1. Al-Farsi YM, Al-Sharbati MM, Waly MI, Al-Farsi OA, Al-Shafaee MA, Al-Khaduri MM, Trivedi MS, Deth RC. {{Effect of suboptimal breast-feeding on occurrence of autism: A case-control study}}. {Nutrition}. 2012; 28(7-8): e27-32.
OBJECTIVE: To evaluate the association between suboptimal breast-feeding practices and autism spectrum disorders (ASDs). METHODS: A case-control study was conducted in 102 ASD cases and 102 matched healthy controls. RESULTS: Based on adjusted odds ratios from logistic regression models, ASD was found to be associated with the late initiation of breast-feeding (odds ratio 1.48, 95% confidence interval 1.01-3.1), a non-intake of colostrum (odds ratio 1.7, 95% confidence interval 1.03-4.3), prelacteal feeding, and bottle-feeding. The risk of ASD was found to decrease in a dose-response fashion over increasing periods of exclusive breast-feeding (P for trend = 0.04) and continued breast-feeding (P for trend = 0.001). CONCLUSION: The study indicates that increased ASD risk is generally associated with suboptimal breast-feeding practices.
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2. Anderson GM. {{Twin studies in autism: what might they say about genetic and environmental influences}}. {J Autism Dev Disord}. 2012; 42(7): 1526-7.
Genetic and epigenetic differences exist within monozygote twin-pairs and might be especially important in the expression of autism. Assuming phenotypic differences between monozygotic twins are due to environmental influences may lead to mistaken conclusions regarding the relative genetic and environmental contribution to autism risk.
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3. Anderson GM, Hertzig ME, McBride PA. {{Brief report: platelet-poor plasma serotonin in autism}}. {J Autism Dev Disord}. 2012; 42(7): 1510-4.
Possible explanations for the well-replicated platelet hyperserotonemia of autism include an alteration in the platelet’s handling of serotonin (5-hydroxyserotonin, 5-HT) or an increased exposure of the platelet to 5-HT. Measurement of platelet-poor plasma (PPP) levels of 5-HT appears to provide the best available index of in vivo exposure of the platelet to 5-HT. Mean (+/-SD) concentrations of PPP 5-HT observed in the autism (N = 18), hyperserotonemic subgroup (N = 5) and control (N = 24) groups were 0.86 +/- 0.53, 0.87 +/- 0.43 and 0.86 +/- 0.36 nM, respectively. The results suggest that the hyperserotonemia of autism is not due to increased exposure of the platelet to 5-HT and make it more likely that the factor(s) contributing to the hyperserotonemia of autism have to do with the platelet’s handling of 5-HT.
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4. Atladottir HO, Henriksen TB, Schendel DE, Parner ET. {{Using Maternally Reported Data to Investigate the Association between Early Childhood Infection and Autism Spectrum Disorder: the Importance of Data Source}}. {Paediatr Perinat Epidemiol}. 2012; 26(4): 373-85.
BACKGROUND: Childhood infections have been found to be associated with autism spectrum disorder (ASD) in previous studies using hospital data or medical records to identify infections. We aimed to replicate these findings using maternal reports of childhood infection. METHODS: We used the Danish National Birth Cohort consisting of 92 583 live singletons born from 1997 to 2003 in Denmark. ASD diagnoses were retrieved from the Danish Psychiatric Central Register, and a total of 945 children from the cohort were diagnosed with ASD. Data were analysed using Cox proportional hazards regression. We studied the association between ASD and maternal reports of infectious disease in the child from birth to 19 months. Furthermore, we performed secondary analyses using hospital registers to investigate the association between ASD and hospital contact in general as well as hospital contact for various infections. RESULTS: We did not find a general association between maternal reports of infectious illness and ASD. However, hospital contact for all causes was associated with an increased risk for an ASD diagnosis. Danish children with ASD do not appear to have a general pattern of illness from infection in early life, but do have more contact with medical specialists for infections and other indications compared with the general population. CONCULSION: Hospital data should be used cautiously when studying the co-morbidity of ASD; if the increased rate of hospital contact overall for children with ASD is not considered, then misleading interpretations might be made of observed associations between specific diseases and ASD.
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5. Baghdadli A, Assouline B, Sonie S, Pernon E, Darrou C, Michelon C, Picot MC, Aussilloux C, Pry R. {{Developmental trajectories of adaptive behaviors from early childhood to adolescence in a cohort of 152 children with autism spectrum disorders}}. {J Autism Dev Disord}. 2012; 42(7): 1314-25.
This study examines change in 152 children over an almost 10-year period (T1: 4.9 (+/-1.3) years; T2: 8.1 (+/-1.3) years; T3: 15(+/-1.6) years) using a group-based, semi-parametric method in order to identify distinct developmental trajectories. Important deficits remain at adolescence in the adaptive abilities of children with Autism spectrum disorders, but changes in adaptive skills show two distinct growth rates. The univariate analysis reveals that low growth trajectories for both social and communication outcome are associated with the following characteristics at age 5: low cognitive and language skills, presence of epilepsy, and severity of autism. The multivariate analysis confirms that risk factors at age 5, were low language and severity of autism for both social and communication outcomes 10 years later, and that hours of early intervention was protective factor for communication.
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6. Bahrami F, Movahedi A, Marandi SM, Abedi A. {{Kata techniques training consistently decreases stereotypy in children with autism spectrum disorder}}. {Res Dev Disabil}. 2012; 33(4): 1183-93.
The effects of 14 weeks of Kata techniques training on stereotypic behaviors of children with autism spectrum disorders (ASD) were investigated. The study included 30 eligible (diagnosed ASD, school age) children with ages ranging from 5 to 16 years whom they assigned to an exercise (n=15) or a no-exercise control group (n=15). Participants of the exercise group received Kata techniques instruction four times per week for 14 weeks (56 sessions). Stereotypy was assessed at baseline (pre-intervention), week 14 (post-intervention), and at one month follow up in both groups. Results showed that Kata techniques training significantly reduced stereotypy in the exercise group. Following participation in Kata techniques training, stereotypy decreased from baseline levels by a M of 42.54% across participants. Interestingly, after 30 days of no practice, stereotypy in the exercise group remained significantly decreased compared to pre-intervention time. The participants of the control group did not show significant changes in the stereotypy. Teaching martial arts techniques to children with ASD for a long period of time consistently decreased their stereotypic behaviors.
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7. Braunschweig D, Duncanson P, Boyce R, Hansen R, Ashwood P, Pessah IN, Hertz-Picciotto I, Van de Water J. {{Behavioral correlates of maternal antibody status among children with autism}}. {J Autism Dev Disord}. 2012; 42(7): 1435-45.
