1. Chanel G, Pichon S, Conty L, Berthoz S, Chevallier C, Grezes J. {{Classification of autistic individuals and controls using cross-task characterization of fMRI activity}}. {Neuroimage Clin};2016;10:78-88.
Multivariate pattern analysis (MVPA) has been applied successfully to task-based and resting-based fMRI recordings to investigate which neural markers distinguish individuals with autistic spectrum disorders (ASD) from controls. While most studies have focused on brain connectivity during resting state episodes and regions of interest approaches (ROI), a wealth of task-based fMRI datasets have been acquired in these populations in the last decade. This calls for techniques that can leverage information not only from a single dataset, but from several existing datasets that might share some common features and biomarkers. We propose a fully data-driven (voxel-based) approach that we apply to two different fMRI experiments with social stimuli (faces and bodies). The method, based on Support Vector Machines (SVMs) and Recursive Feature Elimination (RFE), is first trained for each experiment independently and each output is then combined to obtain a final classification output. Second, this RFE output is used to determine which voxels are most often selected for classification to generate maps of significant discriminative activity. Finally, to further explore the clinical validity of the approach, we correlate phenotypic information with obtained classifier scores. The results reveal good classification accuracy (range between 69% and 92.3%). Moreover, we were able to identify discriminative activity patterns pertaining to the social brain without relying on a priori ROI definitions. Finally, social motivation was the only dimension which correlated with classifier scores, suggesting that it is the main dimension captured by the classifiers. Altogether, we believe that the present RFE method proves to be efficient and may help identifying relevant biomarkers by taking advantage of acquired task-based fMRI datasets in psychiatric populations.
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2. Dewinter J, Vermeiren R, Vanwesenbeeck I, Van Nieuwenhuizen C. {{Adolescent boys with autism spectrum disorder growing up: follow-up of self-reported sexual experience}}. {Eur Child Adolesc Psychiatry};2016 (Jan 20)
Systematic research on sexual development in adolescents with autism spectrum disorder (ASD) remains scant, notwithstanding the often-suggested relation between ASD, atypical, and even sexually offensive behaviours. This study compared follow-up data related to lifetime sexual experience (LTSE) in a homogeneous group of adolescent boys with ASD (n = 30), aged 16-20, with a matched group of boys in the general population (n = 60). Most boys in the ASD and control groups reported masturbation and having experienced an orgasm. The proportion of boys with ASD that had no partnered sexual experience was larger than in the control group. This difference was mostly explained by significantly fewer boys with ASD, compared with controls, who reported experience with kissing and petting; no significant differences emerged relating to more intimate partnered sexual experiences. The results suggest the existence of a subgroup of boys who have not (yet) entered the arena of partnered sexual experiences-a finding in line with research in adult samples. There were no differences relating to sexual abuse or coercion. Exploration of the partnered experiences revealed a variety of types of partners, mostly of comparable age. Several boys with ASD had not anticipated their sexual debut. Although they felt ready for it, some boys reported regret afterward. The hypothesised sexual developmental trajectories are subject to further research, but the sexual experience in this sample and the assumed developmental differences indicate the need for early, attuned, and comprehensive sexuality-related education and communication.
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3. Downs J, Stahlhut M, Wong K, Syhler B, Bisgaard AM, Jacoby P, Leonard H. {{Validating the Rett Syndrome Gross Motor Scale}}. {PLoS One};2016;11(1):e0147555.
Rett syndrome is a pervasive neurodevelopmental disorder associated with a pathogenic mutation on the MECP2 gene. Impaired movement is a fundamental component and the Rett Syndrome Gross Motor Scale was developed to measure gross motor abilities in this population. The current study investigated the validity and reliability of the Rett Syndrome Gross Motor Scale. Video data showing gross motor abilities supplemented with parent report data was collected for 255 girls and women registered with the Australian Rett Syndrome Database, and the factor structure and relationships between motor scores, age and genotype were investigated. Clinical assessment scores for 38 girls and women with Rett syndrome who attended the Danish Center for Rett Syndrome were used to assess consistency of measurement. Principal components analysis enabled the calculation of three factor scores: Sitting, Standing and Walking, and Challenge. Motor scores were poorer with increasing age and those with the p.Arg133Cys, p.Arg294* or p.Arg306Cys mutation achieved higher scores than those with a large deletion. The repeatability of clinical assessment was excellent (intraclass correlation coefficient for total score 0.99, 95% CI 0.93-0.98). The standard error of measurement for the total score was 2 points and we would be 95% confident that a change 4 points in the 45-point scale would be greater than within-subject measurement error. The Rett Syndrome Gross Motor Scale could be an appropriate measure of gross motor skills in clinical practice and clinical trials.
