1. Guyatt AL, Heron J, Knight Ble C, Golding J, Rai D. {{Digit ratio and autism spectrum disorders in the Avon Longitudinal Study of Parents and Children: a birth cohort study}}. {BMJ open}. 2015;5(8):e007433.
OBJECTIVES: To investigate whether second-to-fourth digit ratio (2D:4D), a measure commonly used as a proxy for fetal testosterone exposure, is associated with autism spectrum disorders (ASDs), as predicted by the extreme male brain theory of autism. DESIGN: A birth cohort study. SETTING: The Avon Longitudinal Study of Parents and Children (ALSPAC). PARTICIPANTS: 6015 ALSPAC children with data on digit ratio, at least 1 outcome measure and information on potential confounding variables (parental occupational class, maternal education and age at digit ratio measurement). Digit ratio was measured by the photocopy and calliper method. OUTCOMES: ASD diagnosis (cases were identified previously by record linkage or maternal report) and 4 measures that combine optimally within ALSPAC to predict ASD: the Children’s Communication Checklist (coherence subscale), the Social and Communication Disorders Checklist, a repetitive behaviour measure, and the Emotionality, Activity and Sociability scale (sociability subscale). These measures were dichotomised, with approximately 10% defined as the ‘risk’ group. RESULTS: Using logistic regression, we examined the association of 2D:4D with ASDs and 4 dichotomised ASD traits. Covariates were occupational class, maternal education and age at 2D:4D measurement. 2D:4D was not associated with ASDs in males (adjusted OR per 1 SD increase in mean 2D:4D, 0.88 (95% CI 0.65 to 1.21), p=0.435) or females (adjusted OR=1.36 (95% CI 0.81 to 2.28), p=0.245). Similar results were observed after adjustment for IQ. There was 1 weak association between reduced coherence and increased left 2D:4D in males, in the opposite direction to that predicted by the extreme male brain theory (adjusted OR=1.15 (95% CI 1.02 to 1.29), p=0.023). Given multiple comparisons, this is consistent with chance. CONCLUSIONS: In this population-based study, there was no strong evidence of an association between 2D:4D and ASD diagnosis or traits, although the CIs were wide. These results are not consistent with the extreme male brain theory.
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2. Herrmann S. {{Counting Sheep: Sleep Disorders in Children With Autism Spectrum Disorders}}. {Journal of pediatric health care : official publication of National Association of Pediatric Nurse Associates & Practitioners}. 2015 Aug 22.
INTRODUCTION: This article will discuss the prevalence and types of sleep disorders experienced by children with autism spectrum disorders (ASDs), the risk factors for the development of sleep disorders among children with ASDs, the impact of sleep disorders on children with ASDs, and the role of the primary care provider (PCP) in diagnosing and treating sleep disorders among children with ASDs. METHOD: Review of published literature on the topic. RESULTS: Children with ASDs are at risk for the development of chronic sleep disorders, which can have a negative impact on behavior. Both behavioral and pharmacological interventions exist for the treatment of sleep disorders among children with ASDs, with supplemental melatonin being the most widely studied and proven treatment. DISCUSSION: PCPs will care for children with ASDs. Therefore, it is vital for PCPs to be knowledgeable about this topic and to promptly assess for and manage sleep disorders among children with ASDs.
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3. Huynh TN, Shah M, Koo SY, Faraud KS, Santini E, Klann E. {{eIF4E/Fmr1 Double Mutant Mice Display Cognitive Impairment in Addition to ASD-like Behaviors}}. {Neurobiology of disease}. 2015 Aug 22.
Autism spectrum disorder (ASD) is a group of heritable disorders with complex and unclear etiology. Classic ASD symptoms include social interaction and communication deficits as well as restricted, repetitive behaviors. In addition, ASD is often comorbid with intellectual disability. Fragile X syndrome (FXS) is the leading genetic cause of ASD, and is the most commonly inherited form of intellectual disability. Several mouse models of ASD and FXS exist, however the intellectual disability observed in ASD patients is not well modeled in mice. Using the Fmr1 knockout mouse, and the eIF4E transgenic mouse, two previously characterized mouse models of fragile X syndrome and ASD respectively, we generated the eIF4E/Fmr1 double mutant mouse. Our study shows that the eIF4E/Fmr1 double mutant mice display classic ASD behaviors, as well as cognitive dysfunction. Importantly, the learning impairments displayed by the double mutant mice spanned multiple cognitive tasks. Moreover, the eIF4E/Fmr1 double mutant mice display increased levels of basal protein synthesis. The results of our study suggest that the eIF4E/Fmr1 double mutant mouse may be a reliable model to study cognitive dysfunction in the context of ASD.
