Repetitive Behavior Scale-Revised Research Articles

Investigation of Liver X Receptor Gene Variants and Oxysterol Dysregulation in Autism Spectrum Disorder.

The NR1H2 gene produces the Liver X Receptor Beta (LXRB) protein, which is crucial for brain cholesterol metabolism and neuronal development. However, its involvement in autism spectrum disorder (ASD) remains largely unexplored, aside from animal studies. This study is the first to explore the potential link between autism and rs2695121/rs17373080 single nucleotide polymorphisms (SNPs) in the regulatory regions of NR1H2, known for their association with neuropsychiatric functions. Additionally, we assessed levels of oxysterols (24-Hydroxycholesterol, 25-Hydroxycholesterol, 27-Hydroxycholesterol), crucial ligands of LXR, and lipid profiles. Our cohort comprised 107 children with ASD and 103 healthy children aged 2-18 years. Clinical assessment tools included the Childhood Autism Rating Scale, Autistic Behavior Checklist, and Repetitive Behavior Scale-Revised. Genotyping for SNPs was conducted using PCR-RFLP. Lipid profiles were analyzed with Beckman Coulter kits, while oxysterol levels were determined through liquid chromatography-tandem mass spectrometry. Significantly higher total cholesterol (p = 0.003), LDL (p = 0.008), and triglyceride (p < 0.001) levels were observed in the ASD group. 27-Hydroxycholesterol levels were markedly lower in the ASD group (p ≤ 0.001). ROC analysis indicated the potential of 27-Hydroxycholesterol to discriminate ASD diagnosis. The SNP genotype and allele frequencies were similar in both groups (p > 0.05). Our findings suggest that disturbances in oxysterol metabolism, previously linked to neurodegeneration, may constitute a risk factor for ASD and contribute to its heterogeneous phenotype.

Benefit or Problem: Exploration of How Response Options Affect Self-Reported Behaviors and Interests in Autistic Adults.

Assessment of restricted, repetitive behaviors (RRB) in autism evaluations often assumes that these behaviors negatively impact the individual. Qualitative studies of first-person accounts indicate the negative impact of the stigma associated with RRBs but also provide insights into the positive aspects. The current study explores how framing response options as negative (i.e., level of problem associated with occurrence) or positive (i.e., level of benefit associated with occurrence) affects RRB self-reports in autistic adults. Sixty-six autistic adults aged 18-59 filled out the Repetitive Behavior Scale-Revised (RBS-R) and a modified RBS-R+, assessing problems and benefits of reported behaviors, respectively. There was a moderate to strong correlation between the forms, each assessing problems and benefits in terms of the number of behaviors endorsed (r = 0.746) and the levels of benefits and problems (r = 0.637). Autistic adults reported a higher number of RRBs in the form that assessed problems, but the number of behaviors was comparable between the forms when counting in the response option of the occurrence of behavior without having a benefit. Despite some variability in the level of problems and the benefits across the subdomains of RRB, autistic adults largely rated comparable levels of associated benefits and problems, highlighting the complexity of RRBs as having both positive and negative impacts. Future screening and diagnostic tools for adults should aim to assess both positive and negative aspects of autistic features to afford a more nuanced understanding of individual experiences while still yielding diagnostically relevant information. Qualitative studies are needed to better understand the complex experiences associated with these behaviors; however, it may be important to ensure that options for endorsement of behaviors without a specific benefit are also needed to ensure some behaviors (e.g., self-injurious behaviors) are not missed.

Neurobehavioral Phenotype of Children With Congenital Myotonic Dystrophy.