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4. Fombonne E, Marcin C, Manero AC, Bruno R, Diaz C, Villalobos M, Ramsay K, Nealy B. {{Prevalence of Autism Spectrum Disorders in Guanajuato, Mexico: The Leon survey}}. {J Autism Dev Disord};2016 (Jan 21)
There are no epidemiological data on autism for Mexico. This study was conducted to generate a first estimate of ASD prevalence in Mexico. We surveyed children age eight in Leon (Guanajuato). The sample was stratified in two strata: (1) children having special education and medical records (SEMR; N = 432) and (2) children attending regular schools (GSS; N = 11,684). GSS children were screened with the SRS and those with the highest scores were invited to a diagnostic evaluation. The final sample comprised 36 children (80.6 % male) who had confirmed ASD. A third had intellectual disability, 25 % were non-verbal, 69 % had co-occurring behavioral problems. The prevalence overall was 0.87 % (95 % CI 0.62, 1.1 %). This survey provides an estimate for ASD prevalence in Mexico that is consistent with recent studies.
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5. Gauthier C, Doyen C, Amado I, Loo H, Gaillard R. {{[Therapeutic effects of oxytocin in autism: Current status of the research]}}. {Encephale};2016 (Jan 18)
The neuropeptide oxytocin (OT) is an evolutionary highly conserved molecule that plays a part in the regulation of complex social cognition and behaviours. From a pathophysiological point of view, several studies have evidenced dysfunctions of the oxytocinergic system in autism spectrum disorders (ASD): a lowering of plasma OT and genetic or epigenetic anomalies of the OT receptor. Therefore, some authors have hypothesized that an abnormality in the OT neurotransmission may account for several features of autism and that a treatment restoring a normal OT pathway functioning could improve social abilities. OT administration has thus been used in clinical trials, especially in groups of subjects suffering from autism. Some studies found that OT decreased repetitive behaviours, enhanced emotional understanding of speech intonation, improved performance of the Reading the Mind in the Eyes Test and reinforced cooperation. Nevertheless, the findings of the OT administration studies on clinical samples show great diversity. The context, the personality and childhood experiences of the subject could be moderators influencing the effect of exogenous OT. Besides, three mechanisms could play a part in the action of OT on ASD social symptoms: anxiety reduction (with a lowering in the hypothalamic-pituitary-adrenal axis responsiveness and in the amygdale reactivity to social stimuli), increased affiliative motivation (involving the dopaminergic pathway and several regions of the social brain) and enhanced perceptual selectivity and social stimuli salience. To conclude, OT could be a promising molecule used as a treatment to promote social behaviours, helping individuals with ASD to develop new relationships. OT could be administered during a cognitive-behavioural therapy to reinforce the efficacy of such procedures. More studies are needed, on larger samples, to investigate the safety and efficacy of OT administration and to specify optimal dosages and characteristics of patients who may benefit from this treatment.
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6. Gorman K, Olson L, Hill AP, Lunsford R, Heeman PA, van Santen JP. {{Uh and um in children with autism spectrum disorders or language impairment}}. {Autism Res};2016 (Jan 22)
Atypical pragmatic language is often present in individuals with autism spectrum disorders (ASD), along with delays or deficits in structural language. This study investigated the use of the « fillers » uh and um by children ages 4-8 during the autism diagnostic observation schedule. Fillers reflect speakers’ difficulties with planning and delivering speech, but they also serve communicative purposes, such as negotiating control of the floor or conveying uncertainty. We hypothesized that children with ASD would use different patterns of fillers compared to peers with typical development or with specific language impairment (SLI), reflecting differences in social ability and communicative intent. Regression analyses revealed that children in the ASD group were much less likely to use um than children in the other two groups. Filler use is an easy-to-quantify feature of behavior that, in concert with other observations, may help to distinguish ASD from SLI. Autism Res 2016. (c) 2016 International Society for Autism Research, Wiley Periodicals, Inc.
