of Foxp3+ T regulatory (Treg) cells and increased RORgammat+, T-bet+, GATA-3+, and production by CD4+ T cells as compared to TD. This was confirmed by real-time PCR (RT-PCR) and western blot analyses. Our results suggest that autism impacts transcription factor signaling, which results in an immunological imbalance. Therefore, the restoration of transcription factor signaling may have a great therapeutic potential in the treatment of autistic disorders.

Lien vers le texte intégral (Open Access ou abonnement)

2. Avella-Garcia CB, Julvez J, Fortuny J, Rebordosa C, Garcia-Esteban R, Galan IR, Tardon A, Rodriguez-Bernal CL, Iniguez C, Andiarena A, Santa-Marina L, Sunyer J. {{Acetaminophen use in pregnancy and neurodevelopment: attention function and autism spectrum symptoms}}. {Int J Epidemiol}. 2016.

BACKGROUND: Acetaminophen is extensively used during pregnancy. But there is a lack of population-representative cohort studies evaluating its effects on a range of neuropsychological and behavioural endpoints. We aimed to assess whether prenatal exposure to acetaminophen is adversely associated with neurodevelopmental outcomes at 1 and 5 years of age. METHODS: This Spanish birth cohort study included 2644 mother-child pairs recruited during pregnancy. The proportion of liveborn participants evaluated at 1 and 5 years was 88.8% and 79.9%, respectively. Use of acetaminophen was evaluated prospectively in two structured interviews. Ever/never use and frequency of use (never, sporadic, persistent) were measured. Main neurodevelopment outcomes were assessed using Childhood Autism Spectrum Test (CAST), Conner’s Kiddie Continuous Performance Test (K-CPT) and ADHD-DSM-IV form list. Regression models were adjusted for social determinants and co-morbidities. RESULTS: Over 40% of mothers reported using acetaminophen. Ever-exposed offspring had higher risks of presenting more hyperactivity/impulsivity symptoms [incidence rate ratio (IRR) = 1.41, 95% confidence interval (CI) 1.01-1.98), K-CPT commission errors (IRR = 1.10, 1.03-1.17), and lower detectability scores (coefficient beta = -0.75, -0.13–0.02). CAST scores were increased in ever-exposed males (beta = 0.63, 0.09-1.18). Increased effect sizes of risks by frequency of use were observed for hyperactivity/impulsivity symptoms (IRR = 2.01, 0.95-4.24) in all children, K-CPT commission errors (IRR = 1.32, 1.05-1.66) and detectability (beta = -0.18, -0.36-0.00) in females, and CAST scores in males (beta = 1.91, 0.44-3.38). CONCLUSIONS: Prenatal acetaminophen exposure was associated with a greater number of autism spectrum symptoms in males and showed adverse effects on attention-related outcomes for both genders. These associations seem to be dependent on the frequency of exposure.

Lien vers le texte intégral (Open Access ou abonnement)

3. Benning SD, Kovac M, Campbell A, Miller S, Hanna EK, Damiano CR, Sabatino-DiCriscio A, Turner-Brown L, Sasson NJ, Aaron RV, Kinard J, Dichter GS. {{Late Positive Potential ERP Responses to Social and Nonsocial Stimuli in Youth with Autism Spectrum Disorder}}. {J Autism Dev Disord}. 2016.

We examined the late positive potential (LPP) event related potential in response to social and nonsocial stimuli from youths 9 to 19 years old with (n = 35) and without (n = 34) ASD. Social stimuli were faces with positive expressions and nonsocial stimuli were related to common restricted interests in ASD (e.g., electronics, vehicles, etc.). The ASD group demonstrated relatively smaller LPP amplitude to social stimuli and relatively larger LPP amplitude to nonsocial stimuli. There were no group differences in subjective ratings of images, and there were no significant correlations between LPP amplitude and ASD symptom severity within the ASD group. LPP results suggest blunted motivational responses to social stimuli and heightened motivational responses to nonsocial stimuli in youth with ASD.

Lien vers le texte intégral (Open Access ou abonnement)

4. Bostrom C, Yau SY, Majaess N, Vetrici M, Gil-Mohapel J, Christie BR. {{Hippocampal Dysfunction and Cognitive Impairment in Fragile-X Syndrome}}. {Neurosci Biobehav Rev}. 2016.