To describe the neurobehavioral phenotype of congenital myotonic dystrophy. Congenital myotonic dystrophy (CDM) is the most severe form of myotonic dystrophy, characterized by symptom presentation at birth and later, cognitive impairment, autistic features, and disordered sleep. The neurobehavioral phenotype was assessed in this cross-sectional study by a neuropsychological battery consisting of the Wechsler Preschool and Primary Scale of Intelligence, Third Edition, Weschler Intelligence Scale for Children, Fourth Edition, Vineland Adaptive Behavior Scale, Second Edition (Vineland-II), Behavior Rating Inventory of Executive Function including preschool and teacher reports, Autism Spectrum Screening Questionnaire, Social Communication Scale, and Repetitive Behavior Scale-Revised. Sleep quality was evaluated with the Pediatric Sleep Questionnaire and Pediatric Daytime Sleepiness Scale. Fifty-five children with CDM, ages 5 weeks to 14 years, were enrolled. The mean age and (CTG)n repeats (±SD) were 6.4 ± 3.8 years and 1,263 ± 432, respectively. The mean IQ was 64.1 ± 14.9 on the Weschler scales with 65.6% of participants falling in the extremely low range for IQ. Adaptive functioning was significantly low for 57.1% of participants (n = 20). Caregiver report of executive functioning indicated 23.1% (9/39) of participants had clinically elevated levels of dysfunction, though teacher report was discrepant and indicated 53.3% of participants with CDM fell in this range (8/15). Spearman correlations were strongly positive (p ≤ 0.05) for estimated full scale IQ, overall adaptive functioning and with daily living and socialization domain standard scores on the Vineland-II ranging from r = 0.719 to r = 0.849 for all ages. Aspects of executive function were directly related to features of autism and sleep quality. Social communication was inversely related to all aspects of daily functioning, except communication, and directly related to aspects of autism behavior. Depressed IQ, adaptive skills, and executive functioning, poor sleep quality, and features of autism and altered social functioning individually describe different aspects of the neurobehavioral phenotype in CDM. These neurobehavioral and sleep measures could help quantitatively measure and assess the burden of cognitive impairment in CDM.

Oxytocin treatment for core symptoms in children with autism spectrum disorder: a systematic review and meta-analysis.

The purpose of this article is to examine the efficacy of oxytocin in treating core symptoms of autism spectrum disorder (ASD) with children. A systematic literature search was conducted to identify randomized controlled trials (RCTs) of oxytocin for the treatment of core symptoms in children with ASD. The search included studies published between January 1, 1999 and March 15, 2023, that were randomized, single or double-blinded, and included a placebo control group. Standard screening rules were applied to select relevant studies, resulting in the inclusion of five RCTs involving 486 children with ASD. Ultimately, a total of five RCTs, involving 486 children with ASD, were included in the review using standard screening rules.One of the included studies demonstrated a statistically significant improvement in Social Responsiveness Scale (SRS) and Repetitive Behavior Scale-Revised (RBS) scores when children with ASD were treated with oxytocin (24 IU/2 days for 6 weeks). The improvement in core symptoms persisted at the 6-month follow-up. The meta-analysis findings suggested that oxytocin might have a moderate effect in improving the core symptom of narrow interests and repetitive stereotyped behaviors in children with ASD. While the therapeutic value of oxytocin in treating core symptoms of ASD in children is not fully established, the results of this meta-analysis indicate a potential moderate effect. However, further studies with larger sample sizes and more robust RCTs are needed to directly demonstrate the efficacy of oxytocin. Future research should also focus on effect size and outcome evaluation accuracy while minimizing bias in RCT experiments.

Repetitive and restricted behaviors and interests in autism spectrum disorder: relation to individual characteristics and mental health problems

BackgroundAlthough repetitive and restricted behaviors and interests (RRBIs) may interfere with well-being and functioning in autistic individuals, research on their relation to sex, age, cognitive level, and mental health problems remains unclear. Much of the research to date has used broad categorizations rather than specific categorizations of RRBIs to examine the difference in RRBIs between individuals. The purpose of this study was to explore, in different groups of individuals, the presence of specific RRBI subtypes, and to examine the association of specific RRBI subtypes with symptoms of internalizing and externalizing behaviors.MethodsSecondary data analyses were conducted using the Simons Simplex Collection dataset, which included 2,758 participants (aged 4 to 18). Families of autistic children completed the Repetitive Behavior Scale–Revised (RBS-R) and the Child Behavior Checklist.ResultsAcross all RBS-R subtypes, results revealed no sex differences. Older children showed higher rates of Ritualistic/Sameness behaviors than younger children and adolescents, whereas younger and older children showed more Stereotypy than adolescents. Additionally, lower cognitive level groups showed higher rates of RBS-R subtypes except for Ritualistic/Sameness. After controlling for age and cognitive level, RBS-R subtypes accounted for a substantial amount of variance in internalizing and externalizing behaviors (23% and 25%, respectively). Specifically, Ritualistic/Sameness and Self-Injurious Behavior both predicted internalizing and externalizing behaviors, whereas Stereotypy only predicted internalizing behavior.ConclusionsThese findings have key clinical implications that emphasize not only the consideration of sex, age, and cognitive level, but also specific RRBIs and co-occurring mental health problems, when assessing for ASD and designing individualized interventions.

