1. Brown AC, Chouinard PA, Crewther SG. {{Vision Research Literature May Not Represent the Full Intellectual Range of Autism Spectrum Disorder}}. {Front Hum Neurosci};2017;11:57.
Sensory, in particular visual processing is recognized as often perturbed in individuals with Autism Spectrum Disorder (ASD). However, in terms of the literature pertaining to visual processing, individuals in the normal intelligence range (IQ = 90-110) and above, are more frequently represented in study samples than individuals who score below normal in the borderline intellectual disability (ID) (IQ = 71-85) to ID (IQ < 70) ranges. This raises concerns as to whether or not current research is generalizable to a disorder that is often co-morbid with ID. Thus, the aim of this review is to better understand to what extent the current ASD visual processing literature is representative of the entire ASD population as either diagnosed or recognized under DSM-5. Our recalculation of ASD prevalence figures, using the criteria of DSM-5, indicates approximately 40% of the ASD population are likely to be ID although searching of the visual processing literature in ASD up to July 2016 showed that only 20% of papers included the ASD with-ID population. In the published literature, the mean IQ sampled was found to be 104, with about 80% of studies sampling from the 96-115 of the IQ range, highlighting the marked under-representation of the ID and borderline ID sections of the ASD population. We conclude that current understanding of visual processing and perception in ASD is not based on the mean IQ profile of the DSM-5 defined ASD population that now appears to lie within the borderline ID to ID range. Give the importance of the role of vision for the social and cognitive processing in ASD, we recommend accurately representing ASD via greater inclusion of individuals with IQ below 80, in future ASD research. Lien vers le texte intégral (Open Access ou abonnement)
2. Bu Q, Wang A, Hamzah H, Waldman A, Jiang K, Dong Q, Li R, Kim J, Turner D, Chang Q. {{CREB signaling is involved in Rett syndrome pathogenesis}}. {J Neurosci};2017 (Mar 07)
Rett syndrome (RTT) is a debilitating neurodevelopmental disorder caused by mutations in the MECP2 gene. To facilitate the study of cellular mechanisms in human cells, we established several human stem cell lines: human embryonic stem cell (hESC) line carrying the common T158M mutation (MECP2T158M/T158M ), hESC line expressing no MECP2 (MECP2-KO), congenic pair of wild type and mutant RTT patient-specific induced pluripotent stem cell (iPSC) line carrying the V247fs mutation (V247fs-WT and V247fs-MT), and iPSC line in which the V247fs mutation was corrected by CRISPR/Cas9-based genome editing (V247fs-MT-correction). Detailed analyses of forebrain neurons differentiated from these human stem cell lines revealed genotype-dependent quantitative phenotypes in neurite growth, dendritic complexity, and mitochondrial function. At the molecular level, we found a significant reduction in the level of CREB and phosphorylated CREB in forebrain neurons differentiated from MECP2T158M/T158M , MECP2-KO, and V247fs-MT stem cell lines. Importantly, overexpression of CREB or pharmacological activation of CREB signaling in those forebrain neurons rescued the phenotypes in neurite growth, dendritic complexity, and mitochondrial function. Finally, pharmacological activation of CREB in the female Mecp2 heterozygous mice rescued several behavioral defects. Together, our study establishes a robust in vitro platform for consistent quantitative evaluation of genotype-dependent RTT phenotypes, reveals a previously unappreciated role of CREB signaling in RTT pathogenesis, and identifies a potential therapeutic target for RTT.Significance Statement:Our study establishes a robust human stem cell-based platform for consistent quantitative evaluation of genotype-dependent RTT phenotypes at the cellular level. By providing the first evidence that enhancing CREB signaling can alleviate RTT phenotypes both in vitro and in vivo, we reveal a previously unappreciated role of CREB signaling in RTT pathogenesis, and identify a potential therapeutic target for RTT.
