1. Bailey DB, Jr., Raspa M, Bishop E, Olmsted M, Mallya UG, Berry-Kravis E. {{Medication Utilization for Targeted Symptoms in Children and Adults With Fragile X Syndrome: US Survey}}. {J Dev Behav Pediatr};2011 (Nov 4)
OBJECTIVE:: To identify the most common neurological and behavioral symptoms treated by medications in individuals with fragile X syndrome (FXS), factors associated with treatment variability, and difficulty in swallowing a pill. METHOD:: A total of 1019 caregivers provided information about 1064 sons and 299 daughters with FXS in a US national survey. Caregivers reported (a) current use of medications for attention, anxiety, hyperactivity, mood swings, anger, depression, seizures, self-injury, or sleep; (b) perceived efficacy; and (c) difficulty in swallowing a pill. RESULTS:: Sixty-one percent of males and 38% of females were currently taking medication for at least 1 symptom. The most common symptoms were anxiety, attention, and hyperactivity. Treatments for attention and hyperactivity were common in childhood but declined substantially after the age of 18 years; anxiety treatment remained high in adults. Children perceived to be more impaired and children diagnosed or treated for autism were more likely to be taking medications. Caregivers considered most medications somewhat effective, but less than one-third rated current medication as « a lot » effective. Many children had difficulty swallowing a pill, but only 11% of adult males and 2% of adult females had a lot of difficulty. CONCLUSION:: Symptom-based medication use is common in FXS, although response is incomplete and there is clearly an unmet need for medications with improved efficacy. The persistent use of medications to treat anxiety, mood, and behavior problems throughout adolescence and into the adult years suggests important outcomes when evaluating the efficacy of new medications.
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2. Courchesne E, Mouton PR, Calhoun ME, Semendeferi K, Ahrens-Barbeau C, Hallet MJ, Barnes CC, Pierce K. {{Neuron number and size in prefrontal cortex of children with autism}}. {JAMA};2011 (Nov 9);306(18):2001-2010.
CONTEXT: Autism often involves early brain overgrowth, including the prefrontal cortex (PFC). Although prefrontal abnormality has been theorized to underlie some autistic symptoms, the cellular defects that cause abnormal overgrowth remain unknown. OBJECTIVE: To investigate whether early brain overgrowth in children with autism involves excess neuron numbers in the PFC. DESIGN, SETTING, AND CASES: Postmortem prefrontal tissue from 7 autistic and 6 control male children aged 2 to 16 years was examined by expert anatomists who were blinded to diagnostic status. Number and size of neurons were quantified using stereological methods within the dorsolateral (DL-PFC) and mesial (M-PFC) subdivisions of the PFC. Cases were from the eastern and southeastern United States and died between 2000 and 2006. MAIN OUTCOME MEASURES: Mean neuron number and size in the DL-PFC and M-PFC were compared between autistic and control postmortem cases. Correlations of neuron number with deviation in brain weight from normative values for age were also performed. RESULTS: Children with autism had 67% more neurons in the PFC (mean, 1.94 billion; 95% CI, 1.57-2.31) compared with control children (1.16 billion; 95% CI, 0.90-1.42; P = .002), including 79% more in DL-PFC (1.57 billion; 95% CI, 1.20-1.94 in autism cases vs 0.88 billion; 95% CI, 0.66-1.10 in controls; P = .003) and 29% more in M-PFC (0.36 billion; 95% CI, 0.33-0.40 in autism cases vs 0.28 billion; 95% CI, 0.23-0.34 in controls; P = .009). Brain weight in the autistic cases differed from normative mean weight for age by a mean of 17.6% (95% CI, 10.2%-25.0%; P = .001), while brains in controls differed by a mean of 0.2% (95% CI, -8.7% to 9.1%; P = .96). Plots of counts by weight showed autistic children had both greater total prefrontal neuron counts and brain weight for age than control children. CONCLUSION: In this small preliminary study, brain overgrowth in males with autism involved an abnormal excess number of neurons in the PFC.
