1. Allely CS, Gillberg C, Wilson P. {{Neurobiological abnormalities in the first few years of life in individuals later diagnosed with Autistic Spectrum Disorder: A review of recent data}}. {Behav Neurol}. 2013.
BACKGROUND: Despite the widely-held understanding that the biological changes that lead to autism usually occur during prenatal life, there has been relatively little research into the functional development of the brain during early infancy in individuals later diagnosed with autism spectrum disorder (ASD). OBJECTIVE: This review explores the studies over the last three years which have investigated differences in various brain regions in individuals with ASD or who later go on to receive a diagnosis of ASD. METHODS: We used PRISMA guidelines and selected published articles reporting any neurological abnormalities in very early childhood in individuals with or later diagnosed with ASD. RESULTS: Various brain regions are discussed including; the amygdala; cerebellum; frontal cortex and lateralised abnormalities of the temporal cortex during language processing. This review discusses studies investigating head circumference, electrophysiological markers and inter-hemispheric synchronisation. All the recent findings from the beginning of 2009 across these different aspects of defining neurological abnormalities are discussed in light of earlier findings. CONCLUSIONS: The studies across these different areas reveal the existence of atypicalities in the first year of life, well before ASD is reliably diagnosed. Cross-disciplinary approaches are essential to elucidate the pathophysiological sequence of events that lead to ASD.
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2. Brimberg L, Sadiq A, Gregersen PK, Diamond B. {{Brain-reactive IgG correlates with autoimmunity in mothers of a child with an autism spectrum disorder}}. {Mol Psychiatry}. 2013.
It is believed that in utero environmental factors contribute to autism spectrum disorder (ASD). The goal of this study was to demonstrate, using the largest cohort reported so far, that mothers of an ASD child have an elevated frequency of anti-brain antibodies and to assess whether brain reactivity is associated with an autoimmune diathesis of the mother. We screened plasma of 2431 mothers of an ASD child from Simon Simplex Collection and plasma of 653 unselected women of child-bearing age for anti-brain antibodies using immunohistology on mouse brain. Positive and negative plasma from mothers with an ASD child were analyzed for anti-nuclear antibodies and for autoimmune disorders. Mothers of an ASD child were four times more likely to harbor anti-brain antibodies than unselected women of child-bearing age (10.5 vs 2.6%). A second cohort from The Autism Genetic Resource Exchange with multiplex families displayed an 8.8% prevalence of anti-brain antibodies in the mothers of these families. Fifty-three percent of these mothers with anti-brain antibodies also exhibited anti-nuclear autoantibodies compared with 13.4% of mothers of an ASD child without anti-brain antibodies and 15% of control women of child-bearing age. The analysis of ASD mothers with brain-reactive antibodies also revealed an increased prevalence of autoimmune diseases, especially rheumatoid arthritis and systemic lupus erythematosus. This study provides robust evidence that brain-reactive antibodies are increased in mothers of an ASD child and may be associated with autoimmunity. The current study serves as a benchmark and justification for studying the potential pathogenicity of these antibodies on the developing brain. The detailed characterization of the specificity of these antibodies will provide practical benefits for the management and prevention of this disorder.Molecular Psychiatry advance online publication, 20 August 2013; doi:10.1038/mp.2013.101.
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3. Hoffman K, Vieira VM, Daniels JL. {{Brief Report: Diminishing Geographic Variability in Autism Spectrum Disorders Over Time?}}. {J Autism Dev Disord}. 2013.
We investigated differences in the geographic distribution of autism spectrum disorders (ASD) over time in central North Carolina with data from the Autism and Developmental Disabilities Monitoring Network. Using generalized additive models and geographic information systems we produced maps of ASD risk in 2002-2004 and 2006-2008. Overall the risk of ASD increased 52.9 % from 2002-2004 to 2006-2008. However, the magnitude of change in risk was not uniform across the study area; while some areas experienced dramatic increases in ASD risk (>400 %), others experienced slight decreases. Generally, areas with the lowest risk in 2002-2004 experienced the greatest increases over time. Education and outreach efforts in North Carolina expanded during this period, possibly contributing to the observed leveling of risk over time.
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4. Kern JK, Haley BE, Geier DA, Sykes LK, King PG, Geier MR. {{Thimerosal exposure and the role of sulfation chemistry and thiol availability in autism}}. {Int J Environ Res Public Health}. 2013; 10(8): 3771-800.