Autism spectrum disorders (ASDs) affect approximately 1 in 110 children in the United States. This report profiles fetal-brain reactive autoantibodies of a large cohort of mothers of children with autism and controls, yielding significant associations between the presence of IgG reactivity to fetal brain proteins at 37 and 73 kDa and a childhood diagnosis of full autism (p = 0.0005), which also correlated with lower expressive language scores (p = 0.005). Additionally, we report on reactivity to proteins at 39 and 73 kDa, which correlated with the broader diagnosis of ASD (p = 0.0007) and increased irritability on the Aberrant Behavioral Checklist (p = 0.05). This study provides evidence of multiple patterns of reactivity to fetal brain proteins by maternal antibodies associated with ASD and specific childhood behavioral outcomes.
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8. Burnand G. {{Inter-hemispheric competition relieved in both: Hypotheses for autism and schizophrenia from problem theory}}. {Med Hypotheses}. 2012; 79(1): 25-33.
A logical relationship exists among six general problems that people face in life. Using hope about something for its subjective probability, its expected likelihood, the problems form a series where the method of assessing hope changes in a simple manner from one problem to the next. The central hypothesis is that human beings exploit this. Brain structures and predispositions have evolved accordingly, leading to the hemispheres having different predispositions. The hemispheres are effectively joined at 5months. Infants will then find that they engage in two unrelated activities. Typical infants label the activities in detail, using visual images, as part of gaining control over them. Hypotheses are: (a) autistic children fail labelling at the start, and hence they encounter uncontrolled competition between the hemispheres; (b) with some, serotonin abnormality impairs sensory information processing and hence the labelling; (c) with some, a delay in myelination from autoimmune effects disrupts labelling; (d) the likelihood of this ‘delay autism’ is reduced by long chain omega oils; (e) self-pressuring, which underlies taking on challenges and play like Hide and Seek, brings relief from the competition by raising the influence of one side; (f) the same left-right competition occurs in confused episodes and schizophrenia in vulnerable people who encounter pressures to use both hemispheres at the same time; (g) some symptoms raise the influence on one side ideationally. This leads to coherent theories of autism and schizophrenia. In both competition between the hemispheres is relieved primarily by self-pressuring, which raises influence on one side.
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9. Camacho A, Espin JC, Nunez N, Simon R. {{Levetiracetam-induced reversible autistic regression}}. {Pediatr Neurol}. 2012; 47(1): 65-7.
Levetiracetam is a commonly prescribed antiepileptic drug, and is generally well tolerated, but can eventually cause behavioral disturbances. These disturbances seem more frequent in children and in patients with a previous psychiatric history. We report on reversible autistic regression induced by levetiracetam in a 6-year-old girl with spastic cerebral palsy, mild cognitive deficiency, and focal epilepsy. She was diagnosed with pervasive developmental disorder, and demonstrated mild to moderate impairment in pragmatic language and interactions with peers. After the introduction of levetiracetam, she developed stereotypies, and her social and communicative skills deteriorated severely. She also exhibited mood lability. When the medication was discontinued, a dramatic response occurred, with a complete resolution of new abnormal findings. Levetiracetam can provoke unusual behavioral adverse effects in certain patients who are biologically more vulnerable.
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10. Camacho-Garcia RJ, Planelles MI, Margalef M, Pecero ML, Martinez-Leal R, Aguilera F, Vilella E, Martinez-Mir A, Scholl FG. {{Mutations affecting synaptic levels of neurexin-1beta in autism and mental retardation}}. {Neurobiol Dis}. 2012; 47(1): 135-43.
The identification of mutations in genes encoding proteins of the synaptic neurexin-neuroligin pathway in different neurodevelopmental disorders, including autism and mental retardation, has suggested the presence of a shared underlying mechanism. A few mutations have been described so far and for most of them the biological consequences are unknown. To further explore the role of the NRXN1beta gene in neurodevelopmental disorders, we have sequenced the coding exons of the gene in 86 cases with autism and mental retardation and 200 controls and performed expression analysis of DNA variants identified in patients. We report the identification of four novel independent mutations that affect nearby positions in two regions of the gene/protein: i) sequences important for protein translation initiation, c.-3G>T within the Kozak sequence, and c.3G>T (p.Met1), at the initiation codon; and ii) the juxtamembrane region of the extracellular domain, p.Arg375Gln and p.Gly378Ser. These mutations cosegregate with different psychiatric disorders other than autism and mental retardation, such as psychosis and attention-deficit/hyperactivity disorder. We provide experimental evidence for the use of an alternative translation initiation codon for c.-3G>T and p.Met1 mutations and reduced synaptic levels of neurexin-1beta protein resulting from p.Met1 and p.Arg375Gln. The data reported here support a role for synaptic defects of neurexin-1beta in neurodevelopmental disorders.
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11. Chevallier C, Grezes J, Molesworth C, Berthoz S, Happe F. {{Brief report: selective social anhedonia in high functioning autism}}. {J Autism Dev Disord}. 2012; 42(7): 1504-9.
Diminished social motivation is one of the most striking features in autism. Yet, few studies have directly assessed the value people with an ASD place on social interactions, or how rewarding they report it to be. In the present study, we directly measure social motivation by looking at responses to a questionnaire assessing self-reported pleasure in social and non social situations. Twenty-nine adolescents with ASD and matched controls took part in the study. Our results reveal that children with an ASD differ from the controls with respect to social enjoyment, but not with respect to physical and other sources of hedonism. Further analyses demonstrate that the degree of social anhedonia correlates with autism severity.
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12. Chiri G, Warfield ME. {{Unmet need and problems accessing core health care services for children with autism spectrum disorder}}. {Matern Child Health J}. 2012; 16(5): 1081-91.
To investigate the health care experiences of children with autism spectrum disorder, whether they have unmet needs, and if so, what types, and problems they encounter accessing needed care. We address these issues by identifying four core health care services and access problems related to provider and system characteristics. Using data from the 2005-2006 National Survey of Children with Special Health Care Needs (NS-CSHCN) we compared children with autism spectrum disorder with children with special health care needs with other emotional, developmental or behavioral problems (excluding autism spectrum disorder) and with other children with special health care needs. We used weighted logistic regression to examine differences in parent reports of unmet needs for the three different health condition groups. Overall unmet need for each service type among CSHCN ranged from 2.5% for routine preventive care to 15% for mental health services. After controlling for predisposing, enabling and need factors, some differences across health condition groups remained. Families of children with autism spectrum disorder were in fact significantly more at risk for having unmet specialty and therapy care needs. Additionally, families of children with autism spectrum disorder were more likely to report provider lack of skills to treat the child as a barrier in obtaining therapy and mental health services. Disparities in unmet needs for children with autism suggest that organizational features of managed care programs and provider characteristics pose barriers to accessing care.