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7. Hoffjan S, Ibisler A, Tschentscher A, Dekomien G, Bidinost C, Rosa AL. {{WDR45 mutations in Rett (-like) syndrome and developmental delay: Case report and an appraisal of the literature}}. {Mol Cell Probes};2016 (Jan 11)
Mutations in the WDR45 gene have been identified as causative for the only X-linked type of neurodegeneration with brain iron accumulation (NBIA), clinically characterized by global developmental delay in childhood, followed by a secondary neurological decline with parkinsonism and/or dementia in adolescence or early adulthood. Recent reports suggest that WDR45 mutations are associated with a broader phenotypic spectrum. We identified a novel splice site mutation (c.440-2 A > G) in a 5-year-old Argentinian patient with Rett-like syndrome, exhibiting developmental delay, microcephaly, seizures and stereotypic hand movements, and discuss this finding, together with a review of the literature. Additional patients with a clinical diagnosis of Rett (-like) syndrome were also found to carry WDR45 mutations before (or without) clinical decline or signs of iron accumulation by magnetic resonance imaging (MRI). This information indicates that WDR45 mutations should be added to the growing list of genetic alterations linked to Rett-like syndrome. Further, clinical symptoms associated with WDR45 mutations ranged from early-onset epileptic encephalopathy in a male patient with a deletion of WDR45 to only mild cognitive delay in a female patient, suggesting that analysis of this gene should be considered more often in patients with developmental delay, regardless of severity. The increasing use of next generation sequencing technologies as well as longitudinal follow-up of patients with an early diagnosis will help to gain additional insight into the phenotypic spectrum associated with WDR45 mutations.
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8. Hollway JA, Aman MG, Mendoza-Burcham MI, Silverman L, Arnold LE, Tumuluru R, Handen BL, Lecavalier L, Page K, Sayre P, Smith T. {{Caregiver Satisfaction with a Multisite Trial of Atomoxetine and Parent Training for Attention-Deficit/Hyperactivity Disorder and Behavioral Noncompliance in Children with Autism Spectrum Disorder}}. {J Child Adolesc Psychopharmacol};2016 (Jan 21)
OBJECTIVE: The purpose of this study was to examine caregiver satisfaction with the research experience in a randomized clinical trial of atomoxetine (ATX) and parent training (PT) for attention-deficit/hyperactivity disorder (ADHD) and behavioral noncompliance co-occurring with autism. METHODS: The Children with Hyperactivity and Autism Research Treatment Study (CHARTS) randomly assigned 128 children 5.00-14.11 years of age to four treatment groups (ATX + PT, ATX alone, PT + placebo[PBO], and PBO). Caregivers completed an 18 item questionnaire about their satisfaction with the research experience. We summarized caregiver responses with descriptive statistics and examined whether the responses were associated with demographic variables, treatment assignment, or the child’s response to treatment (positive or negative). RESULTS: Ninety-three percent of caregivers (119) completed the questionnaire. When asked if they would join the study again if given the chance, 87% (103) responded « yes, » 13% (15) responded « maybe, » and 1% (1) responded « no. » When asked if they would recommend the study to other caregivers of children with similar problems, 92% (109) responded « yes » and 8% responded (10) « maybe. » Of the 59 Parent Satisfaction Questionnaire (PSQ) respondents who received PT, 75% (44) felt more confident in managing current child behaviors, 24% (14) felt that their level of confidence was unchanged, and 2% (1) felt less confident. Most caregivers expressed satisfaction with the study procedures, including the number of visits and the safety monitoring protocols. CONCLUSIONS: In general, caregivers were highly satisfied with their research experience. These findings may be useful for informing human subject committees and for designing study protocols that are appealing to families.