The Relations between Repetitive Behaviors and Family Accommodation among Children with Autism: A Mixed-Methods Study

Restricted and repetitive behaviors and interests (RRBI) are a significant component in diagnosing autism spectrum disorder (ASD). They often pose the main challenge in day-to-day functions for children with ASD and their families. Research addressing family accommodation behaviors (FAB) in the ASD population is scarce, and associations with the characteristics of the children's behaviors are unclear. This sequential mixed-methods study assessed the correlation between RRBI and FAB within the ASD group to deepen the understanding of parents' subjective experiences regarding their children's RRBI. It included a quantitative phase with a follow-up qualitative study. A total of 29 parents of children with autism (5-13 yr) completed the study questionnaires; a total of 15 also were interviewed regarding their children's RRBI and related FAB. We used the Repetitive Behavior Scale-Revised (RBS-R) to assess RRBI, and the Family Accommodation Scale (FAS-RRB) to assess FAS. In-depth interviews from phenomenological methodology were used in the qualitative phase. We found significant positive correlations between the RRBI and FAB overall and their subscores. Qualitative research supports these findings, adding descriptive examples of the accommodations families make to address the RRBI-related challenges. The results indicate relations between RRBI and FAB and the importance of practically addressing children with autism's RRBI and their parents' experiences. Both affect and are affected by the children's behaviors.

Sleep Problems, Circadian Rhythms, and Their Relation to Behavioral Difficulties in Children and Adolescents with Autism Spectrum Disorder.

This was an exploratory cross-sectional study comparing 45 children with ASD to 24 typically developing drug-naïve controls, group-matched on age, sex, and body mass index. Objective data was obtained using the following: an ambulatory circadian monitoring device; saliva samples to determine dim light melatonin onset (DLMO): and three parent-completed measures: the Child Behavior Checklist (CBCL); the Repetitive Behavior Scale-Revised (RBS-R); and the General Health Questionnaire (GHQ28). The CBCL and RBS-R scales showed the highest scores amongst poor sleepers with ASD. Sleep fragmentation was associated with somatic complaints and self-injury, leading to a higher impact on family life. Sleep onset difficulties were associated with withdrawal, anxiety, and depression. Those with phase advanced DLMO had lower scores for "somatic complaints"; "anxious/depressed" state; and "social problems", suggesting that this phenomenon has a protective role.

Associations between Symptom Severity of Autism Spectrum Disorder and Screen Time among Toddlers Aged 16 to 36 Months.

There is growing evidence that prevalence rates of autism spectrum disorder (ASD) are increasing. A number of factors appear to contribute to this increase, including excessive screen time. Screen time seems to be linked to the severity of the symptoms of ASD. Given this, the aim of the present cross-sectional study was to investigate the association between early screen time and ASD symptoms severity in the first 36 months of life. To this end, sixty-eight Iranian toddlers (mean age: 27.09 months; 22.1% females) with ASD were recruited. Parents completed the modified checklist for autism in toddlers (M-CHAT), the Repetitive Behavior Scale-Revised (RBS-R), and a lifestyle checklist. Next, parents rated children's daily exposure to content specifically designed (foreground media) and not specifically designed (background media) for children, along with their daily exposure to social interaction. Per day, toddlers spent 5.12 h (±3.77) with foreground media, 3.72 h (±3.57) with background media, and 2.89 h (±2.74) in interaction with other people (parents). To test the hypotheses, we performed a series of Pearson's correlations and multiple regression analyses. Toddlers' higher severity scores for ASD symptoms were associated with longer foreground (r = 0.234, p = 0.001) and longer background (r = 0.180, p = 0.012) media duration, and with shorter duration of interaction with others (r = 0.192, p = 0.009). Toddlers spending 1 h more in foreground screen time and background screen time have 0.38 and 0.29 more units in the ASD symptom severity scale, respectively, while toddlers spending 1 h more in social interactions have 0.42 fewer units in the ASD symptom severity scale. The screen time and interaction duration are related to ASD symptoms severity of toddlers. The cross-sectional study design precludes causal associations, although bi-directional relationships appear plausible.

