1. Anderson GM. {{Autism Risk and Serotonin Reuptake Inhibitors}}. {JAMA Psychiatry};2019 (Mar 6)
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2. Brookman-Frazee L, Roesch S, Chlebowski C, Baker-Ericzen M, Ganger W. {{Effectiveness of Training Therapists to Deliver An Individualized Mental Health Intervention for Children With ASD in Publicly Funded Mental Health Services: A Cluster Randomized Clinical Trial}}. {JAMA Psychiatry};2019 (Mar 6)
Importance: Publicly funded mental health services play an important role in addressing co-occurring mental health problems in children with autism spectrum disorder (ASD); however, therapists report lacking training to effectively serve this complex population. Objective: To test the effectiveness of training community therapists in An Individualized Mental Health Intervention for ASD (AIM HI) on challenging behaviors across 18 months among children with ASD and identify moderators and mediators of any intervention effects. Design, Setting, and Participants: Cluster randomized trial conducted in 29 publicly funded outpatient and school-based mental health programs in southern California from 2012 to 2017. Programs were randomized to receive immediate AIM HI training or provide usual care followed by receipt of AIM HI training. Therapist participants were recruited from enrolled programs, and child participants were recruited from participant therapists’ caseloads. Data were analyzed from 202 children with ASD who were aged 5 to 13 years. Interventions: The AIM HI protocol is a package of parent-mediated and child-focused strategies aimed to reduce challenging behaviors in children with ASD who are 5 to 13 years old. It was designed for delivery in publicly funded mental health services based on a systematic assessment of therapist training needs and child clinical needs. The therapist training and consultation process takes approximately 6 months and includes an introductory workshop, 11 structured consultation meetings as the therapist delivers AIM HI with a current client, and case-specific performance feedback from trainers. Main Outcomes and Measures: Child participants were assessed for challenging behaviors using the Eyberg Child Behavior Inventory (ECBI) and Social Skills Improvement System (SSIS) Competing Problem Behaviors scales based on parent report at baseline and at 6-month intervals for 18 months. Outcomes were analyzed using intent-to-treat models. Results: In total, 202 children with ASD (mean [SD] age, 9.1 [2.4] years; 170 [84.2%] male; 121 [59.9%] Latinx) were eligible, enrolled, and included in the analyses. Statistically significant group by time interactions for the ECBI Intensity (B = -0.38; P = .02) and ECBI Problem (B = -1.00; P = .005) scales were observed, with significantly larger decreases in ECBI Intensity scores in the AIM HI group (B = -1.36; P < .001) relative to the usual care group (B = -0.98; P < .001) and a significantly larger decrease in ECBI Problem scores in the AIM HI group (B = -1.22; P < .001) relative to the usual care group (B = -0.20; P = .29). Therapist fidelity moderated these intervention effects. Conclusions and Relevance: The present findings support the effectiveness of training therapists to deliver the AIM HI model to children with ASD receiving publicly funded mental health services. Trial Registration: ClinicalTrials.gov Identifier: NCT02416323. Lien vers le texte intégral (Open Access ou abonnement)
3. Dunsmore JC, Ashley RA, Zhou Y, Swain DM, Factor RS, Broomell AP, Waldron JC, Bell MA, Scarpa A. {{Marching to the beat of your own drum?: A proof-of-concept study assessing physiological linkage in Autism Spectrum Disorder}}. {Biol Psychol};2019 (Mar 6)
Autism Spectrum Disorder (ASD) is a neurodevelopmental condition characterized by difficulty in dynamically adjusting behavior to interact effectively with others, or social reciprocity. Synchronization of physiological responses between interacting partners, or physiological linkage (PL), is thought to provide a foundation for social reciprocity. In previous work we developed a new technique to measure PL using dynamic linear time series modeling to assess cardiac interbeat interval (IBI) linkage in typically developing same-sex unacquainted dyads (Scarpa et al., 2017). The current article describes a proof-of-concept study with three dyads of young adults with ASD interacting with same-sex unacquainted typically developing (TD) partners. This pilot data is applied to propose potential benefits of using this technique to quantify and assess PL in individuals with ASD, both for basic research and for intervention science. Discussion focuses on applications of this measure to potentially advance knowledge of the biology-behavior link in ASD.
