Pubmed du 07/08/20

vendredi 7 août 2020

1. Brookman-Frazee L, Chlebowski C, Villodas M, Roesch S, Martinez K. Training Community Therapists to Deliver a Mental Health Intervention for Autism Spectrum Disorder : Changes in Caregiver Outcomes and Mediating Role on Child Outcomes. J Am Acad Child Adolesc Psychiatry ;2020 (Jul 31)

OBJECTIVE : This study examines the impact of training therapists to deliver An Individualized Mental Health Intervention for autism spectrum disorder (ASD) (AIM HI) for children with autism spectrum disorder on caregiver outcomes and the mediating role of changes in caregiver outcomes on child outcomes. METHOD : Data were drawn from a cluster randomized trial conducted in 29 publicly-funded mental health programs randomized to receive AIM HI training or usual care. Therapists were recruited from enrolled programs and child/caregiver participants enrolled from therapists’ caseloads. Participants included 202 caregivers of children aged 5 to 13 with autism spectrum disorder. Caregiver strain and sense of competence were assessed at baseline and 6 month post baseline. Child behaviors were assessed at baseline and 6, 12, and 18 months post baseline. Therapist delivery of evidence-based intervention strategies were assessed between baseline and 6 months. RESULTS : A significant training effect was observed for caregiver sense of competence, with AIM HI caregivers reporting significantly greater improvement relative to usual care. There was no significant training effect for caregiver strain. Observer-rated therapist delivery of evidence-based interventions strategies over 6 months mediated training effects for sense of competence at 6 months. Changes in sense of competence from baseline to 6 months was associated with reduced child challenging behaviors at 6 months and mediated child outcomes at 12 and 18 months. CONCLUSION : Combined with research demonstrating effectiveness of therapist AIM HI training on child outcomes, this study provides further evidence of the positive impact of training community therapists in the AIM HI intervention.

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2. Capriola-Hall NN, McFayden T, Ollendick TH, White SW. Caution When Screening for Autism among Socially Anxious Youth. J Autism Dev Disord ;2020 (Aug 7)

Social anxiety disorder (SAD) is commonly comorbid with autism spectrum disorder (ASD). Here, in a sample of 86 children and adolescents (M(AGE) = 12.62 years ; 68.6% male), 28 of whom were diagnosed with ASD, 34 with SAD, and 24 with comorbid ASD and SAD, we compared parent-reported scores from the Social Responsiveness Scale-Second Edition (SRS-2 ; Constantino and Gruber in Social Responsiveness Scale (SRS ; Constantino and Gruber 2012) to determine the sensitivity and specificity of the measure in cases of differential diagnosis between SAD and ASD. Results suggest that neither the subscales, nor the SRS-2 total score, consistently differed between ASD and SAD. Sensitivity and specificity analyses suggested that the SRS-2 total poorly discriminated ASD from SAD. When screening socially anxious youth for possible ASD, caution should be taken.

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3. Gouveia FV, Germann J, Devenyi GA, Morais R, Santos APM, Fonoff ET, Hamani C, Brentani H, Chakravarty MM, Martinez RCR. Refractoriness of aggressive behaviour to pharmacological treatment : cortical thickness analysis in autism spectrum disorder. BJPsych Open ;2020 (Aug 7) ;6(5):e85.

Aggressive behaviour is a highly prevalent and devastating condition in autism spectrum disorder resulting in impoverished quality of life. Gold-standard therapies are ineffective in about 30% of patients leading to greater suffering. We investigated cortical thickness in individuals with autism spectrum disorder with pharmacological-treatment-refractory aggressive behaviour compared with those with non-refractory aggressive behaviour and observed a brain-wide pattern of local increased thickness in key areas related to emotional control and overall decreased cortical thickness in those with refractory aggressive behaviour, suggesting refractoriness could be related to specific morphological patterns. Elucidating the neurobiology of refractory aggressive behaviour is crucial to provide insights and potential avenues for new interventions.