Validating the repetitive behavior scale-revised for children in China aged 9 to 16 with autism spectrum disorder

Restricted and repetitive behavior (RRB) is one of the two core diagnostic features used to determine the severity of autism spectrum disorder (ASD). The Repetitive Behavior Scale‑Revised (RBS-R) is widely used to measure the presence and severity of a variety of RRBs in individuals with ASD. Previous studies have implemented a factor analysis framework to examine the RBS-R, while there’re still inconsistencies in the use of the measure. This study analyzed the validity and reliability of the RBS-R using data from 315 Chinese children aged 9–16 with ASD. The results showed that the original tested items were adaptable to the Chinese cultural environment when treating such disorders. A confirmatory factor analysis indicated that a 6-factor model was most suitable for evaluating RRB in this context. Consistent with previous studies, the 6-factor model was preferred because of its fit statistics in evaluating RRBs using data from Chinese children with ASD aged 9–16. It’s necessary to implement the same structure (e.g. 6-factor model) of the RBS-R to enable efficient comparisons of results across studies. Validating the RBS-R cross different contexts and using longitudinal data are helpful to advance our knowledge of RRB.

Reliability and validity of the repetitive behavior scale-revised for young Chinese children with autism spectrum disorder in Jiangxi Province.

Restricted and repetitive behaviors (RRBs) are one of the two main diagnostic features of autism spectrum disorder (ASD). To date, a growing body of research on RRB in children with ASD has recently attracted academic attention. The Repetitive Behavior Scale-Revised (RBS-R) was primarily intended for use in evaluating RRBs observed in ASD. This study recruited 381 Chinese children with ASD aged 2–4 years to measure the reliability and validity of the RBS-R. Confirmatory factor analysis (CFA) was applied to the structuring models of the four proposed structural models, indicating that a 6-factor model demonstrated good internal consistency and the best fit based on common overall fit indices. These findings suggest the utility of the Chinese version of RBS-R.

COREAT: Developing a Mobile Application to Assess the Severity of Repetitive Behavior in Autism

&lt;p style="text-align: justify;"&gt;Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterised by difficulties in communication and repetitive behaviors. The early detection of ASD is a clinical priority in education centres and medical services. COREAT is a computer adaptation of the Repetitive Behavior Scale-Revised (RBS-R) which has been designed to facilitate the diagnosis of individuals with ASD and intellectual disability. This article describes the development, an initial evaluation of the feasibility and the preliminary outcomes of COREAT. The development of COREAT consists of two phases. Phase 1: Performing a prior analysis of the psychometric properties of the RBS-R scale. Phase 2: Developing the mobile application (pilot tests, testing real cases n = 11, and final feedback). Descriptive data of the pilot study shows that 91.31% of participants indicate that COREAT is very accessible and intuitive. COREAT proves to be a useful diagnostic resource for professionals and families. Cross-cultural differences must be analysed.&lt;/p&gt;

Clinical autism subscales have common genetic liabilities that are heritable, pleiotropic, and generalizable to the general population