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4. Einspieler C, Marschik PB. {{Regression in Rett syndrome: Developmental pathways to its onset}}. {Neurosci Biobehav Rev};2019 (Mar);98:320-332.
Rett syndrome (RTT) is an X-linked genetic disorder that occurs predominantly in females. The clinical picture associated with RTT is defined by core and supportive consensus criteria, with a period of behavioural regression being a conditio sine qua non. This review sheds light on atypical neurofunctions and potential behavioural biomarkers before the onset of regression. The main focus lies on (a) motor development, especially on purposeful hand movements and the occurrence of stereotypies; and (b) speech-language and socio-communicative development. We outline potentially specific atypical behavioural patterns in these domains (e.g., vocalisations on inspiratory airstream) and different developmental traits of regression: (i) non-achievement of certain milestones: ‘regression’, here, might point to the fact that the lack of respective behavioural patterns appeared more and more worrisome with increasing age; and (ii) developmental milestones were achieved and functions deteriorate or even get lost during regression. To conclude, we are not quite there yet, but seem to be on the right track towards defining new and reliable neurofunctional markers for early detection of RTT.
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5. Fontil L, Sladeczek IE, Gittens J, Kubishyn N, Habib K. {{From early intervention to elementary school: A survey of transition support practices for children with autism spectrum disorders}}. {Res Dev Disabil};2019 (Mar 6);88:30-41.
BACKGROUND: Early school transitions can be difficult for children, however, children with autism spectrum disorders (ASDs) often experience greater difficulty making the transition into school. Transition support practices, such as transition meetings, can facilitate successful school beginnings. AIMS: The aim of the present study was to determine what type and amount of transition support practices early intervention (EI) service providers were implementing to support the transition to school of children with ASDs. Barriers and facilitators to transition planning were also evaluated. METHODS AND PROCEDURES: Surveys were completed by program directors of 164 EI service providers across Canada. Program directors reported on transition support practices in use, as well as program level characteristics. OUTCOMES AND RESULTS: Overall, Canadian EI providers reported using a high frequency of high-quality, individualized transition supports for children with ASD. Major barriers included a lack of government support and elementary school engagement. Specialized transition training and offering ASD-specific services were related to an increase in transition supports. CONCLUSIONS AND IMPLICATIONS: The present study highlights areas for improvement in transition support practice and policy. Namely, increased government support could lead to increased levels of elementary school engagement, which has important implications for children’s long- and short-term educational outcomes.
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6. Hansen SN, Schendel DE, Francis RW, Windham GC, Bresnahan M, Levine SZ, Reichenberg A, Gissler M, Kodesh A, Bai D, Yip BHK, Leonard H, Sandin S, Buxbaum JD, Hultman C, Sourander A, Glasson EJ, Wong K, Oberg R, Parner ET. {{Recurrence Risk of Autism in Siblings and Cousins: A Multi-National, Population-Based Study}}. {J Am Acad Child Adolesc Psychiatry};2019 (Mar 6)
OBJECTIVE: Familial recurrence risk is an important population-level measure of the combined genetic and shared familial liability of autism spectrum disorder (ASD). Objectives were to estimate ASD recurrence risk among siblings and cousins by varying degree of relatedness and by sex. METHOD: Population-based cohort study of 1998-2007 livebirths from California, Denmark, Finland, Israel, Sweden and Western Australia followed through 2011-2015. Subjects were monitored for an ASD diagnosis in their older siblings or cousins (exposure) and for their own ASD diagnosis (outcome). The relative recurrence risk was estimated for different sibling- and cousin-pairs, for each site separately and combined, and by sex. RESULTS: During follow-up, 29,998 cases of ASD were observed among the 2,551,918 births used to estimate recurrence in ASD and 33,769 cases of childhood autism (CA) were observed among the 6,110,942 births used to estimate CA recurrence. Compared to the risk in unaffected families, we observed an 8.4-fold increase in the risk of ASD following an older sibling with ASD and an 17.4-fold increase in the risk of CA following an older sibling with CA. A 2-fold increase in the risk for cousin recurrence was observed for both disorders. We also found a significant difference in sibling ASD recurrence risk by sex. CONCLUSION: Our estimates of relative recurrence risks for ASD and CA will assist clinicians and families in understanding autism risk in the context of other families in their population. The observed variation by sex underlines the need to deepen our understanding of factors influencing ASD familial risk.