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13. Cruz I, Vicaria I, Wang NY, Niparko J, Quittner AL. {{Language and Behavioral Outcomes in Children With Developmental Disabilities Using Cochlear Implants}}. {Otol Neurotol}. 2012; 33(5): 751-60.
OBJECTIVE: Over the past decade, the number of deaf children with developmental disabilities receiving cochlear implants has increased dramatically. However, little is known about the developmental outcomes of these children post-implantation. The current study evaluated oral language and behavioral outcomes over 3 years after implantation in a sample of typically developing deaf children and children with developmental disabilities. STUDY DESIGN: A three year longitudinal study of the effects of cochlear implantation on language and behavioral outcomes in children with and without additional disabilities. SETTING: Six cochlear implant centers in the United States. PATIENTS: The study cohort consisted of 188 deaf children. Eighty-five percent of the sample (n = 157) had a single diagnosis of severe to profound hearing loss and 15% (n = 31) had an additional disability. MAIN OUTCOME MEASURES: Oral language was assessed using the Reynell Developmental Language Scales, and behavioral outcomes were assessed using the Child Behavior Checklist. RESULTS: Results using multilevel modeling indicated that deaf children with and without additional disabilities improved significantly in oral language skills post-implantation. However, children with additional disabilities made slower progress. In terms of specific diagnoses, children with developmental disorders, such as autism, made the slowest progress over time. In addition, behavior problems increased significantly in this group, whereas behavior problems decreased over 3 years in the typically developing deaf sample. CONCLUSION: Overall, given the improvements in expressive and receptive language skills documented over 3 years, these findings support the use of cochlear implants for deaf children with developmental disabilities.
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14. Davis LK, Maltman N, Mosconi MW, Macmillan C, Schmitt L, Moore K, Francis SM, Jacob S, Sweeney JA, Cook EH. {{Rare inherited A2BP1 deletion in a proband with autism and developmental hemiparesis}}. {Am J Med Genet A}. 2012; 158A(7): 1654-61.
Ataxin 2 binding protein 1 (A2BP1 aka FOX1, RBFOX1) is an RNA binding protein responsible for regulation of pre-mRNA splicing events in a number of critical developmental genes expressed in muscle, heart and neuronal cells [Shibata et al. (2000); Mamm Genome 12:595-601; Jin et al. (2003); EMBO J 22:905-912; Underwood et al. (2005); Mol Cell Biol 25:10005-10016]. Rare copy number abnormalities of A2BP1 have been previously associated with cognitive impairment, attention deficit disorder and autism [Martin et al. (2007); Am J Med Gen Part B 144B:869-876; Elia et al. (2010); Mol Psychiatry 15:637-646.]. Using a 1M Illumina SNP microarray, we identified a 1.3 kb deletion in A2BP1, which was subsequently validated by quantitative PCR. Here we present an in depth case study of an individual with autism and mild developmental hemiparesis in whom the deletion was detected. This study provides further support for the possible role of rare copy number variants in A2BP1 in the development of autism and associated motor asymmetries. (c) 2012 Wiley Periodicals, Inc.
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15. De Felice C, Signorini C, Durand T, Ciccoli L, Leoncini S, D’Esposito M, Filosa S, Oger C, Guy A, Bultel-Ponce V, Galano JM, Pecorelli A, De Felice L, Valacchi G, Hayek J. {{Partial rescue of Rett syndrome by omega-3 polyunsaturated fatty acids (PUFAs) oil}}. {Genes Nutr}. 2012; 7(3): 447-58.
Evidence of enhanced oxidative stress (O.S.) and lipid peroxidation has been reported in patients with Rett syndrome (RTT), a relatively rare neurodevelopmental disorder progressing in 4-stages, and mainly caused by loss-of-function mutations in the methyl-CpG-binding protein 2. No effective therapy for preventing or arresting the neurologic regression in the disease in its various clinical presentations is available. Based on our prior evidence of enhanced O.S. and lipid peroxidation in RTT patients, herein we tested the possible therapeutic effects of omega-3 polyunsaturated fatty acids (omega-3 PUFAs), known antioxidants with multiple effects, on the clinical symptoms and O.S. biomarkers in the earliest stage of RTT. A total of 20 patients in stage I were randomized (n = 10 subjects per arm) to either oral supplementation with omega-3 PUFAs-containing fish oil (DHA: 72.9 +/- 8.1 mg/kg b.w./day; EPA: 117.1 +/- 13.1 mg/kg b.w./day; total omega-3 PUFAs: 246.0 +/- 27.5 mg/kg b.w./day) for 6 months or no treatment. Primary outcomes were potential changes in clinical symptoms, with secondary outcomes including variations for five O.S. markers in plasma and/or erythrocytes (nonprotein bound iron, F(2)-dihomo-isoprostanes, F(3)-isoprostanes, F(4)-neuroprostanes, and F(2)-isoprostanes). A significant reduction in the clinical severity (in particular, motor-related signs, nonverbal communication deficits, and breathing abnormalities) together with a significant decrease in all the examined O.S. markers was observed in the omega-3 PUFAs supplemented patients, whereas no significant changes were evidenced in the untreated group. For the first time, these findings strongly suggest that a dietary intervention in this genetic disease at an early stage of its natural history can lead to a partial clinical and biochemical rescue.
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16. De Felice C, Signorini C, Leoncini S, Pecorelli A, Durand T, Valacchi G, Ciccoli L, Hayek J. {{The role of oxidative stress in Rett syndrome: an overview}}. {Ann N Y Acad Sci}. 2012; 1259(1): 121-35.
The main cause of Rett syndrome (RTT), a pervasive development disorder almost exclusively affecting females, is a mutation in the methyl-CpG binding protein 2 (MeCP2) gene. To date, no cure for RTT exists, although disease reversibility has been demonstrated in animal models. Emerging evidence from our and other laboratories indicates a potential role of oxidative stress (OS) in RTT. This review examines the current state of the knowledge on the role of OS in explaining the natural history, genotype-phenotype correlation, and clinical heterogeneity of the human disease. Biochemical evidence of OS appears to be related to neurological symptom severity, mutation type, and clinical presentation. These findings pave the way for potential new genetic downstream therapeutic strategies aimed at improving patient quality of life. Further efforts in the near future are needed for investigating the yet unexplored « black box » between the MeCP2 gene mutation and subsequent OS derangement.