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9. Howe FE, Stagg SD. {{How Sensory Experiences Affect Adolescents with an Autistic Spectrum Condition within the Classroom}}. {J Autism Dev Disord};2016 (Jan 20)
Sensory processing difficulties are consistently reported amongst individuals with an autistic spectrum condition (ASC); these have a significant impact on daily functioning. Evidence in this area comes from observer reports and first-hand accounts; both have limitations. The current study used the Adolescent/Adult Sensory Profile (AASP; Brown and Dunn in The Adolescent/Adult Sensory Profile: self questionnaire. Pearson, 2002a), and a qualitative questionnaire to investigate sensory issues in school children with ASC. The AASP found that the participants’ mean scores were outside normal parameters. Participants reported difficulties in at least one sensory domain, with hearing affecting them the most. Content analysis revealed sensory sensitivity to affect the participant’s learning and that sensory experiences were largely negative. Results suggest that schools need to create sensory profiles for each individual with ASC.
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10. Kim H, Lim CS, Kaang BK. {{Neuronal mechanisms and circuits underlying repetitive behaviors in mouse models of autism spectrum disorder}}. {Behav Brain Funct};2016;12(1):3.
Autism spectrum disorder (ASD) refers to a broad spectrum of neurodevelopmental disorders characterized by three central behavioral symptoms: impaired social interaction, impaired social communication, and restricted and repetitive behaviors. However, the symptoms are heterogeneous among patients and a number of ASD mouse models have been generated containing mutations that mimic the mutations found in human patients with ASD. Each mouse model was found to display a unique set of repetitive behaviors. In this review, we summarize the repetitive behaviors of the ASD mouse models and variations found in their neural mechanisms including molecular and electrophysiological features. We also propose potential neuronal mechanisms underlying these repetitive behaviors, focusing on the role of the cortico-basal ganglia-thalamic circuits and brain regions associated with both social and repetitive behaviors. Further understanding of molecular and circuitry mechanisms of the repetitive behaviors associated with ASD is necessary to aid the development of effective treatments for these disorders.
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11. Kronenberg LM, Goossens PJ, van Busschbach JT, van Achterberg T, van den Brink W. {{Burden and Expressed Emotion of Caregivers in Cases of Adult Substance Use Disorder with and Without Attention Deficit/Hyperactivity Disorder or Autism Spectrum Disorder}}. {Int J Ment Health Addict};2016;14:49-63.
OBJECTIVE: To identify and compare caregiver burden and expressed emotion (EE) in adult substance use disorder (SUD) patients with and without co-occurring attention deficit/hyperactivity disorder (ADHD) or autism spectrum disorder (ASD). To examine possible differences in correlations between caregiver burden and EE across patient groups. DESIGN AND METHODS: Cross-sectional study with measures of perceived burden (Involvement Evaluation Questionnaire: IEQ), subjective stress (General Health Questionnaire: GHQ) and perceptions of expressed emotion (Level of Expressed Emotion: LEE) in informal caregivers for patients with SUD, SUD+ADHD or SUD+ASD. FINDINGS: No differences in caregiver burden or expressed emotion when caregivers for patients with SUD were compared to caregivers for patients with SUD+ADHD. A moderate but non-significant difference for caregivers of patients with SUD versus SUD+ASD, which disappeared when the number of contact hours between patient and caregiver for the SUD only group was controlled for. The IEQ sum scores also substantially correlated with the LEE sum scores. CONCLUSION: Informal caregivers for patients with only SUD show higher levels of burden and EE than informal caregivers for patients with SUD and a co-occurring ASD. This difference was largely explained by the higher number of contact hours between patient and caregiver in the SUD only group.
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12. Lucyshyn JM, Fossett B, Bakeman R, Cheremshynski C, Miller L, Lohrmann S, Binnendyk L, Khan S, Chinn S, Kwon S, Irvin LK. {{Transforming Parent-Child Interaction in Family Routines: Longitudinal Analysis with Families of Children with Developmental Disabilities}}. {J Child Fam Stud};2015 (Dec 1);24(12):3526-3541.