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4. Graham Holmes L, Shattuck PT, Nilssen AR, Strassberg DS, Himle MB. Sexual and Reproductive Health Service Utilization and Sexuality for Teens on the Autism Spectrum. J Dev Behav Pediatr ;2020 (Aug 7)

OBJECTIVES : Health care providers and educators play critical roles in supporting healthy sexuality development for youth with autism spectrum disorder. There is limited information about the sexual behavior of these youth, especially girls, and about their access to sexuality education or health care services. METHODS : This study addressed these gaps by surveying parents of youth with autism aged 12-18 years (N = 298, 52.7% boys) with a range of intellectual functioning. RESULTS : According to parent report, most youth experienced sexual attraction and were interested in relationships, including same-sex attraction or relationships (13.2%). Girls were more likely than boys to have had a romantic relationship and less likely to have experienced school or legal consequences for sexual behavior. Around one-fifth of youth had engaged in a socially inappropriate sexual behavior, whereas 6.4% had a known sexual abuse history and 14.5% were bullied by peers for lack of sexual knowledge. Almost 40% received no sex education in school or in the community, including 60.9% of youth with parent-reported intelligence quotient under 70. Some parents consulted with school personnel (36.4%) or health care providers (55.9%) about sexuality issues, whereas 19.5% reported taking no action aside from talking to their child about sexuality. Utilization models including predisposing, enabling, and needs-related factors were applied to parent consultation with providers and use of school-based sexuality education programming. CONCLUSION : The results suggest unmet needs for sexual and reproductive health services, particularly among youth who are younger, those who have co-occurring intellectual disability, or those who are homeschooled or who attend private, charter, or therapeutic versus public schools.

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5. Keogh C, Pini G, Gemo I, Kaufmann WE, Tropea D. Functional Network Mapping Reveals State-Dependent Response to IGF1 Treatment in Rett Syndrome. Brain Sci ;2020 (Aug 3) ;10(8)

Rett Syndrome (RTT) is a neurodevelopmental disorder associated with mutations in the gene MeCP2, which is involved in the development and function of cortical networks. The clinical presentation of RTT is generally severe and includes developmental regression and marked neurologic impairment. Insulin-Like growth factor 1 (IGF1) ameliorates RTT-relevant phenotypes in animal models and improves some clinical manifestations in early human trials. However, it remains unclear whether IGF1 treatment has an impact on cortical electrophysiology in line with MeCP2’s role in network formation, and whether these electrophysiological changes are related to clinical response. We performed clinical assessments and resting-state electroencephalogram (EEG) recordings in eighteen patients with classic RTT, nine of whom were treated with IGF1. Among the treated patients, we distinguished those who showed improvements after treatment (responders) from those who did not show any changes (nonresponders). Clinical assessments were carried out for all individuals with RTT at baseline and 12 months after treatment. Network measures were derived using statistical modelling techniques based on interelectrode coherence measures. We found significant interaction between treatment groups and timepoints, indicating an effect of IGF1 on network measures. We also found a significant effect of responder status and timepoint, indicating that these changes in network measures are associated with clinical response to treatment. Further, we found baseline variability in network characteristics, and a machine learning model using these measures applied to pretreatment data predicted treatment response with 100% accuracy (100% sensitivity and 100% specificity) in this small patient group. These results highlight the importance of network pathology in RTT, as well as providing preliminary evidence for the potential of network measures as tools for the characterisation of disease subtypes and as biomarkers for clinical trials.

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6. Kersten ML, Coxon K, Lee H, Wilson NJ. Developing community mobility and driving with youth on the autism spectrum : A psychosocial perspective. Scand J Occup Ther ;2020 (Aug 5):1-6.

BACKGROUND : Youth on the autism spectrum face particular challenges with community mobility and driving, contributing to reduced community participation. Skill development may be uniquely shaped by complex interactions between autistic traits, psychosocial influences and community environments. Research to guide occupational therapy practice is sparse. OBJECTIVE : This short report explores the complex interplay between psychosocial and environmental influences on community mobility development, to stimulate further occupational therapy research and provide considerations for practice. METHOD : Because of the lack of autism specific research, we firstly discuss psychosocial and environmental influences impacting non-autistic youth, then draw on current research to identify challenges for youth on the spectrum. Finally, we propose considerations for practice and research. CONCLUSION : Psychosocial considerations for developing community mobility and driving include social communication, safety, navigating unpredictable community environments, emotional regulation and motivation for community participation. Future research should explore how to develop foundational community mobility skills ; communication and social skills ; and autistic needs for inclusive design. Supporting normative community mobility skills during adolescence may underpin transition to independence in adulthood. SIGNIFICANCE : Broadening the focus of community mobility and driving research to understand environmental and psychosocial contexts of community environments, is necessary to provide guidance for occupational therapists supporting youth on the spectrum with independent community participation.

