1. Adlof SM, Klusek J, Shinkareva SV, Robinson ML, Roberts JE. {{Phonological awareness and reading in boys with fragile X syndrome}}. {J Child Psychol Psychiatry};2014 (Jun 3)
BACKGROUND: Reading delays are well documented in children with fragile X syndrome (FXS), but few studies have examined linguistic precursors of reading in this population. This study examined the longitudinal development of phonological awareness and its relationship with basic reading in boys with FXS. Individual differences in genetic, social-behavioral and environmental factors were also investigated as predictors of phonological awareness. METHODS: Participants included 54 boys with FXS and 53 typically developing (TD) mental age-matched peers who completed assessments of phonological awareness, nonverbal intelligence, and reading annually for up to 4 years. FMRP level and autism symptomatology were also measured within the FXS group. Hierarchical linear modeling was used to examine change in phonological awareness over time and its predictors. Linear regression was used to examine phonological awareness as a predictor of word reading. RESULTS: Boys with FXS exhibited slower growth than TD peers in phonological awareness only when nonverbal cognitive abilities were not controlled. The rate of change in phonological awareness decreased significantly after age 10 in boys with FXS. Phonological awareness accounted for 18% unique variance in basic reading ability after controlling for nonverbal cognition, with similar relationships across groups. CONCLUSION: Phonological awareness skills in the boys with FXS were commensurate with their nonverbal cognitive abilities, with similar relationships between phonological awareness and reading as observed in the TD mental age-matched peers. More research is needed to examine potential causal relationships between phonological awareness, other language skills, and reading abilities in individuals with FXS and other neurodevelopmental disorders.
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2. An JY, Cristino AS, Zhao Q, Edson J, Williams SM, Ravine D, Wray J, Marshall VM, Hunt A, Whitehouse AJ, Claudianos C. {{Towards a molecular characterization of autism spectrum disorders: an exome sequencing and systems approach}}. {Transl Psychiatry};2014;4:e394.
The hypothetical ‘AXAS’ gene network model that profiles functional patterns of heterogeneous DNA variants overrepresented in autism spectrum disorder (ASD), X-linked intellectual disability, attention deficit and hyperactivity disorder and schizophrenia was used in this current study to analyze whole exome sequencing data from an Australian ASD cohort. An optimized DNA variant filtering pipeline was used to identify loss-of-function DNA variations. Inherited variants from parents with a broader autism phenotype and de novo variants were found to be significantly associated with ASD. Gene ontology analysis revealed that putative rare causal variants cluster in key neurobiological processes and are overrepresented in functions involving neuronal development, signal transduction and synapse development including the neurexin trans-synaptic complex. We also show how a complex gene network model can be used to fine map combinations of inherited and de novo variations in families with ASD that converge in the L1CAM pathway. Our results provide an important step forward in the molecular characterization of ASD with potential for developing a tool to analyze the pathogenesis of individual affected families.
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3. Baron-Cohen S, Auyeung B, Norgaard-Pedersen B, Hougaard DM, Abdallah MW, Melgaard L, Cohen AS, Chakrabarti B, Ruta L, Lombardo MV. {{Elevated fetal steroidogenic activity in autism}}. {Mol Psychiatry};2014 (Jun 3)
Autism affects males more than females, giving rise to the idea that the influence of steroid hormones on early fetal brain development may be one important early biological risk factor. Utilizing the Danish Historic Birth Cohort and Danish Psychiatric Central Register, we identified all amniotic fluid samples of males born between 1993 and 1999 who later received ICD-10 (International Classification of Diseases, 10th Revision) diagnoses of autism, Asperger syndrome or PDD-NOS (pervasive developmental disorder not otherwise specified) (n=128) compared with matched typically developing controls. Concentration levels of Delta4 sex steroids (progesterone, 17alpha-hydroxy-progesterone, androstenedione and testosterone) and cortisol were measured with liquid chromatography tandem mass spectrometry. All hormones were positively associated with each other and principal component analysis confirmed that one generalized latent steroidogenic factor was driving much of the variation in the data. The autism group showed elevations across all hormones on this latent generalized steroidogenic factor (Cohen’s d=0.37, P=0.0009) and this elevation was uniform across ICD-10 diagnostic label. These results provide the first direct evidence of elevated fetal steroidogenic activity in autism. Such elevations may be important as epigenetic fetal programming mechanisms and may interact with other important pathophysiological factors in autism.Molecular Psychiatry advance online publication, 3 June 2014; doi:10.1038/mp.2014.48.