The efficacy and consequential validity of an ecological approach to behavioral intervention with families of children with developmental disabilities was examined. The approach aimed to transform coercive into constructive parent-child interaction in family routines. Ten families participated, including 10 mothers and fathers and 10 children 3-8 years old with developmental disabilities. Thirty-six family routines were selected (2 to 4 per family). Dependent measures included child problem behavior, routine steps completed, and coercive and constructive parent-child interaction. For each family, a single case, multiple baseline design was employed with three phases: baseline, intervention, and follow-up. Visual analysis evaluated the functional relation between intervention and improvements in child behavior and routine participation. Nonparametric tests across families evaluated the statistical significance of these improvements. Sequential analyses within families and univariate analyses across families examined changes from baseline to intervention in the percentage and odds ratio of coercive and constructive parent-child interaction. Multiple baseline results documented functional or basic effects for 8 of 10 families. Nonparametric tests showed these changes to be significant. Follow-up showed durability at 11 to 24 months postintervention. Sequential analyses documented the transformation of coercive into constructive processes for 9 of 10 families. Univariate analyses across families showed significant improvements in 2- and 4-step coercive and constructive processes but not in odds ratio. Results offer evidence of the efficacy of the approach and consequential validity of the ecological unit of analysis, parent-child interaction in family routines. Future studies should improve efficiency, and outcomes for families experiencing family systems challenges.
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13. Majdalany L, Wilder DA, Smeltz L, Lipschultz J. {{The effect of brief delays to reinforcement on the acquisition of tacts in children with autism}}. {J Appl Behav Anal};2016 (Jan 21)
We used discrete-trial training to teach 3 children with autism to tact shapes of countries using 3 levels of reinforcement delay for correct responding: 0 s (immediate delivery), 6 s, and 12 s. Two of the 3 participants acquired the targets more quickly in the immediate-delivery condition, suggesting that delays as brief as 6 s may be detrimental to learning tacts for some children.
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14. Plaisance L, Lerman DC, Laudont C, Wu WL. {{Inserting mastered targets during error correction when teaching skills to children with autism}}. {J Appl Behav Anal};2016 (Jan 21)
Research has identified a variety of effective approaches for responding to errors during discrete-trial training. In one commonly used method, the therapist delivers a prompt contingent on the occurrence of an incorrect response and then re-presents the trial so that the learner has an opportunity to perform the correct response independently. Some authors recommend inserting trials with previously mastered targets between the prompted response and opportunities to respond independently, but no studies have directly examined the benefits of this approach. In this study, we manipulated the placement of trials with mastered targets during discrete-trial training to compare the effectiveness of error correction with and without this recommended insertion procedure. Four children with autism participated, and each was taught 18 targets across 3 target sets. Results indicated that embedding trials with mastered targets into error correction may not confer benefits for most children and that doing so may lead to less efficient instruction.
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15. Pritchard MA, de Dassel T, Beller E, Bogossian F, Johnston L, Paynter J, Russo S, Scott J. {{Autism in Toddlers Born Very Preterm}}. {Pediatrics};2016 (Jan 21)
OBJECTIVE: This study aimed to determine the prevalence of autism spectrum disorder (ASD) by using the Autism Diagnostic Observation Schedule-Generic (ADOS-G) classifications in children born very preterm during their toddler years. METHODS: Two birth cohorts of toddlers (2 and 4 years old) each recruited over 12 months and born at <29 weeks' gestation were administered the Modified Checklist of Autism in Toddlers-Follow-up Interview (M-CHAT-FI) screen, the ADOS-G, and developmental assessments. The ADOS-G was conducted on toddlers with M-CHAT-FI-positive screens. RESULTS: Data were available on 88% (169/192) of children. In total, 22 (13%) toddlers screened positive and 3 (1.8%) were confirmed diagnostically with ASD. These 3 cases reached the highest ADOS-G threshold classification of autism. All but 1 child who scored below the ADOS-G thresholds (11/12) demonstrated some difficulty with social communication. Risk was significantly increased for co-occurring neurodevelopmental problems in 21 of the 22 positive-screen ASD cases. Adaptive behavior (P < .001) was the only co-occurring factor independently predictive of ASD in toddlers. CONCLUSIONS: Children born very preterm are at increased risk of ASD. By using the ADOS-G, we found a lower incidence of ASD in children born at <29 weeks' gestation compared with previous studies. Children who screened positive for ASD on the M-CHAT-FI had developmental delays consistent with subthreshold communication impairment.
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16. Romano A, Tempesta B, Micioni Di Bonaventura MV, Gaetani S. {{From Autism to Eating Disorders and More: The Role of Oxytocin in Neuropsychiatric Disorders}}. {Front Neurosci};2015;9:497.