Lien vers le texte intégral (Open Access ou abonnement)
3. Chen C, Shen YD, Xun GL, Cai WX, Shi LJ, Xiao L, Wu RR, Zhao JP, Ou JJ. {{Aggressive behaviors and treatable risk factors of preschool children with autism spectrum disorder}}. {Autism Res};2017 (Mar 07)
Aggressive behaviors of children with autism spectrum disorder (ASD) are common. We conducted this study to describe the aggressive mode of preschool children with ASD and examine the associations between specific aggressive behaviors and two treatable factors: sleep problems and attention deficit hyperactivity disorder (ADHD) symptoms. In total, 577 typically developing (TD) children and 490 children with ASD were investigated in this study. The Institute for Basic Research – Modified Overt Aggression Scale (IBR-MOAS) was used to assess aggressive behaviors. Children’s social impairments, sleep problems and ADHD symptoms were also measured with specific scales. The total IBR-MOAS score was significantly higher (worse) in the TD group [4.47 (5.36)] than in the ASD group [3.47 (5.63), P = 0.004]. The aggressive modes differed between groups: when compared with each other, the TD group received higher scores on Verbal and Physical Aggression Toward Others (all P < 0.01), while the ASD group had higher scores on Physical Aggression Against Self (P = 0.006). The linear regression model demonstrated that the aggressive behaviors of children with ASD were significantly associated with two treatable factors: sleep problems and ADHD symptoms. These findings have substantial clinical implications: treatment of these two risk factors may be helpful in managing aggressive behavior in children with ASD. Autism Res 2017. (c) 2017 International Society for Autism Research, Wiley Periodicals, Inc. Lien vers le texte intégral (Open Access ou abonnement)
4. Craig F, Fanizza I, Russo L, Lucarelli E, Alessandro L, Pasca MG, Trabacca A. {{Social communication in children with autism spectrum disorder (asd): Correlation between DSM-5 and autism classification system of functioning-social communication (ACSF:SC)}}. {Autism Res};2017 (Mar 07)
The aim of this study was to classify children with Autism Spectrum Disorder (ASD) according to Autism Classification System of Functioning: Social Communication (ACSF:SC) criteria, in order to investigate the association between social communication ability, ASD severity, adaptive functioning, cognitive abilities and psychoeducational profile. The severity of social communication impairment was specified through Diagnostic and Statistical Manual of Mental Disorders-5th edition (DSM-5) and ACSF:SC tool. The ADOS-2, Vineland-II and PEP-3 were administered to all participants. We found a positive correlation between DSM-5 levels and ACSF:SC-Typical Performance (r = 0.35; P = 0.007) and ACSF:SC-Capacity (r = 0.31; P = 0.01) levels. Children included in the five levels of ACSF:SC (Typical Performance and Capacity) showed statistically significant differences in ADOS-2 (Social Affect), Vineland-II (Communication and Socialization), and PEP-3 (Communication, motor skills, maladaptive behavior) scores. The results of this study indicate that ACSF:SC provide a better understanding of functional profile of children with ASD based on the social communication abilities. Children with greater severity of social communication showed more difficulty in adaptive behavior and psychoeducational profiles. In conclusion, the ACSF:SC could help clinicians and therapists not only to understand the strength and weakness of preschool children with ASD but also to devise specific treatment in order to promote their social integration. Autism Res 2017. (c) 2017 International Society for Autism Research, Wiley Periodicals, Inc.
Lien vers le texte intégral (Open Access ou abonnement)
5. Endres D, Tebartz van Elst L, Meyer SA, Feige B, Nickel K, Bubl A, Riedel A, Ebert D, Lange T, Glauche V, Biscaldi M, Philipsen A, Maier SJ, Perlov E. {{Glutathione metabolism in the prefrontal brain of adults with high-functioning autism spectrum disorder: an MRS study}}. {Mol Autism};2017;8:10.
BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental disease characterized by difficulties in social communication, unusually restricted, repetitive behavior and interests, and specific abnormalities in language and perception. The precise etiology of ASD is still unknown and probably heterogeneous. In a subgroup of patients, toxic environmental exposure might lead to an imbalance between oxidative stress and anti-oxidant systems. Previous serum and postmortem studies measuring levels of glutathione (GSH), the main cellular free radical scavenger in the brain, have supported the hypothesis that this compound might play a role in the pathophysiology of autism. METHODS: Using the method of single-voxel proton magnetic resonance spectroscopy (MRS), we analyzed the GSH signal in the dorsal anterior cingulate cortex (dACC) and the dorsolateral prefrontal cortex (DLPFC) of 24 ASD patients with normal or above average IQs and 18 matched control subjects. We hypothesized that we would find decreased GSH concentrations in both regions. RESULTS: We did not find overall group differences in neurometabolites including GSH, neither in the dorsal ACC (Wilks’ lambda test; p = 0.429) nor in the DLPFC (p = 0.288). In the dACC, we found a trend for decreased GSH signals in ASD patients (p = 0.076). CONCLUSIONS: We were unable to confirm our working hypothesis regarding decreased GSH concentrations in the ASD group. Further studies combining MRS, serum, and cerebrospinal fluid measurements of GSH metabolism including other regions of interest or even whole brain spectroscopy are needed.
