1. Alpatov R, Lesch BJ, Nakamoto-Kinoshita M, Blanco A, Chen S, Stutzer A, Armache KJ, Simon MD, Xu C, Ali M, Murn J, Prisic S, Kutateladze TG, Vakoc CR, Min J, Kingston RE, Fischle W, Warren ST, Page DC, Shi Y. {{A Chromatin-Dependent Role of the Fragile X Mental Retardation Protein FMRP in the DNA Damage Response}}. {Cell};2014 (May 8);157(4):869-881.
Fragile X syndrome, a common form of inherited intellectual disability, is caused by loss of the fragile X mental retardation protein FMRP. FMRP is present predominantly in the cytoplasm, where it regulates translation of proteins that are important for synaptic function. We identify FMRP as a chromatin-binding protein that functions in the DNA damage response (DDR). Specifically, we show that FMRP binds chromatin through its tandem Tudor (Agenet) domain in vitro and associates with chromatin in vivo. We also demonstrate that FMRP participates in the DDR in a chromatin-binding-dependent manner. The DDR machinery is known to play important roles in developmental processes such as gametogenesis. We show that FMRP occupies meiotic chromosomes and regulates the dynamics of the DDR machinery during mouse spermatogenesis. These findings suggest that nuclear FMRP regulates genomic stability at the chromatin interface and may impact gametogenesis and some developmental aspects of fragile X syndrome.
Lien vers le texte intégral (Open Access ou abonnement)
2. Ballinger EC, Cordeiro L, Chavez AD, Hagerman RJ, Hessl D. {{Emotion Potentiated Startle in Fragile X Syndrome}}. {J Autism Dev Disord};2014 (May 11)
Social avoidance and anxiety are prevalent in fragile X syndrome (FXS) and are potentially mediated by the amygdala, a brain region critical for social behavior. Unfortunately, functional brain resonance imaging investigation of the amygdala in FXS is limited by the difficulties experienced by intellectually impaired and anxious participants. We investigated the relationship between social avoidance and emotion-potentiated startle, a probe of amygdala activation, in children and adolescents with FXS, developmental disability without FXS (DD), and typical development. Individuals with FXS or DD demonstrated significantly reduced potentiation to fearful faces than a typically developing control group (p < .05). However, among individuals with FXS, social avoidance correlated positively with fearful-face potentiation (p < .05). This suggests that general intellectual disability blunts amygdalar response, but differential amygdala responsiveness to social stimuli contributes to phenotypic variability among individuals with FXS.
Lien vers le texte intégral (Open Access ou abonnement)
3. Blenner S, Augustyn M. {{Is the prevalence of autism increasing in the United States?}}. {BMJ};2014;348:g3088.
4. Calderoni S, Bellani M, Hardan AY, Muratori F, Brambilla P. {{Basal ganglia and restricted and repetitive behaviours in Autism Spectrum Disorders: current status and future perspectives}}. {Epidemiol Psychiatr Sci};2014 (May 12):1-4.
This editorial offers a concise overview of the recent structural magnetic resonance imaging studies that evaluate the basal ganglia (BG) volumes in autism spectrum disorders (ASD). The putative relationship between the repetitive or stereotyped behaviours of ASD and BG volumes is also explored, with a focus on possible translational approaches.
Lien vers le texte intégral (Open Access ou abonnement)
5. Eussen ML, de Bruin EI, Van Gool AR, Louwerse A, van der Ende J, Verheij F, Verhulst FC, Greaves-Lord K. {{Formal thought disorder in autism spectrum disorder predicts future symptom severity, but not psychosis prodrome}}. {Eur Child Adolesc Psychiatry};2014 (May 10)
Formal thought disorder (FTD) is a disruption in the flow of thought, which is inferred from disorganisation of spoken language. FTD in autism spectrum disorders (ASD) might be a precursor of psychotic disorders or a manifestation of ASD symptom severity. The current longitudinal study is a seven-year follow-up of 91 individuals aged 5-12 years with ASD. We tested (1) whether childhood FTD predicted prodromal symptoms of psychosis in adolescence and (2) whether childhood FTD was associated with greater ASD symptom severity in adolescence. ASD symptom severity was assessed in childhood (T1) and 7 years later (T2), using the autism diagnostic observation schedule (ADOS). At T1, the Kiddie-Formal Thought Disorder Rating Scale (KFTDS) was used to measure symptoms of FTD. At T2, the prodromal questionnaire (PQ) was used to assess prodromal symptoms of psychosis. FTD at T1 did not predict prodromal symptoms of psychosis at T2 in children with ASD. FTD symptoms at T1, namely illogical thinking, predicted ASD symptom severity at T2 and this effect remained significant after controlling for T1 ASD symptom severity. In children with ASD, illogical thinking predicts severity of ASD symptoms in adolescence, but FTD does not predict prodromal symptoms of psychosis.