Autism spectrum disorder (ASD) is a neurological disorder in which a significant number of the children experience a developmental regression characterized by a loss of previously acquired skills and abilities. Typically reported are losses of verbal, nonverbal, and social abilities. Several recent studies suggest that children diagnosed with an ASD have abnormal sulfation chemistry, limited thiol availability, and decreased glutathione (GSH) reserve capacity, resulting in a compromised oxidation/reduction (redox) and detoxification capacity. Research indicates that the availability of thiols, particularly GSH, can influence the effects of thimerosal (TM) and other mercury (Hg) compounds. TM is an organomercurial compound (49.55% Hg by weight) that has been, and continues to be, used as a preservative in many childhood vaccines, particularly in developing countries. Thiol-modulating mechanisms affecting the cytotoxicity of TM have been identified. Importantly, the emergence of ASD symptoms post-6 months of age temporally follows the administration of many childhood vaccines. The purpose of the present critical review is provide mechanistic insight regarding how limited thiol availability, abnormal sulfation chemistry, and decreased GSH reserve capacity in children with an ASD could make them more susceptible to the toxic effects of TM routinely administered as part of mandated childhood immunization schedules.
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5. Kitazoe N, Inoue S, Izumoto Y, Kumagai N, Iwasaki Y. {{The Autism-Spectrum Quotient in university students: Pattern of changes in its scores and associated factors}}. {Asia Pac Psychiatry}. 2013.
INTRODUCTION: Support to university students with autism spectrum disorders (ASD) is becoming increasingly important. To determine the validity of the Autism-Spectrum Quotient (AQ) for ASD screening of university students, we conducted longitudinal measurements of the AQ in a large sample of university students and investigated the possibility of changes in the AQ and associated factors. METHODS: The AQ, University Personality Inventory (UPI), and the willingness of the students to be interviewed were determined at admission in students from four departments of Kochi University; the AQ was determined again in the second year. Changes in the AQ and associated factors were analyzed statistically. RESULTS: The number of valid responses in the initial survey was 3427 (87.2%). The AQ was significantly higher in the group with high UPI scores (F = 156.08, P < 0.001). Of the 486 students interviewed at admission, 22 had suspected ASD. The sensitivity/specificity of the AQ for ASD was 81.8%/92.0%. A total of 319 (11.0%) students responded to the second-year survey, which revealed significant decrease of the AQ in the group with high AQ values at admission. DISCUSSION: The AQ measured at admission was correlated with the UPI score, regardless of the sex or department; in the second survey, the scores decreased significantly in those with high AQ values at admission, suggesting that an unstable mental state can produce a temporary increase of the AQ scores.
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6. Nakai Y, Takashima R, Takiguchi T, Takada S. {{Speech intonation in children with autism spectrum disorder}}. {Brain Dev}. 2013.
Objective: The prosody of children with autism spectrum disorder (ASD) has several abnormal features. We assessed the speech tone of children with ASD and of children with typical development (TD) by using a new quantitative acoustic analysis. Methods: Our study participants consisted of 63 children (26 with ASD and 37 with TD). The participants were divided into 4 groups based on their developmental features and age. We assessed the variety of the fundamental frequency (F0) pattern quantitatively, using pitch coefficient of variation (CV), considering the different F0 mean for each word. Results: (1) No significant difference was observed between the ASD and TD group at pre-school age. However, the TD group exhibited significantly greater pitch CV than the ASD group at school age. (2) In pitch CV, range and standard deviation of the whole speech of each participant, no significant differences were observed between the type of participants and age. (3) No significant correlation was found between the pitch CV of each word and the Japanese Autism Screening Questionnaire total score, or between the pitch CV of each word and the intelligence quotient levels in the ASD group. A significant correlation was observed between the pitch CV of each word and social reciprocal interaction score. Conclusions: We assessed the speech tone of children with ASD by using a new quantitative method. Monotonous speech in school-aged children with ASD was detected. The extent of monotonous speech was related to the extent of social reciprocal interaction in children with ASD.
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7. Poslawsky IE, Naber FB, Van Daalen E, Van Engeland H. {{Parental Reaction to Early Diagnosis of Their Children’s Autism Spectrum Disorder: An Exploratory Study}}. {Child Psychiatry Hum Dev}. 2013.
This study explores parental reactions subsequent to receiving their child’s autism spectrum disorder (ASD)-diagnosis. Seventy seven parents of recently diagnosed children participated in the Reaction to Diagnosis Interview. Within this group, associations between parental reaction to diagnosis, parental and child characteristics and prediagnostic circumstances were analysed. In a sub-sample, the stability of reaction to diagnosis was examined. The majority of parents were classified as ‘resolved’ regarding their child’s diagnosis. Conversely, parents of children with more severe ASD symptoms or non-Dutch parents were more likely to be classified as ‘unresolved’. Sub-sample analysis revealed stability of reaction to ASD-diagnosis. The majority of parents adapted well to the circumstances and the care for their child. Autism severity and parental nationality were significant factors affecting parental reactions. Thus, early identification of parental reaction to children’s ASD-diagnosis may aid in providing more tailored parental support programs.