Lien vers le texte intégral (Open Access ou abonnement)
6. Fluegge K. {{Brain-Derived Neurotrophic Factor in Autism Spectrum Disorder}}. {JAMA Pediatr};2017 (Mar 06)
Lien vers le texte intégral (Open Access ou abonnement)
7. Franz L, Chambers N, von Isenburg M, de Vries PJ. {{Autism spectrum disorder in sub-saharan africa: A comprehensive scoping review}}. {Autism Res};2017 (Mar 07)
Autism spectrum disorder (ASD) is recognized as a global public health concern, yet almost everything we know about ASD comes from high-income countries. Here we performed a scoping review of all research on ASD ever published in sub-Saharan Africa (SSA) in order to identify ASD knowledge gaps in this part of the world. Fifty-three publications met inclusion criteria. Themes included the phenotype, genetics and risk factors for ASD in SSA, screening and diagnosis, professional knowledge, interventions for ASD, parental perceptions, and social-cognitive neuroscience. No epidemiological, early intervention, school-based or adult studies were identified. For each identified theme, we aimed to summarize results and make recommendations to fill the knowledge gaps. The quality of study methodologies was generally not high. Few studies used standardized diagnostic instruments, and intervention studies were typically small-scale. Overall, findings suggest a substantial need for large-scale clinical, training, and research programmes to improve the lives of people who live with ASD in SSA. However, SSA also has the potential to make unique and globally-significant contributions to the etiology and treatments of ASD through implementation, interventional, and comparative genomic science. Autism Res 2017. (c) 2017 International Society for Autism Research, Wiley Periodicals, Inc.
Lien vers le texte intégral (Open Access ou abonnement)
8. Gerber AH, McCormick CE, Levine TP, Morrow EM, Anders TF, Sheinkopf SJ. {{Brief Report: Factors Influencing Healthcare Satisfaction in Adults with Autism Spectrum Disorder}}. {J Autism Dev Disord};2017 (Mar 07)
The current study investigated healthcare satisfaction and factors related to satisfaction in 92 adults with Autism Spectrum Disorder (ASD). Participants or their caregiver completed a survey about their experiences with primary care and specialty physicians. Respondents reported a high level of satisfaction with their healthcare. The only factor significantly associated with satisfaction was age, with participants under age 26 reporting significantly higher levels of satisfaction than participants above age 26. Participants under age 26 also were significantly more likely to live at home, have private health insurance, and have others making their healthcare decisions than participants above age 26. Results indicate that healthcare satisfaction can be high for adults with ASD that have good family and community support.
Lien vers le texte intégral (Open Access ou abonnement)
9. Goto M, Mizuno M, Matsumoto A, Yang Z, Jimbo EF, Tabata H, Yamagata T, Nagata KI. {{Role of a circadian-relevant gene NR1D1 in brain development: possible involvement in the pathophysiology of autism spectrum disorders}}. {Sci Rep};2017 (Mar 06);7:43945.
In our previous study, we screened autism spectrum disorder (ASD) patients with and without sleep disorders for mutations in the coding regions of circadian-relevant genes, and detected mutations in several clock genes including NR1D1. Here, we further screened ASD patients for NR1D1 mutations and identified three novel mutations including a de novo heterozygous one c.1499 G > A (p.R500H). We then analyzed the role of Nr1d1 in the development of the cerebral cortex in mice. Acute knockdown of mouse Nr1d1 with in utero electroporation caused abnormal positioning of cortical neurons during corticogenesis. This aberrant phenotype was rescued by wild type Nr1d1, but not by the c.1499 G > A mutant. Time-lapse imaging revealed characteristic abnormal migration phenotypes in Nr1d1-deficient cortical neurons. When Nr1d1 was knocked down, axon extension and dendritic arbor formation of cortical neurons were also suppressed while proliferation of neuronal progenitors and stem cells at the ventricular zone was not affected. Taken together, Nr1d1 was found to play a pivotal role in corticogenesis via regulation of excitatory neuron migration and synaptic network formation. These results suggest that functional defects in NR1D1 may be related to ASD etiology and pathophysiology.
Lien vers le texte intégral (Open Access ou abonnement)
10. Grossekathofer U, Manyakov NV, Mihajlovic V, Pandina G, Skalkin A, Ness S, Bangerter A, Goodwin MS. {{Automated Detection of Stereotypical Motor Movements in Autism Spectrum Disorder Using Recurrence Quantification Analysis}}. {Front Neuroinform};2017;11:9.
A number of recent studies using accelerometer features as input to machine learning classifiers show promising results for automatically detecting stereotypical motor movements (SMM) in individuals with Autism Spectrum Disorder (ASD). However, replicating these results across different types of accelerometers and their position on the body still remains a challenge. We introduce a new set of features in this domain based on recurrence plot and quantification analyses that are orientation invariant and able to capture non-linear dynamics of SMM. Applying these features to an existing published data set containing acceleration data, we achieve up to 9% average increase in accuracy compared to current state-of-the-art published results. Furthermore, we provide evidence that a single torso sensor can automatically detect multiple types of SMM in ASD, and that our approach allows recognition of SMM with high accuracy in individuals when using a person-independent classifier.
