Imbalanced social-communicative and restricted repetitive behavior subtypes of autism spectrum disorder exhibit different neural circuitry.
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SUBMITTER: Bertelsen N
PROVIDER: S-EPMC8121854 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BACKGROUND:This paper is a systematic review and meta-analysis of the efficacy of available medications for the treatment of restricted/repetitive behavior (RRBs) in Autism Spectrum Disorder (ASD). METHOD:We searched MEDLINE, Embase, PsycINFO, The Cochrane Library (Cochrane Database of Systematic Reviews (CDRS), the Cochrane Central Register of Controlled Trials (CENTRAL), database of Abstracts of Reviews of Effects (DARE)), Scopus, Epistimonikos, Clinicaltrials.gov, and included all randomized controlled trials published after 1993 that were directed at RRBs in patients with ASD of all ages. We extracted the relevant data from the published studies with a predefined data extraction form and assessed the risk of bias. The primary outcomes were change in restricted/repetitive behavior. We performed a meta-analysis using the random effect model and included studies with given mean and standard deviation. This study is registered with PROSPERO number CRD42018092660). RESULTS:We identified 14 randomized controlled trials that met initial inclusion criteria. After closer inspection, nine trials - involving 552 patients in total - were included in the final analysis. The meta-analysis found no significant difference between medications (including fluvoxamine, risperidone, fluoxetine, citalopram, oxytocin, N-Acetylcysteine, buspirone) and placebo in the treatment of RRBs in ASD (P?=?0.20). Similarly, the sub-group meta-analysis also showed no significant difference between Selective Serotonin Reuptake Inhibitor (SSRIs) and placebo in the treatment of RRBs in ASD (P?=?0.68). There was no evidence of publication bias. CONCLUSION:This meta-analysis finds little support for the routine use of medications to treat restricted/repetitive behaviors in Autism Spectrum Disorder. Further research of large, balanced trials with precise assessment tools and long-term follow-up are needed. TRIAL REGISTRATION:The study protocol is registered in PROSPERO (Reference number: CRD42018092660).
| S-EPMC7068977 | biostudies-literature
Project description:BackgroundSLC25A12 was previously identified by a linkage-directed association analysis in autism. In this study, we investigated the relationship between three SLC25A12 single nucleotide polymorphisms (SNPs) (rs2056202, rs908670 and rs2292813) and restricted repetitive behavior (RRB) traits in autism spectrum disorders (ASDs), based on a positive correlation between the G allele of rs2056202 and an RRB subdomain score on the Autism Diagnostic Interview-Revised (ADI-R).MethodsWe used the Repetitive Behavior Scale-Revised (RBS-R) as a quantitative RRB measure, and conducted linear regression analyses for individual SNPs and a previously identified haplotype (rs2056202-rs2292813). We examined associations in our University of Illinois at Chicago-University of Florida (UIC-UF) sample (179 unrelated individuals with an ASD), and then attempted to replicate our findings in the Simons Simplex Collection (SSC) sample (720 ASD families).ResultsIn the UIC-UF sample, three RBS-R scores (ritualistic, sameness, sum) had positive associations with the A allele of rs2292813 (p = 0.006-0.012) and with the rs2056202-rs2292813 haplotype (omnibus test, p = 0.025-0.040). The SSC sample had positive associations between the A allele of rs2056202 and four RBS-R scores (stereotyped, sameness, restricted, sum) (p = 0.006-0.010), between the A allele of rs908670 and three RBS-R scores (stereotyped, self-injurious, sum) (p = 0.003-0.015), and between the rs2056202-rs2292813 haplotype and six RBS-R scores (stereotyped, self-injurious, compulsive, sameness, restricted, sum)(omnibus test, p = 0.002-0.028). Taken together, the A alleles of rs2056202 and rs2292813 were consistently and positively associated with RRB traits in both the UIC-UF and SSC samples, but the most significant SNP with phenotype association varied in each dataset.ConclusionsThis study confirmed an association between SLC25A12 and RRB traits in ASDs, but the direction of the association was different from that in the initial study. This could be due to the examined SLC25A12 SNPs being in linkage disequilibrium with another risk allele, and/or genetic/phenotypic heterogeneity of the ASD samples across studies.