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3. Jaarsma P, Gelhaus P, Welin S. {{Living the categorical imperative: autistic perspectives on lying and truth telling-between Kant and care ethics}}. {Med Health Care Philos};2011 (Nov 8)
Lying is a common phenomenon amongst human beings. It seems to play a role in making social interactions run more smoothly. Too much honesty can be regarded as impolite or downright rude. Remarkably, lying is not a common phenomenon amongst normally intelligent human beings who are on the autism spectrum. They appear to be ‘attractively morally innocent’ and seem to have an above average moral conscientious objection against deception. In this paper, the behavior of persons with autism with regard to deception and truthfulness will be discussed in the light of two different ethical theories, illustrated by fragments from autobiographies of persons with autism. A systemizing ‘Kantian’ and an empathizing ‘ethics of care’ perspective reveal insights on high-functioning autism, truthfulness and moral behavior. Both perspectives are problematic from the point of view of a moral agent with autism. High-functioning persons with autism are, generally speaking, strong systemizes and weak empathizers. Particularly, they lack ‘cognitive empathy’ which would allow them to understand the position of the other person. Instead, some tend to invent a set of rules that makes their behavior compatible with the expectations of others. From a Kantian point of view, the autistic tendency to always tell the truth appears praiseworthy and should not be changed, though it creates problems in the social life of persons with autism. From a care ethics perspective, on the other hand, a way should be found to allow the high-functioning persons with autism to respect the feelings and needs of other persons as sometimes overruling the duty of truthfulness. We suggest this may even entail ‘morally educating’ children and adolescents with autism to become socially skilled empathic ‘liars’.
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4. James S, Montgomery P, Williams K. {{Omega-3 fatty acids supplementation for autism spectrum disorders (ASD)}}. {Cochrane Database Syst Rev};2011;11:CD007992.
BACKGROUND: It has been suggested that impairments associated with autism spectrum disorders (ASD) may be partially explained by deficits of omega-3 fatty acids, and that supplementation of these essential fatty acids may lead to improvement of symptoms. OBJECTIVES: To review the efficacy of omega-3 fatty acids for improving core features of ASD (for example, social interaction, communication, and stereotypies) and associated symptoms. SEARCH STRATEGY: We searched the following databases on 2 June 2010: CENTRAL (2010, Issue 2), MEDLINE (1950 to May Week 3 2010), EMBASE (1980 to 2010 Week 21), PsycINFO (1806 to current), BIOSIS (1985 to current), CINAHL (1982 to current), Science Citation Index (1970 to current), Social Science Citation Index (1970 to current), metaRegister of Controlled Trials (20 November 2008) and ClinicalTrials.gov (10 December 2010). Dissertation Abstracts International was searched on 10 December 2008, but was no longer available to the authors or editorial base in 2010. SELECTION CRITERIA: All randomised controlled trials of omega-3 fatty acids supplementation compared to placebo in individuals with ASD. DATA COLLECTION AND ANALYSIS: Three authors independently selected studies, assessed them for risk of bias and extracted relevant data. We conducted meta-analysis of the included studies for three primary outcomes (social interaction, communication, and stereotypy) and one secondary outcome (hyperactivity). MAIN RESULTS: We included two trials with a total of 37 children diagnosed with ASD who were randomised into groups that received either omega-3 fatty acids supplementation or a placebo. We excluded six trials because they were either non-randomised controlled trials, did not contain a control group, or the control group did not receive a placebo. Overall, there was no evidence that omega-3 supplements had an effect on social interaction (mean difference (MD) 0.82, 95% confidence interval (CI) -2.84 to 4.48, I(2) = 0%), communication (MD 0.62, 95% CI -0.89 to 2.14, I(2) = 0%), stereotypy (MD 0.77, 95% CI -0.69 to 2.22, I(2) = 8%), or hyperactivity (MD 3.46, 95% CI -0.79 to 7.70, I(2) = 0%). AUTHORS’ CONCLUSIONS: To date there is no high quality evidence that omega-3 fatty acids supplementation is effective for improving core and associated symptoms of ASD. Given the paucity of rigorous studies in this area, there is a need for large well-conducted randomised controlled trials that examine both high and low functioning individuals with ASD, and that have longer follow-up periods.
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5. Lainhart JE, Lange N. {{Increased neuron number and head size in autism}}. {JAMA};2011 (Nov 9);306(18):2031-2032.