Lien vers le texte intégral (Open Access ou abonnement)
11. Harshini M, Preeti K. {{Autism Behavioural Interventional Research in low-resource settings: Overcoming prevailing challenges – an Asian perspective}}. {Asian J Psychiatr};2017 (Feb);25:224-227.
Acceleration of Autism interventional research is evident in high-income countries (HIC), however, remains limited in low-resource settings. Though studies have established efficacy of behavioural interventions for Autism spectrum disorder, conducting behavioural interventional research in low resource setting poses unique challenges in economic, ethical and cultural facets. This brief communication discusses the prevailing challenges in low resource setting in designing and testing the efficacy of behaviour interventional model that is generalizable to primary care settings.
Lien vers le texte intégral (Open Access ou abonnement)
12. Hirosawa T, Kikuchi M, Ouchi Y, Takahashi T, Yoshimura Y, Kosaka H, Furutani N, Hiraishi H, Fukai M, Yokokura M, Yoshikawa E, Bunai T, Minabe Y. {{A pilot study of serotonergic modulation after long-term administration of oxytocin in autism spectrum disorder}}. {Autism Res};2017 (Mar 07)
Oxytocin (OT) and the serotonergic system putatively play important roles in autism spectrum disorder (ASD) etiology and symptoms, but no direct neurobiological evidence exists for long-term OT administration effects on the brain’s serotonergic system. This pilot study examined 10 male participants with ASD who were administered OT intranasally for 8-10 weeks in an open-label, single-arm, nonrandomized, and uncontrolled manner. Positron emission tomography (PET) with a radiotracer (11 C)-3-amino-4-(2-[(dimethylamino)methyl]phenylthio)benzonitrile (11 C-DASB) was used before and after OT treatment. The binding potential of serotonin transporter (11 C-DASB BPND ) was then estimated. The main outcome measures were changes in 11 C-DASB BPND and their correlation with changes in symptoms. ASD participants showed significantly elevated 11 C-DASB BPND in the left inferior frontal gyrus extending to the left middle frontal gyrus. No significant correlation was found between the change in any clinical symptom and the change in 11 C-DASB BPND . This report of a pilot study is the first describing long-term effects of OT on the brain’s serotonin system in ASD. Additional randomized controlled studies must be conducted to confirm whether activation of the serotonergic system contributes to the prosocial effect of OT in people with ASD. Autism Res 2017. (c) 2017 International Society for Autism Research, Wiley Periodicals, Inc.
Lien vers le texte intégral (Open Access ou abonnement)
13. Hulbert SW, Jiang YH. {{Cellular and Circuitry Bases of Autism: Lessons Learned from the Temporospatial Manipulation of Autism Genes in the Brain}}. {Neurosci Bull};2017 (Apr);33(2):205-218.
Transgenic mice carrying mutations that cause Autism Spectrum Disorders (ASDs) continue to be valuable for determining the molecular underpinnings of the disorders. Recently, researchers have taken advantage of such models combined with Cre-loxP and similar systems to manipulate gene expression over space and time. Thus, a clearer picture is starting to emerge of the cell types, circuits, brain regions, and developmental time periods underlying ASDs. ASD-causing mutations have been restricted to or rescued specifically in excitatory or inhibitory neurons, different neurotransmitter systems, and cells specific to the forebrain or cerebellum. In addition, mutations have been induced or corrected in adult mice, providing some evidence for the plasticity and reversibility of core ASD symptoms. The limited availability of Cre lines that are highly specific to certain cell types or time periods provides a challenge to determining the cellular and circuitry bases of autism, but other technological advances may eventually overcome this obstacle.
Lien vers le texte intégral (Open Access ou abonnement)
14. K DP, Srinath DS, Seshadri DS, Girimaji DS, Kommu DJ. {{Lost time-Need for more awareness in early intervention of autism spectrum disorder}}. {Asian J Psychiatr};2017 (Feb);25:13-15.
Delay in the diagnosis and early intervention for Autism spectrum disorders has been observed across cultures and within the same cultural context. With the current evidence base for early intervention there is a need for greater awareness for early recognition, evaluation and intervention. This brief report discusses the average age at recognition to initiation of intervention and possible ways to address delay. Since early intervention programs for ASD results in favourable outcome, it would be good practice to routinely screen children at first consultation and initiate intervention in any child suspected to be ‘At Risk’ for ASD.
Lien vers le texte intégral (Open Access ou abonnement)
15. Kaub-Wittemer D, Hall DA, Kumpf U, Padberg F, Schneider SA. {{Fragile X-associated tremor ataxia syndrome presenting as chronic fatigue syndrome}}. {Parkinsonism Relat Disord};2017 (Mar 07)
Lien vers le texte intégral (Open Access ou abonnement)
16. LaGasse AB. {{Social outcomes in children with autism spectrum disorder: a review of music therapy outcomes}}. {Patient Relat Outcome Meas};2017;8:23-32.