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7. Kubota M, Fujino J, Tei S, Takahata K, Matsuoka K, Tagai K, Sano Y, Yamamoto Y, Shimada H, Takado Y, Seki C, Itahashi T, Aoki YY, Ohta H, Hashimoto RI, Zhang MR, Suhara T, Nakamura M, Takahashi H, Kato N, Higuchi M. Binding of Dopamine D1 Receptor and Noradrenaline Transporter in Individuals with Autism Spectrum Disorder : A PET Study. Cereb Cortex ;2020 (Aug 7)

Although previous studies have suggested the involvement of dopamine (DA) and noradrenaline (NA) neurotransmissions in the autism spectrum disorder (ASD) pathophysiology, few studies have examined these neurotransmissions in individuals with ASD in vivo. Here, we investigated DA D1 receptor (D1R) and noradrenaline transporter (NAT) binding in adults with ASD (n = 18) and neurotypical controls (n = 20) by utilizing two different PET radioligands, [11C]SCH23390 and (S,S)-[18F]FMeNER-D2, respectively. We found no significant group differences in DA D1R (striatum, anterior cingulate cortex, and temporal cortex) or NAT (thalamus and pons) binding. However, in the ASD group, there were significant negative correlations between DA D1R binding (striatum, anterior cingulate cortex and temporal cortex) and the "attention to detail" subscale score of the Autism Spectrum Quotient. Further, there was a significant positive correlation between DA D1R binding (temporal cortex) and emotion perception ability assessed by the neurocognitive battery. Associations of NAT binding with empathic abilities and executive function were found in controls, but were absent in the ASD group. Although a lack of significant group differences in binding might be partly due to the heterogeneity of ASD, our results indicate that central DA and NA function might play certain roles in the clinical characteristics of ASD.

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8. Marks K, Vincent A, Coutinho E. Maternal-Autoantibody-Related (MAR) Autism : Identifying Neuronal Antigens and Approaching Prospects for Intervention. J Clin Med ;2020 (Aug 7) ;9(8)

Recent studies indicate the existence of a maternal-autoantibody-related subtype of autism spectrum disorder (ASD). To date, a large number of studies have focused on describing patterns of brain-reactive serum antibodies in maternal-autoantibody-related (MAR) autism and some have described attempts to define the antigenic targets. This article describes evidence on MAR autism and the various autoantibodies that have been implicated. Among other possibilities, antibodies to neuronal surface protein Contactin Associated Protein 2 (CASPR2) have been found more frequently in mothers of children with neurodevelopmental disorders or autism, and two independent experimental studies have shown pathogenicity in mice. The N-methyl-D-aspartate receptor (NMDAR) is another possible target for maternal antibodies as demonstrated in mice. Here, we discuss the growing evidence, discuss issues regarding biomarker definition, and summarise the therapeutic approaches that might be used to reduce or prevent the transfer of pathogenic maternal antibodies.

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9. McClemont AJ, Morton HE, Gillis JM, Romanczyk RG. Brief Report : Predictors of School Refusal Due to Bullying in Children with Autism Spectrum Disorder and Attention-Deficit/Hyperactivity Disorder. J Autism Dev Disord ;2020 (Aug 7)

Children with Autism Spectrum Disorder (ASD) or Attention-Deficit/Hyperactivity Disorder (ADHD) are at increased risk for bullying victimization. School refusal is a ’red flag’ for identification of bullying in children with ASD and/or ADHD. This study examined the impact of diagnoses, demographics, and school variables on school refusal due to bullying. Participants were 97 parents of 154 children with ASD, ADHD, ASD + ADHD, other diagnoses, or no diagnosis. Children with ASD + ADHD were most likely to refuse school due to bullying. Classroom aides and behavior problems were protective and risk factors, respectively. In the final regression model, child diagnosis no longer predicted school refusal. School refusal and problem behavior warrant consideration as a marker of distress for victimized children.

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10. Mukherjee SB, Neelam, Kapoor S, Sharma S. Identification of Essential, Equivocal and Complex Autism by the Autism Dysmorphology Measure : An Observational Study. J Autism Dev Disord ;2020 (Aug 7)

The Autism Dysmorphology Measure is designed for non-expert clinicians. It uses an algorithm to assess 12 body regions and categorizes Autism on the number of dysmorphic regions identified ; Essential (≤ 3), Equivocal (4-5) or Complex (≥ 6). We evaluated 200 Indian children with Autism (mean age 3.7 years) in a hospital-based cross-sectional study and compared inter-group profiles. We found 31% Essential, 49% Equivocal and 20% Complex Autism. On comparing results with existing literature, it appeared that genetic ancestry and age significantly influenced dysmorphism and hence categorization. No significant differences were observed between complex and essential autism in epilepsy, severity of autism or development, as reported earlier. These shortcomings make the present tool unsuitable for use in young Indian children with Autism.