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7. Hong SJ, de Wael RV, Bethlehem RAI, Lariviere S, Paquola C, Valk SL, Milham MP, Di Martino A, Margulies DS, Smallwood J, Bernhardt BC. {{Atypical functional connectome hierarchy in autism}}. {Nat Commun};2019 (Mar 4);10(1):1022.
One paradox of autism is the co-occurrence of deficits in sensory and higher-order socio-cognitive processing. Here, we examined whether these phenotypical patterns may relate to an overarching system-level imbalance-specifically a disruption in macroscale hierarchy affecting integration and segregation of unimodal and transmodal networks. Combining connectome gradient and stepwise connectivity analysis based on task-free functional magnetic resonance imaging (fMRI), we demonstrated atypical connectivity transitions between sensory and higher-order default mode regions in a large cohort of individuals with autism relative to typically-developing controls. Further analyses indicated that reduced differentiation related to perturbed stepwise connectivity from sensory towards transmodal areas, as well as atypical long-range rich-club connectivity. Supervised pattern learning revealed that hierarchical features predicted deficits in social cognition and low-level behavioral symptoms, but not communication-related symptoms. Our findings provide new evidence for imbalances in network hierarchy in autism, which offers a parsimonious reference frame to consolidate its diverse features.
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8. Iwama K, Mizuguchi T, Takeshita E, Nakagawa E, Okazaki T, Nomura Y, Iijima Y, Kajiura I, Sugai K, Saito T, Sasaki M, Yuge K, Saikusa T, Okamoto N, Takahashi S, Amamoto M, Tomita I, Kumada S, Anzai Y, Hoshino K, Fattal-Valevski A, Shiroma N, Ohfu M, Moroto M, Tanda K, Nakagawa T, Sakakibara T, Nabatame S, Matsuo M, Yamamoto A, Yukishita S, Inoue K, Waga C, Nakamura Y, Watanabe S, Ohba C, Sengoku T, Fujita A, Mitsuhashi S, Miyatake S, Takata A, Miyake N, Ogata K, Ito S, Saitsu H, Matsuishi T, Goto YI, Matsumoto N. {{Genetic landscape of Rett syndrome-like phenotypes revealed by whole exome sequencing}}. {J Med Genet};2019 (Mar 6)
BACKGROUND: Rett syndrome (RTT) is a characteristic neurological disease presenting with regressive loss of neurodevelopmental milestones. Typical RTT is generally caused by abnormality of methyl-CpG binding protein 2 (MECP2). Our objective to investigate the genetic landscape of MECP2-negative typical/atypical RTT and RTT-like phenotypes using whole exome sequencing (WES). METHODS: We performed WES on 77 MECP2-negative patients either with typical RTT (n=11), atypical RTT (n=22) or RTT-like phenotypes (n=44) incompatible with the RTT criteria. RESULTS: Pathogenic or likely pathogenic single-nucleotide variants in 28 known genes were found in 39 of 77 (50.6%) patients. WES-based CNV analysis revealed pathogenic deletions involving six known genes (including MECP2) in 8 of 77 (10.4%) patients. Overall, diagnostic yield was 47 of 77 (61.0 %). Furthermore, strong candidate variants were found in four novel genes: a de novo variant in each of ATPase H(+) transporting V0 subunit A1 (ATP6V0A1), ubiquitin-specific peptidase 8 (USP8) and microtubule-associated serine/threonine kinase 3 (MAST3), as well as biallelic variants in nuclear receptor corepressor 2 (NCOR2). CONCLUSIONS: Our study provides a new landscape including additional genetic variants contributing to RTT-like phenotypes, highlighting the importance of comprehensive genetic analysis.