The complexity of autism’s phenotypic spectra is well-known, yet most genetic research uses case-control status as the target trait. It is undetermined if autistic symptom domain severity underlying this heterogeneity is heritable and pleiotropic with other psychiatric and behavior traits in the same manner as autism case-control status. In N = 6064 autistic children in the SPARK cohort, we investigated the common genetic properties of twelve subscales from three clinical autism instruments measuring autistic traits: the Social Communication Questionnaire (SCQ), the Repetitive Behavior Scale-Revised (RBS-R), and the Developmental Coordination Disorder Questionnaire (DCDQ). Educational attainment polygenic scores (PGS) were significantly negatively correlated with eleven subscales, while ADHD and major depression PGS were positively correlated with ten and eight of the autism subscales, respectively. Loneliness and neuroticism PGS were also positively correlated with many subscales. Significant PGS by sex interactions were found—surprisingly, the autism case-control PGS was negatively correlated in females and had no strong correlation in males. SNP-heritability of the DCDQ subscales ranged from 0.04 to 0.08, RBS-R subscales ranged from 0.09 to 0.24, and SCQ subscales ranged from 0 to 0.12. GWAS in SPARK followed by estimation of polygenic scores (PGS) in the typically-developing ABCD cohort (N = 5285), revealed significant associations of RBS-R subscale PGS with autism-related behavioral traits, with several subscale PGS more strongly correlated than the autism case-control PGS. Overall, our analyses suggest that the clinical autism subscale traits show variability in SNP-heritability, PGS associations, and significant PGS by sex interactions, underscoring the heterogeneity in autistic traits at a genetic level. Furthermore, of the three instruments investigated, the RBS-R shows the greatest evidence of genetic signal in both (1) autistic samples (greater heritability) and (2) general population samples (strongest PGS associations).

Bumetanide Effects on Resting-State EEG in Tuberous Sclerosis Complex in Relation to Clinical Outcome: An Open-Label Study.

Neuronal excitation-inhibition (E/I) imbalances are considered an important pathophysiological mechanism in neurodevelopmental disorders. Preclinical studies on tuberous sclerosis complex (TSC), suggest that altered chloride homeostasis may impair GABAergic inhibition and thereby E/I-balance regulation. Correction of chloride homeostasis may thus constitute a treatment target to alleviate behavioral symptoms. Recently, we showed that bumetanide—a chloride-regulating agent—improved behavioral symptoms in the open-label study Bumetanide to Ameliorate Tuberous Sclerosis Complex Hyperexcitable Behaviors trial (BATSCH trial; Eudra-CT: 2016-002408-13). Here, we present resting-state EEG as secondary analysis of BATSCH to investigate associations between EEG measures sensitive to network-level changes in E/I balance and clinical response to bumetanide. EEGs of 10 participants with TSC (aged 8–21 years) were available. Spectral power, long-range temporal correlations (LRTC), and functional E/I ratio (fE/I) in the alpha-frequency band were compared before and after 91 days of treatment. Pre-treatment measures were compared against 29 typically developing children (TDC). EEG measures were correlated with the Aberrant Behavioral Checklist-Irritability subscale (ABC-I), the Social Responsiveness Scale-2 (SRS-2), and the Repetitive Behavior Scale-Revised (RBS-R). At baseline, TSC showed lower alpha-band absolute power and fE/I than TDC. Absolute power increased through bumetanide treatment, which showed a moderate, albeit non-significant, correlation with improvement in RBS-R. Interestingly, correlations between baseline EEG measures and clinical outcomes suggest that most responsiveness might be expected in children with network characteristics around the E/I balance point. In sum, E/I imbalances pointing toward an inhibition-dominated network are present in TSC. We established neurophysiological effects of bumetanide although with an inconclusive relationship with clinical improvement. Nonetheless, our results further indicate that baseline network characteristics might influence treatment response. These findings highlight the possible utility of E/I-sensitive EEG measures to accompany new treatment interventions for TSC.Clinical Trial RegistrationEU Clinical Trial Register, EudraCT 2016-002408-13 (www.clinicaltrialsregister.eu/ctr-search/trial/2016-002408-13/NL). Registered 25 July 2016.

Repetitive and stereotyped behaviors in neurodevelopmental disorders: an observational analysis of four diagnostic groups.

