1. Dominick KC, Andrews HF, Kaufmann WE, Berry-Kravis E, Erickson CA. Psychotropic Drug Treatment Patterns in Persons with Fragile X Syndrome. Journal of child and adolescent psychopharmacology. 2021; 31(10): 659-69.

Objective: Psychiatric comorbidity is common in fragile X syndrome (FXS) and often addressed through pharmacological management. Here we examine data in the Fragile X Online Registry With Accessible Research Database (FORWARD) to characterize specific symptoms being treated with psychotropic medication, patterns of medication use, as well as the influence of gender, intellectual disability (ID), age, and autism spectrum disorder (ASD) diagnosis. Methods: Data were drawn from the 975 participants who have a completed clinician form. We explored the frequency of psychotropic medication use for the following symptom clusters: attention, hyperactivity, anxiety, hypersensitivity, obsessive-compulsive disorder (OCD), mood swings, irritability/agitation, aggression, and self-injury (IAAS). Results: A majority of participants (617 or 63.3%) were taking a psychotropic medication, including investigational drugs. Medications were often targeting multiple symptoms. Psychotropic medication use was more common in males, adolescents, and those with comorbid ID and ASD. Anxiety was the most frequently targeted symptom, followed by attention-deficit/hyperactivity disorder symptoms and IAAS. Selective serotonin reuptake inhibitors (SSRIs) were the most frequently prescribed medication class among all patients (n = 266, 43%), followed by stimulants (n = 235, 38%), each with no gender difference. Antipsychotics were the third most frequently prescribed medication class (n = 205, 33%), and were more frequently prescribed to males and those with ID and ASD. Conclusions: Anxiety, attention and hyperactivity were the most common symptom targets for psychopharmacologic intervention in FXS. Our results support clinical knowledge that males with comorbid ASD and ID have a more severe presentation requiring more intervention including medications. These results highlight the need for examination of symptom overlap and interaction.

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2. Du JB, Ding Y, Huang L, Jiang YQ, Meng QX, Song C, Lyu G, Liu XY, Xu B, Lin Y, Ma HX, Jin GF, Li H, Ling XF, Ke XY, Shen HB, Hu ZB. [The Autism Spectrum Disorder Cohort-the sub-cohort of China National Birth Cohort]. Zhonghua liu xing bing xue za zhi = Zhonghua liuxingbingxue zazhi. 2021; 42(4): 591-6.

Autism spectrum disorder (ASD), a representative disease of children’s neurodevelopmental disorders, brings huge pressure and financial burden to families and society. It is of great significance to explore its etiology and pathogenesis. Therefore, we established an ASD Cohort based on the existing China National Birth Cohort (CNBC), which applied parallel design to recruit and follow up families who achieved pregnancy after receiving assisted reproductive technologies (ART) and families with spontaneous conception. The main aims of this study are to compare the incidence of ASD among children born after ART with those born under spontaneous pregnancy, and to evaluate the impact of ART on the neurobehavioral development of offspring. Additionally, with a variety of clinical and behavioral related information collected during pregnancy and at early life of offspring, we are able to investigate the risk factors associated with ASD comprehensively. This article briefly introduces the objectives, contents, preliminary progress, strength and limitations, as well as further prospects of the ASD cohort study, mainly focusing on the overall design and current progress.

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3. Hart CM, Curtin S. Trajectories of Vocabulary Development in Children with Autism Spectrum Disorder Across Multiple Measures. Journal of autism and developmental disorders. 2021.

This longitudinal study examined how receptive and expressive vocabulary assessments capture vocabulary development in children with Autism Spectrum Disorder (ASD) and typically developing (TD) children. Using mixed regression modelling, we explored when children with ASD significantly different from TD children. We also examined the variability of individual trajectories of vocabulary development in children with ASD. Children with ASD showed slowed trajectories and significantly differed from TD children by 24 months on all assessments except for picture-based assessments. Children with ASD also showed high heterogeneity in trajectories, with some showing inconsistent patterns of growth, stagnation, and regression across assessments. This suggests that conclusions based on individual assessments of vocabulary can vary and assessment characteristics must be considered when monitoring vocabulary development.