Lien vers le texte intégral (Open Access ou abonnement)
6. Gelbar NW, Smith I, Reichow B. {{Systematic Review of Articles Describing Experience and Supports of Individuals with Autism Enrolled in College and University Programs}}. {J Autism Dev Disord};2014 (May 11)
The increase in the number of higher-functioning individuals with autism spectrum disorders (ASD) is likely to lead to an increased interest in postsecondary opportunities including degree-granting college and university programs. To provide an understanding of the current evidence-base for supporting individuals with ASD in higher education, this article reports the results of a systematic review of the literature concerning college students with ASD. Overall, 20 articles describing 69 individuals met the inclusion criteria. This small number of articles and participants indicates the scarcity of research on this topic and only two of these studies were experimental in nature. These studies described a video-self modeling intervention and a counseling intervention respectively. Eighteen « case studies » were also present in the literature that described difficulties ranging from anxiety to housing concerns. This review deliniates the limitation of our understanding of effective college programming for individuals with ASD.
Lien vers le texte intégral (Open Access ou abonnement)
7. Hagerman RJ, Des-Portes V, Gasparini F, Jacquemont S, Gomez-Mancilla B. {{Translating molecular advances in fragile X syndrome into therapy: a review}}. {J Clin Psychiatry};2014 (Apr);75(4):e294-307.
Fragile X syndrome is an inherited disease with cognitive, behavioral, and neurologic manifestations, resulting from a single genetic mutation. A variety of treatments that target individual symptoms of fragile X syndrome are currently utilized with limited efficacy. Research in animal models has resulted in the development of potential novel pharmacologic treatments that target the underlying molecular defect in fragile X syndrome, rather than the resultant symptoms. This review describes recent advances in our understanding of the molecular basis of fragile X syndrome and summarizes the ongoing clinical research programs.
Lien vers le texte intégral (Open Access ou abonnement)
8. Harigaya Y, Parker R. {{Fragile x mental retardation protein and the ribosome}}. {Mol Cell};2014 (May 8);54(3):330-332.
In this issue of Molecular Cell, Chen et al. (2014) provide evidence that FMRP represses translation by binding the ribosome, suggesting a novel form of translational control.
Lien vers le texte intégral (Open Access ou abonnement)
9. Marler S, Sanders KB, Veenstra-Vanderweele J. {{N-Acetylcysteine as Treatment for Self-Injurious Behavior in a Child with Autism}}. {J Child Adolesc Psychopharmacol};2014 (May 9)
Lien vers le texte intégral (Open Access ou abonnement)
10. Ranson NJ, Byrne MK. {{Promoting Peer Acceptance of Females with Higher-functioning Autism in a Mainstream Education Setting: A Replication and Extension of the Effects of an Autism Anti-Stigma Program}}. {J Autism Dev Disord};2014 (May 10)
This study evaluated the effects of an eight-session female higher-functioning autism anti-stigma program on the knowledge, attitudes and behavioural intentions of adolescent girls. Participants were seventh-, eighth- and ninth-grade students (N = 273) in a mainstream school. Two-eighth-grade classes were randomly allocated to the intervention condition. The remaining students were either allocated to the no-intervention peer or no-intervention non-peer condition. The anti-stigma program positively influenced knowledge, attitudes and to a lesser extent behavioural intentions towards peers with higher-functioning autism within the intervention condition. Some degree of attitudinal improvement occurred across all conditions following the program suggesting some spill over effects. Overall, findings provide preliminary evidence supporting the efficacy of an anti-stigma program tailored to support females with higher-functioning autism.
Lien vers le texte intégral (Open Access ou abonnement)
11. Samadi SA, McConkey R, Bunting B. {{Parental wellbeing of Iranian families with children who have developmental disabilities}}. {Res Dev Disabil};2014 (Jul);35(7):1639-1647.