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17. Dempsey AG, Llorens A, Brewton C, Mulchandani S, Goin-Kochel RP. {{Emotional and behavioral adjustment in typically developing siblings of children with autism spectrum disorders}}. {J Autism Dev Disord}. 2012; 42(7): 1393-402.
Research findings describing the emotional and behavioral functioning of typically developing (TD) siblings of children with autism spectrum disorders (ASD) are contradictory. Methodological issues, such as small study sample sizes and reliance on parent report, may contribute to inconsistent findings. The purpose of this study was to use parent and teacher report to describe presence of internalizing and externalizing behaviors among a large sample (n = 486) of TD siblings of children with ASD. Results indicated that siblings did not exhibit a disproportionate prevalence of internalizing or externalizing symptoms in comparison to the standardization sample of the rating scale. The presence of a sibling with an ASD may not be considered a risk-factor for adjustment problems among TD siblings.
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18. Djukic A, Valicenti McDermott M, Mavrommatis K, Martins CL. {{Rett syndrome: basic features of visual processing-a pilot study of eye-tracking}}. {Pediatr Neurol}. 2012; 47(1): 25-9.
Consistently observed « strong eye gaze » has not been validated as a means of communication in girls with Rett syndrome, ubiquitously affected by apraxia, unable to reply either verbally or manually to questions during formal psychologic assessment. We examined nonverbal cognitive abilities and basic features of visual processing (visual discrimination attention/memory) by analyzing patterns of visual fixation in 44 girls with Rett syndrome, compared with typical control subjects. To determine features of visual fixation patterns, multiple pictures (with the location of the salient and presence/absence of novel stimuli as variables) were presented on the screen of a TS120 eye-tracker. Of the 44, 35 (80%) calibrated and exhibited meaningful patterns of visual fixation. They looked longer at salient stimuli (cartoon, 2.8 +/- 2 seconds S.D., vs shape, 0.9 +/- 1.2 seconds S.D.; P = 0.02), regardless of their position on the screen. They recognized novel stimuli, decreasing the fixation time on the central image when another image appeared on the periphery of the slide (2.7 +/- 1 seconds S.D. vs 1.8 +/- 1 seconds S.D., P = 0.002). Eye-tracking provides a feasible method for cognitive assessment and new insights into the « hidden » abilities of individuals with Rett syndrome.
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19. Edwards DJ, Perlman A, Reed P. {{Unsupervised Categorization in a sample of children with autism spectrum disorders}}. {Res Dev Disabil}. 2012; 33(4): 1264-9.
Studies of supervised Categorization have demonstrated limited Categorization performance in participants with autism spectrum disorders (ASD), however little research has been conducted regarding unsupervised Categorization in this population. This study explored unsupervised Categorization using two stimulus sets that differed in their difficulty of Categorization according to the simplicity model. ASD participants displayed a greater tendency to categorise according to one dimension as compared with mental-aged matched participants in the easily categorised sets, but both ASD and Control groups became more prone to one-dimensional sorting as the difficulty of the Categorization task increased. These results are discussed in terms of the processes underlying over-selective responding.
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20. Esposito G, Nakazawa J, Venuti P, Bornstein MH. {{Perceptions of distress in young children with autism compared to typically developing children: a cultural comparison between Japan and Italy}}. {Res Dev Disabil}. 2012; 33(4): 1059-67.
This study investigates how adults in two contrasting cultures (Italian and Japanese) perceive episodes of crying of typically developing (TD) children and children with Autism Disorder (AD). Although cries of children with AD have been reported to elicit more distress in Western cultures, it is not known whether similar findings hold in Eastern cultures. In Experiment 1, we artificially modified structural parameters (fundamental frequency, duration of pauses, waveform modulation) of cries and asked Italian and Japanese adults to judge levels of expressed and felt distress in the cries. In Experiment 2, we asked Italian and Japanese adults to report these levels of distress on hearing cries of AD and TD children. In both cultures, cries with higher fundamental frequency and shorter pause durations were judged more distressing and distressed and observers perceived cries of children with AD as more distressing and distressed than cries of TD children. The similar responses in adults from two contrasting societies constitute evidence that reactions to cries of children with AD might be universal.
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21. Fitzgerald M. {{Loss of autism in DSM-5}}. {Br J Psychiatry}. 2012; 201: 74-5.
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22. Gadow KD, Drabick DA. {{Symptoms of autism and schizophrenia spectrum disorders in clinically referred youth with oppositional defiant disorder}}. {Res Dev Disabil}. 2012; 33(4): 1157-68.
Examined autism spectrum disorder (ASD) and schizophrenia spectrum disorder (SSD) symptoms in a clinically referred, non-ASD sample (N=1160; ages 6-18) with and without oppositional defiant disorder (ODD). Mothers and teachers completed DSM-IV-referenced symptom checklists. Youth with ODD were subdivided into angry/irritable symptom (AIS) or noncompliant symptom (NS) subtypes. Two different classification strategies were used: within-informant (source-specific) and between-informant (source-exclusive). For the source-specific strategy, youth were classified AIS, NS, or Control (C) according to mothers’ and teachers’ ratings separately. A second set of analyses focused on youth classified AIS according to mother or teacher report but not both (source-exclusive) versus both mother and teacher (cross-informant) AIS. Results indicated the mother-defined source-specific AIS groups generally evidenced the most severe ASD and SSD symptoms (AIS>NS>C), but this was more pronounced among younger youth. Teacher-defined source-specific ODD groups exhibited comparable levels of symptom severity (AIS, NS>C) with the exception of SSD (AIS>NS>C; younger youth). Source-exclusive AIS groups were clearly differentiated from each other, but there was little evidence of differential symptom severity in cross-informant versus source-exclusive AIS. These findings were largely dependent on the informant used to define the source-exclusive groups. AIS and NS groups differed in their associations with ASD and SSD symptoms. Informant discrepancy provides valuable information that can inform nosological and clinical concerns and has important implications for studies that use different strategies to configure clinical phenotypes.
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23. Gadow KD, Guttmann-Steinmetz S, Rieffe C, Devincent CJ. {{Depression symptoms in boys with autism spectrum disorder and comparison samples}}. {J Autism Dev Disord}. 2012; 42(7): 1353-63.