Repetitive and Stereotyped Behaviors (ST) are one of the key features of autism spectrum disorder (ASD) and they frequently occur in children with developmental delay/intellectual disability or sensory deprivation, but they are also described in children otherwise typical. This study aims to describe and compare ST in children with different neurodevelopmental disorders and in children having stereotypies but no other medical diagnosis (primary stereotypies). The study sample comprised children with autism spectrum disorder (ASD) developmental delay (DD), severe visual impairment (VI) and primary stereotypies (PS), aged between 2 and 12 years old. The characteristics of the ST (age of onset, frequency, duration, triggers, phenomenology) were collected from their clinical history. The children's caregivers completed the Repetitive Behavior Scalerevised (RBS-R) and the Child Behavior Checklist (CBCL) to assess the ST and to screen for behavioral problems, respectively. Data concerning family history and comorbidity were also collected. 87 children (ASD [n=23]; DD [n=21]; VI [n=20]; PS [n=23]) were assessed. Mean age of ST onset was before 24 months in the whole sample. Symptoms usually occurred more than once a day in all groups, but Self-Injurious Behavior (SIB) and ST were reported at higher scores on the RBS-R in Secondary group. Stereotypies lasted less than 5 minutes in all but VI sample, in which lasted longer. Stereotypies of locomotion were mostly reported in ASD, self-injurious behaviors in VI, upper limb stereotypies in PS and DD. Parents reported several repetitive behaviors on the RBS-R, while attention deficit and withdrawn behavior appeared to be the main findings of the sample in the CBCL. Finally, a high number of comorbidities and family history for neurodevelopmental disorders was found in all groups. The study showed that some specific patterns of stereotypies could be identified in most groups of disorders. At the same time the behavioral profile of children with stereotypies shows a significant overlap among different groups. These preliminary results suggest that stereotypies are strongly linked to neurodevelopmental disorders, but their association needs to be clarified with further studies.

Executive functions predict restricted and repetitive behaviors in toddlers under 36 months old with autism spectrum disorder

BackgroundExecutive functions (EFs) and restricted and repetitive behaviors (RRBs) have been studied mainly in older individuals with autism spectrum disorder (ASD), while little is known about the relationship between EFs and RRBs in toddlers. AimsThe purpose of this study was to investigate the relationship between EFs and RRBs of toddlers with ASD symptoms. In addition, we tested whether EFs were predictive of RRBs in toddlers. MethodsCross-sectional data were collected from parents of forty-five toddlers under 36 months old. The modified checklist for autism in toddlers (M-CHAT), the Gilliam autism rating scale (GARS-2), the behavior rating inventory of executive functioning-preschool version (BRIEF-P), and the repetitive behavior scale- revised (RBS-R) administered to parents. ResultsWe found significant associations between EFs and (1) stereotyped behaviors, (2) self-injurious behaviors, (3) ritualistic behaviors, (4) sameness behaviors, (5) restricted behaviors, (6) compulsive behaviors, and (7) repetitive behaviors total score. Increases in EFs differences predicted an increase in RRBs. ConclusionsOur results indicate a link between EFs and RRBs. Future research on RRBs in ASD may benefit from focusing on specific EFs rather than general categories.

An open-label prospective pilot trial of nucleus accumbens deep brain stimulation for children with autism spectrum disorder and severe, refractory self-injurious behavior: study protocol

BackgroundChildren and youth with autism spectrum disorder (ASD) may manifest self-injurious behaviors (SIB) that may become severe and refractory with limited pharmacologic or behavioral treatment options. Here, we present the protocol of a prospective, mixed-methods study to assess the safety and efficacy of deep brain stimulation (DBS) of the nucleus accumbens (NAcc) for children and youth with ASD and severe, refractory SIB.MethodsThis is a prospective, single-center, single-cohort, open-label, non-randomized pilot trial of 6 patients. Participants will be recruited through specialized behavioral clinics with persistent severe and refractory SIB following standard and intensive interventions. Following NAcc-DBS, participants will be enrolled in the study for 12 months. The primary objectives of the study are safety and feasibility, assessed by rate of recruitment and identification of factors impacting adherence to follow-up and study protocol. Potential treatment efficacy will be assessed by changes in the Children’s Yale-Brown Obsessive-Compulsive Scale in ASD (CYBOCS-ASD), the Behavior Problems Index (BPI), the Inventory of Statements about Self-Injury (ISAS) and the Repetitive Behavior Scale-Revised (RBS-R) questionnaires. Additional clinical outcomes will be assessed, including measures of participant and caregiver quality of life, actigraph measurements, and positron emission tomography (PET) changes following DBS.DiscussionThis study will be the first to evaluate the effect of DBS of the NAcc on a pediatric population in a controlled, prospective trial. Secondary outcomes will improve the understanding of behavioral, neuro-imaging, and electrophysiologic changes in children with ASD and SIB treated with DBS. This trial will provide an estimated effect size of NAcc-DBS for severe refractory SIB in children with ASD in preparation for future comparative trials.Trial registrationRegistration on ClinicalTrials.gov was completed on 12 June 2019 with the Identifier: NCT03982888.