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4. Duffy FH, Shankardass A, McAnulty GB, Eksioglu YZ, Coulter D, Rotenberg A, Als H. {{Corticosteroid therapy in regressive autism: a retrospective study of effects on the Frequency Modulated Auditory Evoked Response (FMAER), language, and behavior}}. {BMC Neurol};2014;14(1):70.
BACKGROUND: Up to a third of children with Autism Spectrum Disorder (ASD) manifest regressive autism (R-ASD).They show normal early development followed by loss of language and social skills. Absent evidence-based therapies, anecdotal evidence suggests improvement following use of corticosteroids. This study examined the effects of corticosteroids for R-ASD children upon the 4 Hz frequency modulated evoked response (FMAER) arising from language cortex of the superior temporal gyrus (STG) and upon EEG background activity, language, and behavior. An untreated clinical convenience sample of ASD children served as control sample. METHODS: Twenty steroid-treated R-ASD (STAR) and 24 not-treated ASD patients (NSA), aged 3 – 5 years, were retrospectively identified from a large database. All study participants had two sequential FMAER and EEG studies;Landau-Kleffner syndrome diagnosis was excluded. All subjects’ records contained clinical receptive and expressive language ratings based upon a priori developed metrics. The STAR group additionally was scored behaviorally regarding symptom severity as based on the Diagnostic and Statistical Manual IV (DSM-IV) ASD criteria list. EEGs were visually scored for abnormalities. FMAER responses were assessed quantitatively by spectral analysis. Treated and untreated group means and standard deviations for the FMAER, EEG, language, and behavior, were compared by paired t-test and Fisher’s exact tests. RESULTS: The STAR group showed a significant increase in the 4 Hz FMAER spectral response and a significant reduction in response distortion compared to the NSA group. Star group subjects’ language ratings were significantly improved and more STAR than NSA group subjects showed significant language improvement. Most STAR group children showed significant behavioral improvement after treatment. STAR group language and behavior improvement was retained one year after treatment. Groups did not differ in terms of minor EEG abnormalities. Steroid treatment produced no lasting morbidity. CONCLUSIONS: Steroid treatment was associated with a significantly increased FMAER response magnitude, reduction of FMAER response distortion, and improvement in language and behavior scores. This was not observed in the non-treated group. These pilot findings warrant a prospective randomized validation trial of steroid treatment for R-ASD utilizing FMAER, EEG, and standardized ASD, language and behavior measures, and a longer follow-up period.Please see related article http://www.biomedcentral.com/1741-7015/12/79.
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5. Golla S, Sweeney JA. {{Corticosteroid therapy in regressive autism: Preliminary findings from a retrospective study}}. {BMC Med};2014;12(1):79.
Some children with autism spectrum disorders (ASD; 15% to 30% of patients) show a significant and persistent regression in speech and social function during early childhood. There are no established treatments for the regressive symptoms. However, there are some known causes of this type of regression, such as Rett syndrome and Landau-Kleffner syndrome (LKS). In LKS, steroids have been used as a treatment. Some evidence suggests an autoimmune contribution to the pathophysiology of autism (Chez MG, Guido-Estrada N: Immune therapy in autism: historical experience and future directions with immunomodulatory therapy. Neurotherapeutics 2010, 7:293-301, Wasilewska J, Kaczmarski M, Stasiak-Barmuta A, Tobolczyk J, Kowalewska E: Low serum IgA and increased expression of CD23 on B lymphocytes in peripheral blood in children with regressive autism aged 3-6 years old. Arch Med Sci 2012, 8:324-331, Stefanatos G: Changing perspectives on Landau-Kleffner syndrome. Clin Neuropsychol 2011, 25:963-988), raising the possibility that steroids might be a useful therapy for regression in ASD. A retrospective study published in BMC Neurology by Duffy et al. (Duffy, et al: Corticosteroid therapy in regressive autism: A retrospective study of effects on the Frequency Modulated Auditory Evoked Response (FMAER), language, and behavior. BMC Neurol 2014, 14:70) reviewed 20 steroid treated R-ASD (STAR) patients and 24 ASD control patients not treated with steroids (NSA). Improvements in clinical function and in a neurophysiological biomarker were seen in the steroid-treated children pre- to post-prednisolone treatment. This research provides a rationale for a randomized trial with steroid therapy to determine the longer term benefits and complications of steroids in this population.Please see related article http://www.biomedcentral.com/1471-2377/14/70/abstract.
