1. Dunaway KW, Islam MS, Coulson RL, Lopez SJ, Vogel Ciernia A, Chu RG, Yasui DH, Pessah IN, Lott P, Mordaunt C, Meguro-Horike M, Horike SI, Korf I, LaSalle JM. {{Cumulative Impact of Polychlorinated Biphenyl and Large Chromosomal Duplications on DNA Methylation, Chromatin, and Expression of Autism Candidate Genes}}. {Cell Rep};2016 (Dec 13);17(11):3035-3048.
Rare variants enriched for functions in chromatin regulation and neuronal synapses have been linked to autism. How chromatin and DNA methylation interact with environmental exposures at synaptic genes in autism etiologies is currently unclear. Using whole-genome bisulfite sequencing in brain tissue and a neuronal cell culture model carrying a 15q11.2-q13.3 maternal duplication, we find that significant global DNA hypomethylation is enriched over autism candidate genes and affects gene expression. The cumulative effect of multiple chromosomal duplications and exposure to the pervasive persistent organic pollutant PCB 95 altered methylation of more than 1,000 genes. Hypomethylated genes were enriched for H2A.Z, increased maternal UBE3A in Dup15q corresponded to reduced levels of RING1B, and bivalently modified H2A.Z was altered by PCB 95 and duplication. These results demonstrate the compounding effects of genetic and environmental insults on the neuronal methylome that converge upon dysregulation of chromatin and synaptic genes.
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2. Greydanus DE, Gregoire-Bottex MM, Merrick J. {{Gastrointestinal dysfunction and autism: caution with misdiagnoses as many mysteries remain to be unraveled!}}. {Int J Adolesc Med Health};2016 (Dec 15)
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3. Hitzert B, Schmidt R, Geurts HM, van Alphen SP. {{[Diagnostics and treatment of autism spectrum disorders in older adults: a study by experts]}}. {Tijdschr Psychiatr};2016;58(12):854-862.
BACKGROUND: Empirical research into the diagnostics and treatment of older adults with autism spectrum disorders (ASD) is very limited; so far, only 17 studies have been published. ASD, however, is not confined to child and adult psychiatry. Increasingly, ASD is being identified and treated within the domain of geriatric psychiatry.
AIM: To investigate diagnostic and therapeutic aspects of ASD in older adults, and to obtain insight into how these aspects are related to ageing.
METHOD: Delphi techniques were employed via rounds of questionnaires put to experts; consensus was considered to have been achieved when a minimum of two-thirds of the experts ‘agreed’ or ‘fully agreed’ to a statement on a five-point scale.
RESULTS: Consensus was achieved for 10 of the 17 statements. According to the experts, older patients with ASD, form a specific group in psychiatry. With regard to diagnosis, there was a consensus that increased attention needs to be given to age-related aspects by linking symptoms more specifically to the patient’s phase of life and to the ageing process. In the treatment of older adults with ASD, adjustments need to be made in relation to ageing.
CONCLUSION: This study by experts provides additional starting points for more research into specific topics relating to diagnostic and therapeutic aspects of ASD in geriatric psychiatry; these topics include validation of screening and diagnostic instruments, the adjustment of protocols for treatment, psycho-education and the effects of ageing in patients with ASD.
4. Ipci M, Inci SB, Akyol Ardic U, Ercan ES. {{A Case of Asperger Syndrome With Comorbidity of Posttraumatic Stress Disorder and Selective Mutism: Significant Remission With the Combination of Aripiprazole and Eye Movement Desensitization and Reprocessing}}. {J Clin Psychopharmacol};2016 (Dec 13)
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5. Jones RM, Southerland A, Hamo A, Carberry C, Bridges C, Nay S, Stubbs E, Komarow E, Washington C, Rehg JM, Lord C, Rozga A. {{Increased Eye Contact During Conversation Compared to Play in Children With Autism}}. {J Autism Dev Disord};2016 (Dec 16)
Children with autism have atypical gaze behavior but it is unknown whether gaze differs during distinct types of reciprocal interactions. Typically developing children (N = 20) and children with autism (N = 20) (4-13 years) made similar amounts of eye contact with an examiner during a conversation. Surprisingly, there was minimal eye contact during interactive play in both groups. Gaze behavior was stable across 8 weeks in children with autism (N = 15). Lastly, gaze behavior during conversation but not play was associated with autism social affect severity scores (ADOS CSS SA) and the Social Responsiveness Scale (SRS-2). Together findings suggests that eye contact in typical and atypical development is influenced by subtle changes in context, which has implications for optimizing assessments of social communication skills.