This study compares severity of specific depression symptoms in boys with autism spectrum disorder (ASD), attention-deficit hyperactivity disorder (ADHD), or chronic multiple tic disorder (CMTD) and typically developing boys (Controls). Children were evaluated with parent and teacher versions of the Child Symptom Inventory-4 (CSI-4) and a demographic questionnaire. Mothers’ and teachers’ ratings generally indicated the most severe symptoms in boys with ASD +/- ADHD. Associations of depression with ASD severity and IQ varied considerably for specific symptoms of depression, ASD functional domain, and informant. Findings provide additional support for the differential influence of neurobehavioral syndromes on co-occurring symptom severity and illustrate how more fine-grained analyses of clinical phenotypes may contribute to a better understanding of etiology and current nosology.
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24. Goebel-Goody SM, Wilson-Wallis ED, Royston S, Tagliatela SM, Naegele JR, Lombroso PJ. {{Genetic manipulation of STEP reverses behavioral abnormalities in a fragile X syndrome mouse model}}. {Genes Brain Behav}. 2012; 11(5): 586-600.
Fragile X syndrome (FXS), the most common inherited form of intellectual disability and prevailing known genetic basis of autism, is caused by an expansion in the Fmr1 gene that prevents transcription and translation of fragile X mental retardation protein (FMRP). FMRP binds to and controls translation of mRNAs downstream of metabotropic glutamate receptor (mGluR) activation. Recent work shows that FMRP interacts with the transcript encoding striatal-enriched protein tyrosine phosphatase (STEP; Ptpn5). STEP opposes synaptic strengthening and promotes synaptic weakening by dephosphorylating its substrates, including ERK1/2, p38, Fyn and Pyk2, and subunits of N-methyl-d-aspartate (NMDA) and AMPA receptors. Here, we show that basal levels of STEP are elevated and mGluR-dependent STEP synthesis is absent in Fmr1(KO) mice. We hypothesized that the weakened synaptic strength and behavioral abnormalities reported in FXS may be linked to excess levels of STEP. To test this hypothesis, we reduced or eliminated STEP genetically in Fmr1(KO) mice and assessed mice in a battery of behavioral tests. In addition to attenuating audiogenic seizures and seizure-induced c-Fos activation in the periaqueductal gray, genetically reducing STEP in Fmr1(KO) mice reversed characteristic social abnormalities, including approach, investigation and anxiety. Loss of STEP also corrected select nonsocial anxiety-related behaviors in Fmr1(KO) mice, such as light-side exploration in the light/dark box. Our findings indicate that genetically reducing STEP significantly diminishes seizures and restores select social and nonsocial anxiety-related behaviors in Fmr1(KO) mice, suggesting that strategies to inhibit STEP activity may be effective for treating patients with FXS.
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25. Griesi-Oliveira K, Moreira Dde P, Davis-Wright N, Sanders S, Mason C, Orabona GM, Vadasz E, Bertola DR, State MW, Passos-Bueno MR. {{A complex chromosomal rearrangement involving chromosomes 2, 5, and X in autism spectrum disorder}}. {Am J Med Genet B Neuropsychiatr Genet}. 2012; 159(5): 529-36.
Here, we describe a female patient with autism spectrum disorder and dysmorphic features that harbors a complex genetic alteration, involving a de novo balanced translocation t(2;X)(q11;q24), a 5q11 segmental trisomy and a maternally inherited isodisomy on chromosome 5. All the possibly damaging genetic effects of such alterations are discussed. In light of recent findings on ASD genetic causes, the hypothesis that all these alterations might be acting in orchestration and contributing to the phenotype is also considered. (c) 2012 Wiley Periodicals, Inc.
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26. Grillo E, Villard L, Clarke A, Ben Zeev B, Pineda M, Bahi-Buisson N, Hryniewiecka-Jaworska A, Bienvenu T, Armstrong J, Martinez AR, Mari F, Veneselli E, Russo S, Vignoli A, Pini G, Djuric M, Bisgaard AM, Mejaski Bosnjak V, Polgar N, Cogliati F, Ravn K, Pintaudi M, Melegh B, Craiu D, Djukic A, Renieri A. {{Rett networked database: An integrated clinical and genetic network of rett syndrome databases}}. {Hum Mutat}. 2012; 33(7): 1031-6.
Rett syndrome (RTT) is a neurodevelopmental disorder with one principal phenotype and several distinct, atypical variants (Zappella, early seizure onset and congenital variants). Mutations in MECP2 are found in most cases of classic RTT but at least two additional genes, CDKL5 and FOXG1, can underlie some (usually variant) cases. There is only limited correlation between genotype and phenotype. The Rett Networked Database (http://www.rettdatabasenetwork.org/) has been established to share clinical and genetic information. Through an « adaptor » process of data harmonization, a set of 293 clinical items and 16 genetic items was generated; 62 clinical and 7 genetic items constitute the core dataset; 23 clinical items contain longitudinal information. The database contains information on 1838 patients from 11 countries (December 2011), with or without mutations in known genes. These numbers can expand indefinitely. Data are entered by a clinician in each center who supervises accuracy. This network was constructed to make available pooled international data for the study of RTT natural history and genotype-phenotype correlation and to indicate the proportion of patients with specific clinical features and mutations. We expect that the network will serve for the recruitment of patients into clinical trials and for developing quality measures to drive up standards of medical management. Hum Mutat 33:1031-1036, 2012. (c) 2012 Wiley Periodicals, Inc.
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27. Hagebeuk EE, Bijlmer RP, Koelman JH, Poll-The BT. {{Respiratory disturbances in rett syndrome: don’t forget to evaluate upper airway obstruction}}. {J Child Neurol}. 2012; 27(7): 888-92.
Rett syndrome is characterized by loss of motor and social functions, development of stereotypic hand movements, seizures, and breathing disturbances. This study evaluates the presence of overnight respiratory disturbances. Polysomnography in combination with a questionnaire (the Sleep Disturbance Scale for Children) was performed in 12 Dutch patients with Rett. Respiratory disturbances were present in all, clinically relevant in 10 (apnea hypopnea per hour 1.0-14.5). In 8 children, central apneas were present during the day often with obstructive apneas at night. In 6, obstructive sleep apnea syndrome was diagnosed, in 3 severe, with frequent oxygen desaturations. Significant respiratory complaints were present in 3 patients, all had obstructive sleep apnea syndrome. Of the 12 patients with Rett, 8 (67%) snored, and in 5 obstructive sleep apnea syndrome was present. In children, hypertrophied tonsils and adenoids are a common cause of obstructive sleep apnea syndrome, which may benefit from therapeutic intervention. We recommend performing polysomnography in patients with Rett syndrome and respiratory complaints.