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11. Nayeri T, Sarvi S, Moosazadeh M, Hosseininejad Z, Sharif M, Amouei A, Daryani A. Relationship between toxoplasmosis and autism : A systematic review and meta-analysis. Microb Pathog ;2020 (Aug 7):104434.

Toxoplasma gondii (T. gondii) is a foodborne parasite that is investigated in many psychiatric diseases, such as autism spectrum disorders (ASD). Therefore, a systematic literature review was conducted searching seven electronic databases on the prevalence of T. gondii antibodies among autism patients. The current study involved sensitivity analysis, meta-regression, subgroup analysis, publication bias test, and quality assessment of studies. On the basis of the findings, the odd ratio (OR) of latent Toxoplasma infection 1.93 (95% confidence intervals (CI) : 1.01-3.66) was associated with ASD risk. However, there was no relationship between acute infection and ASD 0.39 (95% CI : 0.18-0.87). The obtained results of Begg’s and Egger’s tests showed no publication bias (P = 0.851 and P = 0.297, respectively). The sensitivity analysis confirmed robust and stable estimates with a significant level of heterogeneity (I(2) = 78.1%, P < 0.000). Of the investigated patients’ characteristics, only the gender variable was analyzed, indicating the combined ORs of 2.63 (95% CI : 0.29-23.63) in female and 2.62 (95% CI : 0.94-7.30) in male participants. This study showed that toxoplasmosis plays an important role as a risk factor for autism. However, further prospective investigations are highly recommended to illuminate the developmental pathways to this disorder and provide new strategies for the prevention and treatment of this disease.

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12. Spanos M, Chandrasekhar T, Kim SJ, Hamer RM, King BH, McDougle CJ, Sanders KB, Gregory SG, Kolevzon A, Veenstra-VanderWeele J, Sikich L. Rationale, design, and methods of the autism centers of excellence (ACE) network study of oxytocin in autism to improve reciprocal social behaviors (SOARS-B). Contemp Clin Trials ;2020 (Aug 7):106103.

OBJECTIVE : To describe the rationale, design, and methods of the Autism Centers of Excellence (ACE) network Study of Oxytocin in Autism to improve Reciprocal Social Behaviors (SOARS-B). METHOD : This phase 2 clinical trial was designed to evaluate the use of intranasal oxytocin treatment to improve social difficulties in individuals with autism spectrum disorder (ASD). In total, 290 participants ages 3 to 17 years with a DSM-5 diagnosis of ASD were enrolled to receive 24 weeks of treatment with either oxytocin or a matched placebo. Participants were subsequently treated with open-label oxytocin for 24 additional weeks. Post-treatment assessments were done 4 weeks after treatment discontinuation. Plasma oxytocin and oxytocin receptor gene (OXTR) methylation level were measured at baseline, week 8, 24 and 36 to explore potential relationships between these biomarkers and treatment response. RESULTS : This report describes the rationale, design, and methods of the SOARS-B clinical trial. CONCLUSIONS : There is a tremendous unmet need for effective pharmacological treatment options that target the core symptoms of ASD. Several studies support the hypothesis that intranasal oxytocin could improve social orienting and the salience of social rewards in ASD, thereby enhancing reciprocal social behaviors. However, due to conflicting results from a number of pilot studies on the prosocial effects of exogenous oxytocin, this hypothesis remains controversial and inconclusive. SOARS-B is the best powered study to date to address this hypothesis and promises to improve our understanding of the safety and efficacy of intranasal oxytocin in the treatment of social deficits in children with ASD.

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13. Stewart GR, Corbett A, Ballard C, Creese B, Aarsland D, Hampshire A, Charlton RA, Happé F. The mental and physical health profiles of older adults who endorse elevated autistic traits. J Gerontol B Psychol Sci Soc Sci ;2020 (Aug 5)

OBJECTIVE : The mental and physical health profile of autistic people has been studied in adolescence and adulthood, with elevated rates of most conditions being reported. However, this has been little studied taking a dimensional approach to autistic traits, and in older age. METHODS : A total of 20,220 adults aged 50-81 years from the PROTECT study reported whether they experienced persistent socio-communicative traits characteristic of autism. Approximately 1%, 276 individuals, were identified as endorsing elevated autistic traits in childhood and currently, henceforth the ’Autism Spectrum Trait’ (AST) group. An age and gender matched comparison group was formed of 10,495 individuals who did not endorse any autistic behavioral traits, henceforth the ’Control Older Adults’ (COA) group. Differences between AST and COA groups were explored in self-reported psychiatric diagnoses, self-reported symptoms of current depression and anxiety, and self-reported physical health diagnoses. Associations were also examined between autistic traits and health across the whole sample. RESULTS : The AST group reported significantly elevated rates of psychiatric diagnoses compared to COAs. Additionally, the AST group showed significantly higher self-reported symptoms of current depression and anxiety than COAs. However, few differences were observed in individual physical health conditions, and no differences in total co-occurring physical diagnoses between groups. Similar associations between autistic traits and health were also found taking a dimensional approach across the whole sample. DISCUSSION : These findings suggest that older adults with elevated autistic traits may be at greater risk of poorer mental, but not physical, health in later life. Future studies should incorporate polygenic scores to elucidate the possible genetic links between propensity to autism/high autistic traits and to psychiatric conditions, and to explore whether those with elevated autistic traits experience particular barriers to mental health care.