| S-EPMC3123633 | biostudies-literature
Project description:BackgroundRestricted and repetitive behaviors (RRBs), detectable by 12 months in many infants in whom autism spectrum disorder (ASD) is later diagnosed, may represent some of the earliest behavioral markers of ASD. However, brain function underlying the emergence of these key behaviors remains unknown.MethodsBehavioral and resting-state functional connectivity (fc) magnetic resonance imaging data were collected from 167 children at high and low familial risk for ASD at 12 and 24 months (n = 38 at both time points). Twenty infants met criteria for ASD at 24 months. We divided RRBs into four subcategories (restricted, stereotyped, ritualistic/sameness, self-injurious) and used a data-driven approach to identify functional brain networks associated with the development of each RRB subcategory.ResultsHigher scores for ritualistic/sameness behavior were associated with less positive fc between visual and control networks at 12 and 24 months. Ritualistic/sameness and stereotyped behaviors were associated with less positive fc between visual and default mode networks at 12 months. At 24 months, stereotyped and restricted behaviors were associated with more positive fc between default mode and control networks. Additionally, at 24 months, stereotyped behavior was associated with more positive fc between dorsal attention and subcortical networks, whereas restricted behavior was associated with more positive fc between default mode and dorsal attention networks. No significant network-level associations were observed for self-injurious behavior.ConclusionsThese observations mark the earliest known description of functional brain systems underlying RRBs, reinforce the construct validity of RRB subcategories in infants, and implicate specific neural substrates for future interventions targeting RRBs.
| S-EPMC6557405 | biostudies-literature
Project description:Restricted, repetitive behaviors (RRBs) are patterns of behavior that exhibit little variation in form and have no obvious function. RRBs although transdiagonstic are a particularly prominent feature of certain neurodevelopmental disorders, yet relatively little is known about the neural circuitry of RRBs. Past work in this area has focused on isolated brain regions and neurotransmitter systems, but implementing a neural circuit approach has the potential to greatly improve understanding of RRBs. Magnetic resonance imaging (MRI) is well-suited to studying the structural and functional connectivity of the nervous system, and is a highly translational research tool. In this review, we synthesize MRI research from both neurodevelopmental disorders and relevant animal models that informs the neural circuitry of RRB. Together, these studies implicate distributed neural circuits between the cortex, basal ganglia, and cerebellum. Despite progress in neuroimaging of RRB, there are many opportunities for conceptual and methodological improvement. We conclude by suggesting future directions for MRI research in RRB, and how such studies can benefit from complementary approaches in neuroscience.
| S-EPMC6169529 | biostudies-literature
Project description:Restricted, repetitive behaviors (RRBs) are heterogeneous ranging from stereotypic body movements to rituals to restricted interests. RRBs are most strongly associated with autism but occur in a number of other clinical disorders as well as in typical development. There does not seem to be a category of RRB that is unique or specific to autism and RRB does not seem to be robustly correlated with specific cognitive, sensory or motor abnormalities in autism. Despite its clinical significance, little is known about the pathophysiology of RRB. Both clinical and animal models studies link repetitive behaviors to genetic mutations and a number of specific genetic syndromes have RRBs as part of the clinical phenotype. Genetic risk factors may interact with experiential factors resulting in the extremes in repetitive behavior phenotypic expression that characterize autism. Few studies of individuals with autism have correlated MRI findings and RRBs and no attempt has been made to associate RRB and post-mortem tissue findings. Available clinical and animal models data indicate functional and structural alterations in cortical-basal ganglia circuitry in the expression of RRB, however. Our own studies point to reduced activity of the indirect basal ganglia pathway being associated with high levels of repetitive behavior in an animal model. These findings, if generalizable, suggest specific therapeutic targets. These, and perhaps other, perturbations to cortical basal ganglia circuitry are mediated by specific molecular mechanisms (e.g., altered gene expression) that result in long-term, experience-dependent neuroadaptations that initiate and maintain repetitive behavior. A great deal more research is needed to uncover such mechanisms. Work in areas such as substance abuse, OCD, Tourette syndrome, Parkinson's disease, and dementias promise to provide findings critical for identifying neurobiological mechanisms relevant to RRB in autism. Moreover, basic research in areas such as birdsong, habit formation, and procedural learning may provide additional, much needed clues. Understanding the pathophysioloy of repetitive behavior will be critical to identifying novel therapeutic targets and strategies for individuals with autism.