Fragile-X Syndrome (FXS) is the most common form of inherited intellectual disability and the leading genetic cause of autism spectrum disorder. FXS is caused by transcriptional silencing of the Fragile X Mental Retardation 1 (Fmr1) gene due to a CGG repeat expansion, resulting in the loss of Fragile X Mental Retardation Protein (FMRP). FMRP is involved in transcriptional regulation and trafficking of mRNA from the nucleus to the cytoplasm and distal sites both in pre- and post-synaptic terminals. Consequently, FXS is a multifaceted disorder associated with impaired synaptic plasticity. One region of the brain that is significantly impacted by the loss of FMRP is the hippocampus, a structure that plays a critical role in the regulation of mood and cognition. This review provides an overview of the neuropathology of Fragile-X Syndrome, highlighting how structural and synaptic deficits in hippocampal subregions, including the CA1 exhibiting exaggerated metabotropic glutamate receptor dependent long-term depression and the dentate gyrus displaying hypofunction of N-methyl-D-aspartate receptors, contribute to cognitive impairments associated with this neurodevelopmental disorder.

Lien vers le texte intégral (Open Access ou abonnement)

5. Green SA, Hernandez L, Bookheimer SY, Dapretto M. {{Salience Network Connectivity in Autism Is Related to Brain and Behavioral Markers of Sensory Overresponsivity}}. {J Am Acad Child Adolesc Psychiatry}. 2016; 55(7): 618-26 e1.

OBJECTIVE: The salience network, an intrinsic brain network thought to modulate attention to internal versus external stimuli, has been consistently found to be atypical in autism spectrum disorders (ASD). However, little is known about how this altered resting-state connectivity relates to brain activity during information processing, which has important implications for understanding sensory overresponsivity (SOR), a common and impairing condition in ASD related to difficulty downregulating brain responses to sensory stimuli. This study examined how SOR in youth with ASD relates to atypical salience network connectivity and whether these atypicalities are associated with abnormal brain response to basic sensory information. METHOD: Functional magnetic resonance imaging was used to examine how parent-rated SOR symptoms related to salience network connectivity in 61 youth (aged 8-17 years; 28 with ASD and 33 IQ-matched typically developing youth). Correlations between resting-state salience network connectivity and brain response to mildly aversive tactile and auditory stimuli were examined. RESULTS: SOR in youth with ASD was related to increased resting-state functional connectivity between salience network nodes and brain regions implicated in primary sensory processing and attention. Furthermore, the strength of this connectivity at rest was related to the extent of brain activity in response to auditory and tactile stimuli. CONCLUSION: Results support an association between intrinsic brain connectivity and specific atypical brain responses during information processing. In addition, findings suggest that basic sensory information is overly salient to individuals with SOR, leading to overattribution of attention to this information. Implications for intervention include incorporating sensory coping strategies into social interventions for individuals with SOR.

Lien vers le texte intégral (Open Access ou abonnement)

6. Hirsch LE, Pringsheim T. {{Aripiprazole for autism spectrum disorders (ASD)}}. {Cochrane Database Syst Rev}. 2016; 6: CD009043.