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28. Hallett V, Ronald A, Rijsdijk F, Happe F. {{Disentangling the associations between autistic-like and internalizing traits: a community based twin study}}. {J Abnorm Child Psychol}. 2012; 40(5): 815-27.
Internalizing difficulties are prevalent in children with autism spectrum disorders (ASD), yet little is known about the underlying cause of this comorbidity. It is also unclear which types of autistic-like and internalizing difficulties are most strongly associated. The current study investigated the phenotypic and etiological associations between specific autistic-like traits and internalizing traits within a population-based sample. Parent-reported data were analyzed from 7,311 twin pairs at age 7 to 8 years. Structural equation modeling revealed distinguishable patterns of overlap between the three autistic-like traits (social difficulties, communication problems and repetitive/restricted behaviors) and four subtypes of internalizing traits (social anxiety, fears, generalized anxiety, negative affect). Although all phenotypic associations were modest (rph = 0.00-0.36), autistic-like communication impairments and repetitive/restricted behaviors correlated most strongly with generalized anxiety and negative affect both phenotypically and genetically. Conversely, autistic-like social difficulties showed little overlap with internalizing behaviors. Disentangling these associations and their etiological underpinnings may help contribute to the conceptualization and diagnosis of ‘comorbidity’ within ASD and internalizing disorders.
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29. Hambly C, Fombonne E. {{The impact of bilingual environments on language development in children with autism spectrum disorders}}. {J Autism Dev Disord}. 2012; 42(7): 1342-52.
The impact of bilingual exposure on language learning has not been systematically studied in children with Autism Spectrum Disorders. This study compared the social abilities and language levels of children (mean age = 56 months) with ASDs from bilingual (n = 45) and monolingual (n = 30) environments. Bilingually-exposed children were subgrouped based on simultaneous bilingual exposure from infancy (SIM, n = 24) versus sequential post-infancy bilingual exposure (SEQ, n = 21). Despite significantly different amounts of bilingual exposure across all groups (p = <0.001) and significantly stronger social interaction scores in the SIM group compared to the SEQ group on the Vineland Adaptive Behavior Scales-II Interpersonal subdomain (p = 0.025), there were no significant group differences in language level. Bilingually-exposed children with ASDs did not experience additional delays in language development.
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30. Hammock E, Veenstra-Vanderweele J, Yan Z, Kerr TM, Morris M, Anderson GM, Carter CS, Cook EH, Jacob S. {{Examining autism spectrum disorders by biomarkers: example from the oxytocin and serotonin systems}}. {J Am Acad Child Adolesc Psychiatry}. 2012; 51(7): 712-21 e1.
OBJECTIVE: Autism spectrum disorder (ASD) is a heritable but highly heterogeneous neuropsychiatric syndrome, which poses challenges for research relying solely on behavioral symptoms or diagnosis. Examining biomarkers may give us ways to identify individuals who demonstrate specific developmental trajectories and etiological factors related to ASD. Plasma oxytocin (OT) and whole-blood serotonin (5-HT) levels are consistently altered in some individuals with ASD. Reciprocal relationships have been described between brain oxytocin and serotonin systems during development. We therefore investigated the relationship between these peripheral biomarkers as well as their relationships with age. METHOD: In our first study, we analyzed correlations between these two biomarkers in 31 children and adolescents who were diagnosed with autism and were not on medications. In our second study, we explored whether whole-blood 5-HT levels are altered in mice lacking the oxytocin receptor gene Oxtr. RESULTS: In humans, OT and 5-HT were negatively correlated with each other (p < .05) and this relationship was most prominent in children less than 11 years old. Paralleling human findings, mice lacking Oxtr showed increased whole-blood 5-HT levels (p = .05), with this effect driven exclusively by mice less than 4 months old (p < .01). CONCLUSIONS: Identifying relationships between identified ASD biomarkers may be a useful approach to connect otherwise disparate findings that span multiple systems in this heterogeneous disorder. Using neurochemical biomarkers to perform parallel studies in animal and human populations within a developmental context is a plausible approach to probe the root causes of ASD and to identify potential interventions.
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31. Harfterkamp M, van de Loo-Neus G, Minderaa RB, van der Gaag RJ, Escobar R, Schacht A, Pamulapati S, Buitelaar JK, Hoekstra PJ. {{A randomized double-blind study of atomoxetine versus placebo for attention-deficit/hyperactivity disorder symptoms in children with autism spectrum disorder}}. {J Am Acad Child Adolesc Psychiatry}. 2012; 51(7): 733-41.
OBJECTIVE: The efficacy of atomoxetine as treatment of symptoms of attention-deficit/hyperactivity disorder (ADHD) in patients with autism spectrum disorder (ASD) has not been established. METHOD: In this study, 97 patients aged 6 to 17 years with ADHD and ASD were randomly assigned to double-blind treatment with 1.2 mg/kg/day atomoxetine or placebo for 8 weeks. The primary endpoint was the ADHD Rating Scale (ADHD-RS) score; secondary endpoints were the Clinical Global Impression of ADHD-Improvement (CGI-I) and the Conners Teacher Rating Scale-Revised: Short Form (CTRS-R:S) score. RESULTS: Baseline mean ADHD-RS scores for atomoxetine versus placebo were 40.7 and 38.6; after 8 weeks, mixed-effect model repeated-measure means were 31.6 (95% confidence interval 29.2-33.9) and 38.3 (36.0-40.6), respectively, with a difference in least square means of -6.7 (-10.0 to -3.4; p < .001). The CTRS-R:S Hyperactivity subscore also improved significantly for atomoxetine compared with placebo, but not the other CTRS-R:S subscores. However, there were not significantly more patients on atomoxetine (20.9%) who improved much, or very much according to the CGI-I, than on placebo (8.7%; p = 0.14). Adverse events (mostly nausea, decrease in appetite, fatigue, and early morning awakening) were reported in 81.3% of atomoxetine patients and 65.3% of placebo patients (p > .1). There were no serious adverse events. CONCLUSIONS: Atomoxetine moderately improved ADHD symptoms in patients with ASD and was generally well tolerated. Adverse events in this study were similar to those in other studies with ADHD patients without ASD. Clinical trial registration information-A Randomized Double-Blind Study of Atomoxetine Versus Placebo for ADHD Symptoms in Children with ASD; www.clinicaltrials.gov; NCT00380692.
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32. Ho JD, Nystrom PC, Calvo DV, Berris MS, Norlin JF, Clinton JE. {{Prehospital chemical restraint of a noncommunicative autistic minor by law enforcement}}. {Prehosp Emerg Care}. 2012; 16(3): 407-11.