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9. Janecka M, Sandin S, Reichenberg A. {{Autism Risk and Serotonin Reuptake Inhibitors-Reply}}. {JAMA Psychiatry};2019 (Mar 6)
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10. Kwon MK, Moore A, Barnes CC, Cha D, Pierce K. {{Typical Levels of Eye-Region Fixation in Toddlers With ASD Across Multiple Contexts}}. {J Am Acad Child Adolesc Psychiatry};2019 (Mar 6)
OBJECTIVE: Unusual eye contact is a common clinical feature in ASD, yet eye tracking studies that quantify eye fixation reveal inconsistent results, possibly due to small sample sizes, varied stimuli, and considerable heterogeneity of eye-region fixation even within typical development. Goals were to examine: (1) eye-region fixation levels in a large, very young cohort; (2) the degree to which the presence of speech, hand gestures, and a geometric distractor influence eye-region fixation; and (3) possible developmental changes across time. METHOD: In Experiment 1, 385 toddlers (143 with ASD; 242 non-ASD, 11 to 47 months) watched an actress engaging in child-directed speech with hand gestures against a plain background. Ninety-one toddlers participated again approximately 8 months later. In Experiment 2, another 231 toddlers (74 with ASD; 157 non-ASD, 12 to 47 months) watched the same video, but with embedded geometric distractors. Total fixation duration within facial and body (e.g., eyes, hands), and geometric distractor regions (Experiment 2 only) while the actress was speaking or silent, with or without gesturing was examined as were relationships with clinical traits. RESULTS: Overall, across both experiments and both cross-sectional and longitudinal samples, eye-region fixation duration did not differ between toddlers with and without ASD, although fixation towards the face overall was reduced in toddlers with ASD. This reduction became more apparent with the presence of geometric distractors (Experiment 2) as indexed by a geometric preference score, and this score was associated with autism severity. CONCLUSION: Within the context of viewing child-friendly vignettes, reduced eye-region fixation does not reliably characterize toddlers with ASD. An index of competition between faces and external distractors might be a more robust measure.
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11. Marsack-Topolewski CN, Church HL. {{Impact of Caregiver Burden on Quality of Life for Parents of Adult Children With Autism Spectrum Disorder}}. {Am J Intellect Dev Disabil};2019 (Mar);124(2):145-156.
This study sought to examine the impact of time, developmental, emotional, and financial burdens on the quality of life (QOL) for parents (aged 50+) of an adult child with autism spectrum disorder (ASD). Participants ( N = 320) completed a web-based survey and could indicate interest in participating in one-on-one follow up interviews. Multiple linear regression analysis indicated that two variables, developmental burden and impact of caregiving on finances, were statistically significant predictors of parents’ QOL. Developmental burden was the strongest predictor of parental QOL, demonstrating an inverse relationship. Qualitatively, reported findings indicated that many parents were experiencing all four burdens. Findings highlighted the need to provide services and supports to alleviate burden among aging parents of adult children with ASD.