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4. Jaarsma P, Welin S. {{Autism, Accommodation and Treatment: A Rejoinder to Chong-Ming Lim’s Critique}}. {Bioethics}. 2015 Aug 26.
We are very grateful to Chong-Ming Lim for his thoughtful reply published in this journal on one of our articles, which motivated us to think more carefully about accommodating autistic individuals and treating autism. However we believe there are some confusions in Lim’s argument. Lim uses the accommodation thesis, according to which we should accommodate autistic individuals rather than treat autism, as the starting point for his reasoning. He claims that if the accommodation thesis is right, then we should not treat autistic individuals for their autism, not even low-functioning (i.e. intellectually disabled) ones, because this would be disrespectful to all autistic individuals. We should instead limit ourselves to accommodate all autistic individuals. However, the opposition between accommodation and treatment is not valid in the case of autism, because of ambiguity in the concepts of accommodation and treatment. Moreover there is confusion in Lim’s reasoning caused by omitting important facts about the practice of treating autism.
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5. Kuschner ES, Eisenberg IW, Orionzi B, Simmons WK, Kenworthy L, Martin A, Wallace GL. {{A Preliminary Study of Self-Reported Food Selectivity in Adolescents and Young Adults with Autism Spectrum Disorder}}. {Research in autism spectrum disorders}. 2015 Jul 1;15-16:53-9.
Although it is well-established that picky eating is a common feature of early development in autism spectrum disorder (ASD), far less is known about food selectivity during adolescence and adulthood. Using portions of the Adult/Adolescent Sensory Profile, food selectivity self-ratings were obtained from 65 high-functioning adolescents/young adults with ASD and compared to those of 59 typically developing controls matched on age, IQ, and sex ratio. Individuals with ASD reported preferring familiar foods (food neophobia) and disliking foods with particular textures and strong flavors. Providing linkage to everyday behavior, parent ratings of daily living skills were lower among individuals with ASD and food neophobia than among those without food neophobia. Food selectivity continues to be an important issue for adolescents/young adults with ASD.
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6. Martin BS, Martinez-Botella G, Loya CM, Salituro FG, Robichaud AJ, Huntsman MM, Ackley MA, Doherty JJ, Corbin JG. {{Rescue of deficient amygdala tonic gamma-aminobutyric acidergic currents in the Fmr mouse model of fragile X syndrome by a novel gamma-aminobutyric acid type A receptor-positive allosteric modulator}}. {Journal of neuroscience research}. 2015 Aug 26.
Alterations in the ratio of excitatory to inhibitory transmission are emerging as a common component of many nervous system disorders, including autism spectrum disorders (ASDs). Tonic gamma-aminobutyric acidergic (GABAergic) transmission provided by peri- and extrasynaptic GABA type A (GABAA ) receptors powerfully controls neuronal excitability and plasticity and, therefore, provides a rational therapeutic target for normalizing hyperexcitable networks across a variety of disorders, including ASDs. Our previous studies revealed tonic GABAergic deficits in principal excitatory neurons in the basolateral amygdala (BLA) in the Fmr1-/y knockout (KO) mouse model fragile X syndrome. To correct amygdala deficits in tonic GABAergic neurotransmission in Fmr1-/y KO mice, we developed a novel positive allosteric modulator of GABAA receptors, SGE-872, based on endogenously active neurosteroids. This study shows that SGE-872 is nearly as potent and twice as efficacious for positively modulating GABAA receptors as its parent molecule, allopregnanolone. Furthermore, at submicromolar concentrations (</=1 muM), SGE-872 is selective for tonic, extrasynaptic alpha4beta3delta-containing GABAA receptors over typical synaptic alpha1beta2gamma2 receptors. We further find that SGE-872 strikingly rescues the tonic GABAergic transmission deficit in principal excitatory neurons in the Fmr1-/y KO BLA, a structure heavily implicated in the neuropathology of ASDs. Therefore, the potent and selective action of SGE-872 on tonic GABAA receptors containing alpha4 subunits may represent a novel and highly useful therapeutic avenue for ASDs and related disorders involving hyperexcitability of neuronal networks. (c) 2015 Wiley Periodicals, Inc.
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7. Oberman LM, Boccuto L, Cascio L, Sarasua S, Kaufmann WE. {{Autism spectrum disorder in Phelan-McDermid syndrome: initial characterization and genotype-phenotype correlations}}. {Orphanet journal of rare diseases}. 2015;10(1):105.