| S-EPMC3090677 | biostudies-literature
Project description:Corollary discharge (CD) signals are "copies" of motor signals sent to sensory regions that allow animals to adjust sensory consequences of self-generated actions. Autism spectrum disorder (ASD) is characterized by sensory and motor deficits, which may be underpinned by altered CD signaling. We evaluated oculomotor CD using the blanking task, which measures the influence of saccades on visual perception, in 30 children with ASD and 35 typically developing (TD) children. Participants were instructed to make a saccade to a visual target. Upon saccade initiation, the presaccadic target disappeared and reappeared to the left or right of the original position. Participants indicated the direction of the jump. With intact CD, participants can make accurate perceptual judgements. Otherwise, participants may use saccade landing site as a proxy of the presaccadic target and use it to inform perception. We used multilevel modeling to examine the influence of saccade landing site on trans-saccadic perceptual judgements. We found that, compared with TD participants, children with ASD were more sensitive to target displacement and less reliant on saccade landing site when spatial uncertainty of the post-saccadic target was high. This pattern was driven by ASD participants with less severe restricted and repetitive behaviors. These results suggest a relationship between altered CD signaling and core ASD symptoms.
| S-EPMC8354038 | biostudies-literature
Project description:Several instruments have been proposed to investigate restricted, repetitive behaviors (RRBs) in individuals with Autism Spectrum Disorder (ASD). Systematic video observations may overcome questionnaire and interview limitations to investigate RRBs. This study aimed to analyze stereotypic patterns through video recordings and to determine the correlation between the number and appearance of RRBs to ASD severity. Twenty health professionals wearing a body cam recorded 780 specific RRBs during everyday activities of 67 individuals with ASD (mean age: 14.2 ± 3.72 years) for three months. Each stereotypy was classified according to its complexity pattern (i.e., simple or complex) based on body parts and sensory channels involved. The RRBs spectrum for each subject ranged from one to 33 different patterns (mean: 11.6 ± 6.82). Individuals with a lower number of stereotypies shown a lower ASD severity compared to subjects with a higher number of stereotypies (p = 0.044). No significant differences were observed between individuals exhibiting simple (n = 40) and complex patterns (n = 27) of stereotypies on ASD severity, age, sex, and the number of stereotypes. This study represents the first attempt to systematically document expression patterns of RRBs with a data-driven approach. This may provide a better understanding of the pathophysiology and management of RRBs.
| S-EPMC8224357 | biostudies-literature
Project description:BackgroundAutism spectrum disorder (ASD) is a neurodevelopmental disorder defined by persistent deficits in social functioning and the presence of restricted and repetitive behaviours (RRBs). RRBs refer to four subtypes of behaviour including repetitive movements, speech, or use of objects; insistence on sameness; restricted interests; and sensory processing abnormalities. Many individuals with ASD also experience anxiety, which compounds ASD-related difficulties and inhibits daily functioning. RRBs have been found to be positively associated with anxiety; however, our understanding of the interplay between RRB subtypes and anxiety remains unclear. Thus, the current review aims to clarify the association between RRBs and anxiety by conducting a systematic review and meta-analysis.MethodsTo identify relevant studies, we will search five databases: CINAHL Plus, Cochrane Central Register of Controlled Trials, Ovid MEDLINE, PsycINFO, and Scopus. Articles included in the review will have their titles, abstracts, and full texts reviewed by two independent authors and their methodological quality assessed via the modified Newcastle-Ottawa Scale. Random-effects meta-analyses will then be conducted to calculate the pooled association between RRB subtypes and anxiety. Sensitivity analyses will also be conducted to assess the potential impact of bias, missing data, outliers, and methodological differences on this relationship. Additionally, this review will collate the factors which may influence the anxiety-RRB relationship to help identify who is most vulnerable to developing anxiety.DiscussionThis will be the first review to examine the association between the four subtypes of RRBs and anxiety in individuals with ASD. Understanding this relationship, and the factors associated with this, may help clinicians understand the different underpinnings and presentations of anxiety within this population with potential implications for assessment and treatment.Systematic review registrationPROSPERO CRD42020185434.