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14. Ventura P, de Giambattista C, Spagnoletta L, Trerotoli P, Cavone M, Di Gioia A, Margari L. Methylphenidate in Autism Spectrum Disorder : A Long-Term Follow up Naturalistic Study. J Clin Med ;2020 (Aug 7) ;9(8)

Autism spectrum disorder (ASD) often co-occurs with attention deficit/hyperactivity disorder (ADHD). Although methylphenidate (MPH) efficacy and safety are well-demonstrated for ADHD, evidences are scant in the context of ASD. This naturalistic study aimed to analyze long-term MPH efficacy and safety in 40 ADHD children and adolescents with comorbid ASD, comparing them with 40 ones affected by ADHD without ASD. Treatment lasted from 6 to 156 months (longer than 24 months in more than three quarters of patients). Efficacy and safety were measured by clinical global impression and children global assessment scales ; influence of intellectual functioning was examined. Comparisons between groups were made by Wilcoxon or Friedmann tests ; relationships between functioning scores and other characteristics were analyzed by ordinal logistic and linear regression. Results demonstrated that MPH in patients with ASD was associated with significative reduction of illness severity, clinical improvement and amelioration of global functioning, without significant differences with patients having ADHD without ASD. The trend of reduction of illness severity and increase of global functioning were favorably related with intellectual functioning. No serious adverse events were reported. The findings showed that long-term MPH was effective and well-tolerated in ADHD children and adolescents with comorbid high functioning ASD.

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15. Vermeirsch J, Verhaeghe L, Casaer A, Faes F, Oostra A, Roeyers H. Diagnosing Autism Spectrum Disorder in Toddlers Born Very Preterm : Estimated Prevalence and Usefulness of Screeners and the Autism Diagnostic Observation Schedule (ADOS). J Autism Dev Disord ;2020 (Aug 5)

This study estimated ASD prevalence in a cohort of 3-year-old very preterm children (N = 55) and investigated the usefulness of parent-reported ASD screeners and the ADOS-2. 12.7% received an ASD diagnosis by clinical judgment based on DSM-5 criteria. An additional 14.5% were classified as having a broader-autism-phenotype outcome. Sensitivity values for the screeners were poor, whereas specificity values ranged from poor to excellent. The ADOS-2 identified all children with ASD and had a fair specificity. These findings confirm the elevated ASD prevalence made by previous studies with preterm children but also highlight the challenges of successfully identifying ASD in this at-risk group. Caution is warranted when interpreting results of ASD instruments with the currently available cut-off scores and algorithms, especially when developmental challenges are present.

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16. Warrier V, Greenberg DM, Weir E, Buckingham C, Smith P, Lai MC, Allison C, Baron-Cohen S. Elevated rates of autism, other neurodevelopmental and psychiatric diagnoses, and autistic traits in transgender and gender-diverse individuals. Nat Commun ;2020 (Aug 7) ;11(1):3959.

It is unclear whether transgender and gender-diverse individuals have elevated rates of autism diagnosis or traits related to autism compared to cisgender individuals in large non-clinic-based cohorts. To investigate this, we use five independently recruited cross-sectional datasets consisting of 641,860 individuals who completed information on gender, neurodevelopmental and psychiatric diagnoses including autism, and measures of traits related to autism (self-report measures of autistic traits, empathy, systemizing, and sensory sensitivity). Compared to cisgender individuals, transgender and gender-diverse individuals have, on average, higher rates of autism, other neurodevelopmental and psychiatric diagnoses. For both autistic and non-autistic individuals, transgender and gender-diverse individuals score, on average, higher on self-report measures of autistic traits, systemizing, and sensory sensitivity, and, on average, lower on self-report measures of empathy. The results may have clinical implications for improving access to mental health care and tailoring adequate support for transgender and gender-diverse individuals.

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