BACKGROUND: Autism spectrum disorders (ASD) include autistic disorder, Asperger’s disorder and pervasive developmental disorder – not otherwise specified (PDD-NOS). Antipsychotics have been used as a medication intervention for irritability related to ASD. Aripiprazole, a third-generation, atypical antipsychotic, is a relatively new drug that has a unique mechanism of action different from that of other antipsychotics. This review updates a previous Cochrane review on the safety and efficacy of aripiprazole for individuals with ASD, published in 2011 (Ching 2011). OBJECTIVES: To assess the safety and efficacy of aripiprazole as medication treatment for individuals with ASD. SEARCH METHODS: In October 2015, we searched the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL) and seven other databases as well as two trial registers. We searched for records published in 1990 or later, as this was the year aripiprazole became available. SELECTION CRITERIA: Randomised controlled trials (RCTs) of aripiprazole (administered orally and at any dosage) versus placebo for treatment of individuals with a diagnosis of ASD. DATA COLLECTION AND ANALYSIS: Two review authors independently collected, evaluated and analysed data. We performed meta-analysis for primary and secondary outcomes, when possible. We used the GRADE (Grades of Recommendation, Assessment, Development and Evaluation) approach to rate the overall quality of the evidence. MAIN RESULTS: We included three trials in this review. Two were included in the previous published review, and the results of one, placebo-controlled discontinuation study were added to this review. Although we searched for studies across age groups, we found only studies conducted in children and youth. Included trials had low risk of bias across most domains. High risk of bias was seen in only one trial with incomplete outcome data. We judged the overall quality of the evidence for most outcomes to be moderate.Two RCTs with similar methods evaluated use of aripiprazole for a duration of eight weeks in 316 children/adolescents with ASD. Meta-analysis of study results revealed a mean improvement of -6.17 points on the Aberrant Behavior Checklist (ABC) – Irritability subscale (95% confidence intervals (CIs) -9.07 to -3.26, two studies, 308 children/adolescents, moderate-quality evidence), -7.93 points on the ABC – Hyperactivity subscale (95% CI -10.98 to -4.88, two studies, 308 children/adolescents, moderate-quality evidence) and -2.66 points on the ABC – Stereotypy subscale (95% CI -3.55 to -1.77, two studies, 308 children/adolescents, moderate-quality evidence) in children/adolescents taking aripiprazole relative to children/adolescents taking placebo. In terms of side effects, children/adolescents taking aripiprazole had a greater increase in weight, with a mean increase of 1.13 kg relative to placebo (95% CI 0.71 to 1.54, two studies, 308 children/adolescents, moderate-quality evidence), and had a higher risk ratio (RR) for sedation (RR 4.28, 95% CI 1.58 to 11.60, two studies, 313 children/adolescents, moderate-quality evidence) and tremor (RR 10.26, 95% CI 1.37 to 76.63, two studies, 313 children/adolescents, moderate-quality evidence). A randomised, placebo-controlled discontinuation study found that 35% of children/adolescents randomised to continue intervention with aripiprazole relapsed with respect to their symptoms of irritability, compared with 52% of children/adolescents randomised to placebo, for a hazard ratio of 0.57 (95% CI 0.28 to 1.12, 85 children/adolescents, low-quality evidence).All three included trials were supported by Bristol-Myers Squibb (Princeton, NJ) and Otsuka Pharmaceutical Company, Ltd. (Tokyo, Japan), with editorial support provided by Ogilvy Healthworld Medical Education and Bristol-Myers Squibb. AUTHORS’ CONCLUSIONS: Evidence from two RCTs suggests that aripiprazole can be effective as a short-term medication intervention for some behavioural aspects of ASD in children/adolescents. After a short-term medication intervention with aripiprazole, children/adolescents showed less irritability and hyperactivity and fewer stereotypies (repetitive, purposeless actions). However, notable side effects, such as weight gain, sedation, drooling and tremor, must be considered. One long-term, placebo discontinuation study found that relapse rates did not differ between children/adolescents randomised to continue aripiprazole versus children/adolescents randomised to receive placebo, suggesting that re-evaluation of aripiprazole use after a period of stabilisation in irritability symptoms is warranted. Studies included in this review used criteria from the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) (APA 2000) for ASD diagnosis; however, the diagnostic criteria for ASD changed significantly with release of the fifth edition of the DSM (DSM-5) in 2013 (APA 2013).

Lien vers le texte intégral (Open Access ou abonnement)

7. Ikejiri K, Hosozawa M, Mitomo S, Tanaka K, Shimizu T. {{Reduced growth during early infancy in very low birth weight children with autism spectrum disorder}}. {Early Hum Dev}. 2016; 98: 23-7.

Lien vers le texte intégral (Open Access ou abonnement)

8. Karaminis T, Cicchini GM, Neil L, Cappagli G, Aagten-Murphy D, Burr D, Pellicano E. {{Central tendency effects in time interval reproduction in autism}}. {Sci Rep}. 2016; 6: 28570.

Central tendency, the tendency of judgements of quantities (lengths, durations etc.) to gravitate towards their mean, is one of the most robust perceptual effects. A Bayesian account has recently suggested that central tendency reflects the integration of noisy sensory estimates with prior knowledge representations of a mean stimulus, serving to improve performance. The process is flexible, so prior knowledge is weighted more heavily when sensory estimates are imprecise, requiring more integration to reduce noise. In this study we measure central tendency in autism to evaluate a recent theoretical hypothesis suggesting that autistic perception relies less on prior knowledge representations than typical perception. If true, autistic children should show reduced central tendency than theoretically predicted from their temporal resolution. We tested autistic and age- and ability-matched typical children in two child-friendly tasks: (1) a time interval reproduction task, measuring central tendency in the temporal domain; and (2) a time discrimination task, assessing temporal resolution. Central tendency reduced with age in typical development, while temporal resolution improved. Autistic children performed far worse in temporal discrimination than the matched controls. Computational simulations suggested that central tendency was much less in autistic children than predicted by theoretical modelling, given their poor temporal resolution.

Lien vers le texte intégral (Open Access ou abonnement)

9. Ku KM, Weir RK, Silverman JL, Berman RF, Bauman MD. {{Behavioral Phenotyping of Juvenile Long-Evans and Sprague-Dawley Rats: Implications for Preclinical Models of Autism Spectrum Disorders}}. {PLoS One}. 2016; 11(6): e0158150.