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6. Lord C, Petkova E, Hus V, Gan W, Lu F, Martin DM, Ousley O, Guy L, Bernier R, Gerdts J, Algermissen M, Whitaker A, Sutcliffe JS, Warren Z, Klin A, Saulnier C, Hanson E, Hundley R, Piggot J, Fombonne E, Steiman M, Miles J, Kanne SM, Goin-Kochel RP, Peters SU, Cook EH, Guter S, Tjernagel J, Green-Snyder LA, Bishop S, Esler A, Gotham K, Luyster R, Miller F, Olson J, Richler J, Risi S. {{A Multisite Study of the Clinical Diagnosis of Different Autism Spectrum Disorders}}. {Arch Gen Psychiatry};2011 (Nov 7)
CONTEXT: Best-estimate clinical diagnoses of specific autism spectrum disorders (autistic disorder, pervasive developmental disorder-not otherwise specified, and Asperger syndrome) have been used as the diagnostic gold standard, even when information from standardized instruments is available. OBJECTIVE: To determine whether the relationships between behavioral phenotypes and clinical diagnoses of different autism spectrum disorders vary across 12 university-based sites. DESIGN: Multisite observational study collecting clinical phenotype data (diagnostic, developmental, and demographic) for genetic research. Classification trees were used to identify characteristics that predicted diagnosis across and within sites. SETTING: Participants were recruited through 12 university-based autism service providers into a genetic study of autism. PARTICIPANTS: A total of 2102 probands (1814 male probands) between 4 and 18 years of age (mean [SD] age, 8.93 [3.5] years) who met autism spectrum criteria on the Autism Diagnostic Interview-Revised and the Autism Diagnostic Observation Schedule and who had a clinical diagnosis of an autism spectrum disorder. Main Outcome Measure Best-estimate clinical diagnoses predicted by standardized scores from diagnostic, cognitive, and behavioral measures. RESULTS: Although distributions of scores on standardized measures were similar across sites, significant site differences emerged in best-estimate clinical diagnoses of specific autism spectrum disorders. Relationships between clinical diagnoses and standardized scores, particularly verbal IQ, language level, and core diagnostic features, varied across sites in weighting of information and cutoffs. CONCLUSIONS: Clinical distinctions among categorical diagnostic subtypes of autism spectrum disorders were not reliable even across sites with well-documented fidelity using standardized diagnostic instruments. Results support the move from existing subgroupings of autism spectrum disorders to dimensional descriptions of core features of social affect and fixated, repetitive behaviors, together with characteristics such as language level and cognitive function.
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7. Nummenmaa L, Engell AD, von dem Hagen E, Henson RN, Calder AJ. {{Autism spectrum traits predict the neural response to eye gaze in typical individuals}}. {Neuroimage};2011 (Oct 28)
Autism Spectrum Disorders (ASD) are neurodevelopmental disorders characterised by impaired social interaction and communication, restricted interests and repetitive behaviours. The severity of these characteristics are posited to lie on a continuum extending into the typical population, and typical adults’ performance on behavioural tasks that are impaired in ASD is correlated with the extent to which they display autistic traits (as measured by Autism Spectrum Quotient, AQ). Individuals with ASD also show structural and functional differences in brain regions involved in social perception. Here we show that variation in AQ in typically developing individuals is associated with altered brain activity in the neural circuit for social attention perception while viewing others’ eye gaze. In an fMRI experiment, participants viewed faces looking at variable or constant directions. In control conditions, only the eye region was presented or the heads were shown with eyes closed but oriented at variable or constant directions. The response to faces with variable vs. constant eye gaze direction was associated with AQ scores in a number of regions (posterior superior temporal sulcus, intraparietal sulcus, temporoparietal junction, amygdala, and MT/V5) of the brain network for social attention perception. No such effect was observed for heads with eyes closed or when only the eyes were presented. The results demonstrate a relationship between neurophysiology and autism spectrum traits in the typical (non-ASD) population and suggest that changes in the functioning of the neural circuit for social attention perception is associated with an extended autism spectrum in the typical population.
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8. Pertusa A, Bejerot S, Eriksson J, Fernandez de la Cruz L, Bonde S, Russell A, Mataix-Cols D. {{Do patients with hoarding disorder have autistic traits?}}. {Depress Anxiety};2011 (Nov 7)
Background: Hoarding symptoms have been described in individuals with autism spectrum disorders (ASD). Furthermore, individuals with hoarding disorder (HD) may display some ASD-like features. In order to further refine the diagnostic boundaries of HD, we examined the presence of autistic traits and theory of mind deficits in individuals with HD and of hoarding behavior in patients with ASD. Methods: Two hundred and twenty-one participants in five groups (HD, ASD, obsessive-compulsive disorder (OCD), anxiety disorders (AD), and healthy controls (HC)) were administered measures of autistic traits (Autism-Spectrum Quotient), theory of mind (eyes test-revised), and hoarding severity (saving inventory-revised; SI-R (add acronym)). Results: Hoarders displayed more autistic traits compared to healthy individuals but not to psychiatric controls. Participants with ASD had significantly higher scores on the SI-R than both psychiatric (OCD or AD) and HC groups, indicating more severe hoarding behavior, but had lower scores than participants with HD. The presence of autistic traits in individuals with HD was related to the presence of comorbid OCD, but the presence of hoarding symptoms in individuals with ASD was unrelated to comorbid OCD. Conclusions: We conclude that individuals with HD do not display more autistic traits than psychiatric controls, thus supporting its status as an independent diagnostic entity. More research is needed to further understand the phenomenology and clinical relevance of hoarding symptoms in ASD. Depression and Anxiety 0:1-9, 2011. (c) 2011 Wiley Periodicals, Inc.