To date, most research with families who have a child with developmental disabilities has been undertaken in English speaking countries. Poorer health, allied with increased levels of stress has been commonly reported for mothers but less is known about the impact on fathers and on overall family functioning. This study aimed to document the correlates of these parental impacts with Iranian mothers and fathers who had children with either intellectual disabilities (ID) or with autism spectrum disorders (ASD). In all 121 parents (69 mothers and 52 fathers from 94 families) who had a child with a diagnosis of ADS, along with 115 parents of children with ID (83 mothers and 32 fathers from 101 families) volunteered to take part in the study. Each participant completed through interview standardised rating scales of parenting stress, emotional well-being, family functioning and satisfaction with caring role along with demographic information and details of informal supports. Structural Equation Modeling identified that family functioning was much poorer in families whose child had ASD and both mothers and fathers reported higher levels of stress. Poorer emotional well-being contributed to higher stress and was more frequent among mothers, single parents and those whose children had behaviour problems. Having other dependents living at home and more sources of informal support improved the emotional wellbeing of parents but not their stress or family functioning. Parents who derived greater satisfaction from their caring role tended to have better emotional health and less stress. Although the impact on Iranian parents of having a child with developmental disabilities is broadly similar to those of parents in other cultures, there are indications that children with ASD present distinct challenges to these families. The model derived in this study is a useful guide both for further research as well as family-centred interventions.
Lien vers le texte intégral (Open Access ou abonnement)
12. Smith CB, Liu Z. {{Lithium: A Promising Treatment for Fragile X Syndrome}}. {ACS Chem Neurosci};2014 (May 11)
Fragile X syndrome is an inherited disorder that results in intellectual disability and a characteristic behavioral profile that includes autism spectrum disorder, attention deficit hyperactivity disorder, sensory hypersensitivity, hyperarousal, and anxiety. The silencing of FMR1 and the consequent absence of its protein product, FMRP, is the most common cause of fragile X. The development of animal models of fragile X syndrome 20 years ago has produced a considerable increase in our understanding of the consequences of the absence of FMRP on the structure and function of the nervous system. Some of the insights gained have led to proposals of treatment strategies that are based on cellular and molecular changes observed in animals lacking FMRP. One such proposal is treatment with lithium, a drug with a long history of clinical efficacy in psychiatry and a drug with newly described uses in degenerative disorders of the nervous system. Lithium treatment has been studied extensively in both mouse and fruit fly models of FXS, and it has been shown to reverse numerous behavioral, physiological, cellular, and molecular phenotypes. A report of a pilot clinical trial on a limited number of adult FXS patients indicated that measureable improvements in behavior and function were seen after two months of lithium treatment. A double-blind clinical trial of lithium treatment in FXS patients is now needed.
Lien vers le texte intégral (Open Access ou abonnement)
13. Spillers JL, Sensui LM, Linton KF. {{Concerns about Identity and Services Among People with Autism and Asperger’s Regarding DSM-5 Changes}}. {J Soc Work Disabil Rehabil};2014 (May 9)
The DSM-5 now includes a new Autism Spectrum Diagnosis (ASD) diagnosis with previous separate diagnoses of Autism removed. This study explores the concerns of people with Asperger’s Syndrome (AS) and Autistic Disorder (AD). Discussion forum data of people with AS and AD (N = 76) was analyzed using phenomenological, inductive-content analysis to gather qualitative data about the concerns of people with AS and AD regarding the changes in the DSM-5. People with AS and AD were concerned about identity, community, the cure movement, and services. They also discussed using advocacy and solidarity to address their concerns.