Abstract When responders are dealing with an agitated patient in the field, safety for all involved may sometimes only be accomplished with physical or chemical restraints. While experiences using chemical restraint in the prehospital setting are found in the medical literature, the use of this by law enforcement as a first-response restraint has not previously been described. We report a case of successful law enforcement-administered sedation of a noncommunicative, autistic, and violent minor using intramuscular droperidol and diphenhydramine. Although this case has some unique characteristics that allowed chemical restraint to be given by the law enforcement agency, it calls attention to some specific prehospital issues that need to be addressed when dealing with autistic patients with extreme agitation.
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33. Hunter JE, Leslie M, Novak G, Hamilton D, Shubeck L, Charen K, Abramowitz A, Epstein MP, Lori A, Binder E, Cubells JF, Sherman SL. {{Depression and anxiety symptoms among women who carry the FMR1 premutation: Impact of raising a child with fragile X syndrome is moderated by CRHR1 polymorphisms}}. {Am J Med Genet B Neuropsychiatr Genet}. 2012; 159(5): 549-59.
The fragile X mental retardation gene, FMR1, contains a polymorphic CGG repeat in the 5′-untranslated region of exon 1. Once unstable, this repeat is capable of expansion across generations. Women who carry a premutation allele (55-199 repeats) are at risk of passing on a full mutation allele (>200 repeats) to their offspring. A full mutation leads to the most common form of inherited intellectual disability, fragile X syndrome (FXS). Mounting evidence suggests that premutation carriers may be vulnerable to symptoms of anxiety and depression. The goal of this study was to test the hypothesis that among women who carry a premutation, the stress of raising a child with FXS would be moderated by genetic factors influencing endogenous cortisol responses, which could in turn modulate anxiety and depression symptoms. To this end, we genotyped single nucleotide polymorphisms (SNPs) at the corticotrophin releasing hormone receptor 1 locus (CRHR1) in 460 women. Participants completed self-report questionnaires assessing symptoms of depression [Centers for Epidemiological Studies Depression Scale (CESD)], anxiety [State-Trait Anxiety Inventory (STAI) and Social Phobia and Anxiety Inventory (SPAI)], and mood [Positive and Negative Affect Schedule (PANAS)]. Results indicate a statistically significant interaction between CRHR1 genotype and the status of raising a child with FXS to predict social anxiety symptoms reported on the SPAI (rs7209436, P = 0.0001). Our data suggest that genetic variants in CRHR1 that associate with differential cortisol activation may also modulate levels of anxiety related to the stress of raising a child with FXS among women who carry an FMR1 premutation. (c) 2012 Wiley Periodicals, Inc.
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34. Jacot-Descombes S, Uppal N, Wicinski B, Santos M, Schmeidler J, Giannakopoulos P, Heinsein H, Schmitz C, Hof PR. {{Decreased pyramidal neuron size in Brodmann areas 44 and 45 in patients with autism}}. {Acta Neuropathol}. 2012; 124(1): 67-79.
Autism is a neurodevelopmental disorder characterized by deficits in social interaction and social communication, as well as by the presence of repetitive and stereotyped behaviors and interests. Brodmann areas 44 and 45 in the inferior frontal cortex, which are involved in language processing, imitation function, and sociality processing networks, have been implicated in this complex disorder. Using a stereologic approach, this study aims to explore the presence of neuropathological differences in areas 44 and 45 in patients with autism compared to age- and hemisphere-matched controls. Based on previous evidence in the fusiform gyrus, we expected to find a decrease in the number and size of pyramidal neurons as well as an increase in volume of layers III, V, and VI in patients with autism. We observed significantly smaller pyramidal neurons in patients with autism compared to controls, although there was no difference in pyramidal neuron numbers or layer volumes. The reduced pyramidal neuron size suggests that a certain degree of dysfunction of areas 44 and 45 plays a role in the pathology of autism. Our results also support previous studies that have shown specific cellular neuropathology in autism with regionally specific reduction in neuron size, and provide further evidence for the possible involvement of the mirror neuron system, as well as impairment of neuronal networks relevant to communication and social behaviors, in this disorder.
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35. Jacot-Descombes S, Uppal N, Wicinski B, Santos M, Schmeidler J, Giannakopoulos P, Heinsen H, Schmitz C, Hof PR. {{Erratum to: Decreased pyramidal neuron size in Brodmann areas 44 and 45 in patients with autism}}. {Acta Neuropathol}. 2012; 124(1): 81.
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36. Kalkbrenner AE, Braun JM, Durkin MS, Maenner MJ, Cunniff C, Lee LC, Pettygrove S, Nicholas JS, Daniels JL. {{Maternal Smoking during Pregnancy and the Prevalence of Autism Spectrum Disorders, Using Data from the Autism and Developmental Disabilities Monitoring Network}}. {Environ Health Perspect}. 2012; 120(7): 1042-8.
Background: Reported associations between gestational tobacco exposure and autism spectrum disorders (ASDs) have been inconsistent.Objective: We estimated the association between maternal smoking during pregnancy and ASDs among children 8 years of age.Methods: This population-based case-cohort study included 633,989 children, identified using publicly available birth certificate data, born in 1992, 1994, 1996, and 1998 from parts of 11 U.S. states subsequently under ASD surveillance. Of these children, 3,315 were identified as having an ASD by the active, records-based surveillance of the Autism and Developmental Disabilities Monitoring Network. We estimated prevalence ratios (PRs) of maternal smoking from birth certificate report and ASDs using logistic regression, adjusting for maternal education, race/ethnicity, marital status, and maternal age; separately examining higher- and lower-functioning case subgroups; and correcting for assumed under-ascertainment of autism by level of maternal education.Results: About 13% of the source population and 11% of children with an ASD had a report of maternal smoking in pregnancy: adjusted PR (95% confidence interval) of 0.90 (0.80, 1.01). The association for the case subgroup autistic disorder (1,310 cases) was similar: 0.88 (0.72, 1.08), whereas that for ASD not otherwise specified (ASD-NOS) (375 cases) was positive, albeit including the null: 1.26 (0.91, 1.75). Unadjusted associations corrected for assumed under-ascertainment were 1.06 (0.98, 1.14) for all ASDs, 1.12 (0.97, 1.30) for autistic disorder, and 1.63 (1.30, 2.04) for ASD-NOS.Conclusions: After accounting for the potential of under-ascertainment bias, we found a null association between maternal smoking in pregnancy and ASDs, generally. The possibility of an association with a higher-functioning ASD subgroup was suggested, and warrants further study.
