1. El-Ansary A, Al-Ayadhi L. {{Lipid mediators in plasma of autism spectrum disorders}}. {Lipids Health Dis};2012 (Nov 21);11(1):160.
ABSTRACT: BACKGROUND: Inflammation is increasingly recognized as being of both physiological and pathological importance in the immature brain. Cerebellar pathology occurs in autism, as a neurodevelopmental disorder with genetic and environmental origins. The genesis of this disorder is still not understood but inflammation in utero or early in childhood is an environmental risk factor. METHODS: Prostaglandin E2 (PGE2), cysteinyl leukotriene as two important lipid mediators together with 8 isoprostane as marker of oxidative stress were measured using ELISA in plasma of 20 male autistic patients compared to 19 age and gender matching control participants. RESULTS: PGE2, leukotrienes and isoprostanes recorded significantly elevated levels in autistics compared to controls. Role of these measured parameters in inflammation and autoimmunity as two etiological factors in autism were discussed in details. CONCLUSION: Receiver Operating Characteristic (ROC) curve analysis shows satisfactory values of area under the curve (AUC) which could reflect the high degree of specificity and sensitivity of the altered PGE2, leukotrienes and isoprostanes as predictive biomarkers in autistic patients from Saudi Arabia.
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2. El-Kordi A, Winkler D, Hammerschmidt K, Kastner A, Krueger D, Ronnenberg A, Ritter C, Jatho J, Radyushkin K, Bourgeron T, Fischer J, Brose N, Ehrenreich H. {{Development of an autism severity score for mice using Nlgn4 null mutants as a construct-valid model of heritable monogenic autism}}. {Behav Brain Res};2012 (Nov 23)
Autism is the short name of a complex and heterogeneous group of disorders (autism spectrum disorders, ASD) with several lead symptoms required for classification, including compromised social interaction, reduced verbal communication and stereotyped repetitive behaviors/restricted interests. The etiology of ASD is still unknown in most cases but monogenic heritable forms exist that have provided insights into ASD pathogenesis and have led to the notion of autism as a ‘synapse disorder’. Among the most frequent monogenic causes of autism are loss-of-function mutations of the NLGN4X gene which encodes the synaptic cell adhesion protein neuroligin-4X (NLGN4X). We previously described autism-like behaviors in male Nlgn4 null mutant mice, including reduced social interaction and ultrasonic communication. Here, we extend the phenotypical characterization of Nlgn4 null mutant mice to both genders and add a series of additional autism-relevant behavioral readouts. We now report similar social interaction and ultrasonic communication deficits in females as in males. Furthermore, aggression, nest-building parameters, as well as self-grooming and circling as indicators of repetitive behaviors/stereotypies were explored in both genders. The construction of a gender-specific autism severity composite score for Nlgn4 mutant mice markedly diminishes population/sample heterogeneity typically obtained for single tests, resulting in p values of <0.00001 and a genotype predictability of 100% for male and of >83% for female mice. Taken together, these data underscore the similarity of phenotypical consequences of Nlgn4/NLGN4X loss-of-function in mouse and man, and emphasize the high relevance of Nlgn4 null mutant mice as an ASD model with both construct and face validity.
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3. Floris DL, Chura LR, Holt RJ, Suckling J, Bullmore ET, Baron-Cohen S, Spencer MD. {{Psychological Correlates of Handedness and Corpus Callosum Asymmetry in Autism: The left Hemisphere Dysfunction Theory Revisited}}. {J Autism Dev Disord};2012 (Nov 23)
Rightward cerebral lateralization has been suggested to be involved in the neuropathology of autism spectrum conditions. We investigated functional and neuroanatomical asymmetry, in terms of handedness and corpus callosum measurements in male adolescents with autism, their unaffected siblings and controls, and their associations with executive dysfunction and symptom severity. Adolescents with autism did not differ from controls in functional asymmetry, but neuroanatomically showed the expected pattern of stronger rightward lateralization in the posterior and anterior midbody based on their hand-preference. Measures of symptom severity were related to rightward asymmetry in three subregions (splenium, posterior midbody and rostral body). We found the opposite pattern for the isthmus and rostrum with better cognitive and less severe clinical scores associated with rightward lateralization.