BACKGROUND: Phelan-McDermid syndrome (PMS) is a neurodevelopmental disorder associated with a terminal deletion affecting chromosome 22 (22q13) that results in the loss of function of the SHANK3 gene. SHANK3 has also been identified in gene-linkage studies to be associated with autism spectrum disorder (ASD). Diagnosis of ASD in individuals with PMS is complicated by the presence of moderate to profound global developmental delay/intellectual disability as well as other co-morbid systemic and neurological symptoms. METHODS: The current study aimed to characterize the symptoms of ASD in patients with PMS and to do a preliminary exploration of genotype-ASD phenotype correlations. We conducted a standardized interview with 40 parents/guardians of children with PMS. Further, we conducted analyses on the relationship between disruption of SHANK3 and adjacent genes on specific characteristic symptoms of ASD in PMS in small subset of the sample. RESULTS: The majority of PMS participants in our sample displayed persistent deficits in Social communication, but only half met diagnostic criteria under the restricted, repetitive patterns of behavior, interests, or activities domain. Furthermore, logistic regressions indicated that general developmental delay significantly contributed to the ASD diagnosis. The analyses relating the PMS genotype to the behavioral phenotype revealed additional complex relationships with contributions of genes in both deleted and preserved SHANK3 regions to the ASD phenotype and other neurobehavioral impairments. CONCLUSIONS: There appears to be a unique behavioral phenotype associated with ASD in individuals with PMS. There also appears to be contributions of genes in both deleted and preserved SHANK3 regions to the ASD phenotype and other neurobehavioral impairments. Better characterization of the behavioral phenotype using additional standardized assessments and further analyses exploring the relationship between the PMS genotype and behavioral phenotype in a larger sample are warranted.
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8. Rahbar MH, Samms-Vaughan M, Ma J, Bressler J, Dickerson AS, Hessabi M, Loveland KA, Grove ML, Shakespeare-Pellington S, Beecher C, McLaughlin W, Boerwinkle E. {{Synergic effect of GSTP1 and blood manganese concentrations in Autism Spectrum Disorder}}. {Research in autism spectrum disorders}. 2015 Oct 1;18:73-82.
We used data from 100 age- and sex-matched case-control pairs (age 2-8 years) from Jamaica to investigate whether there is an interaction between glutathione-S-transferase (GST) genes and blood manganese concentrations (BMC) in relation to Autism Spectrum Disorder (ASD). Our findings, indicate that among children who had the Ile/Ile genotype for GST pi 1 (GSTP1), those with BMC >/= 12microg/L had about 4 times higher odds of ASD than those with BMC < 12microg/L, (P=0.03) under a co-dominant genetic model. After adjusting for potential confounders, among the subgroup of children with genotype Ile/Ile, those with BMC >/= 12microg/L had about six times higher odds of ASD than those with BMC < 12microg/L, (P=0.04). The results were similar when a recessive genetic model was used. These findings suggest a possible synergic effect of BMC and GSTP1 in ASD. Since our analysis included a variety of genetic models and was not adjusted for multiple testing, replication in other populations is warranted.
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9. Simas T, Chattopadhyay S, Hagan C, Kundu P, Patel A, Holt R, Floris D, Graham J, Ooi C, Tait R, Spencer M, Baron-Cohen S, Sahakian B, Bullmore E, Goodyer I, Suckling J. {{Semi-Metric Topology of the Human Connectome: Sensitivity and Specificity to Autism and Major Depressive Disorder}}. {PloS one}. 2015;10(8):e0136388.
INTRODUCTION: The human functional connectome is a graphical representation, consisting of nodes connected by edges, of the inter-relationships of blood oxygenation-level dependent (BOLD) time-series measured by MRI from regions encompassing the cerebral cortices and, often, the cerebellum. Semi-metric analysis of the weighted, undirected connectome distinguishes an edge as either direct (metric), such that there is no alternative path that is accumulatively stronger, or indirect (semi-metric), where one or more alternative paths exist that have greater strength than the direct edge. The sensitivity and specificity of this method of analysis is illustrated by two case-control analyses with independent, matched groups of adolescents with autism spectrum conditions (ASC) and major depressive disorder (MDD). RESULTS: Significance differences in the global percentage of semi-metric edges was observed in both groups, with increases in ASC and decreases in MDD relative to controls. Furthermore, MDD was associated with regional differences in left frontal and temporal lobes, the right limbic system and cerebellum. In contrast, ASC had a broadly increased percentage of semi-metric edges with a more generalised distribution of effects and some areas of reduction. In summary, MDD was characterised by localised, large reductions in the percentage of semi-metric edges, whilst ASC is characterised by more generalised, subtle increases. These differences were corroborated in greater detail by inspection of the semi-metric backbone for each group; that is, the sub-graph of semi-metric edges present in >90% of participants, and by nodal degree differences in the semi-metric connectome. CONCLUSION: These encouraging results, in what we believe is the first application of semi-metric analysis to neuroimaging data, raise confidence in the methodology as potentially capable of detection and characterisation of a range of neurodevelopmental and psychiatric disorders.