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9. Robinson EB, Koenen KC, McCormick MC, Munir K, Hallett V, Happe F, Plomin R, Ronald A. {{Evidence that autistic traits show the same etiology in the general population and at the quantitative extremes (5%, 2.5%, and 1%)}}. {Arch Gen Psychiatry};2011 (Nov);68(11):1113-1121.
CONTEXT: Genetic factors play an important role in the etiology of both autism spectrum disorders and autistic traits. However, little is known about the etiologic consistency of autistic traits across levels of severity. OBJECTIVE: To compare the etiology of typical variation in autistic traits with extreme scoring groups (including top 1%) that mimicked the prevalence of diagnosed autism spectrum disorders in the largest twin study of autistic traits to date. DESIGN: Twin study using phenotypic analysis and genetic model-fitting in the total sample and extreme scoring groups (top 5%, 2.5%, and 1%). SETTING: A nationally representative twin sample from the general population of England. PARTICIPANTS: The families of 5968 pairs aged 12 years old in the Twins’ Early Development Study. Main Outcome Measure Autistic traits as assessed by the Childhood Autism Spectrum Test. RESULTS: Moderate to high heritability was found for autistic traits in the general population (53% for females and 72% for males). High heritability was found in extreme-scoring groups. There were no differences in heritability among extreme groups or between the extreme groups and the general population. A continuous liability shift toward autistic trait affectedness was seen in the cotwins of individuals scoring in the top 1%, suggesting shared etiology between extreme scores and normal variation. CONCLUSION: This evidence of similar etiology across normal variation and the extremes has implications for molecular genetic models of autism spectrum disorders and for conceptualizing autism spectrum disorders as the quantitative extreme of a neurodevelopmental continuum.
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10. Saalasti S, Katsyri J, Tiippana K, Laine-Hernandez M, von Wendt L, Sams M. {{Audiovisual Speech Perception and Eye Gaze Behavior of Adults with Asperger Syndrome}}. {J Autism Dev Disord};2011 (Nov 9)
Audiovisual speech perception was studied in adults with Asperger syndrome (AS), by utilizing the McGurk effect, in which conflicting visual articulation alters the perception of heard speech. The AS group perceived the audiovisual stimuli differently from age, sex and IQ matched controls. When a voice saying /p/ was presented with a face articulating /k/, the controls predominantly heard /k/. Instead, the AS group heard /k/ and /t/ with almost equal frequency, but with large differences between individuals. There were no differences in gaze direction or unisensory perception between the AS and control participants that could have contributed to the audiovisual differences. We suggest an explanation in terms of weak support from the motor system for audiovisual speech perception in AS.