| S-EPMC8638349 | biostudies-literature
Project description:BackgroundIndividuals on the autism spectrum commonly have differences from non-autistic people in expressing their emotions using communicative behaviors, such as facial expressions. However, it is not yet clear if this reduced expressivity stems from reduced physiological reactivity in emotional contexts or if individuals react internally, but do not show these reactions externally to others. We hypothesized that autism is characterized by a discordance between in-the-moment internal psychophysiological arousal and external communicative expressions of emotion.MethodsForty-one children on the autism spectrum and 39 non-autistic, typically developing (TD) children of two age groups (2-4 and 8-12 years) participated in a low-level stress task whilst wearing a wireless electrocardiogram. Children's negative emotional expressions (facial, vocal, bodily) were coded following standardized protocols. Alexithymia traits were assessed using the Children's Alexithymia Measure with school-aged children only. Data analyses involved ANOVAs, correlations, and sensitivity analyses.ResultsThere were no group differences in physiological arousal (heart rate) or in communicative expressions of stress to the stress task. For TD preschoolers, physiological arousal during the stress task was associated with vocal expressions and for TD school-aged children, they were associated with facial and bodily expressions. By contrast, for children on the autism spectrum, physiological arousal during the stress tasks was not associated with communicative expressions across age groups.ConclusionsOur findings suggest that children on the autism spectrum might experience emotional disconcordance, in that their physiological arousal does not align with their communicative expressions. Therefore, the internally experienced stress of children on the autism spectrum may be inadvertently missed by teachers and caregivers and, consequently, learning opportunities for teaching emotional communication and regulation may be also missed. Our results support the use of wearable biosensors to facilitate such interventions in children on the autism spectrum.
| S-EPMC11373183 | biostudies-literature
Project description:Restricted and repetitive behavior (RRB) is a core diagnostic feature of autism spectrum disorder (ASD). Previous research shows that RRB is prevalent early in life and observed in neurotypical development as well. Less is known, however, about early RRB patterns, developmental trajectories, and the relation to outcomes for autistic children. The purpose of this systematic review was to synthesize findings from studies examining RRB in autistic children from birth through age 3. A detailed protocol was designed a priori based on PRISMA guidelines for systematic reviews. From the published literature, 41 peer reviewed journal articles were identified and included in this review. Our synthesis of the literature suggests that differences in RRB are evident prior to age 2 in children with or who go onto be diagnosed with autism. These differences were evident for both frequency and intensity of RRB across multiple topographies. There were mixed results regarding functional outcomes associated with early RRB, such as cognitive and adaptive behavior, though relations appeared to become stronger as children aged beyond toddlerhood. Notably, level of RRB appears unrelated to autism severity in young autistic children. A wide range of RRB have been reported to be elevated in autistic children during the first years of life, including repetitive motor behaviors, atypical sensory behaviors, insistence on sameness (IS), and self-injurious behaviors (SIBs). In contrast to studies of older children, RRB in very young autistic children do not appear to be associated with functional outcomes but may be valuable to include in early screening efforts.Systematic review registrationhttps://osf.io/huzf3, unique identifier: doi: 10.17605/OSF.IO/HUZF3.
| S-EPMC9661964 | biostudies-literature