Oxytocin (oxy) is a pituitary neuropeptide hormone synthesized from the paraventricular and supraoptic nuclei within the hypothalamus. Like other neuropeptides, oxy can modulate a wide range of neurotransmitter and neuromodulator activities. Additionally, through the neurohypophysis, oxy is secreted into the systemic circulation to act as a hormone, thereby influencing several body functions. Oxy plays a pivotal role in parturition, milk let-down and maternal behavior and has been demonstrated to be important in the formation of pair bonding between mother and infants as well as in mating pairs. Furthermore, oxy has been proven to play a key role in the regulation of several behaviors associated with neuropsychiatric disorders, including social interactions, social memory response to social stimuli, decision-making in the context of social interactions, feeding behavior, emotional reactivity, etc. An increasing body of evidence suggests that deregulations of the oxytocinergic system might be involved in the pathophysiology of certain neuropsychiatric disorders such as autism, eating disorders, schizophrenia, mood, and anxiety disorders. The potential use of oxy in these mental health disorders is attracting growing interest since numerous beneficial properties are ascribed to this neuropeptide. The present manuscript will review the existing findings on the role played by oxy in a variety of distinct physiological and behavioral functions (Figure 1) and on its role and impact in different psychiatric disorders. The aim of this review is to highlight the need of further investigations on this target that might contribute to the development of novel more efficacious therapies. Figure 1Oxytocin regulatory control of different and complex processes.
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17. Rynkiewicz A, Schuller B, Marchi E, Piana S, Camurri A, Lassalle A, Baron-Cohen S. {{An investigation of the ‘female camouflage effect’ in autism using a computerized ADOS-2 and a test of sex/gender differences}}. {Mol Autism};2016;7:10.
BACKGROUND: Autism spectrum conditions (autism) are diagnosed more frequently in boys than in girls. Females with autism may have been under-identified due to not only a male-biased understanding of autism but also females’ camouflaging. The study describes a new technique that allows automated coding of non-verbal mode of communication (gestures) and offers the possibility of objective, evaluation of gestures, independent of human judgment. The EyesWeb software platform and the Kinect sensor during two demonstration activities of ADOS-2 (Autism Diagnostic Observation Schedule, Second Edition) were used. METHODS: The study group consisted of 33 high-functioning Polish girls and boys with formal diagnosis of autism or Asperger syndrome aged 5-10, with fluent speech, IQ average and above and their parents (girls with autism, n = 16; boys with autism, n = 17). All children were assessed during two demonstration activities of Module 3 of ADOS-2, administered in Polish, and coded using Polish codes. Children were also assessed with Polish versions of the Eyes and Faces Tests. Parents provided information on the author-reviewed Polish research translation of SCQ (Social Communication Questionnaire, Current and Lifetime) and Polish version of AQ Child (Autism Spectrum Quotient, Child). RESULTS: Girls with autism tended to use gestures more vividly as compared to boys with autism during two demonstration activities of ADOS-2. Girls with autism made significantly more mistakes than boys with autism on the Faces Test. All children with autism had high scores in AQ Child, which confirmed the presence of autistic traits in this group. The current communication skills of boys with autism reported by parents in SCQ were significantly better than those of girls with autism. However, both girls with autism and boys with autism improved in the social and communication abilities over the lifetime. The number of stereotypic behaviours in boys significantly decreased over life whereas it remained at a comparable level in girls with autism. CONCLUSIONS: High-functioning females with autism might present better on non-verbal (gestures) mode of communication than boys with autism. It may camouflage other diagnostic features. It poses risk of under-diagnosis or not receiving the appropriate diagnosis for this population. Further research is required to examine this phenomenon so appropriate gender revisions to the diagnostic assessments might be implemented.
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18. Srinivasan SM, Kaur M, Park IK, Gifford TD, Marsh KL, Bhat AN. {{The Effects of Rhythm and Robotic Interventions on the Imitation/Praxis, Interpersonal Synchrony, and Motor Performance of Children with Autism Spectrum Disorder (ASD): A Pilot Randomized Controlled Trial}}. {Autism Res Treat};2015;2015:736516.