The laboratory rat is emerging as an attractive preclinical animal model of autism spectrum disorder (ASD), allowing investigators to explore genetic, environmental and pharmacological manipulations in a species exhibiting complex, reciprocal social behavior. The present study was carried out to compare two commonly used strains of laboratory rats, Sprague-Dawley (SD) and Long-Evans (LE), between the ages of postnatal day (PND) 26-56 using high-throughput behavioral phenotyping tools commonly used in mouse models of ASD that we have adapted for use in rats. We detected few differences between young SD and LE strains on standard assays of exploration, sensorimotor gating, anxiety, repetitive behaviors, and learning. Both SD and LE strains also demonstrated sociability in the 3-chamber social approach test as indexed by spending more time in the social chamber with a constrained age/strain/sex matched novel partner than in an identical chamber without a partner. Pronounced differences between the two strains were, however, detected when the rats were allowed to freely interact with a novel partner in the social dyad paradigm. The SD rats in this particular testing paradigm engaged in play more frequently and for longer durations than the LE rats at both juvenile and young adult developmental time points. Results from this study that are particularly relevant for developing preclinical ASD models in rats are threefold: (i) commonly utilized strains exhibit unique patterns of social interactions, including strain-specific play behaviors, (ii) the testing environment may profoundly influence the expression of strain-specific social behavior and (iii) simple, automated measures of sociability may not capture the complexities of rat social interactions.

Lien vers le texte intégral (Open Access ou abonnement)

10. Li R, Dong Q, Yuan X, Zeng X, Gao Y, Chiao C, Li H, Zhao X, Keles S, Wang Z, Chang Q. {{Misregulation of Alternative Splicing in a Mouse Model of Rett Syndrome}}. {PLoS Genet}. 2016; 12(6): e1006129.

Mutations in the human MECP2 gene cause Rett syndrome (RTT), a severe neurodevelopmental disorder that predominantly affects girls. Despite decades of work, the molecular function of MeCP2 is not fully understood. Here we report a systematic identification of MeCP2-interacting proteins in the mouse brain. In addition to transcription regulators, we found that MeCP2 physically interacts with several modulators of RNA splicing, including LEDGF and DHX9. These interactions are disrupted by RTT causing mutations, suggesting that they may play a role in RTT pathogenesis. Consistent with the idea, deep RNA sequencing revealed misregulation of hundreds of splicing events in the cortex of Mecp2 knockout mice. To reveal the functional consequence of altered RNA splicing due to the loss of MeCP2, we focused on the regulation of the splicing of the flip/flop exon of Gria2 and other AMPAR genes. We found a significant splicing shift in the flip/flop exon toward the flop inclusion, leading to a faster decay in the AMPAR gated current and altered synaptic transmission. In summary, our study identified direct physical interaction between MeCP2 and splicing factors, a novel MeCP2 target gene, and established functional connection between a specific RNA splicing change and synaptic phenotypes in RTT mice. These results not only help our understanding of the molecular function of MeCP2, but also reveal potential drug targets for future therapies.

Lien vers le texte intégral (Open Access ou abonnement)

11. Mazurek MO, Engelhardt CR, Hilgard J, Sohl K. {{Bedtime Electronic Media Use and Sleep in Children with Autism Spectrum Disorder}}. {J Dev Behav Pediatr}. 2016.

OBJECTIVES: The purpose of this study was to better understand the use of screen-based media at bedtime among children with autism spectrum disorder (ASD). The study specifically examined whether the presence of media devices in the child’s bedroom, the use of media as part of the bedtime routine, and exposure to media with violent content just before bedtime were associated with sleep difficulties. METHODS: Parents of 101 children with ASD completed questionnaires assessing their children’s sleep habits, bedroom media access (including television, video game devices, and computers), and patterns of nighttime media use (including timing of media exposure and violent media content). RESULTS: Children with ASD who used media as part of the bedtime routine showed significantly greater sleep onset latency than those who did not (39.8 vs 16.0 minutes). Similarly, children who were exposed to media with violent content within the 30-minute period before bedtime experienced significantly greater sleep onset delays and shorter overall sleep duration. In contrast, the mere presence of bedroom media was not associated with either sleep onset latency or sleep duration. CONCLUSION: Overall, these findings indicate that incorporating television and video games into the bedtime routine is associated with sleep onset difficulties among children with ASD. Exposure to violent media before bed is also associated with poor sleep. Families of children with ASD should be encouraged to regulate and monitor the timing and content of television and video game use, whether or not such devices are physically present in the child’s bedroom.

Lien vers le texte intégral (Open Access ou abonnement)

12. McMahon AC, Rosbash M. {{Promiscuous or discriminating: Has the favored mRNA target of Fragile X Mental Retardation Protein been overlooked?}}. {Proc Natl Acad Sci U S A}. 2016; 113(26): 7009-11.

Lien vers le texte intégral (Open Access ou abonnement)

13. Mikita N, Simonoff E, Pine DS, Goodman R, Artiges E, Banaschewski T, Bokde AL, Bromberg U, Buchel C, Cattrell A, Conrod PJ, Desrivieres S, Flor H, Frouin V, Gallinat J, Garavan H, Heinz A, Ittermann B, Jurk S, Martinot JL, Paillere Martinot ML, Nees F, Papadopoulos Orfanos D, Paus T, Poustka L, Smolka MN, Walter H, Whelan R, Schumann G, Stringaris A. {{Disentangling the autism-anxiety overlap: fMRI of reward processing in a community-based longitudinal study}}. {Transl Psychiatry}. 2016; 6(6): e845.

