1. Davis PE, Peters JM, Krueger DA, Sahin M. {{Tuberous Sclerosis: A New Frontier in Targeted Treatment of Autism}}. {Neurotherapeutics};2015 (May 19)
Tuberous sclerosis complex (TSC) is a genetic disorder with a high prevalence of autism spectrum disorder (ASD). Tremendous progress in understanding the pathogenesis of TSC has been made in recent years, along with initial trials of medical treatment aimed specifically at the underlying mechanism of the disorder. At the cellular level, loss of TSC1 or TSC2 results in upregulation of the mechanistic target of rapamycin (mTOR) pathway. At the circuitry level, TSC and mTOR play crucial roles in axonal, dendritic, and synaptic development and function. In this review, we discuss the molecular mechanism underlying TSC, and how this disease results in aberrant neural connectivity at multiple levels in the central nervous system, leading to ASD symptoms. We then review recent advances in mechanism-based treatments of TSC, and the promise that these treatments provide for future mechanism-based treatment of ASD. Because of these recent advances, TSC represents an ideal model for how to make progress in understanding and treating the mechanisms that underlie ASD in general.
Lien vers le texte intégral (Open Access ou abonnement)
2. Fang SY, Wang S, Huang N, Yeh HH, Chen CY. {{Prenatal Infection and Autism Spectrum Disorders in Childhood: A Population-Based Case-Control Study in Taiwan}}. {Paediatr Perinat Epidemiol};2015 (May 19)
BACKGROUND: Infection in pregnancy has long been linked with negative postnatal development and health. This study aims to assess the association between prenatal infections and autism spectrum disorders (ASDs) across three trimesters and to probe possible sex heterogeneity in such link. METHOD: A total of 4184 children with incident ASDs and 16 734 matched children were identified from the 2000-2007 National Health Insurance Research Database. For each child, information pertaining to the mother’s infection during pregnancy, sociodemographics, and medical history was retrieved from healthcare records. Conditional logistic analyses were carried out to estimate the strength of associations with adjustment for multiple comparisons. RESULT: Pooled analyses demonstrated that having two or more outpatient visits for genital infection [adjusted odds ratio (aOR): 1.34; 95% confidence interval (95% CI) 1.12, 1.60; false discovery rate (FDR) < 0.01] and bacterial infection (aOR: 1.24; 95% CI 1.06, 1.43; FDR < 0.05) in the third trimester were slightly associated with increased risk of ASDs. No statistically significant sex differences were found. CONCLUSION: The present study contributes updated population-based evidence about the connection between prenatal infection and ASDs. Potential effect of bacterial and genital tract infections during the third trimester on risk of ASDs warrants further exploration.
Lien vers le texte intégral (Open Access ou abonnement)
3. Gross C, Hoffmann A, Bassell GJ, Berry-Kravis EM. {{Therapeutic Strategies in Fragile X Syndrome: From Bench to Bedside and Back}}. {Neurotherapeutics};2015 (May 19)
Fragile X syndrome (FXS), an inherited intellectual disability often associated with autism, is caused by the loss of expression of the fragile X mental retardation protein. Tremendous progress in basic, preclinical, and translational clinical research has elucidated a variety of molecular-, cellular-, and system-level defects in FXS. This has led to the development of several promising therapeutic strategies, some of which have been tested in larger-scale controlled clinical trials. Here, we will summarize recent advances in understanding molecular functions of fragile X mental retardation protein beyond the well-known role as an mRNA-binding protein, and will describe current developments and emerging limitations in the use of the FXS mouse model as a preclinical tool to identify therapeutic targets. We will review the results of recent clinical trials conducted in FXS that were based on some of the preclinical findings, and discuss how the observed outcomes and obstacles will inform future therapy development in FXS and other autism spectrum disorders.