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6. Matagne V, Ehinger Y, Saidi L, Borges-Correia A, Barkats M, Bartoli M, Villard L, Roux JC. {{A codon-optimized Mecp2 transgene corrects breathing deficits and improves survival in a mouse model of Rett syndrome}}. {Neurobiol Dis};2016 (Dec 11)
Rett syndrome (RTT) is a severe X-linked neurodevelopmental disorder that is primarily caused by mutations in the methyl CpG binding protein 2 gene (MECP2). RTT is the second most prevalent cause of intellectual disability in girls and there is currently no cure for the disease. The finding that the deficits caused by the loss of Mecp2 are reversible in the mouse has bolstered interest in gene therapy as a cure for RTT. In order to assess the feasibility of gene therapy in a RTT mouse model, and in keeping with translational goals, we investigated the efficacy of a self-complementary AAV9 vector expressing a codon-optimized version of Mecp2 (AAV9-MCO) delivered via a systemic approach in early symptomatic Mecp2-deficient (KO) mice. Our results show that AAV9-MCO administered at a dose of 2×1011 viral genome (vg)/mouse was able to significantly increase survival and weight gain, and delay the occurrence of behavioral deficits. Apneas, which are one of the core RTT breathing deficits, were significantly decreased to WT levels in Mecp2 KO mice after AAV9-MCO administration. Semi-quantitative analysis showed that AAV9-MCO administration in Mecp2 KO mice resulted in 10 to 20% Mecp2 immunopositive cells compared to WT animals, with the highest Mecp2 expression found in midbrain regions known to regulate cardio-respiratory functions. In addition, we also found a cell autonomous increase in tyrosine hydroxylase levels in the A1C1 and A2C2 catecholaminergic Mecp2+ neurons in treated Mecp2 KO mice, which may partly explain the beneficial effect of AAV9-MCO administration on apneas occurrence.
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7. Thorup E, Kleberg JL, Falck-Ytter T. {{Gaze Following in Children with Autism: Do High Interest Objects Boost Performance?}}. {J Autism Dev Disord};2016 (Dec 16)
This study tested whether including objects perceived as highly interesting by children with autism during a gaze following task would result in increased first fixation durations on the target objects. It has previously been found that autistic children differentiate less between an object another person attends to and unattended objects in terms of this measure. Less differentiation between attended and unattended objects in ASD as compared to control children was found in a baseline condition, but not in the high interest condition. However, typically developing children differentiated less between attended and unattended objects in the high interest condition than in the baseline condition, possibly reflecting reduced influence of gaze cues on object processing when objects themselves are highly interesting.
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8. Vakorin VA, Doesburg SM, Leung RC, Vogan VM, Anagnostou E, Taylor MJ. {{Developmental changes in neuromagnetic rhythms and network synchrony in autism}}. {Ann Neurol};2016 (Dec 15)
OBJECTIVE: There is gathering consensus that altered connectivity is a hallmark of the autistic brain. This includes atypical neural oscillations and their coordination across brain regions, which are understood to mediate information processing and integration. It remains unclear if and how connectivity in various neurophysiological frequency ranges develops atypically in autism spectrum disorder. METHODS: To address this in a cross-sectional sample, we recorded resting-state magnetoencephalography (MEG) from 134 children and adolescents with and without ASD, and calculated resting spectral power and inter-regional synchrony (functional connectivity). RESULTS: While no overall group differences were observed, significant alterations in linear and non-linear age-related changes in resting oscillatory power and network synchrony were found. These differences were frequency- and region-specific and implicated brain systems thought to play a prominent role in ASD, such as the frontal cortex and cerebellum. We also found correlations between the Autism Diagnostic Observation Schedule (ADOS) scores and the degree to which connectivity in cerebellar networks is ‘idiosyncratic’ in an individual with autism. INTERPRETATION: We provide the first evidence that it is the curvatures of maturational changes in neurophysiological oscillations and synchrony, rather than disturbances in a particular direction, which characterizes the brain function in individuals with ASD. Moreover, the patterns of idiosyncratic distortions of network synchrony relative to the group curve are associated with behavioral symptoms of ASD. This article is protected by copyright. All rights reserved.
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9. Vanya M, Szucs S, Vetro A, Bartfai G. {{The potential role of oxytocin and perinatal factors in the pathogenesis of autism spectrum disorders – review of the literature}}. {Psychiatry Res};2016 (Dec 06);247:288-290.
Autism Spectrum Disorders (ASD) are characterized by: social and communication impairments, and by restricted repetitive behaviors. The aim of the present paper is to review abnormalities of oxytocin (OXT) and related congenital malformations in ASD. A literature search was conducted in the PubMed database up to 2016 for articles related to the pathomechanism of ASD, abnormalities of OXT and the OXT polymorphism in ASD. The pathomechanism of ASD has yet to be. The development of ASD is suggested to be related to abnormalities of the oxytocin-arginin-vasopressin system. Previous results suggest that OXT and arginine vasopressin (AVP) may play a role in the etiopathogenesis of ASD.
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10. Yang Y, Tian Y, Fang J, Lu H, Wei K, Yi L. {{Trust and Deception in Children with Autism Spectrum Disorders: A Social Learning Perspective}}. {J Autism Dev Disord};2016 (Dec 16)
Previous research has demonstrated abnormal trust and deception behaviors in children with Autism Spectrum Disorders (ASD), and we aimed to examine whether these abnormalities were primarily due to their specific deficits in social learning. We tested 42 high-functioning children with ASD and 38 age- and ability-matched typically developing (TD) children in trust and deception tasks and a novel condition with reduced social components. Results indicated that while TD children improved their performance with more social components, children with ASD lacked this additional performance gain, though they performed similarly as TD children in the condition with reduced social components. Our findings highlight that deficits of ASD in trust and deception are primarily associated with failure of use of social cues.