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8. Visser E, Zwiers MP, Kan CC, Hoekstra L, van Opstal AJ, Buitelaar JK. {{Atypical vertical sound localization and sound-onset sensitivity in people with autism spectrum disorders}}. {J Psychiatry Neurosci}. 2013; 38(5): 120177.
BACKGROUND: Autism spectrum disorders (ASDs) are associated with auditory hyper- or hyposensitivity; atypicalities in central auditory processes, such as speech-processing and selective auditory attention; and neural connectivity deficits. We sought to investigate whether the low-level integrative processes underlying sound localization and spatial discrimination are affected in ASDs. METHODS: We performed 3 behavioural experiments to probe different connecting neural pathways: 1) horizontal and vertical localization of auditory stimuli in a noisy background, 2) vertical localization of repetitive frequency sweeps and 3) discrimination of horizontally separated sound stimuli with a short onset difference (precedence effect). RESULTS: Ten adult participants with ASDs and 10 healthy control listeners participated in experiments 1 and 3; sample sizes for experiment 2 were 18 adults with ASDs and 19 controls. Horizontal localization was unaffected, but vertical localization performance was significantly worse in participants with ASDs. The temporal window for the precedence effect was shorter in participants with ASDs than in controls. LIMITATIONS: The study was performed with adult participants and hence does not provide insight into the developmental aspects of auditory processing in individuals with ASDs. CONCLUSION: Changes in low-level auditory processing could underlie degraded performance in vertical localization, which would be in agreement with recently reported changes in the neuroanatomy of the auditory brainstem in individuals with ASDs. The results are further discussed in the context of theories about abnormal brain connectivity in individuals with ASDs.
9. Williams K, Brignell A, Randall M, Silove N, Hazell P. {{Selective serotonin reuptake inhibitors (SSRIs) for autism spectrum disorders (ASD)}}. {Cochrane Database Syst Rev}. 2013; 8: CD004677.
BACKGROUND: Autism spectrum disorders (ASD) are characterised by abnormalities in social interaction and communication skills, as well as stereotypic behaviours and restricted activities and interests. Selective serotonin reuptake inhibitors (SSRIs) are prescribed for the treatment of conditions often comorbid with ASD such as depression, anxiety and obsessive-compulsive behaviours. OBJECTIVES: To determine if treatment with an SSRI:1. improves the core features of autism (social interaction, communication and behavioural problems);2. improves other non-core aspects of behaviour or function such as self-injurious behaviour;3. improves the quality of life of adults or children and their carers;4. has short- and long-term effects on outcome;5. causes harm. SEARCH METHODS: We searched the following databases up until March 2013: CENTRAL, Ovid MEDLINE, Embase, CINAHL, PsycINFO, ERIC and Sociological Abstracts. We also searched ClinicalTrials.gov and the International Clinical Trials Registry Platform (ICTRP). This was supplemented by searching reference lists and contacting known experts in the field. SELECTION CRITERIA: Randomised controlled trials (RCTs) of any dose of oral SSRI compared with placebo, in people with ASD. DATA COLLECTION AND ANALYSIS: Two authors independently selected studies for inclusion, extracted data and appraised each study’s risk of bias. MAIN RESULTS: Nine RCTs with a total of 320 participants were included. Four SSRIs were evaluated: fluoxetine (three studies), fluvoxamine (two studies), fenfluramine (two studies) and citalopram (two studies). Five studies included only children and four studies included only adults. Varying inclusion criteria were used with regard to diagnostic criteria and intelligence quotient of participants. Eighteen different outcome measures were reported. Although more than one study reported data for Clinical Global Impression (CGI) and obsessive-compulsive behaviour (OCB), different tool types or components of these outcomes were used in each study. As such, data were unsuitable for meta-analysis, except for one outcome (proportion improvement). One large, high-quality study in children showed no evidence of positive effect of citalopram. Three small studies in adults showed positive outcomes for CGI and OCB; one study showed improvements in aggression, and another in anxiety. AUTHORS’ CONCLUSIONS: There is no evidence of effect of SSRIs in children and emerging evidence of harm. There is limited evidence of the effectiveness of SSRIs in adults from small studies in which risk of bias is unclear.