We assessed the effects of three interventions, rhythm, robotic, and standard-of-care, on the imitation/praxis, interpersonal synchrony, and overall motor performance of 36 children with Autism Spectrum Disorder (ASD) between 5 and 12 years of age. Children were matched on age, level of functioning, and services received, prior to random assignment to one of the three groups. Training was provided for 8 weeks with 4 sessions provided each week. We assessed generalized changes in motor skills from the pretest to the posttest using a standardized test of motor performance, the Bruininks-Oseretsky Test of Motor Proficiency, 2nd edition (BOT-2). We also assessed training-specific changes in imitation/praxis and interpersonal synchrony during an early and a late session. Consistent with the training activities practiced, the rhythm and robot groups improved on the body coordination composite of the BOT-2, whereas the comparison group improved on the fine manual control composite of the BOT-2. All three groups demonstrated improvements in imitation/praxis. The rhythm and robot groups also showed improved interpersonal synchrony performance from the early to the late session. Overall, socially embedded movement-based contexts are valuable in promoting imitation/praxis, interpersonal synchrony, and motor performance and should be included within the standard-of-care treatment for children with ASD.
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19. Su CC, Chi MH, Lin SH, Yang YK. {{Bidirectional association between autism spectrum disorder and epilepsy in child and adolescent patients: a population-based cohort study}}. {Eur Child Adolesc Psychiatry};2016 (Jan 20)
This study aimed to assess whether there is a bidirectional association between autism spectrum disorder (ASD) and epilepsy in child and adolescent patients. The National Health Insurance Research Database of Taiwan was used to conduct two cohort studies of patients who were under 18 years of age during the period 1997-2008. Cohort 1 comprised patients with newly diagnosed ASD but excluded those diagnosed with epilepsy prior to ASD. A non-ASD comparison group was matched to each case in terms of age and sex. Cohort 2 comprised patients with newly diagnosed epilepsy but excluded those diagnosed with ASD prior to epilepsy. A non-epilepsy comparison group was matched to each case in terms of age and sex. We calculated the incidence of epilepsy in patients with ASD and hazard ratio (HR) to estimate the risk of epilepsy in association with ASD in cohort 1, and the reverse in cohort 2. In cohort 1, the incidence of epilepsy was 13.7 in the ASD group and 1.3 in the non-ASD group (per 1000 person-years). The adjusted HR for epilepsy was 8.4 (95 % CI 5.5-12.7) in the ASD group when compared with the non-ASD group. In cohort 2, the incidence of ASD was 3.4 in the epilepsy group and 0.3 in the non-epilepsy group (per 1000 person-years). The adjusted HR for ASD was 8.4 (95 % CI 6.2-11.4) in the epilepsy group when compared with the non-epilepsy group. A bidirectional association was, therefore, found to exist between ASD and epilepsy. These findings implicate that ASD and epilepsy probably share common risk factors. However, further studies are required to reveal more detail on the mechanism of this bidirectional association.
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20. Wright B, Marshall D, Adamson J, Ainsworth H, Ali S, Allgar V, Collingridge Moore D, Cook E, Dempster P, Hackney L, McMillan D, Trepel D, Williams C. {{Social Stories to alleviate challenging behaviour and social difficulties exhibited by children with autism spectrum disorder in mainstream schools: design of a manualised training toolkit and feasibility study for a cluster randomised controlled trial with nested qualitative and cost-effectiveness components}}. {Health Technol Assess};2016 (Jan);20(6):1-258.
