1. Martinez-Murcia FJ, Lai MC, Gorriz JM, Ramirez J, Young AM, Deoni SC, Ecker C, Lombardo MV, Baron-Cohen S, Murphy DG, Bullmore ET, Suckling J. {{On the brain structure heterogeneity of autism: Parsing out acquisition site effects with significance-weighted principal component analysis}}. {Hum Brain Mapp};2016 (Oct 24)
Neuroimaging studies have reported structural and physiological differences that could help understand the causes and development of Autism Spectrum Disorder (ASD). Many of them rely on multisite designs, with the recruitment of larger samples increasing statistical power. However, recent large-scale studies have put some findings into question, considering the results to be strongly dependent on the database used, and demonstrating the substantial heterogeneity within this clinically defined category. One major source of variance may be the acquisition of the data in multiple centres. In this work we analysed the differences found in the multisite, multi-modal neuroimaging database from the UK Medical Research Council Autism Imaging Multicentre Study (MRC AIMS) in terms of both diagnosis and acquisition sites. Since the dissimilarities between sites were higher than between diagnostic groups, we developed a technique called Significance Weighted Principal Component Analysis (SWPCA) to reduce the undesired intensity variance due to acquisition site and to increase the statistical power in detecting group differences. After eliminating site-related variance, statistically significant group differences were found, including Broca’s area and the temporo-parietal junction. However, discriminative power was not sufficient to classify diagnostic groups, yielding accuracies results close to random. Our work supports recent claims that ASD is a highly heterogeneous condition that is difficult to globally characterize by neuroimaging, and therefore different (and more homogenous) subgroups should be defined to obtain a deeper understanding of ASD. Hum Brain Mapp, 2016. (c) 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.
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2. Pardo M, Beurel E, Jope RS. {{Cotinine administration improves impaired cognition in the mouse model of Fragile X syndrome}}. {Eur J Neurosci};2016 (Oct 24)
Cotinine is the major metabolite of nicotine and has displayed some capacity for improving cognition in mouse models following chronic administration. We tested if acute cotinine treatment is capable of improving cognition in the mouse model of Fragile X syndrome, Fmr1-/- knockout mice, and if this is related to inhibition by cotinine treatment of glycogen synthase kinase-3beta (GSK3beta), which is abnormally active in Fmr1-/- mice. Acute cotinine treatment increased the inhibitory serine-phosphorylation of GSK3beta and the activating phosphorylation of AKT, which can mediate serine-phosphorylation of GSK3beta, in both wild-type and Fmr1-/- mouse hippocampus. Acute cotinine treatment improved cognitive functions of Fmr1-/- mice in coordinate and categorical spatial processing, novel object recognition, and temporal ordering. However, cotinine failed to restore impaired cognition in GSK3beta knockin mice, in which a serine9-to-alanine9 mutation blocks the inhibitory serine phosphorylation of GSK3beta, causing GSK3beta to be hyperactive. These results indicate that acute cotinine treatment effectively repairs impairments of these four cognitive tasks in Fmr1-/- mice, and suggest that this cognition-enhancing effect of cotinine is linked to its induction of inhibitory serine-phosphorylation of GSK3. Taken together, these results show nicotinic receptor agonists can act as cognitive enhancers in a mouse model of Fragile X syndrome and highlight the potential role of inhibiting GSK3beta in mediating the effects of cotinine on memory. This article is protected by copyright. All rights reserved.