Lien vers le texte intégral (Open Access ou abonnement)
4. Janvier YM, Harris JF, Coffield CN, Louis B, Xie M, Cidav Z, Mandell DS. {{Screening for autism spectrum disorder in underserved communities: Early childcare providers as reporters}}. {Autism};2015 (May 19)
Early diagnosis of autism typically is associated with earlier access to intervention and improved outcomes. Daycares and preschools largely have been ignored as possible venues for early identification. This may be especially important for minority children in the United States who are typically diagnosed with autism later than White children, limiting their access to early specialized interventions and possibly resulting in poorer outcomes. Early childcare providers within underserved communities completed autism screening tools for a sample of low-risk young children (n = 967) in their programs. Early childcare providers returned screening tools for 90% of the children for whom parental consent had been received. A total of 14% of children screened positive for autism spectrum disorder and 3% of the sample met criteria for autism spectrum disorder. Among those who screened positive, 34% were lost to follow-up. Findings suggest that early childcare providers can effectively screen young children for autism spectrum disorder in preschool/daycare settings, thus improving access to early diagnosis and reducing potential healthcare disparities among underserved populations.
Lien vers le texte intégral (Open Access ou abonnement)
5. Mandic-Maravic V, Pejovic-Milovancevic M, Mitkovic-Voncina M, Kostic M, Aleksic-Hil O, Radosavljev-Kircanski J, Mincic T, Lecic-Tosevski D. {{Sex differences in autism spectrum disorders: does sex moderate the pathway from clinical symptoms to adaptive behavior?}}. {Sci Rep};2015;5:10418.
We explored sex differences in diagnostic categories, clinical symptoms and adaptive behavior of persons with autism spectrum disorders, as well as sex-specific correlations of clinical and adaptive caracteristics. The study involved 108 patients (83 males, 6.73 +/- 4.33 years old) diagnosed with autism spectrum disorders (ASD). Assessment included ADI-R and Vineland Adaptive Behavior Scale II. Males were more often diagnosed with typical autism. There were no sex differences in the autistic symptoms, while females showed better functioning in Daily living skills, without reaching statistically significant difference (p = 0.062). We have found different associations of autistic symptoms with different aspects of adaptive behavior in males and females. Social reciprocity in females correlated with social domain of adaptive behavior, in a positive direction. Our findings have shown that although there are no sex differences in autistic symptoms, females tend to be somewhat more functional, and are also less frequently diagnosed with typical autism. Our results have also shown that sex might moderate the way clinical symptoms are expressed in adaptive behavior. Social reciprocity might be the core feature regarding sex differences in ASD. Our findings might have diagnostic and therapeutical implications, pointing out to the need for individualized, sex-specific treatment in this group of disorders.
Lien vers le texte intégral (Open Access ou abonnement)
6. O’Neill S. {{The countertransference impact of autistic defence in an otherwise neurotic patient}}. {Int J Psychoanal};2015 (May 19)
This paper investigates the question of why, in the psychoanalytic psychotherapy of a patient with encapsulated autistic pathology, the steady maintenance of a therapeutically neutral stance can be especially difficult. Transference and countertransference vicissitudes are examined. The author notices that the patient’s intolerance of ‘opposites’ (cf. Tustin, 1986), combined with extreme antipathy to having that intolerance noticed, can elicit corresponding, and potentially destabilizing, countertransference reactions. These reactions comprise an unstable tension between co-existing pressures towards fusion with, or expulsion of, the patient, their co-existence under further pressure to remain unnoticed. Until perceived, this state of affairs risks collusion with the pressure either to merge with or to expel the patient, and compromises the capacity to notice the detail of the transference process and even to notice co-existent positive and negative transference images. Detailed clinical illustration is given, including a session where it was difficult to notice the patient’s experience of a couple as a combined object. The author finds these observations of bipolar countertransference tensions illuminated by Green’s concepts of positive and negative narcissism and of the disobjectalizing function, and specifically accounted for by Ribas’s theory of autism as radical drive defusion.
Lien vers le texte intégral (Open Access ou abonnement)
7. Rueda JR, Guillen V, Ballesteros J, Tejada MI, Sola I. {{L-acetylcarnitine for treating fragile X syndrome}}. {Cochrane Database Syst Rev};2015 (May 19);5:CD010012.