Autism spectrum disorder (ASD) affects approximately one in 68 children, substantially affecting the child’s ability to acquire social skills. The application of effective interventions to facilitate and develop social skills is essential due to the lifelong impact that social skills may have on independence and functioning. Research indicates that music therapy can improve social outcomes in children with ASD. Outcome measures are primarily assessed using standardized nonmusical scales of social functioning from the parent or clinician perspective. Certified music therapists may also assess musical engagement and outcomes as a part of the individual’s profile. These measures provide an assessment of the individual’s social functioning within the music therapy session and generalizability to nonmusical settings.
Lien vers le texte intégral (Open Access ou abonnement)
17. Naigles LR, Tek S. {{‘Form is easy, meaning is hard’ revisited: (re) characterizing the strengths and weaknesses of language in children with autism spectrum disorder}}. {Wiley Interdiscip Rev Cogn Sci};2017 (Mar 06)
Children with autism spectrum disorder (ASD) demonstrate impairments in social interaction and communication, and in repetitive/stereotypical behaviors. The degree to which children with ASD also manifest impairments in structural language-such as lexicon and grammar-is currently quite controversial. We reframe this controversy in terms of Naigles’ (Naigles, Cognition 2002, 86: 157-199) ‘form is easy, meaning is hard’ thesis, and propose that the social difficulties of children with ASD will lead the meaning-related components of their language to be relatively more impaired than the form-related components. Our review of the extant literature supports this proposal, with studies (1) reporting that children with ASD demonstrate significant challenges in the areas of pragmatics and lexical/semantic organization and (2) highlighting their good performance on grammatical assessments ranging from wh-questions to reflexive pronouns. Studies on children with ASD who might have a co-morbid grammatical impairment are discussed in light of the absence of relevant lexical-semantic data from the same children. Most importantly, we present direct comparisons of assessments of lexical/semantic organization and grammatical knowledge from the same children from our laboratory, all of which find more children at a given age demonstrating grammatical knowledge than semantic organization. We conclude with a call for additional research in which in-depth grammatical knowledge and detailed semantic organization are assessed in the same children. For further resources related to this article, please visit the WIREs website.
Lien vers le texte intégral (Open Access ou abonnement)
18. Qin XY, Cheng Y. {{Brain-Derived Neurotrophic Factor in Autism Spectrum Disorder-Reply}}. {JAMA Pediatr};2017 (Mar 06)
Lien vers le texte intégral (Open Access ou abonnement)
19. Reim D, Distler U, Halbedl S, Verpelli C, Sala C, Bockmann J, Tenzer S, Boeckers TM, Schmeisser MJ. {{Proteomic Analysis of Post-synaptic Density Fractions from Shank3 Mutant Mice Reveals Brain Region Specific Changes Relevant to Autism Spectrum Disorder}}. {Front Mol Neurosci};2017;10:26.
Disruption of the human SHANK3 gene can cause several neuropsychiatric disease entities including Phelan-McDermid syndrome, autism spectrum disorder (ASD), and intellectual disability. Although, a wide array of neurobiological studies strongly supports a major role for SHANK3 in organizing the post-synaptic protein scaffold, the molecular processes at synapses of individuals harboring SHANK3 mutations are still far from being understood. In this study, we biochemically isolated the post-synaptic density (PSD) fraction from striatum and hippocampus of adult Shank3Delta11-/- mutant mice and performed ion-mobility enhanced data-independent label-free LC-MS/MS to obtain the corresponding PSD proteomes (Data are available via ProteomeXchange with identifier PXD005192). This unbiased approach to identify molecular disturbances at Shank3 mutant PSDs revealed hitherto unknown brain region specific alterations including a striatal decrease of several molecules encoded by ASD susceptibility genes such as the serine/threonine kinase Cdkl5 and the potassium channel KCa1.1. Being the first comprehensive analysis of brain region specific PSD proteomes from a Shank3 mutant line, our study provides crucial information on molecular alterations that could foster translational treatment studies for SHANK3 mutation-associated synaptopathies and possibly also ASD in general.