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4. Huynh MT, Tran CT, Joubert M, Bénéteau C. Intragenic Deletion of the ZMYND11 Gene in 10p15.3 is Associated with Developmental Delay Phenotype: A Case Report. Cytogenetic and genome research. 2021; 161(8-9): 445-8.

Submicroscopic 10p15.3 microdeletions were previously reported to be associated with developmental delay, and the smallest region of overlap of 10p15.3 deletion including DIP2C and ZMYND11 was defined. Moreover, pathogenic ZMYND11 truncating variants were subsequently identified in a cohort of patients with developmental delay. Of interest, patients harboring 10p15.3 microdeletions or pathogenic ZMYND11 truncating variants share similar clinical features including hypotonia, intellectual disability, facial dysmorphisms, speech and motor delays, seizures, and significant behavioral problems. Only 1 patient with whole ZMYND11 gene deletion was recorded, and no intragenic ZMYND11 deletion was reported up to date. Here, we describe a 7-year-old boy with developmental delay, carrying the smallest de novo 10p15.3 microdeletion, harboring the 5’UTR and the first 2 exons of ZMYND11. Taken together, our report contributes to expand the clinical and mutational spectrum of ZMYND11 and confirms haploinsufficiency as the underlying disease mechanism.

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5. Liu H, Huang X, Xu J, Mao H, Li Y, Ren K, Ma G, Xue Q, Tao H, Wu S, Wang W. Dissection of the relationship between anxiety and stereotyped self-grooming using the Shank3B mutant autistic model, acute stress model and chronic pain model. Neurobiology of stress. 2021; 15: 100417.

Self-grooming is an innate, cephalo-caudal progression of body cleaning behaviors that are found in normal rodents but exhibit repetitive and stereotyped patterns in several mouse models, such as autism spectrum disorders (ASDs). It is also recognized as a marker of stress and anxiety. Mice with Shank3B gene knockout (KO) exhibit typical ASD-like behavioral abnormalities, including stereotyped self-grooming and increased levels of anxiety. However, the exact relationship between anxiety and stereotyped self-grooming in certain types of animal models is not clear. We selected three animal models with high anxiety to compare their self-grooming parameters. First, we confirmed that Shank3B KO mice (ASD model), acute restraint stress mouse model (stress model), and chronic inflammatory pain mouse model (pain model) all showed increased anxiety levels in the open field test (OFT) and elevated plus maze (EPM). We found that only the ASD model and the stress model produced increased total grooming duration. The pain model only exhibited an increasing trend of mean self-grooming duration. We used the grooming analysis algorithm to examine the self-grooming microstructure and assess the cephalo-caudal progression of grooming behavior. The results showed distinct self-grooming microstructures in these three models. The anxiolytic drug diazepam relieved the anxiety level and the total time of grooming in the ASD and stress models. The grooming microstructure was not restored in Shank3B KO mice but was partially relieved in the stress model, which suggested that anxiety aggravated stereotyped self-grooming duration but not the grooming microstructure in the ASD mouse model. Our results indicated that stereotyped behavior and anxiety may be shared by separate, but interacting, neural circuits in distinct disease models, which may be useful to understand the mechanisms and develop potential treatments for stereotyped behaviors and anxiety.

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6. Schaaf RC, Carroll A, Waskie EC, Dumont RL, Ridgway E. Choosing Performance-Based Outcome Measures of Daily Living Skills and Socialization for Clinical Trials in Autistic Children. The American journal of occupational therapy : official publication of the American Occupational Therapy Association. 2021; 75(6).