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6. Hervas A, Toma C, Romaris P, Ribases M, Salgado M, Bayes M, Balmana N, Cormand B, Maristany M, Guijarro S, Arranz MJ. {{The involvement of serotonin polymorphisms in autistic spectrum symptomatology}}. {Psychiatr Genet};2014 (Jun 2)
BACKGROUND: Autism spectrum disorders (ASD) are highly inherited developmental syndromes, resulting from a complex interaction between environmental and genetic factors. To date, only a limited number of genetic variants have been discovered with respect to autism, and their contribution to the development of the disorder has not been clearly determined. Investigation of specific autistic symptomatology may improve the chances of identifying related genes and may help to better understand these disorders. MATERIALS AND METHODS: We investigated the contribution of 80 genetic variants in 15 serotonin genes to ASD phenotypes [intelligence quotation (IQ), intellectual disability (ID) and language onset delay (LD)] in a cohort of 141 children and young adults (121 male patients and 20 female patients, average age 14.5+/-5.1 years). RESULTS: Two polymorphisms in the HTR2B gene, rs10194776 and rs16827801, were associated with IQ (P=0.0004 and 0.003, respectively), ID (P=0.02 and 0.03) and LD (P=0.04 and 0.004). Nominal associations were also detected between the ASD phenotypes investigated and 5-HT2A, 5-HT4 and 5-HT6 genetic variants. CONCLUSION: Our study provides evidence of the contribution of serotonergic variants to IQ, ID and LD in ASD patients.
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7. Hiller RM, Young RL, Weber N. {{Sex Differences in Autism Spectrum Disorder based on DSM-5 Criteria: Evidence from Clinician and Teacher Reporting}}. {J Abnorm Child Psychol};2014 (Jun 3)
In the absence of intellectual impairment autism spectrum disorder (ASD) is diagnosed both less and later in females. This study used clinician and teacher report to explore sex differences in the behavioural presentation of 69 girls and 69 boys all diagnosed with high-functioning ASD. Evidence from DSM-IV-TR and DSM-5 are presented. Sex differences in teacher concerns were also explored. While no sex differences were found in the broad social criteria presented in the DSM-IV-TR or DSM-5, numerous differences were evident in how boys and girls came to meet each criterion. For example, girls were more likely to show an ability to integrate non-verbal and verbal behaviours, maintain a reciprocal conversation, and be able to initiate, but not maintain friendships. Moreover, girls presented with both less and different restricted interests. Teachers also reported substantially fewer concerns for girls than boys, including for externalising behaviours and social skills. Results suggest girls with ASD may present with a surface-level ‘look’ different from the ‘classic’ presentation of ASD, and present as less impaired when in a school setting. Consequently, results provide insight in to why the disorder may be more difficult to detect in cognitively-able girls.
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8. Hollocks MJ, Howlin P, Papadopoulos AS, Khondoker M, Simonoff E. {{Differences in HPA-axis and heart rate responsiveness to psychosocial stress in children with autism spectrum disorders with and without co-morbid anxiety}}. {Psychoneuroendocrinology};2014 (Aug);46:32-45.
Children and adolescents with autism spectrum disorder (ASD) have much higher rates of anxiety disorders relative to their typically developing peers. However, there have been few attempts to investigate what physiological parameters may be associated with this elevated rate of anxiety. Therefore, this study investigated the physiological correlates of anxiety in ASD, with a focus on whether measures of heart rate and cortisol responsiveness to psychosocial stress differentiate those participants with ASD with and without a co-occurring anxiety disorder. A total of 75 male participants aged 10-16 years with normal intellectual ability underwent a psychosocial stress test. The participants included healthy controls (n=23), ASD only (ASD; n=20) and ASD with a comorbid anxiety disorder (ASDanx; n=32). Heart rate, heart rate variability and salivary cortisol were compared by fitting a piecewise regression model to examine baseline levels and change over time within and between the rest, stress and recovery phases of the stress test. The ASDanx group had different response patterns from both the ASD and control groups. The ASDanx group was characterized by a blunted cortisol and heart rate response to psychosocial stress. Furthermore, in the ASDanx group, reduced heart rate and cortisol responsiveness were significantly related to increased anxiety symptoms. This is the first study to report a possible physiological basis for co-occurring anxiety disorders in children and adolescents with ASD. It is possible that a non-adaptive physiological response to psychosocial stress may be related to the high prevalence of co-occurring anxiety disorders in people with ASD.
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9. Hubbard KL, Bandini LG, Folta SC, Wansink B, Must A. {{The Adaptation of a School-based Health Promotion Programme for Youth with Intellectual and Developmental Disabilities: A Community-Engaged Research Process}}. {J Appl Res Intellect Disabil};2014 (Jun 3)
BACKGROUND: Evidenced-based health promotion programmes for youth with intellectual and developmental disabilities (I/DD) are notably absent. Barriers include a lack of understanding of how to adapt existing evidence-based programmes to their needs, maximize inclusion and support mutual goals of health and autonomy. METHODS: We undertook a community-engaged process to adapt a school-based nutrition intervention in a residential school for youth with I/DD. Focus groups and interviews with school staff elicited recommendations for adaptation strategies; these were then reviewed by an expert panel. RESULTS: Adaptations were developed to address needs in three categories: food-related challenges among students, adjusting to change and transition and social environment factors. Choice and heterogeneity were overarching themes across the adaptation categories. CONCLUSIONS: Future research should consider community-engaged approaches for adaptation so that youth with I/DD can participate and benefit from evidence-based health promotion programmes to their maximum potential.