BACKGROUND: People with fragile X syndrome (FXS) have an intellectual dysfunction that can range from very mild to severe. Symptoms can include speech and language delays and behavioural difficulties such as aggression or self injurious behaviours, emotional lability, and anxiety-related problems (for example obsessive-compulsive symptoms and perseverative behaviours). In some cases, affected people may have an additional diagnosis of attention deficit hyperactivity disorder or an autism spectrum disorder. OBJECTIVES: To review the efficacy and safety of L-acetylcarnitine in improving the psychological, intellectual, and social performance of people with FXS. SEARCH METHODS: In May 2015 we searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, PsycINFO, Web of Science, and two other databases. We also searched three trials registers, four theses databases, and the reference lists of relevant studies and reviews. SELECTION CRITERIA: Randomised controlled trials (RCTs) that assessed the efficacy of L-acetylcarnitine, at any dose, in people of any age diagnosed with FXS compared with placebo. DATA COLLECTION AND ANALYSIS: For each trial, two review authors independently extracted data on the children included and interventions compared, and assessed the risk of bias of the studies across the following domains: randomisation sequence generation, allocation concealment, blinding (of participants, personnel, and outcome assessors), incomplete outcome data, selective outcome reporting, and other potential sources of bias. MAIN RESULTS: We found only two RCTs that compared oral L-acetylcarnitine (LAC) with oral placebo in children with FXS. The studies included a total of 83 participants, all of them male, who were treated and followed for one year. The age of participants at the start of treatment ranged from 6 to 13 years, with a mean age of 9 years. Neither study provided information on randomisation, allocation concealment procedures, or blinding of outcome assessment, and we received no responses from the authors we emailed for clarification. We therefore rated studies as being at unclear risk of bias on these domains. We judged both studies to be at low risk of bias for blinding of participants and personnel, incomplete outcome data, and selective reporting, but to be at high risk of other bias, as at least one study was funded by a drug company, and in both studies people working for the company were part of the research team.We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to rate the quality of the available evidence. Overall, the quality of the evidence was low due to the imprecision of results and high risk of other bias.Regarding the primary outcome of psychological and learning capabilities, both studies assessed the effect of interventions on children’s verbal and non-verbal intellectual functioning using the Wechsler Intelligence Scale for Children – Revised. The authors did not provide detailed data on those results but said that they found no important differences between treatment and placebo.Both studies evaluated the impact of the treatment on hyperactive behaviour using the Conners’ Abbreviated Parent-Teacher Questionnaire. In one study, teachers’ assessments of the children found no clear evidence of a difference (mean difference (MD) 0.50, 95% confidence interval (CI) -5.08 to 6.08, n = 51; low-quality evidence). The other study stated that there were no differences between treated and untreated participants, but did not provide detailed data for inclusion in the meta-analysis.Parents’ assessments favoured LAC in one study (MD -0.57, 95% CI -0.94 to -0.19, n = 17; low-quality evidence), but not in the other (MD -2.80, 95% CI -7.61 to 2.01, n = 51; low-quality evidence), though changes were not large enough to be considered clinically relevant.Regarding social skills, one study reported no clear evidence of a difference in Vineland Adaptive Behavior composite scores (MD 8.20, 95% CI -0.02 to 16.42, n = 51; low-quality evidence), yet results in the socialisation domain favoured LAC (MD 11.30, 95% CI 2.52 to 20.08, n = 51; low-quality evidence).Both studies assessed the safety of the active treatment and recorded no side effects. Neither of the included studies assessed the secondary outcome of caregiver burden. AUTHORS’ CONCLUSIONS: Low-quality evidence from two small trials showed that when compared to placebo, LAC may not improve intellectual functioning or hyperactive behaviour in children with FXS.