Associations Between Sex Hormone Levels and Autistic Traits in Infertile Patients With Polycystic Ovary Syndrome and Their Offspring.

Objectives1) To explore the associations between autistic traits and sex hormone changes in patients with polycystic ovary syndrome (PCOS); 2) To explore the influence of PCOS parental autistic traits and related sex hormone changes on autistic traits in their offspring.MethodThis is a case–control study that recruited two groups: polycystic ovarian syndrome-induced infertile subjects as the observation group and fallopian tube factor-induced infertility subjects as the control group. Both cohorts were patients undergoing infertility treatment in the Productive Medicine Center, Peking University People’s Hospital. Two types of questionnaires were completed by patients between May 1st, 2015, and May 1st, 2016: 1. The autism-spectrum quotient (AQ) 2. Repetitive behavior scale-revised (RBS-r). Levels of sex hormones in serum were measured in patients. The correlations between the levels of these biochemical factors and scores of the autistic traits were analysed. From July 1st, 2020 to September 1st, 2021, these patients were followed up by telephone and asked to fill out a questionnaire online. The questionnaire included date of delivery, complications, medicine used and negative events during pregnancy (e.g., death of relatives, divorce, etc.), delivery condition, breastfeeding, AQ scale and Autism Behavior Checklist (ABC) of their children.ResultsThe patients in the PCOS group had significantly higher AQ scores than those in the control group. Levels of luteinizing hormone and testosterone were also higher in the PCOS group. No significant differences were found between the two groups in RBS-r levels, follicle-stimulating hormone, estradiol or progesterone. In the two combined groups, there were significantly positive correlations between the AQ scores and the luteinizing hormone concentration, as well as between scores of RBS-r and testosterone concentration. Moreover, there was a significantly negative correlation between the level of progesterone and the RBS-r score. According to the follow-up data, the AQ scores of offspring were positively correlated with the RBS-r scores of their mothers. The ABC scores of offspring were positively correlated with the RBS-r scores and the childbearing age of their mothers. No significant difference was found between the two groups in age of delivery, complications, special medication used, negative events during pregnancy, delivery situation, postpartum breastfeeding, age of children, or AQ scores or ABC scores of children. There were no significant correlations between the scale scores of children and the related sex hormone levels of mothers. This could indicate that the higher levels of luteinizing hormone and testosterone and the lower level of progesterone accompanied more pronounced autistic traits in PCOS. Furthermore, the higher delivery age and RBS-r score in mothers accompanied the higher AQ and ABC scores in children.ConclusionCompared with the control group, PCOS patients had more autistic traits (especially social dysfunction). The autistic traits in PCOS patients might be related to the elevation in testosterone concentration and luteinizing hormone levels and the decline in progesterone level. Moreover, the autistic traits in the offspring of PCOS patients might be related to the parental high delivery age and high tendency to autism traits.

Advancing methodologies to improve RRB outcome measures in autism research: Evaluation of the RBS-R.