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11. Shulha HP, Cheung I, Whittle C, Wang J, Virgil D, Lin CL, Guo Y, Lessard A, Akbarian S, Weng Z. {{Epigenetic Signatures of Autism: Trimethylated H3K4 Landscapes in Prefrontal Neurons}}. {Arch Gen Psychiatry};2011 (Nov 7)
CONTEXT: Neuronal dysfunction in cerebral cortex and other brain regions could contribute to the cognitive and behavioral defects in autism. OBJECTIVE: To characterize epigenetic signatures of autism in prefrontal cortex neurons. DESIGN: We performed fluorescence-activated sorting and separation of neuronal and nonneuronal nuclei from postmortem prefrontal cortex, digested the chromatin with micrococcal nuclease, and deeply sequenced the DNA from the mononucleosomes with trimethylated H3K4 (H3K4me3), a histone mark associated with transcriptional regulation. Approximately 15 billion base pairs of H3K4me3-enriched sequences were collected from 32 brains. SETTING: Academic medical center. PARTICIPANTS: A total of 16 subjects diagnosed as having autism and 16 control subjects ranging in age from 0.5 to 70 years. MAIN OUTCOME MEASURES: Identification of genomic loci showing autism-associated H3K4me3 changes in prefrontal cortex neurons. RESULTS: Subjects with autism showed no evidence for generalized disruption of the developmentally regulated remodeling of the H3K4me3 landscape that defines normal prefrontal cortex neurons in early infancy. However, excess spreading of H3K4me3 from the transcription start sites into downstream gene bodies and upstream promoters was observed specifically in neuronal chromatin from 4 of 16 autism cases but not in controls. Variable subsets of autism cases exhibit altered H3K4me3 peaks at numerous genes regulating neuronal connectivity, social behaviors, and cognition, often in conjunction with altered expression of the corresponding transcripts. Autism-associated H3K4me3 peaks were significantly enriched in genes and loci implicated in neurodevelopmental diseases. CONCLUSIONS: Prefrontal cortex neurons from subjects with autism show changes in chromatin structures at hundreds of loci genome-wide, revealing considerable overlap between genetic and epigenetic risk maps of developmental brain disorders.
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12. Siegel M, Beaulieu AA. {{Psychotropic Medications in Children with Autism Spectrum Disorders: A Systematic Review and Synthesis for Evidence-Based Practice}}. {J Autism Dev Disord};2011 (Nov 9)
This paper presents a systematic review, rating and synthesis of the empirical evidence for the use of psychotropic medications in children with autism spectrum disorders (ASD). Thirty-three randomized controlled trials (RCTs) published in peer-reviewed journals qualified for inclusion and were coded and analyzed using a systematic evaluative method specific to autism research (Reichow et al. in Journal of Autism and Developmental Disorders 38:1311-1319, 2008). Results are presented by agent and primary target symptom(s). The findings suggest established evidence for relatively few agents, with preliminary and promising evidence for a larger group. Challenges and opportunities in the developing field of ASD psychopharmacology are identified, and recommendations for further research are provided.
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13. Tobiasova Z, Lingen KH, Scahill L, Leckman JF, Zhang Y, Chae W, McCracken JT, McDougle CJ, Vitiello B, Tierney E, Aman MG, Arnold LE, Katsovich L, Hoekstra PJ, Volkmar F, Bothwell AL, Kawikova I. {{Risperidone-Related Improvement of Irritability in Children with Autism Is not Associated with Changes in Serum of Epidermal Growth Factor and Interleukin-13}}. {J Child Adolesc Psychopharmacol};2011 (Nov 9)
Abstract Risperidone has been shown to improve serious behavioral problems in children with autism. Here we asked whether risperidone-associated improvement was related to changes in concentrations of inflammatory molecules in the serum of these subjects. Seven molecules were identified as worthy of further assessment by performing a pilot analysis of 31 inflammatory markers in 21 medication-free subjects with autism versus 15 healthy controls: epidermal growth factor (EGF), interferon-? (IFN-?), interleukin (IL)-13, IL-17, monocyte chemoattractant protein-1 (MCP-1), IL-1 and IL-1-receptor antagonist. Serum concentrations of these markers were then established in a different set of subjects that participated in a double-blind, clinical trial and an expanded group of healthy subjects. In the first analysis, samples obtained from subjects with autism at baseline visits were compared to visits after 8-week treatment with placebo (n=37) or risperidone (n=40). The cytokine concentrations remained stable over the 8-week period for both risperidone and placebo groups. In the second analysis, we explored further the differences between medication-free subjects with autism (n=77) and healthy controls (recruited independently; n=19). Serum levels of EGF were elevated in subjects with autism (median=103?pg/mL, n=75) in comparison to healthy controls (75?pg/mL, n=19; p<0.05), and levels of IL-13 were decreased in autism (median=0.8?pg/mL, n=77) in comparison to controls (9.8?pg/mL, n=19; p=0.0003). These changes did not correlate with standardized measures used for a diagnosis of autism. In summary, risperidone-induced clinical improvement in subjects with autism was not associated with changes in the serum inflammatory markers measured. Whether altered levels of EGF and IL-13 play a role in the pathogenesis or phenotype of autism requires further investigation.
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14. Waters H. {{Autism, authenticated}}. {Nat Med};2011;17(11):1336-1338.
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15. Williams SC. {{New mouse models of autism highlight need for standardized tests}}. {Nat Med};2011;17(11):1324.