Up to 40% of youth with autism spectrum disorder (ASD) also suffer from anxiety, and this comorbidity is linked with significant functional impairment. However, the mechanisms of this overlap are poorly understood. We investigated the interplay between ASD traits and anxiety during reward processing, known to be affected in ASD, in a community sample of 1472 adolescents (mean age=14.4 years) who performed a modified monetary incentive delay task as part of the Imagen project. Blood-oxygen-level dependent (BOLD) responses to reward anticipation and feedback were compared using a 2×2 analysis of variance test (ASD traits: low/high; anxiety symptoms: low/high), controlling for plausible covariates. In addition, we used a longitudinal design to assess whether neural responses during reward processing predicted anxiety at 2-year follow-up. High ASD traits were associated with reduced BOLD responses in dorsal prefrontal regions during reward anticipation and negative feedback. Participants with high anxiety symptoms showed increased lateral prefrontal responses during anticipation, but decreased responses following feedback. Interaction effects revealed that youth with combined ASD traits and anxiety, relative to other youth, showed high right insula activation when anticipating reward, and low right-sided caudate, putamen, medial and lateral prefrontal activations during negative feedback (all clusters PFWE<0.05). BOLD activation patterns in the right dorsal cingulate and right medial frontal gyrus predicted new-onset anxiety in participants with high but not low ASD traits. Our results reveal both quantitatively enhanced and qualitatively distinct neural correlates underlying the comorbidity between ASD traits and anxiety. Specific neural responses during reward processing may represent a risk factor for developing anxiety in ASD youth. Lien vers le texte intégral (Open Access ou abonnement)

14. Perlis RH. {{Autism and antidepressant use in pregnancy}}. {J Pediatr}. 2016; 174: 278.

Lien vers le texte intégral (Open Access ou abonnement)

15. Ragland JD, Solomon M. {{Categorical Dimensions of Social Impairment and Disrupted Functional Connectivity in Autism Spectrum Disorders: When Does Continuous Become Discrete?}}. {Biol Psychiatry}. 2016; 80(2): 90-1.

Lien vers le texte intégral (Open Access ou abonnement)

16. Santa Maria L, Aliaga S, Faundes V, Morales P, Pugin A, Curotto B, Soto P, Pena MI, Salas I, Alliende MA. {{FMR1 gene mutations in patients with fragile X syndrome and obligate carriers: 30 years of experience in Chile}}. {Genet Res (Camb)}. 2016; 98: e11.

Fragile X syndrome (FXS) is the most common form of inherited intellectual disability (ID) and co-morbid autism. It is caused by an amplification of the CGG repeat (>200), which is known as the full mutation, within the 5’UTR of the FMR1 gene. Expansions between 55-200 CGG repeats are termed premutation and are associated with a greater risk for fragile X-associated tremor/ataxia syndrome and fragile X-associated premature ovarian insufficiency. Intermediate alleles, also called the grey zone, include approximately 45-54 repeats and are considered borderline. Individuals with less than 45 repeats have a normal FMR1 gene. We report the occurrence of CGG expansions of the FMR1 gene in Chile among patients with ID and families with a known history of FXS. Here, we present a retrospective review conducted on 2321 cases (2202 probands and 119 relatives) referred for FXS diagnosis and cascade screening at the Institute of Nutrition and Food Technology (INTA), University of Chile. Samples were analysed using traditional cytogenetic methods and/or PCR. Southern blot was used to confirm the diagnosis. Overall frequency of FMR1 expansions observed among probands was 194 (8.8%), the average age of diagnosis was 8.8 +/- 5.4 years. Of 119 family members studied, 72 (60%) were diagnosed with a CGG expansion. Our results indicated that the prevalence of CGG expansions of the FMR1 gene among probands is relatively higher than other populations. The average age of diagnosis is also higher than reference values. PCR and Southern blot represent a reliable molecular technique in the diagnosis of FXS.

Lien vers le texte intégral (Open Access ou abonnement)

17. Scahill L, Bearss K, Lecavalier L, Smith T, Swiezy N, Aman MG, Sukhodolsky DG, McCracken C, Minshawi N, Turner K, Levato L, Saulnier C, Dziura J, Johnson C. {{Effect of Parent Training on Adaptive Behavior in Children With Autism Spectrum Disorder and Disruptive Behavior: Results of a Randomized Trial}}. {J Am Acad Child Adolesc Psychiatry}. 2016; 55(7): 602-9 e3.