BACKGROUND: A Social Story (Carol Gray) is a child-friendly intervention that is used to give children with autism spectrum disorders (ASDs) social information in situations where they have social difficulties. Limited evidence mainly using single-case designs suggests that they can reduce anxiety and challenging behaviour. OBJECTIVES: The objectives were to conduct a systematic review, use this to develop a manualised intervention and run a feasibility trial to inform a fully powered randomised controlled trial (RCT) on their clinical effectiveness and cost-effectiveness in schools. DESIGN: This is a three-stage study following the Medical Research Council framework for complex interventions. Specifically, it involved a theoretical phase, a qualitative stage and a feasibility trial stage. SETTING: Qualitative interviews and focus groups took place in Child and Adolescent Mental Health Service and primary care settings. The feasibility study took place in 37 local mainstream schools. PARTICIPANTS: Fifty children (aged 5-15 years) in mainstream school settings with a diagnosis of ASD were entered into the trial. For each child, an associated teacher and parent was also recruited. INTERVENTIONS: The intervention was a goal-setting session followed by a manualised toolkit (including a training session) for creating Social Stories for use with school-aged children. The comparator treatment was a goal-setting session followed by an attention control. Both arms received treatment as usual. MAIN OUTCOME MEASURES: Outcomes tested as part of the feasibility study included child- and proxy-completed questionnaires for mental health, quality of life and goal-based outcome measures. Adults additionally completed behaviour diaries and the parental stress index. RESULTS: The review found that the research into social stories is predominantly based in the USA, carried out in under-12-year-olds and using single-case designs. Most studies either did not follow established Social Story criteria or did not report if they did. The assessment of effectiveness presents a largely positive picture but is limited by methodological issues. There were no adequate RCTs and insufficient information to assess a number of important sources of potential bias in most studies. A manualised intervention was produced using an iterative process between user focus groups and a writing team, and assessed in the feasibility study. All 50 participant groups were recruited within the study time frame. Two outcome measures, the Social Responsiveness Scale-2 and the custom-made goal-based measure, showed high levels of completion rates and appeared to be capturing social and behaviour skills targeted by the use of Social Stories. Detailed recommendations for a full trial are provided. LIMITATIONS: Blinding of participants was not feasible. Treatment fidelity was not assessed because of low levels of story return rates. CONCLUSIONS: The study showed that a fully powered RCT is feasible with an extended geographical footprint. A large amount of data and information has helped to inform the design of this RCT, which will be the subject of a future research grant application. Future work could focus on developing an appropriate blinded outcome measure for this population. STUDY REGISTRATION: This study is registered as PROSPERO CRD42011001440. TRIAL REGISTRATION: Current Controlled Trials ISRCTN96286707. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 20, No. 6. See the NIHR Journals Library website for further project information.
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21. Young AM, Chakrabarti B, Roberts D, Lai MC, Suckling J, Baron-Cohen S. {{From molecules to neural morphology: understanding neuroinflammation in autism spectrum condition}}. {Mol Autism};2016;7:9.
Growing evidence points toward a critical role for early (prenatal) atypical neurodevelopmental processes in the aetiology of autism spectrum condition (ASC). One such process that could impact early neural development is inflammation. We review the evidence for atypical expression of molecular markers in the amniotic fluid, serum, cerebrospinal fluid (CSF), and the brain parenchyma that suggest a role for inflammation in the emergence of ASC. This is complemented with a number of neuroimaging and neuropathological studies describing microglial activation. Implications for treatment are discussed.
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22. Zhang Y, Hodgson NW, Trivedi MS, Abdolmaleky HM, Fournier M, Cuenod M, Do KQ, Deth RC. {{Decreased Brain Levels of Vitamin B12 in Aging, Autism and Schizophrenia}}. {PLoS One};2016;11(1):e0146797.
Many studies indicate a crucial role for the vitamin B12 and folate-dependent enzyme methionine synthase (MS) in brain development and function, but vitamin B12 status in the brain across the lifespan has not been previously investigated. Vitamin B12 (cobalamin, Cbl) exists in multiple forms, including methylcobalamin (MeCbl) and adenosylcobalamin (AdoCbl), serving as cofactors for MS and methylmalonylCoA mutase, respectively. We measured levels of five Cbl species in postmortem human frontal cortex of 43 control subjects, from 19 weeks of fetal development through 80 years of age, and 12 autistic and 9 schizophrenic subjects. Total Cbl was significantly lower in older control subjects (> 60 yrs of age), primarily reflecting a >10-fold age-dependent decline in the level of MeCbl. Levels of inactive cyanocobalamin (CNCbl) were remarkably higher in fetal brain samples. In both autistic and schizophrenic subjects MeCbl and AdoCbl levels were more than 3-fold lower than age-matched controls. In autistic subjects lower MeCbl was associated with decreased MS activity and elevated levels of its substrate homocysteine (HCY). Low levels of the antioxidant glutathione (GSH) have been linked to both autism and schizophrenia, and both total Cbl and MeCbl levels were decreased in glutamate-cysteine ligase modulatory subunit knockout (GCLM-KO) mice, which exhibit low GSH levels. Thus our findings reveal a previously unrecognized decrease in brain vitamin B12 status across the lifespan that may reflect an adaptation to increasing antioxidant demand, while accelerated deficits due to GSH deficiency may contribute to neurodevelopmental and neuropsychiatric disorders.