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12. Ornoy A, Weinstein-Fudim L, Ergaz Z. {{Prevention or Amelioration of Autism-Like Symptoms in Animal Models: Will it Bring Us Closer to Treating Human ASD?}}. {Int J Mol Sci};2019 (Mar 1);20(5)
Since the first animal model of valproic acid (VPA) induced autistic-like behavior, many genetic and non-genetic experimental animal models for Autism Spectrum Disorder (ASD) have been described. The more common non-genetic animal models induce ASD in rats and mice by infection/inflammation or the prenatal or early postnatal administration of VPA. Through the establishment of these models, attempts have been made to ameliorate or even prevent ASD-like symptoms. Some of the genetic models have been successfully treated by genetic manipulations or the manipulation of neurotransmission. Different antioxidants have been used (i.e., astaxanthin, green tea, piperine) to reduce brain oxidative stress in VPA-induced ASD models. Agents affecting brain neurotransmitters (donepezil, agmatine, agomelatine, memantine, oxytocin) also successfully reduced ASD-like symptoms. However, complete prevention of the development of symptoms was achieved only rarely. In our recent study, we treated mouse offspring exposed on postnatal day four to VPA with S-adenosine methionine (SAM) for three days, and prevented ASD-like behavior, brain oxidative stress, and the changes in gene expression induced by VPA. In this review, we describe, in addition to our data, the existing literature on the prevention/amelioration of ASD-like symptoms. We also discuss the possible mechanisms underlying some of these phenomena. Finally, we describe some of the clinical trials in children with ASD that were carried out as a result of data from animal studies, especially those with polyunsaturated fatty acids (PUFAs).
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13. Plesa Skwerer D, Joseph RM, Eggleston B, Meyer SR, Tager-Flusberg H. {{Prevalence and Correlates of Psychiatric Symptoms in Minimally Verbal Children and Adolescents With ASD}}. {Front Psychiatry};2019;10:43.
Despite many studies documenting the prevalence of various co-occurring psychiatric symptoms in children and adults with ASD, less is known about how these symptoms relate to subtypes defined by particular phenotypic features within the ASD population. We examined the severity and prevalence of comorbid symptoms of psychopathology, emotion dysregulation, and maladaptive behaviors, as well as adaptive functioning, in a group of 65 minimally verbal children (n = 33) and adolescents (n = 32) with ASD. On the Child and Adolescent Symptom Inventory (CASI-5), for all the symptom classifications except oppositional defiant disorder and conduct disorder, more participants in our sample showed elevated or clinically concerning severity scores relative to the general population. On the Emotion Dysregulation Inventory (EDI), the mean scores for Reactivity and Dysphoria factors in our sample were lower than in the autism calibration sample, which included a large number of inpatient youth with ASD. Overall, few differences were found between the children and adolescents within this severely impaired group of ASD individuals based on clinical cutoff scores on the CASI-5 and EDI factor scores. Psychiatric comorbidities and emotion dysregulation measures were not correlated with autism symptom severity or with measures of adaptive functioning, and were largely unrelated to IQ in our sample. The number of clinically significant psychiatric symptoms on the CASI-5 emerged as the main predictor of maladaptive behaviors. Findings suggest a wide range of co-occurring psychopathology and high degree of maladaptive behavior among minimally verbal children and adolescents with ASD, which are not directly attributable to autism symptom severity, intellectual disability or limitations in adaptive functioning.
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14. Qian X, Larson SA, Ticha R, Stancliffe R, Pettingell SL. {{Active Support Training, Staff Assistance, and Engagement of Individuals With Intellectual and Developmental Disabilities in the United States: Randomized Controlled Trial}}. {Am J Intellect Dev Disabil};2019 (Mar);124(2):157-173.
Two non-U.S. quasi-experimental studies reported Active Support training was associated with increased engagement in individuals with IDD, but no randomized controlled trials (RCTs) exist. We evaluated effects of Active Support training on staff assistance, and social and nonsocial engagement in 75 individuals with intellectual and developmental disabilities (IDD) in U.S. group homes. We detected no significant effects of active support training. Individuals with more skills and less challenging behavior engaged more in nonsocial activities. Younger individuals with more skills living in homes with fewer staff changes were more socially engaged. Factors associated with nonsocial engagement mirrored those reported in Qian, Ticha, Larson, Stancliffe, & Wuorio, (2015) . Staffing-related implementation challenges and statistical power limited our ability to detect differences.