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4. Gkogkas CG, Khoutorsky A, Ran I, Rampakakis E, Nevarko T, Weatherill DB, Vasuta C, Yee S, Truitt M, Dallaire P, Major F, Lasko P, Ruggero D, Nader K, Lacaille JC, Sonenberg N. {{Autism-related deficits via dysregulated eIF4E-dependent translational control}}. {Nature};2012 (Nov 21)
Hyperconnectivity of neuronal circuits due to increased synaptic protein synthesis is thought to cause autism spectrum disorders (ASDs). The mammalian target of rapamycin (mTOR) is strongly implicated in ASDs by means of upstream signalling; however, downstream regulatory mechanisms are ill-defined. Here we show that knockout of the eukaryotic translation initiation factor 4E-binding protein 2 (4E-BP2)-an eIF4E repressor downstream of mTOR-or eIF4E overexpression leads to increased translation of neuroligins, which are postsynaptic proteins that are causally linked to ASDs. Mice that have the gene encoding 4E-BP2 (Eif4ebp2) knocked out exhibit an increased ratio of excitatory to inhibitory synaptic inputs and autistic-like behaviours (that is, social interaction deficits, altered communication and repetitive/stereotyped behaviours). Pharmacological inhibition of eIF4E activity or normalization of neuroligin 1, but not neuroligin 2, protein levels restores the normal excitation/inhibition ratio and rectifies the social behaviour deficits. Thus, translational control by eIF4E regulates the synthesis of neuroligins, maintaining the excitation-to-inhibition balance, and its dysregulation engenders ASD-like phenotypes.
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5. Kamio Y, Inada N, Moriwaki A, Kuroda M, Koyama T, Tsujii H, Kawakubo Y, Kuwabara H, Tsuchiya KJ, Uno Y, Constantino JN. {{Quantitative autistic traits ascertained in a national survey of 22 529 Japanese schoolchildren}}. {Acta Psychiatr Scand};2012 (Nov 22)
OBJECTIVE: Recent epidemiologic studies worldwide have documented a rise in prevalence rates for autism spectrum disorders (ASD). Broadening of diagnostic criteria for ASD may be a major contributor to the rise in prevalence, particularly if superimposed on an underlying continuous distribution of autistic traits. This study sought to determine the nature of the population distribution of autistic traits using a quantitative trait measure in a large national population sample of children. METHOD: The Japanese version of the Social Responsiveness Scale (SRS) was completed by parents on a nationally representative sample of 22 529 children, age 6-15. RESULTS: Social Responsiveness Scale scores exhibited a skewed normal distribution in the Japanese population with a single-factor structure and no significant relation to IQ within the normal intellectual range. There was no evidence of a natural ‘cutoff’ that would differentiate populations of categorically affected children from unaffected children. CONCLUSION: This study provides evidence of the continuous nature of autistic symptoms measured by the SRS, a validated quantitative trait measure. The findings reveal how paradigms for diagnosis that rest on arbitrarily imposed categorical cutoffs can result in substantial variation in prevalence estimation, especially when measurements used for case assignment are not standardized for a given population.
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6. Lombardo MV, Chakrabarti B, Lai MC, Baron-Cohen S. {{Self-referential and social cognition in a case of autism and agenesis of the corpus callosum}}. {Mol Autism};2012 (Nov 21);3(1):14.
ABSTRACT: BACKGROUND: While models of autism spectrum conditions (ASC) are emerging at the genetic level of analysis, clear models at higher levels of analysis, such as neuroanatomy, are lacking. Here we examine agenesis of the corpus callosum (AgCC) as a model at the level of neuroanatomy that may be relevant for understanding self-referential and social-cognitive difficulties in ASC. METHODS: We examined performance on a wide array of tests in self-referential and social-cognitive domains in a patient with both AgCC and a diagnosis of ASC. Tests included a depth-of-processing memory paradigm with self-referential and social-cognitive manipulations, self-report measures of self-consciousness, alexithymia, and empathy, as well as performance measures of first-person pronoun usage and mentalizing ability. The performance of the AgCC patient was compared to a group of individuals with ASC but without AgCC and with neurotypical controls. These comparison groups come from a prior study where group differences were apparent across many measures. We used bootstrapping to assess whether the AgCC patient exhibited scores that were within or outside the 95% bias-corrected and accelerated bootstrap confidence intervals observed in both comparison groups. RESULTS: Within the depth-of-processing memory paradigm, the AgCC patient showed decreased memory sensitivity that was more extreme than both comparison groups across all conditions. The patient’s most pronounced difficulty on this task emerged in the social-cognitive domain related to information-processing about other people. The patient was similar to the ASC group in benefiting less from self-referential processing compared to the control group. Across a variety of other self-referential (i.e. alexithymia, private self-consciousness) and social-cognitive measures (i.e. self-reported imaginative and perspective-taking subscales of empathy, mentalizing), the AgCC patient also showed more extreme scores than those observed for both of the comparison groups. However, the AgCC patient scored within the range observed in the comparison groups on measures of first-person pronoun usage and self-reported affective empathy subscales. CONCLUSIONS: We conclude that AgCC co-occurring with a diagnosis of ASC may be a relevant model at the level of neuroanatomy for understanding mechanisms involved in self-referential and high-level social-cognitive difficulties in ASC.