OBJECTIVE: This study examined the impact of parent training on adaptive behavior in children with autism spectrum disorder (ASD) and disruptive behavior. METHODS: This was a 24-week, 6-site, randomized trial of parent training versus parent education in 180 children with ASD (aged 3-7 years; 158 boys and 22 girls) and moderate or greater behavioral problems. Parent training included specific strategies to manage disruptive behavior over 11 to 13 sessions, 2 telephone boosters, and 2 home visits. Parent education provided useful information about autism but no behavior management strategies over 12 core sessions and 1 home visit. In a previous report, we showed that parent training was superior to parent education in reducing disruptive behavior in young children with ASD. Here, we test whether parent training is superior to parent education in improving daily living skills as measured by the parent-rated Vineland Adaptive Behavior Scales II. The long-term impact of parent training on adaptive functioning is also presented. RESULTS: At week 24, the parent training group showed a 5.7-point improvement from baseline on the Daily Living domain compared to no change in parent education (p = .004; effect size = 0.36). On the Socialization domain, there was a 5.9-point improvement in parent training versus a 3.1-point improvement in parent education (p = .11; effect size = 0.29). Gains in the Communication domain were similar across treatment groups. The gain in Daily Living was greater in children with IQ of >70. However, the interaction of treatment-by-IQ was not significant. Gains in Daily Living at week 24 were maintained upon re-evaluation at 24 weeks posttreatment. CONCLUSION: These results support the model that reduction in disruptive behavior can lead to improvement in activities of daily living. By contrast, the expected trajectory for adaptive behavior in children with ASD is often flat and predictably declines in children with intellectual disability. In the parent training group, higher-functioning children achieved significant gains in daily living skills. Children with intellectual disability kept pace with time. Clinical trial registration information-Randomized Trial of Parent Training for Young Children With Autism (RUBI); http://clinicaltrials.gov/; NCT01233414.

Lien vers le texte intégral (Open Access ou abonnement)

18. Schulte-Ruther M, Otte E, Adiguzel K, Firk C, Herpertz-Dahlmann B, Koch I, Konrad K. {{Intact mirror mechanisms for automatic facial emotions in children and adolescents with autism spectrum disorder}}. {Autism Res}. 2016.

It has been suggested that an early deficit in the human mirror neuron system (MNS) is an important feature of autism. Recent findings related to simple hand and finger movements do not support a general dysfunction of the MNS in autism. Studies investigating facial actions (e.g., emotional expressions) have been more consistent, however, mostly relied on passive observation tasks. We used a new variant of a compatibility task for the assessment of automatic facial mimicry responses that allowed for simultaneous control of attention to facial stimuli. We used facial electromyography in 18 children and adolescents with Autism spectrum disorder (ASD) and 18 typically developing controls (TDCs). We observed a robust compatibility effect in ASD, that is, the execution of a facial expression was facilitated if a congruent facial expression was observed. Time course analysis of RT distributions and comparison to a classic compatibility task (symbolic Simon task) revealed that the facial compatibility effect appeared early and increased with time, suggesting fast and sustained activation of motor codes during observation of facial expressions. We observed a negative correlation of the compatibility effect with age across participants and in ASD, and a positive correlation between self-rated empathy and congruency for smiling faces in TDC but not in ASD. This pattern of results suggests that basic motor mimicry is intact in ASD, but is not associated with complex social cognitive abilities such as emotion understanding and empathy. Autism Res 2016. (c) 2016 International Society for Autism Research, Wiley Periodicals, Inc.

Lien vers le texte intégral (Open Access ou abonnement)

19. Schweitzer J, James C, Jenkins W, Reiff MI, Stein MT. {{Acute Agitation and Self-Injury in a 5-Year Old with Autism}}. {J Dev Behav Pediatr}. 2016.

CASE: A 5-year-old nonverbal child with autism spectrum disorder (ASD) was admitted to inpatient pediatrics with new onset agitation and self-injurious behavior. His parents described him as a pleasant child without previous episodes of self-injury. Four days before admission, the parents noted new irritability followed by 2 days of self-injury to the face without clear precipitant. His hitting intensified with closed fist to face, and he required parental physical restraint to prevent further injury. Car rides and ibuprofen provided only temporary relief. He consumed minimal liquid and ate no solid food for 2 days. The parents denied any changes to the environment or routine and denied recent travel, sick contacts, fevers, cough, otalgia, vomiting, diarrhea, and constipation. The patient had been diagnosed with ASD at age 18 months old but had no other significant medical history.On examination, the child was alert but distressed and restless, wearing padded mitts as his parents attempted to calm him by pushing him in a stroller. He had multiple areas of severe bruising and facial swelling in the right periorbital area, cheek, and jaw. The rest of the physical examination was unremarkable. Laboratory results included a leukocytosis with left shift, a normal metabolic panel, and an elevated creatine kinase. Other investigations included a normal lumber puncture, chest radiograph, head and face computerized tomography without contrast, and brain magnetic resonance imaging. A dentist consultant examined him and noted an erupting molar but no decay or abscesses. A psychiatric evaluation was requested as there was no clear medical source for the patient’s distress.