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15. Schmidt EK, Hand BN, Simpson KN, Darragh AR. {{Sexually transmitted infections in privately insured adults with intellectual and developmental disabilities}}. {J Comp Eff Res};2019 (Mar 6)
AIM: Individuals with intellectual and developmental disabilities (I/DD) may have an increased risk of sexually transmitted infections (STIs) due to limited sexual health education and higher rates of sexual abuse, yet little is known about the prevalence of STIs and STI testing in this population. METHODS: This study compared national samples of privately insured individuals with (n = 25,193) and without I/DD (n = 25,193) on the prevalence of STIs and STI testing. RESULTS: In multivariable models, individuals with I/DD were significantly less likely to have an STI diagnosis and no difference was found between groups on the odds of STI testing overall. CONCLUSION: Findings may, in part, be explained by fewer sexual experiences, increased supervision in social settings and delayed onset of sexual activity among those with I/DD.
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16. Shea LL, Field R, Xie M, Marcus S, Newschaffer C, Mandell D. {{Transition-Age Medicaid Coverage for Adolescents With Autism and Adolescents With Intellectual Disability}}. {Am J Intellect Dev Disabil};2019 (Mar);124(2):174-185.
Although the majority of adolescents with autism spectrum disorder (ASD) rely on healthcare coverage through Medicaid during their transition into adulthood, little is known about their continuing eligibility. This study used Medicaid Analytic Extract (MAX) data to examine Medicaid coverage in a national sample using a cohort of adolescents with ASD ( n = 4,179) and a like-aged cohort with intellectual disability (ID, n = 21,844) over 5 years using survival analysis and Cox regression models. More than 1 in 4 adolescents with ASD lost coverage and fewer than half subsequently regained it. They were more likely to disenroll than adolescents with ID. Similarities in overall patterns among the 2 groups suggest that the experience of adolescents with ASD was characteristic of more general aspects of behavioral health coverage and indicate the need for programmatic reforms.
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17. Wigby K, Nicolas S, Carpinello M, Ricciardi MT, Willis MJ. {{Whole Exome Sequencing Guides Pharmacotherapy for an Adolescent With Autism Spectrum Disorder and Psychosis}}. {J Am Acad Child Adolesc Psychiatry};2019 (Mar);58(3):376-377.
Genomic testing, including whole exome sequencing (WES), can result in specific changes to medical management. To illustrate the clinical utility of WES for complex neuropsychiatric disease, we report a male adolescent with autism spectrum disorder, psychosis, and regression and discuss how the WES findings guided his pharmacologic management.
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18. Young A, Ferguson-Coleman E, Wright B, Le Couteur A. {{Parental Conceptualizations of Autism and Deafness in British Deaf Children}}. {J Deaf Stud Deaf Educ};2019 (Mar 6)
The co-occurrence of childhood deafness and autism raises complex challenges for diagnosis and family support. In this article, we explore with hearing and Deaf parents their observations of the interaction between deafness and autism and identify how the intersections of deafness and autism are conceptualized in everyday life. Eight parents participated (two of whom were Deaf BSL users) in semi-structured interviews in either BSL or spoken English. Data analysis was underpinned by a phenomenological approach in the hermeneutic tradition. Findings are discussed in terms of parents’ perceptions of the relevance of deafness to their understanding of autism for their particular child, the effects of autism on sign and spoken language development and the relationship between deafness and autism in terms of their own and others’ attributions of their children’s characteristics. The significance of the findings for parental contributions’ to diagnostic assessment and the tailoring of family support are considered.
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19. Zhao X, Gazy I, Hayward B, Pintado E, Hwang YH, Tassone F, Usdin K. {{Repeat Instability in the Fragile X-Related Disorders: Lessons from a Mouse Model}}. {Brain Sci};2019 (Mar 1);9(3)
The fragile X-related disorders (FXDs) are a group of clinical conditions that result primarily from an unusual mutation, the expansion of a CGG-repeat tract in exon 1 of the FMR1 gene. Mouse models are proving useful for understanding many aspects of disease pathology in these disorders. There is also reason to think that such models may be useful for understanding the molecular basis of the unusual mutation responsible for these disorders. This review will discuss what has been learnt to date about mechanisms of repeat instability from a knock-in FXD mouse model and what the implications of these findings may be for humans carrying expansion-prone FMR1 alleles.