IMPORTANCE: Robust and psychometrically sound performance-based outcome measures are needed for clinical trials of occupational therapy interventions for children with autism. OBJECTIVE: To demonstrate a systematic approach for choosing psychometrically sound performance-based outcome measures of daily living skills and socialization for use in clinical trials of occupational therapy interventions for children with autism. DESIGN: Rapid literature review to identify appropriate measures for studies with this population followed by quality indicator ratings and a nominal group process. SETTING: University. PARTICIPANTS: Four experts in autism and pediatric outcome measurement. Outcomes and Measures: Twenty-one outcome measures of daily living skills and socialization were identified and reviewed. RESULTS: Seven measures met the inclusion criteria. The Assessment of Motor and Process Skills and the Evaluation of Social Interaction-Second Edition, received the highest ratings and group consensus. Several other measures were also scored highly. CONCLUSIONS AND RELEVANCE: Careful assessment of psychometric properties is an important component of choosing outcome measures for a clinical trial, but burden of assessment and study objectives are important considerations. What This Article Adds: This project demonstrates use of a systematic process for choosing outcome measures for a planned clinical trial.

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7. Tonizzi I, Giofrè D, Usai MC. Inhibitory Control in Autism Spectrum Disorders: Meta-analyses on Indirect and Direct Measures. Journal of autism and developmental disorders. 2021.

This manuscript aimed to advance our understanding of inhibitory control (IC) in autism spectrum disorders (ASD), adopting a meta-analytic multilevel approach. The first meta-analysis, on 164 studies adopting direct measures, indicated a significant small-to-medium (g = 0.484) deficit in the group with ASD (n = 5140) compared with controls (n = 6075). Similar effect sizes between response inhibition and interference control were found, but they were differentially affected by intellectual functioning and age. The second meta-analysis, on 24 studies using indirect measures, revealed a large deficit (g = 1.334) in the group with ASD (n = 985) compared with controls (n = 1300). Presentation format, intellectual functioning, and age were significant moderators. The effect of comorbidity with ADHD was not statistically significant. Implications are discussed for IC research and practice in autism.

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8. Vandenberg GG, Thotakura A, Scott AL. Mitochondrial bioenergetics of astrocytes in Fragile X syndrome: new perspectives on culture conditions and sex effects. American journal of physiology Cell physiology. 2022; 322(2): C125-c35.

Fragile X syndrome (FXS) is a genetic disorder that is characterized by a range of cognitive and behavioral deficits, including mild-moderate intellectual disability. The disease is characterized by an X-linked mutation of the Fmr1 gene, which causes silencing of the gene coding for fragile X mental retardation protein (FMRP), a translational regulator integral for neurodevelopment. Mitochondrial dysfunction has been recently associated with FXS, with reports of increases in oxidative stress markers, reactive oxygen species, and lipid peroxidation being present in the brain tissue. Astrocytes, a prominent glial cell within the central nervous system (CNS), play a large role in regulating oxidative homeostasis within the developing brain and dysregulation of astrocyte redox balance in FXS, which may contribute to oxidative stress. Astrocyte function and mitochondrial bioenergetics are significantly influenced by oxygen availability and circulating sex hormones; yet, these parameters are rarely considered during in vitro experimentation. Given that the brain normally develops in a range of hypoxic conditions and FXS is a sex-linked genetic disorder, we investigated how different oxygen levels (normoxic vs. hypoxic) and biological sex affected mitochondrial bioenergetics of astrocytes in FXS. Our results demonstrate that both mitochondrial respiration capacity and reactive oxygen species emission are altered with Fmr1 deletion in astrocytes and these changes were dependent upon both sexual dimorphism and oxygen availability.

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9. Zhang W, Thompson KL, Watson LR, LaForett DR. Health Care Utilization for Privately and Publicly Insured Children During Autism Insurance Reform. Journal of autism and developmental disorders. 2021.

We examined the effects of insurance type on health service utilization among children with autism spectrum disorder (ASD) following autism insurance reform by analyzing the most recent data from the 2019 National Survey of Children’s Health. Families with private insurance were less likely to report that their health insurance covered needed services compared to families with public insurance. Privately versus publicly insured children were not significantly different in receiving behavioral or medication treatment, or in parental frustration in efforts to obtain services. However, parents’ frustration escalated with increased ASD severity. Findings from this study suggest the need for continuing to improve implementation of health insurance reform legislation and providing adequate ASD-related services for children with private insurance.

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