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37. Kao B, Romero-Bosch L, Plante W, Lobato D. {{The experiences of Latino siblings of children with developmental disabilities}}. {Child Care Health Dev}. 2012; 38(4): 545-52.
Objective This qualitative study explored the experiences of Latino siblings of children with developmental disabilities. Methods Parents and typically developing siblings from 15 Latino families with a child with a developmental disability participated in separate interviews. Results Using consensual qualitative research methodology, domains reflecting siblings’ relationships, emotional experiences and communication about the disability were identified. The child’s need for caregiving was a prominent topic in the sibling and parent narratives. Parents reported concerns about siblings’ experience of differential treatment, whereas siblings reported concerns about restricted social activities because of their brother/sister. Conclusions Including multiple informants revealed commonalities and differences in parents’ and siblings’ perspectives on the impact of a child’s disability. The importance of considering sibling adaptation in sociocultural context is discussed.
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38. Kita Y, Inagaki M. {{[Face recognition in patients with autism spectrum disorders]}}. {Brain Nerve}. 2012; 64(7): 821-30.
Abstract The present study aimed to review previous research conducted on face recognition in patients with autism spectrum disorders (ASD). Face recognition is a key question in the ASD research field because it can provide clues for elucidating the neural substrates responsible for the social impairment of these patients. Historically, behavioral studies have reported low performance and/or unique strategies of face recognition among ASD patients. However, the performance and strategy of ASD patients is comparable to those of the control group, depending on the experimental situation or developmental stage, suggesting that face recognition of ASD patients is not entirely impaired. Recent brain function studies, including event-related potential and functional magnetic resonance imaging studies, have investigated the cognitive process of face recognition in ASD patients, and revealed impaired function in the brain’s neural network comprising the fusiform gyrus and amygdala. This impaired function is potentially involved in the diminished preference for faces, and in the atypical development of face recognition, eliciting symptoms of unstable behavioral characteristics in these patients. Additionally, face recognition in ASD patients is examined from a different perspective, namely self-face recognition, and facial emotion recognition. While the former topic is intimately linked to basic social abilities such as self-other discrimination, the latter is closely associated with mentalizing. Further research on face recognition in ASD patients should investigate the connection between behavioral and neurological specifics in these patients, by considering developmental changes and the spectrum clinical condition of ASD.
39. Kumari D, Lokanga R, Yudkin D, Zhao XN, Usdin K. {{Chromatin changes in the development and pathology of the Fragile X-associated disorders and Friedreich ataxia}}. {Biochim Biophys Acta}. 2012; 1819(7): 802-10.
The Fragile X-associated disorders (FXDs) and Friedreich ataxia (FRDA) are genetic conditions resulting from expansion of a trinucleotide repeat in a region of the affected gene that is transcribed but not translated. In the case of the FXDs, pathology results from expansion of CGG*CCG-repeat tract in the 5′ UTR of the FMR1 gene, while pathology in FRDA results from expansion of a GAA*TTC-repeat in intron 1 of the FXN gene. Expansion occurs during gametogenesis or early embryogenesis by a mechanism that is not well understood. Associated Expansion then produces disease pathology in various ways that are not completely understood either. In the case of the FXDs, alleles with 55-200 repeats express higher than normal levels of a transcript that is thought to be toxic, while alleles with >200 repeats are silenced. In addition, alleles with >200 repeats are associated with a cytogenetic abnormality known as a fragile site, which is apparent as a constriction or gap in the chromatin that is seen when cells are grown in presence of inhibitors of thymidylate synthase. FRDA alleles show a deficit of the FXN transcript. This review will address the role of repeat-mediated chromatin changes in these aspects of FXD and FRDA disease pathology. This article is part of a Special Issue entitled: Chromatin in time and space.
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40. Kylliainen A, Wallace S, Coutanche MN, Leppanen JM, Cusack J, Bailey AJ, Hietanen JK. {{Affective-motivational brain responses to direct gaze in children with autism spectrum disorder}}. {J Child Psychol Psychiatry}. 2012; 53(7): 790-7.
Background: It is unclear why children with autism spectrum disorders (ASD) tend to be inattentive to, or even avoid eye contact. The goal of this study was to investigate affective-motivational brain responses to direct gaze in children with ASD. To this end, we combined two measurements: skin conductance responses (SCR), a robust arousal measure, and asymmetry in frontal electroencephalography (EEG) activity which is associated with motivational approach and avoidance tendencies. We also explored whether degree of eye openness and face familiarity modulated these responses. Methods: Skin conductance responses and frontal EEG activity were recorded from 14 children with ASD and 15 typically developing children whilst they looked at familiar and unfamiliar faces with eyes shut, normally open or wide-open. Stimuli were presented in such a way that they appeared to be looming towards the children. Results: In typically developing children, there were no significant differences in SCRs between the different eye conditions, whereas in the ASD group the SCRs were attenuated to faces with closed eyes and increased as a function of the degree of eye openness. In both groups, familiar faces elicited marginally greater SCRs than unfamiliar faces. In typically developing children, normally open eyes elicited greater relative left-sided frontal EEG activity (associated with motivational approach) than shut eyes and wide-open eyes. In the ASD group, there were no significant differences between the gaze conditions in frontal EEG activity. Conclusions: Collectively, the results replicate previous finding in showing atypical modulation of arousal in response to direct gaze in children with ASD but do not support the assumption that this response is associated with an avoidant motivational tendency. Instead, children with ASD may lack normative approach-related motivational response to eye contact.
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41. Lai B, Milano M, Roberts MW, Hooper SR. {{Unmet dental needs and barriers to dental care among children with autism spectrum disorders}}. {J Autism Dev Disord}. 2012; 42(7): 1294-303.
Mail-in pilot-tested questionnaires were sent to a stratified random sample of 1,500 families from the North Carolina Autism Registry. Multivariate logistic regression analysis was used to determine the significance of unmet dental needs and other predictors. Of 568 surveys returned (Response Rate = 38%), 555 were complete and usable. Sixty-five (12%) children had unmet dental needs. Of 516 children (93%) who had been to a dentist, 11% still reported unmet needs. The main barriers were child’s behavior, cost, and lack of insurance. The significant predictor variables of unmet needs were child’s behavior (p = 0.01), child’s dental health (p < 0.001), and caregiver’s last dental visit greater than 6 months (p = 0.002). Type of ASD did not have an effect on having unmet dental needs.
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42. Landrigan PJ, Lambertini L, Birnbaum LS. {{A research strategy to discover the environmental causes of autism and neurodevelopmental disabilities}}. {Environ Health Perspect}. 2012; 120(7): a258-60.