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7. Mathersul D, McDonald S, Rushby JA. {{Psychophysiological correlates of social judgement in high-functioning adults with autism spectrum disorder}}. {Int J Psychophysiol};2012 (Nov 23)
Neural structures involved in social cognition (e.g., amygdala, orbitofrontal cortex) have been implicated in judgements of trustworthiness. These regions are also functionally atypical in individuals with autism spectrum disorders (ASDs). Studies investigating judgements of trustworthiness in ASDs have suggested possible disruptions in the allocation of significance to social stimuli. Concurrent measures of autonomic responses provide further insight into these deficits, given their role in the direction of attention and allocation of significance. Thirty high-functioning adults with ASDs and 31 non-clinical controls viewed neutral images piloted as most « positive » and « negative ». Skin conductance (SCR, SCL) and evoked cardiac deceleration (ECD) were recorded. Adults with ASDs did not differ from controls in ratings of trustworthiness. However, they displayed atypical SCRs, providing further support for a disruption in the allocation of emotional significance.
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8. Molen MJ, Molen WM. {{Title: Reduced alpha and exaggerated theta power during the resting-state EEG in fragile X syndrome}}. {Biol Psychol};2012 (Nov 23)
This study characterizes the resting-state EEG in males with fragile X syndrome to reveal abnormalities in oscillatory brain dynamics. Analyses of the eyes-closed EEG epochs showed that the resting-state EEG in FXS can be characterized by elevated relative theta power (4-8Hz) and reduced relative upper-alpha power (10-12Hz). Although preliminary, these findings suggest that the well-documented imbalance in excitatory/inhibitory cortical circuit activity in FXS can be revealed the level of oscillatory behavior at the scalp. A next step for future studies is linking the EEG resting-state indices to cognitive and behavioral measures.
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9. Petalas MA, Hastings RP, Nash S, Reilly D, Dowey A. {{The perceptions and experiences of adolescent siblings who have a brother with autism spectrum disorder}}. {J Intellect Dev Disabil};2012 (Dec);37(4):303-314.
Abstract Background There is a dearth of research on the perspectives of adolescent siblings growing up with a brother or sister with an autism spectrum disorder (ASD). Method Semistructured interviews were used to elicit the perceptions and experiences of 12 typically developing adolescents with a brother with an ASD. Interpretative phenomenological analysis was used. Results The data analysis of the siblings’ perceptions yielded 6 themes: (a) difficulties and negative impact of their brother’s condition on themselves and their family, (b) how others’ reactions to their brother negatively affected them as siblings, (c) how their histories with their brothers contextualised their present circumstances, (d) the varying degrees of acceptance and tolerance towards their brothers, (e) positive perceptions and experiences with their brothers, and (f) their thoughts and worries about the future. Conclusions The main implications are for supports to adolescent siblings by helping them to develop skills in managing others’ reactions and openly discussing concerns about their brother’s future.
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10. Safe A, Joosten A, Molineux M. {{The experiences of mothers of children with autism: Managing multiple roles}}. {J Intellect Dev Disabil};2012 (Dec);37(4):294-302.
Abstract Background Mothers of children with autism experience poorer health and wellbeing compared to mothers of children with other disabilities or typically-developing children. This qualitative phenomenological study aimed to explore the daily life experiences of mothers of children with autism, and the strategies they use to manage their roles, their emotions, and their child’s behaviours. Method In-depth interviews were conducted with 7 mothers and the data were analysed using interpretative phenomenological analysis. Results Findings revealed that the mothers were challenged by the demands of their multiple roles while dealing with the paradox of accepting their child for who they were, and at the same time also desiring their typical growth and development. However, the mothers reported various strategies they used to manage their roles, their emotions, and their child’s behaviours. Conclusions The findings indicate that health professionals working with these families must support mothers in managing various aspects of their lives, including those not directly related to their child with autism.