Lien vers le texte intégral (Open Access ou abonnement)
20. RK CY, Merico D, Bookman M, J LH, Thiruvahindrapuram B, Patel RV, Whitney J, Deflaux N, Bingham J, Wang Z, Pellecchia G, Buchanan JA, Walker S, Marshall CR, Uddin M, Zarrei M, Deneault E, D’Abate L, Chan AJ, Koyanagi S, Paton T, Pereira SL, Hoang N, Engchuan W, Higginbotham EJ, Ho K, Lamoureux S, Li W, MacDonald JR, Nalpathamkalam T, Sung WW, Tsoi FJ, Wei J, Xu L, Tasse AM, Kirby E, Van Etten W, Twigger S, Roberts W, Drmic I, Jilderda S, Modi BM, Kellam B, Szego M, Cytrynbaum C, Weksberg R, Zwaigenbaum L, Woodbury-Smith M, Brian J, Senman L, Iaboni A, Doyle-Thomas K, Thompson A, Chrysler C, Leef J, Savion-Lemieux T, Smith IM, Liu X, Nicolson R, Seifer V, Fedele A, Cook EH, Dager S, Estes A, Gallagher L, Malow BA, Parr JR, Spence SJ, Vorstman J, Frey BJ, Robinson JT, Strug LJ, Fernandez BA, Elsabbagh M, Carter MT, Hallmayer J, Knoppers BM, Anagnostou E, Szatmari P, Ring RH, Glazer D, Pletcher MT, Scherer SW. {{Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder}}. {Nat Neurosci};2017 (Mar 06)
We are performing whole-genome sequencing of families with autism spectrum disorder (ASD) to build a resource (MSSNG) for subcategorizing the phenotypes and underlying genetic factors involved. Here we report sequencing of 5,205 samples from families with ASD, accompanied by clinical information, creating a database accessible on a cloud platform and through a controlled-access internet portal. We found an average of 73.8 de novo single nucleotide variants and 12.6 de novo insertions and deletions or copy number variations per ASD subject. We identified 18 new candidate ASD-risk genes and found that participants bearing mutations in susceptibility genes had significantly lower adaptive ability (P = 6 x 10-4). In 294 of 2,620 (11.2%) of ASD cases, a molecular basis could be determined and 7.2% of these carried copy number variations and/or chromosomal abnormalities, emphasizing the importance of detecting all forms of genetic variation as diagnostic and therapeutic targets in ASD.
Lien vers le texte intégral (Open Access ou abonnement)
21. Siscoe KS, Lohr WD. {{L-Methylfolate supplementation in a child with autism and methyltetrahydrofolate reductase, enzyme gene C677TT allele}}. {Psychiatr Genet};2017 (Mar 07)
Errors in folate metabolism may play a role in the pathology of autism spectrum disorders because of increased vulnerability to oxidative stress. We report a case where L-methylfolate supplementation improved symptoms of aggression and disruptive behavior in a child with autism who tested positive for the C677TT allele of the methyltetrahydrofolate reductase enzyme gene. To our knowledge, this is the first report of L-methylfolate administration in this situation. Further controlled studies of L-methylfolate in this population are warranted.
Lien vers le texte intégral (Open Access ou abonnement)
22. South M, Carr AW, Stephenson KG, Maisel ME, Cox JC. {{Short report: Symptom overlap on the srs-2 adult self-report between adults with asd and adults with high anxiety}}. {Autism Res};2017 (Mar 07)
Many people diagnosed with autism spectrum disorder (ASD) also experience significant symptoms of anxiety, while many people with anxiety disorders likewise experience social difficulties. These concerns can be difficult to tease apart in general clinical settings. The Social Responsiveness Scale (SRS) is one of the most frequently used measures of dimensional ASD symptoms. In order to investigate the overlap of autism and anxiety on the SRS, we compared three groups of adults (an ASD group, n = 40; a high anxious group, n = 56; and a typical comparison group, n = 29) using the new Adult Self Report version of the SRS-2nd Edition (SRS-2-ASR) alongside a battery of anxiety questionnaires. Based on previous research with children from the parent-report SRS (first edition), we hypothesized that the SRS-2-ASR would have difficulty discriminating between the ASD and high anxious groups. Results showed that both these clinical groups scored significantly higher on the SRS than a typical control group. Discriminant validity was poor, including sensitivity of 0.65 when including all participants and 0.48 when only the two clinical groups were included. In particular, the Social Motivation subscale of the SRS-ASR failed to distinguish between ASD and anxiety groups. As recommended in the SRS-2 manual, we highlight the need for caution when using the SRS-2-ASR to support diagnostic decision making, especially in clinical settings involving anxiety, ADHD, or other concerns that can affect reciprocal social communication and/or behavioral flexibility. Autism Res 2017. (c) 2017 International Society for Autism Research, Wiley Periodicals, Inc.