Lien vers le texte intégral (Open Access ou abonnement)
8. Rumbak DM, Mowrey W, Schwartz SW, Sarwahi V, Djukic A, Killinger JS, Katyal C. {{Spinal Fusion for Scoliosis in Rett Syndrome With an Emphasis on Respiratory Failure and Opioid Usage}}. {J Child Neurol};2015 (May 19)
Our objective was to characterize our experience with 8 patients with Rett syndrome undergoing scoliosis surgery in regard to rates of respiratory failure and rates of ventilator-acquired pneumonia in comparison to patients with neurologic scoliosis and adolescent idiopathic scoliosis. This study was a retrospective chart review of patients undergoing scoliosis surgery at a tertiary children’s hospital. Patients were divided into 3 groups: (1) adolescent idiopathic scoliosis, (2) neurologic scoliosis, and (3) Rett syndrome. There were 133 patients with adolescent idiopathic scoliosis, 48 patients with neurologic scoliosis, and 8 patients with Rett syndrome. We found that patients with Rett syndrome undergoing scoliosis surgery have higher rates of respiratory failure and longer ventilation times in the postoperative period when compared with both adolescent idiopathic scoliosis and neurologic scoliosis patients. There is insufficient evidence to suggest a difference in the incidence of ventilator-acquired pneumonia between the Rett syndrome and the neurologic scoliosis group. We believe our findings are the first in the literature to show a statistically significant difference between these 3 groups in regard to incidence of respiratory failure.
Lien vers le texte intégral (Open Access ou abonnement)
9. Smith MJ, Fleming MF, Wright MA, Losh M, Humm LB, Olsen D, Bell MD. {{Brief Report: Vocational Outcomes for Young Adults with Autism Spectrum Disorders at Six Months After Virtual Reality Job Interview Training}}. {J Autism Dev Disord};2015 (May 19)
Young adults with high-functioning autism spectrum disorder (ASD) have low employment rates and job interviewing presents a critical barrier to employment for them. Results from a prior randomized controlled efficacy trial suggested virtual reality job interview training (VR-JIT) improved interviewing skills among trainees with ASD, but not controls with ASD. We conducted a brief survey with 23 of 26 participants from this study to evaluate their vocational outcomes at 6-month follow-up with a focus on whether or not they attained a competitive position (employment or competitive volunteering). Logistic regression indicated VR-JIT trainees had greater odds of attaining a competitive position than controls (OR 7.82, p < 0.05). Initial evidence suggests VR-JIT is a promising intervention that enhances vocational outcomes among young adults with high-functioning ASD.
Lien vers le texte intégral (Open Access ou abonnement)
10. Viaggi C, Gerace C, Pardini C, Corsini GU, Vaglini F. {{Serotonin abnormalities in engrailed-2 knockout mice: new insight relevant for a model of autism spectrum disorder}}. {Neurochem Int};2015 (May 19)
Autism spectrum disorder (ASD) is a congenital neurodevelopmental behavioral disorder that appears in early childhood. Recent human genetic studies identified the homeobox transcription factor, Engrailed 2 (EN2), as a possible ASD susceptibility gene. En2 knockout mice (En2-/-) display subtle cerebellar neuropathological changes and reduced levels of tyrosine hydroxylase, noradrenaline and serotonin in the hippocampus and cerebral cortex similar to those ones which have been observed in the ASD brain. Furthermore other similarities link En2 knockout mice to ASD patients. Several lines of evidence suggest that serotonin may play an important role in the pathophysiology of the disease. In the present study we measured, by using an HPLC, the 5-HT levels in different brain areas and at different ages in En2-/- mice. In the frontal and occipital cortex, the content of 5HT was reduced in En2-/- one and three months old mice; in six months old mice, the difference was still present, but it was not statistically significant. The 5-HT content of cerebellar cortex was significantly reduced at one month old but significantly high when the KO mice reached three months of age. The increase was present even at six months of age. A similar trend was highlighted by SERT immunolabelling in En2-/- mice compared to control in the same areas and age analyzed. Our findings, in agreement with the current knowledge on the 5-HT system alterations in ASD, confirm the early neurotransmitter deficit with a late compensatory recovery in En2 KO-mice further suggesting that this experimental animal may be considered a good predictive model for the human disease.