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3. Pickles A, Le Couteur A, Leadbitter K, Salomone E, Cole-Fletcher R, Tobin H, Gammer I, Lowry J, Vamvakas G, Byford S, Aldred C, Slonims V, McConachie H, Howlin P, Parr JR, Charman T, Green J. {{Parent-mediated social communication therapy for young children with autism (PACT): long-term follow-up of a randomised controlled trial}}. {Lancet};2016 (Oct 24)
BACKGROUND: It is not known whether early intervention can improve long-term autism symptom outcomes. We aimed to follow-up the Preschool Autism Communication Trial (PACT), to investigate whether the PACT intervention had a long-term effect on autism symptoms and continued effects on parent and child social interaction. METHODS: PACT was a randomised controlled trial of a parent-mediated social communication intervention for children aged 2-4 years with core autism. Follow-up ascertainment was done at three specialised clinical services centres in the UK (London, Manchester, and Newcastle) at a median of 5.75 years (IQR 5.42-5.92) from the original trial endpoint. The main blinded outcomes were the comparative severity score (CSS) from the Autism Diagnostic Observation Schedule (ADOS), the Dyadic Communication Assessment Measure (DCMA) of the proportion of child initiatiations when interacting with the parent, and an expressive-receptive language composite. All analyses followed the intention-to-treat principle. PACT is registered with the ISRCTN registry, number ISRCTN58133827. FINDINGS: 121 (80%) of the 152 trial participants (59 [77%] of 77 assigned to PACT intervention vs 62 [83%] of 75 assigned to treatment as usual) were traced and consented to be assessed between July, 2013, and September, 2014. Mean age at follow-up was 10.5 years (SD 0.8). Group difference in favour of the PACT intervention based on ADOS CSS of log-odds effect size (ES) was 0.64 (95% CI 0.07 to 1.20) at treatment endpoint and ES 0.70 (95% CI -0.05 to 1.47) at follow-up, giving an overall reduction in symptom severity over the course of the whole trial and follow-up period (ES 0.55, 95% CI 0.14 to 0.91, p=0.004). Group difference in DCMA child initiations at follow-up showed a Cohen’s d ES of 0.29 (95% CI -0.02 to 0.57) and was significant over the course of the study (ES 0.33, 95% CI 0.11 to 0.57, p=0.004). There were no group differences in the language composite at follow-up (ES 0.15, 95% CI -0.23 to 0.53). INTERPRETATION: The results are the first to show long-term symptom reduction after a randomised controlled trial of early intervention in autism spectrum disorder. They support the clinical value of the PACT intervention and have implications for developmental theory. FUNDING: Medical Research Council.
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4. Sigafoos J, Waddington H. {{6 year follow-up supports early autism intervention}}. {Lancet};2016 (Oct 24)
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5. Strang JF, Meagher H, Kenworthy L, de Vries AL, Menvielle E, Leibowitz S, Janssen A, Cohen-Kettenis P, Shumer DE, Edwards-Leeper L, Pleak RR, Spack N, Karasic DH, Schreier H, Balleur A, Tishelman A, Ehrensaft D, Rodnan L, Kuschner ES, Mandel F, Caretto A, Lewis HC, Anthony LG. {{Initial Clinical Guidelines for Co-Occurring Autism Spectrum Disorder and Gender Dysphoria or Incongruence in Adolescents}}. {J Clin Child Adolesc Psychol};2016 (Oct 24):1-11.
Evidence indicates an overrepresentation of youth with co-occurring autism spectrum disorders (ASD) and gender dysphoria (GD). The clinical assessment and treatment of adolescents with this co-occurrence is often complex, related to the developmental aspects of ASD. There are no guidelines for clinical care when ASD and GD co-occur; however, there are clinicians and researchers experienced in this co-occurrence. This study develops initial clinical consensus guidelines for the assessment and care of adolescents with co-occurring ASD and GD, from the best clinical practices of current experts in the field. Expert participants were identified through a comprehensive international search process and invited to participate in a two-stage Delphi procedure to form clinical consensus statements. The Delphi Method is a well-studied research methodology for obtaining consensus among experts to define appropriate clinical care. Of 30 potential experts identified, 22 met criteria as expert in co-occurring ASD and GD youth and participated. Textual data divided into the following data nodes: guidelines for assessment; guidelines for treatment; six primary clinical/psychosocial challenges: social functioning, medical treatments and medical safety, risk of victimization/safety, school, and transition to adulthood issues (i.e., employment and romantic relationships). With a cutoff of 75% consensus for inclusion, identified experts produced a set of initial guidelines for clinical care. Primary themes include the importance of assessment for GD in ASD, and vice versa, as well as an extended diagnostic period, often with overlap/blurring of treatment and assessment.
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6. Wang S, Fan S, Chen B, Hakimi S, Paul LK, Zhao Q, Adolphs R. {{Revealing the world of autism through the lens of a camera}}. {Curr Biol};2016 (Oct 24);26(20):R909-R910.
People with autism spectrum disorder (ASD) show atypical attention to social stimuli [1] and gaze at faces [2] and complex images [3] in unusual ways. But all studies to date are limited by the experimenter’s selected stimuli, which are generally photographs taken by people without autism. What might participants with ASD show us if they were the ones taking the photos? We gave participants a digital camera and analysed the photos they took: images taken by participants with ASD had unusual features and showed strikingly different ways of photographing other people.