Lien vers le texte intégral (Open Access ou abonnement)
23. Uljarevic M, Baranek G, Vivanti G, Hedley D, Hudry K, Lane A. {{Heterogeneity of sensory features in autism spectrum disorder: Challenges and perspectives for future research}}. {Autism Res};2017 (Mar 07)
Pronounced heterogeneity is apparent across every facet of autism spectrum disorder (ASD) and it remains difficult to predict likely future potential among individuals who share a common diagnosis of ASD on the basis of early presentation. In this commentary we argue that a fine-grained understanding of individual differences in sensory features and their influence across the life span can constrain noted clinical heterogeneity in ASD. We organize our discussion around the following three critical themes: (a) considering sensory features as dimensional construct; (b) taking an « individual differences » approach; and (c) adopting a comprehensive, multidimensional and multimodal approach to measurement of sensory features. We conclude that future research will need to investigate individual differences in sensory features via: (1) multidimensional and cross-disciplinary examination, (2) prospective longitudinal designs, and (3) dimensional and developmental frameworks that emphasize the potential value of early individual variability as indicators of later outcomes, not only in relation to the categorical diagnostic outcome status but also the presence of other clinical features. This is a key time for sensory-related research and in this commentary we provide some of the steps that, in our opinion, can shape future research in this area. Autism Res 2017. (c) 2017 International Society for Autism Research, Wiley Periodicals, Inc.
Lien vers le texte intégral (Open Access ou abonnement)
24. Van der Hallen R, Lemmens L, Steyaert J, Noens I, Wagemans J. {{Ensemble perception in autism spectrum disorder: Member-identification versus mean-discrimination}}. {Autism Res};2017 (Mar 07)
To efficiently represent the outside world our brain compresses sets of similar items into a summarized representation, a phenomenon known as ensemble perception. While most studies on ensemble perception investigate this perceptual mechanism in typically developing (TD) adults, more recently, researchers studying perceptual organization in individuals with autism spectrum disorder (ASD) have turned their attention toward ensemble perception. The current study is the first to investigate the use of ensemble perception for size in children with and without ASD (N = 42, 8-16 years). We administered a pair of tasks pioneered by Ariely [2001] evaluating both member-identification and mean-discrimination. In addition, we varied the distribution types of our sets to allow a more detailed evaluation of task performance. Results show that, overall, both groups performed similarly in the member-identification task, a test of « local perception, » and similarly in the mean identification task, a test of « gist perception. » However, in both tasks performance of the TD group was affected more strongly by the degree of stimulus variability in the set, than performance of the ASD group. These findings indicate that both TD children and children with ASD use ensemble statistics to represent a set of similar items, illustrating the fundamental nature of ensemble coding in visual perception. Differences in sensitivity to stimulus variability between both groups are discussed in relation to recent theories of information processing in ASD (e.g., increased sampling, decreased priors, increased precision). Autism Res 2017. (c) 2017 International Society for Autism Research, Wiley Periodicals, Inc.
Lien vers le texte intégral (Open Access ou abonnement)
25. Vargason T, Howsmon DP, Melnyk S, James SJ, Hahn J. {{Mathematical modeling of the methionine cycle and transsulfuration pathway in individuals with autism spectrum disorder}}. {J Theor Biol};2017 (Mar 07);416:28-37.
Previous research has shown a connection between metabolic abnormalities in the methionine cycle and transsulfuration pathway and autism spectrum disorder. Using clinical data from a case-control study investigating measurements of transmethylation and transsulfuration metabolites, a steady-state model of these metabolites in liver cells was developed and participant-specific parameters were identified. Comparison of mean parameter values and parameter distributions between neurotypical study participants and those on the autism spectrum revealed significant differences for four model parameters. Sensitivity analysis identified the parameter describing the rate of glutamylcysteine synthesis, the rate-limiting step in glutathione production, to be particularly important in determining steady-state metabolite concentrations. These results may provide insight into key reactions to target for potential intervention strategies relating to autism spectrum disorder.
Lien vers le texte intégral (Open Access ou abonnement)
26. Vorstman JA, Parr JR, Moreno-De-Luca D, Anney RJ, Nurnberger JI, Jr., Hallmayer JF. {{Autism genetics: opportunities and challenges for clinical translation}}. {Nat Rev Genet};2017 (Mar 06)
Genetic studies have revealed the involvement of hundreds of gene variants in autism. Their risk effects are highly variable, and they are frequently related to other conditions besides autism. However, many different variants converge on common biological pathways. These findings indicate that aetiological heterogeneity, variable penetrance and genetic pleiotropy are pervasive characteristics of autism genetics. Although this advancing insight should improve clinical care, at present there is a substantial discrepancy between research knowledge and its clinical application. In this Review, we discuss the current challenges and opportunities for the translation of autism genetics knowledge into clinical practice.
Lien vers le texte intégral (Open Access ou abonnement)
27. Vuillermot S, Luan W, Meyer U, Eyles D. {{Vitamin D treatment during pregnancy prevents autism-related phenotypes in a mouse model of maternal immune activation}}. {Mol Autism};2017;8:9.