This study evaluates the psychometric properties (dimensionality, item bias, reliability) of the Repetitive Behavior Scale-Revised (RBS-R), provides scoring guidelines for the dimensional measure, and makes recommendations for future RRB measure development. Participants included individuals from three large autism data repositories; Simon Foundation Powering Autism Research for Knowledge (SPARK), Simons Simplex Collection (SSC), and National Database for Autism Research (NDAR). The total sample included N = 15,318 autistic individuals ages 3-18. Confirmatory factor analysis was used to evaluate competing theoretical factor structures. Item response theory (IRT) was used to evaluate differential item functioning, estimate the reliability of each RBS-R subdomain, and score the subdomains. A unidimensional factor structure demonstrated clearly inadequate model fit, calling into question the practice of reporting a total score on the RBS-R. A five-dimensional factor structure was supported by the theoretical and empirical evidence, though the fifth factor (restricted interests) was not sufficiently reliable for use. IRT-based scoring tools were generated for use in research. The present study illustrates the promise in the future development of measures for RRBs, particularly in the development of measures to separately and specifically assess RRB constructs using rigorous methodological guidelines. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Antioxidant interventions in autism spectrum disorders: A meta-analysis

BackgroundAutism spectrum disorder (ASD) might be associated with oxidative stress, and antioxidants are commonly used in the treatment of young people with ASD. However, the evidence about the effectiveness of these interventions remains debatable. We performed a meta-analysis to evaluate the effect of antioxidants on the symptoms of patients with autism. MethodsData sources: PubMed and Web of Science databases. Study selection: We selected placebo-controlled, double-blind, randomized clinical trials published until February 2021 to evaluate the efficacy of antioxidant interventions on ASD. Data analysis: Aberrant Behavior Checklist (ABC), Repetitive Behavior Scale-Revised (RBS), Social Responsiveness Scale (SRS), Developmental Behavior Checklist (DBC) and Clinical Global Impressions Severity scale (CGIS) were used to evaluate the 22 different symptom outcomes. The Hedges-adjusted g value was used to estimate the effect of each dietary intervention relative to the placebo. ResultsIn this meta-analysis, we examined 13 double-blind randomized clinical trials, comprising a total of 570 patients with ASD: 293 in the intervention group and 277 in the placebo group. Antioxidants (N-acetylcysteine (NAC), other antioxidants) are more effective than placebos in improving the irritability among symptoms in the ABC and communication disturbance symptoms in the DBC. There was a good trend of improvement in the stereotypic behavior symptoms in the ABC. Treatment with NAC antioxidants showed a good trend of improvement in irritability in the ABC and symptoms of hyperactivity. The effect size was small, and there was a low risk of statistical heterogeneity and publication bias. Limitations: The number of studies in this meta-analysis was small and the sample size was small. ConclusionThis meta-analysis suggests that antioxidant intervention has a potential role in the management of some symptoms in patients with ASD, and indicates the feasibility of using antioxidants to treat autism in the future.

Prediction of Behavioral Improvement Through Resting-State Electroencephalography and Clinical Severity in a Randomized Controlled Trial Testing Bumetanide in Autism Spectrum Disorder

BackgroundMechanism-based treatments such as bumetanide are being repurposed for autism spectrum disorder. We recently reported beneficial effects on repetitive behavioral symptoms that might be related to regulating excitation-inhibition (E/I) balance in the brain. Here, we tested the neurophysiological effects of bumetanide and the relationship to clinical outcome variability and investigated the potential for machine learning–based predictions of meaningful clinical improvement. MethodsUsing modified linear mixed models applied to intention-to-treat population, we analyzed E/I-sensitive electroencephalography (EEG) measures before and after 91 days of treatment in the double-blind, randomized, placebo-controlled Bumetanide in Autism Medication and Biomarker study. Resting-state EEG of 82 subjects out of 92 participants (7–15 years) were available. Alpha frequency band absolute and relative power, central frequency, long-range temporal correlations, and functional E/I ratio treatment effects were related to the Repetitive Behavior Scale-Revised (RBS-R) and the Social Responsiveness Scale 2 as clinical outcomes. ResultsWe observed superior bumetanide effects on EEG, reflected in increased absolute and relative alpha power and functional E/I ratio and in decreased central frequency. Associations between EEG and clinical outcome change were restricted to subgroups with medium to high RBS-R improvement. Using machine learning, medium and high RBS-R improvement could be predicted by baseline RBS-R score and EEG measures with 80% and 92% accuracy, respectively. ConclusionsBumetanide exerts neurophysiological effects related to clinical changes in more responsive subsets, in whom prediction of improvement was feasible through EEG and clinical measures.