Lien vers le texte intégral (Open Access ou abonnement)
11. Walton KM, Ingersoll BR. {{The utility of Thin Slice ratings for predicting language growth in children with autism spectrum disorder}}. {Autism};2015 (May 19)
Literature on « Thin Slice » ratings indicates that a number of personality characteristics and behaviors can be accurately predicted by ratings of very short segments (<5 min) of behavior. This study examined the utility of Thin Slice ratings of young children with autism spectrum disorder for predicting developmental skills and language gains over time. A total of 22 preschool-aged children with autism spectrum disorder participated in a battery of developmental assessments and a video-taped therapist-child interaction at Time 1. They then participated in follow-up testing of language skills and a second therapist-child interaction 6 months later (Time 2). Groups of approximately 25 naive undergraduate students provided impression ratings (« Thin Slice ratings ») about each child’s skills and behaviors during 2-min segments taken from the therapist-child interaction videos at each time point. Thin Slice ratings at Time 1 were highly correlated with child scores on several developmental assessments at Time 1. In addition, Thin Slice ratings at Time 1 predicted gain in parent-reported expressive vocabulary over the course of 6 months, over and above the predictive utility of Time 1 vocabulary size. These findings provide preliminary evidence for the concurrent and predictive validity of Thin Slice ratings in young children with autism spectrum disorder.
Lien vers le texte intégral (Open Access ou abonnement)
12. Wilkinson B, Grepo N, Thompson BL, Kim J, Wang K, Evgrafov OV, Lu W, Knowles JA, Campbell DB. {{The autism-associated gene chromodomain helicase DNA-binding protein 8 (CHD8) regulates noncoding RNAs and autism-related genes}}. {Transl Psychiatry};2015;5:e568.
Chromodomain helicase DNA-binding protein 8 (CHD8) was identified as a leading autism spectrum disorder (ASD) candidate gene by whole-exome sequencing and subsequent targeted-sequencing studies. De novo loss-of-function mutations were identified in 12 individuals with ASD and zero controls, accounting for a highly significant association. Small interfering RNA-mediated knockdown of CHD8 in human neural progenitor cells followed by RNA sequencing revealed that CHD8 insufficiency results in altered expression of 1715 genes, including both protein-coding and noncoding RNAs. Among the 10 most changed transcripts, 4 (40%) were noncoding RNAs. The transcriptional changes among protein-coding genes involved a highly interconnected network of genes that are enriched in neuronal development and in previously identified ASD candidate genes. These results suggest that CHD8 insufficiency may be a central hub in neuronal development and ASD risk.
Lien vers le texte intégral (Open Access ou abonnement)
13. Zaidel A, Goin-Kochel RP, Angelaki DE. {{Self-motion perception in autism is compromised by visual noise but integrated optimally across multiple senses}}. {Proc Natl Acad Sci U S A};2015 (May 19);112(20):6461-6466.
Perceptual processing in autism spectrum disorder (ASD) is marked by superior low-level task performance and inferior complex-task performance. This observation has led to theories of defective integration in ASD of local parts into a global percept. Despite mixed experimental results, this notion maintains widespread influence and has also motivated recent theories of defective multisensory integration in ASD. Impaired ASD performance in tasks involving classic random dot visual motion stimuli, corrupted by noise as a means to manipulate task difficulty, is frequently interpreted to support this notion of global integration deficits. By manipulating task difficulty independently of visual stimulus noise, here we test the hypothesis that heightened sensitivity to noise, rather than integration deficits, may characterize ASD. We found that although perception of visual motion through a cloud of dots was unimpaired without noise, the addition of stimulus noise significantly affected adolescents with ASD, more than controls. Strikingly, individuals with ASD demonstrated intact multisensory (visual-vestibular) integration, even in the presence of noise. Additionally, when vestibular motion was paired with pure visual noise, individuals with ASD demonstrated a different strategy than controls, marked by reduced flexibility. This result could be simulated by using attenuated (less reliable) and inflexible (not experience-dependent) Bayesian priors in ASD. These findings question widespread theories of impaired global and multisensory integration in ASD. Rather, they implicate increased sensitivity to sensory noise and less use of prior knowledge in ASD, suggesting increased reliance on incoming sensory information.