BACKGROUND: Prenatal exposure to infection is a recognized environmental risk factor for neuropsychiatric disorders of developmental origins such as autism or schizophrenia. Experimental work in animals indicates that this link is mediated by maternal immune activation (MIA) involving interactions between cytokine-associated inflammatory events, oxidative stress, and other pathophysiological processes such as hypoferremia and zinc deficiency. Maternal administration of the viral mimic polyriboinosinic-polyribocytidylic acid (poly(I:C)) in mice produces several behavioral phenotypes in adult offspring of relevance to autism spectrum disorder (ASD) and other neurodevelopmental disorders. METHODS: Here, we investigated whether some of these phenotypes might also present in juveniles. In addition, given the known immunomodulatory and neuroprotective effects of vitamin D, we also investigated whether the co-administration of vitamin D could block MIA-induced ASD-related behaviors. We co-administered the hormonally active form of vitamin D, 1alpha,25 dihydroxy vitamin D3 (1,25OHD), simultaneously with poly(I:C) and examined (i) social interaction, stereotyped behavior, emotional learning and memory, and innate anxiety-like behavior in juveniles and (ii) the levels of the pro-inflammatory cytokines IL-1beta, IL-6 and TNF-alpha in maternal plasma and fetal brains. RESULTS: We show that like adult offspring that were exposed to MIA, juveniles display similar deficits in social approach behavior. Juvenile MIA offspring also show abnormal stereotyped digging and impaired acquisition and expression of tone-cued fear conditioning. Importantly, our study reveals that prenatal administration of 1,25OHD abolishes all these behavioral deficits in poly(I:C)-treated juveniles. However, prenatal administration of vitamin D had no effect on pro-inflammatory cytokine levels in dams or in fetal brains suggesting the anti-inflammatory actions of vitamin D are not the critical mechanism for its preventive actions in this ASD animal model. CONCLUSIONS: This work raises the possibility that early dietary supplementation with vitamin D may open new avenues for a successful attenuation or even prevention of neurodevelopmental disorders following maternal inflammation during pregnancy.
Lien vers le texte intégral (Open Access ou abonnement)
28. Ward J, Hoadley C, Hughes JE, Smith P, Allison C, Baron-Cohen S, Simner J. {{Atypical sensory sensitivity as a shared feature between synaesthesia and autism}}. {Sci Rep};2017 (Mar 07);7:41155.
Several studies have suggested that there is a link between synaesthesia and autism but the nature of that link remains poorly characterised. The present study considers whether atypical sensory sensitivity may be a common link between the conditions. Sensory hypersensitivity (aversion to certain sounds, touch, etc., or increased ability to make sensory discriminations) and/or hyposensitivity (desire to stimulate the senses , or a reduced response to sensory stimuli are a recently introduced diagnostic feature of autism spectrum conditions (ASC). Synaesthesia is defined by unusual sensory experiences and has also been linked to a typical cortical hyper-excitability. The Glasgow Sensory Questionnaire (GSQ) was administered to synaesthetes and people with ASC. Both groups reported increased sensory sensitivity relative to controls with a large effect size. Both groups also reported a similar pattern of both increased hyper- and hypo-sensitivities across multiple senses. The AQ (Autism-Spectrum Quotient) scores were elevated in the synaesthetes, and one subscale of this measure (attention to detail) placed synaesthetes within the autistic range. A standard laboratory test of visual stress (the Pattern Glare Test), administered online, corroborated the findings of increased sensitivity to aversive visual stimuli in synaesthetes. We conclude that atypical sensory sensitivity is an important shared feature between autism and synaesthesia.
Lien vers le texte intégral (Open Access ou abonnement)
29. Zaki MM, Abdel-Al H, Al-Sawi M. {{Assessment of plasma amino acid profile in autism using cation-exchange chromatography with postcolumn derivatization by ninhydrin}}. {Turk J Med Sci};2017 (Feb 27);47(1):260-267.
BACKGROUND/AIM: Autism is a heterogeneous neurodevelopmental disorder. This study aimed to assess the clinical significance of amino acid profile assay in autism using cation-exchange chromatography with ninhydrin postcolumn derivatization. MATERIALS AND METHODS: This study included 42 autistic children and 26 apparently healthy children. All participants were subjected to the assay of plasma amino acids (essential, nonessential, and nonstandard) using cation-exchange chromatography with postcolumn derivatization by ninhydrin. RESULTS: The levels of most of the essential amino acids were significantly lower in autistic children than controls. As regards nonessential amino acids, significantly lower levels for plasma cysteine, tyrosine, and serine and significantly higher levels for plasma glutamic acid were recorded in autistic children than controls. Finally, the autistic group demonstrated significantly lower levels of alpha-aminoadipic acid, carnosine, and beta-alanine and significantly higher levels of hydroxyproline, phosphoserine, beta-amino-isobutyric acid, and ammonia as compared to controls. CONCLUSION: The study revealed that autistic children exhibit distinct alterations in the plasma levels of some amino acids, which can in turn participate in the disease etiology and can be applied as a diagnostic tool for early detection of autism.