Lien vers le texte intégral (Open Access ou abonnement)
14. Taylor LE, Swerdfeger AL, Eslick GD. {{Vaccines are not associated with autism: An evidence-based meta-analysis of case-control and cohort studies}}. {Vaccine};2014 (May 6)
There has been enormous debate regarding the possibility of a link between childhood vaccinations and the subsequent development of autism. This has in recent times become a major public health issue with vaccine preventable diseases increasing in the community due to the fear of a ‘link’ between vaccinations and autism. We performed a meta-analysis to summarise available evidence from case-control and cohort studies on this topic (MEDLINE, PubMed, EMBASE, Google Scholar up to April, 2014). Eligible studies assessed the relationship between vaccine administration and the subsequent development of autism or autism spectrum disorders (ASD). Two reviewers extracted data on study characteristics, methods, and outcomes. Disagreement was resolved by consensus with another author. Five cohort studies involving 1,256,407 children, and five case-control studies involving 9920 children were included in this analysis. The cohort data revealed no relationship between vaccination and autism (OR: 0.99; 95% CI: 0.92 to 1.06) or ASD (OR: 0.91; 95% CI: 0.68 to 1.20), or MMR (OR: 0.84; 95% CI: 0.70 to 1.01), or thimerosal (OR: 1.00; 95% CI: 0.77 to 1.31), or mercury (Hg) (OR: 1.00; 95% CI: 0.93 to 1.07). Similarly the case-control data found no evidence for increased risk of developing autism or ASD following MMR, Hg, or thimerosal exposure when grouped by condition (OR: 0.90, 95% CI: 0.83 to 0.98; p=0.02) or grouped by exposure type (OR: 0.85, 95% CI: 0.76 to 0.95; p=0.01). Findings of this meta-analysis suggest that vaccinations are not associated with the development of autism or autism spectrum disorder. Furthermore, the components of the vaccines (thimerosal or mercury) or multiple vaccines (MMR) are not associated with the development of autism or autism spectrum disorder.
Lien vers le texte intégral (Open Access ou abonnement)
15. Verhoeff B. {{Stabilizing autism: A Fleckian account of the rise of a neurodevelopmental spectrum disorder}}. {Stud Hist Philos Biol Biomed Sci};2014 (May 8);46C:65-78.
Using the conceptual tools of philosopher of science Ludwik Fleck, I argue that the reframing of autism as a neurodevelopmental spectrum disorder is constrained by two governing ‘styles of thought’ of contemporary psychiatry. The first is the historically conditioned ‘readiness for directed perception’ of, and thinking in terms of, ontologically distinct diseases. The clinical gaze of mental health professionals, the bureaucratic needs of health administration, the clinical and scientific utility of disease categories, and the practices of autism-oriented advocacy groups all imply a bias toward thinking about autism and related disorders as ontologically distinct psychiatric and scientific entities. Second, within the ‘neuromolecular style of thought’, mental disorders are more and more located at the neurobiological levels of the brain. In autism research, one of the biggest challenges is the identification of autism’s neurobiological singularity. However, at a moment when biological and categorical approaches toward autism face serious empirical difficulties, a balance is established that holds together these two styles of thought. With a need to account for some of the most persistent uncertainties and conflicts in autism research, namely ubiquitous heterogeneity and a failure to identify disease specific biomarkers, the reframing of autism as a neurodevelopmental spectrum disorder satisfies the scientific, institutional and socio-political needs for stability and homogenization.
Lien vers le texte intégral (Open Access ou abonnement)
16. Waltes R, Gfesser J, Haslinger D, Schneider-Momm K, Biscaldi M, Voran A, Freitag CM, Chiocchetti AG. {{Common EIF4E variants modulate risk for autism spectrum disorders in the high-functioning range}}. {J Neural Transm};2014 (May 13)
The genetic architecture of Autism Spectrum Disorders (ASD) is complex. Common genetic variation has especially been related to high-functioning ASD. In addition, some studies favoured analysis of strictly diagnosed autism individuals, which resulted in more robust findings than the combined analysis of all spectrum individuals. Functional variants modulating EIF4E expression have previously been indicated as risk factors for ASD. Pharmacological modulation of glutamate receptors which regulate EIF4E activity resulted in reduced repetitive behaviours in human and animal studies. Based on these findings, we tested common EIF4E variants for association with overall ASD, with strict autism and with the strict high-functioning autism (strict HFA) subgroup, and their effect on repetitive and/or stereotypic behaviour. We observed over-transmission of rs13109000G in the strict HFA and the strict autism cohort but not in the larger ASD cohort. We report protective effects for the minor allele of rs4699369T on stereotyped and ritualized behaviour in the overall ASD cohort, the strict autism but not in the strict HFA group. In addition, a protective role for rs4699369T and a risk effect of rs12498533G on hand and finger mannerisms was observed. These results need to be replicated in larger ASD and strict autism samples. The predicted impact on transcription through the ASD associated EIF4E variants rs4699369T and rs12498533G as well as the association of the EIF4E interaction partners FMRP and CYFIP1 with ASD point to an mRNA mediated pathomechanism for ASD.