Lien vers le texte intégral (Open Access ou abonnement)

20. Shah P. {{Interoception: The Eighth Sensory System: Practical Solutions for Improving Self-Regulation, Self-Awareness and Social Understanding of Individuals with Autism Spectrum and Related Disorders : K. J. Mahler: Shawnee Mission KS, AAPC, 2015, 186 pp, $29.95 (paper), ISBN 978-1-942197-14-0}}. {J Autism Dev Disord}. 2016.

Lien vers le texte intégral (Open Access ou abonnement)

21. Tabet R, Moutin E, Becker JA, Heintz D, Fouillen L, Flatter E, Krezel W, Alunni V, Koebel P, Dembele D, Tassone F, Bardoni B, Mandel JL, Vitale N, Muller D, Le Merrer J, Moine H. {{Fragile X Mental Retardation Protein (FMRP) controls diacylglycerol kinase activity in neurons}}. {Proc Natl Acad Sci U S A}. 2016; 113(26): E3619-28.

Fragile X syndrome (FXS) is caused by the absence of the Fragile X Mental Retardation Protein (FMRP) in neurons. In the mouse, the lack of FMRP is associated with an excessive translation of hundreds of neuronal proteins, notably including postsynaptic proteins. This local protein synthesis deregulation is proposed to underlie the observed defects of glutamatergic synapse maturation and function and to affect preferentially the hundreds of mRNA species that were reported to bind to FMRP. How FMRP impacts synaptic protein translation and which mRNAs are most important for the pathology remain unclear. Here we show by cross-linking immunoprecipitation in cortical neurons that FMRP is mostly associated with one unique mRNA: diacylglycerol kinase kappa (Dgkkappa), a master regulator that controls the switch between diacylglycerol and phosphatidic acid signaling pathways. The absence of FMRP in neurons abolishes group 1 metabotropic glutamate receptor-dependent DGK activity combined with a loss of Dgkkappa expression. The reduction of Dgkkappa in neurons is sufficient to cause dendritic spine abnormalities, synaptic plasticity alterations, and behavior disorders similar to those observed in the FXS mouse model. Overexpression of Dgkkappa in neurons is able to rescue the dendritic spine defects of the Fragile X Mental Retardation 1 gene KO neurons. Together, these data suggest that Dgkkappa deregulation contributes to FXS pathology and support a model where FMRP, by controlling the translation of Dgkkappa, indirectly controls synaptic proteins translation and membrane properties by impacting lipid signaling in dendritic spine.

Lien vers le texte intégral (Open Access ou abonnement)

22. Taylor CE, Bush K. {{Unintended consequences of inhibiting dihydrofolate reductase through folic acid supplementation: inattentive-type attention deficit hyperactivity disorder and ASD connections}}. {Int J Food Sci Nutr}. 2016: 1-2.

Lien vers le texte intégral (Open Access ou abonnement)

23. Theoharides TC, Tsilioni I, Patel AB, Doyle R. {{Atopic diseases and inflammation of the brain in the pathogenesis of autism spectrum disorders}}. {Transl Psychiatry}. 2016; 6(6): e844.

Autism spectrum disorders (ASDs) affect as many as 1 in 45 children and are characterized by deficits in sociability and communication, as well as stereotypic movements. Many children also show severe anxiety. The lack of distinct pathogenesis and reliable biomarkers hampers the development of effective treatments. As a result, most children with ASD are prescribed psychopharmacologic agents that do not address the core symptoms of ASD. Autoantibodies against brain epitopes in mothers of children with ASD and many such children strongly correlate with allergic symptoms and indicate an aberrant immune response, as well as disruption of the blood-brain barrier (BBB). Recent epidemiological studies have shown a strong statistical correlation between risk for ASD and either maternal or infantile atopic diseases, such as asthma, eczema, food allergies and food intolerance, all of which involve activation of mast cells (MCs). These unique tissue immune cells are located perivascularly in all tissues, including the thalamus and hypothalamus, which regulate emotions. MC-derived inflammatory and vasoactive mediators increase BBB permeability. Expression of the inflammatory molecules interleukin (IL-1beta), IL-6, 1 L-17 and tumor necrosis factor (TNF) is increased in the brain, cerebrospinal fluid and serum of some patients with ASD, while NF-kB is activated in brain samples and stimulated peripheral blood immune cells of other patients; however, these molecules are not specific. Instead the peptide neurotensin is uniquely elevated in the serum of children with ASD, as is corticotropin-releasing hormone, secreted from the hypothalamus under stress. Both peptides trigger MC to release IL-6 and TNF, which in turn, stimulate microglia proliferation and activation, leading to disruption of neuronal connectivity. MC-derived IL-6 and TGFbeta induce maturation of Th17 cells and MCs also secrete IL-17, which is increased in ASD. Serum IL-6 and TNF may define an ASD subgroup that benefits most from treatment with the natural flavonoid luteolin. Atopic diseases may create a phenotype susceptible to ASD and formulations targeting focal inflammation of the brain could have great promise in the treatment of ASD.