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10. Janusonis S. {{Serotonin dynamics in and around the central nervous system: Is autism solvable without fundamental insights?}}. {Int J Dev Neurosci};2014 (May 30)
Altered serotonin (5-hydroxytryptamine, 5-HT) signaling has been implicated in some developmental abnormalities of autism spectrum disorder (ASD). However, the presumed role of 5-HT in ASD raises new questions in fundamental neuroscience. Specifically, it is not clear if the current piecemeal approach to 5-HT signaling in the mammalian body is effective and whether new conceptual approaches may be required. This review briefly discusses 5-HT production and circulation in the central nervous system and outside of it, especially with regard to ASD, and proposes a more encompassing approach that questions the utility of the « neurotransmitter » concept. It then introduces the idea of a generalized 5-HT packet that may offer insights into possible links between serotonergic varicosities and blood platelets. These approaches have theoretical significance, but they are also well positioned to advance our understanding of some long-standing problems in autism research.
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11. McKenney EL, Bristol RM. {{Supporting Intensive Interventions for Students With Autism Spectrum Disorder: Performance Feedback and Discrete Trial Teaching}}. {Sch Psychol Q};2014 (Jun 2)
This study evaluated the impact of performance feedback on nine public educators’ level of procedural integrity to Discrete Trial Teaching (DTT) procedures for students with Autism Spectrum Disorder (ASD). Procedural integrity was observed during four phases: no feedback, general feedback, performance feedback, and maintenance, in a multiple baseline across participants design. Results indicate that for most educators, performance feedback is necessary to improve and maintain integrity at or above 80%. Most participants’ performance during no feedback and general feedback was characterized by high rates of variability. One participant required in vivo feedback to achieve and maintain acceptable levels of integrity. Procedural modifications necessary to adapt this procedure to the applied environment of school are discussed. Findings suggest that highly structured evidence-based interventions for students with ASD require consultation support to be implemented with integrity in schools, and the duration and intensity of support needed may be higher than for other interventions. These promising findings emphasize the important role of school psychologists and other support personnel in ensuring that services are delivered as intended. (PsycINFO Database Record (c) 2014 APA, all rights reserved).
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12. Murphy SK. {{Obesity: Paternal obesity-a risk factor for autism?}}. {Nat Rev Endocrinol};2014 (Jun 3)
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13. Nadal-Desbarats L, Aidoud N, Emond P, Blasco H, Filipiak I, Sarda P, Bonnet-Brilhault F, Mavel S, Andres CR. {{Combined (1)H-NMR and (1)H-(13)C HSQC-NMR to improve urinary screening in autism spectrum disorders}}. {Analyst};2014 (Jun 3);139(13):3460-3468.
Autism spectrum disorders (ASD) are neurodevelopmental diseases with complex genetic and environmental etiological factors. Although genetic causes play a significant part in the etiology of ASD, metabolic disturbances may also play a causal role or modulate the clinical features of ASD. The number of ASD studies involving metabolomics is increasing, and sometime with conflicting findings. We assessed the metabolomics profiling of urine samples to determine a comprehensive biochemical signature of ASD. Furthermore, to date no study has combined metabolic profiles obtained from different analytical techniques to distinguish patient with ASD from healthy individuals. We obtained (1)H-NMR spectra and 2D (1)H-(13)C HSQC NMR spectra from urine samples of patients with ASD or healthy controls. We analyzed these spectra by multivariate statistical data analysis. The OPLS-DA model obtained from (1)H NMR spectra showed a good discrimination between ASD samples and non-ASD samples (R(2)Y(cum) = 0.70 and Q(2) = 0.51). Combining the (1)H NMR spectra and the 2D (1)H-(13)C HSQC NMR spectra increased the overall quality and predictive value of the OPLS-DA model (R(2)Y(cum) = 0.84 and Q(2) = 0.71), leading to a better sensitivity and specificity. Urinary excretion of succinate, glutamate and 3-methyl-histidine differed significantly between ASD and non-ASD samples. Urinary screening of children with neurodevelopmental disorders by combining NMR spectroscopies (1D and 2D) in multivariate analysis is a better sensitive and a straightforward method that could help the diagnosis ASD.