Lien vers le texte intégral (Open Access ou abonnement)

24. van Schalkwyk GI, Beyer C, Martin A, Volkmar FR. {{College students with Autism Spectrum Disorders: A growing role for adult psychiatrists}}. {J Am Coll Health}. 2016: 0.

OBJECTIVE: Adolescents with autism spectrum disorders (ASD) are increasingly attending college. This case report highlights the nature of the psychiatric difficulties these individuals may face and the potential role for college mental health practitioners. PARTICIPANTS: A case of a female student with ASD presenting with significant inattentive symptoms. METHODS: We describe the unique features of this patient’s clinical presentation, relevant diagnostic considerations, and make recommendations about how to best approach treatment. RESULTS: This student presented with symptoms of ADHD which were first relevant during her time at college, owing to increased demands on planning and other executive functions. She was eventually responsive to treatment with a stimulant, but had more side-effects early on. CONCLUSIONS: As individuals with ASD attend college, their mental health needs will require treatment. However, such treatment draws on a comparatively limited evidence base, and providers need to be aware of potential challenges that may arise.

Lien vers le texte intégral (Open Access ou abonnement)

25. Vanwong N, Prommas S, Puangpetch A, Hongkaew Y, Nuntamool N, Nakorn CN, Ngamsamut N, Limsila P, Sukasem C. {{Development and Validation of Liquid Chromatography/Tandem Mass Spectrometry Analysis for Therapeutic Drug Monitoring of Risperidone and 9-Hydroxyrisperidone in Pediatric Patients with Autism Spectrum Disorders}}. {J Clin Lab Anal}. 2016.

BACKGROUND: Risperidone (RIS) is a widely used atypical antipsychotic drug. We developed and validated a sensitive and accurate LC-MS/MS method, which requires a small-volume of plasma and small-volume injection for measurement of RIS levels in ASD pediatric patients. We also investigated the relationship between RIS levels and RIS dosages, including prolactin levels. METHOD: Blood samples were processed by protein precipitation extraction. Only 1 mul of sample was injected. Plasma samples were separated on a C18 column (4.6 cm x 50 mm; 1.8 mum particle size). Detection was by MS-MS with an analytical run time of 6 min. RESULTS: The inter-day accuracy of RIS was 101.33-107.68% and 95.24-103.67% for 9-OH-RIS. The inter-day precision of RIS was Lien vers le texte intégral (Open Access ou abonnement)

26. Zhang HF, Dai YC, Wu J, Jia MX, Zhang JS, Shou XJ, Han SP, Zhang R, Han JS. {{Plasma Oxytocin and Arginine-Vasopressin Levels in Children with Autism Spectrum Disorder in China: Associations with Symptoms}}. {Neurosci Bull}. 2016.

Autism spectrum disorder (ASD) is defined by impairments of social interaction and the presence of obsessive behaviors. The « twin » nonapeptides oxytocin (OXT) and arginine-vasopressin (AVP) are known to play regulatory roles in social behaviors. However, the plasma levels and behavioral relevance of OXT and AVP in children with ASD have seldom been investigated. It is also unknown whether their mothers have abnormal plasma peptide levels. Here, using well-established methods of neuropeptide measurement and a relatively large sample size, we determined the plasma levels of the two neuropeptides in 85 normal children, 84 children with ASD, and 31 mothers from each group of children. As expected, children with ASD had lower plasma OXT levels than gender-matched controls (P = 0.028). No such difference was found for plasma AVP concentrations. Correlation analysis showed that ASD children with higher plasma OXT concentrations tended to have less impairment of verbal communication (Rho = -0.22, P = 0.076), while those with higher plasma AVP levels tended to have lower levels of repetitive use of objects (Rho = -0.231, P = 0.079). Unlike the findings in children, maternal plasma OXT levels showed no group difference. However, plasma AVP levels in the mothers of ASD children tended to be lower than in the mothers of normal children (P = 0.072). In conclusion, our results suggest that the OXT system is dysregulated in children with ASD, and that OXT and AVP levels in plasma seem to be associated with specific autistic symptoms. The plasma levels of OXT or AVP in mothers and their ASD children did not seem to change in the same direction.

Lien vers le texte intégral (Open Access ou abonnement)