scholarly journals Repetitive and Restricted Behaviours and Anxiety in Autism Spectrum Disorder: Protocol for a Systematic Review and Meta-Analysis

2020 ◽  
Author(s):  
Tegan Sellick ◽  
Alexandra Ure ◽  
Katrina Williams

Abstract 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 systematically review and meta-analyse the association between RRBs and anxiety. Methods This review will collate studies which analyse the association between RRBs and anxiety in individuals with ASD. 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 risk of bias assessed via the modified Newcastle-Ottawa Scale. DiscussionThis will be the first review to examine the association between anxiety and the four subtypes of RRBs 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 Registration PROSPERO CRD42020185434

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Tegan Sellick ◽  
Alexandra Ure ◽  
Katrina Williams

Abstract Background Autism 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. Methods To 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. Discussion This 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 registration PROSPERO CRD42020185434


2021 ◽  
Author(s):  
Jiawei Zhang ◽  
Hao Zhang

Abstract Background Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder marked by characteristic impairments in social communication and interaction, as well as restricted and repetitive behavior. There is a continued need for exploring effective interventions and evaluating treatment options for ASD. Transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) are non-invasive neurostimulation techniques which have shown clinical benefits in adult psychiatric conditions. While in ASD patients, no guideline has so-far recommended on the application of NIBS due to a lack of high-quality synthetic evidence. Therefore, objective of this study will be to systematically evaluate the evidence on clinical effects of non-invasive neurostimulation in patients with ASD. Methods We designed and registered a study protocol for a systematic review. A comprehensive search from database inception onwards will be conducted in PubMed, EMBASE and Cochrane library. Randomized and non-randomized sham-controlled studies assessing the effects of noninvasive neurostimulation in patients with ASD will be identified. Eligibility of citations retrieved will be independently screened by two reviewers. The risk of bias and quality of included studies will be appraised using appropriate tools. A narrative synthesis around the features of the evidences will provided. There may be a chance for meta-analysis to pool the estimates of studies included if three studies or more meet the requirements for meta-analysis. If so, a random-effects model maybe applied. And we will evaluate heterogeneity between studies using the I² statistic. Discussion This systematic review will provide a broad and comprehensive evaluation of the evidence on clinical effects of TMS and tDCS in patients with ASD. Our findings will be reported according to the PRISMA guidelines and may add more confidence when healthcare professionals are making informed decisions about the choice of this therapy. Results will be published in a peer-reviewed journal. Systematic review registration: Submitted to PROSPERO, 20/11/2021


2021 ◽  
Vol 11 (8) ◽  
pp. 784
Author(s):  
Daniel A. Rossignol ◽  
Richard E. Frye

Autism spectrum disorder (ASD) is a common neurodevelopmental disorder affecting 2% of children in the United States. Biochemical abnormalities associated with ASD include impaired methylation and sulphation capacities along with low glutathione (GSH) redox capacity. Potential treatments for these abnormalities include cobalamin (B12). This systematic review collates the studies using B12 as a treatment in ASD. A total of 17 studies were identified; 4 were double-blind, placebo-controlled studies (2 examined B12 injections alone and 2 used B12 in an oral multivitamin); 1 was a prospective controlled study; 6 were prospective, uncontrolled studies, and 6 were retrospective (case series and reports). Most studies (83%) used oral or injected methylcobalamin (mB12), while the remaining studies did not specify the type of B12 used. Studies using subcutaneous mB12 injections (including 2 placebo-controlled studies) used a 64.5–75 µg/kg/dose. One study reported anemia in 2 ASD children with injected cyanocobalamin that resolved with switching to injected mB12. Two studies reported improvements in markers of mitochondrial metabolism. A meta-analysis of methylation metabolites demonstrated decreased S-adenosylhomocysteine (SAH), and increased methionine, S-adenosylmethionine (SAM), SAM/SAH ratio, and homocysteine (with small effect sizes) with mB12. Meta-analysis of the transsulfuration and redox metabolism metabolites demonstrated significant improvements with mB12 in oxidized glutathione (GSSG), cysteine, total glutathione (GSH), and total GSH/GSSG redox ratio with medium to large effect sizes. Improvements in methylation capacity and GSH redox ratio were significantly associated with clinical improvements (with a mean moderate effect size of 0.59) in core and associated ASD symptoms, including expressive communication, personal and domestic daily living skills, and interpersonal, play-leisure, and coping social skills, suggesting these biomarkers may predict response to B12. Other clinical improvements observed with B12 included sleep, gastrointestinal symptoms, hyperactivity, tantrums, nonverbal intellectual quotient, vision, eye contact, echolalia, stereotypy, anemia, and nocturnal enuresis. Adverse events identified by meta-analysis included hyperactivity (11.9%), irritability (3.4%), trouble sleeping (7.6%), aggression (1.8%), and worsening behaviors (7.7%) but were generally few, mild, not serious, and not significantly different compared to placebo. In one study, 78% of parents desired to continue mB12 injections after the study conclusion. Preliminary clinical evidence suggests that B12, particularly subcutaneously injected mB12, improves metabolic abnormalities in ASD along with clinical symptoms. Further large multicenter placebo-controlled studies are needed to confirm these data. B12 is a promising treatment for ASD.


2019 ◽  
Vol 22 (3) ◽  
pp. 118-124
Author(s):  
Julie A Hadwin ◽  
Emma Lee ◽  
Robert Kumsta ◽  
Samuele Cortese ◽  
Hanna Kovshoff

BackgroundThe cortisol awakening response (CAR) is characterised by an increase in cortisol in the 30 to 60 min after waking. Research has found significant associations between an atypical CAR and symptoms of stress and anxiety in typically developing (TD) children and adolescents. A number of studies have explored the CAR in autism spectrum disorder (ASD), but no evidence synthesis is available to date.Objective and methodsBased on a preregistered protocol (PROSPERO: CRD42017051187), we carried out a systematic review (SR) and meta-analysis (MA) of CAR studies to explore potential significant differences between children and adolescents with ASD and TD controls. Web of Science, PubMed and PsychInfo were searched until January 2019. A random-effects model was used to pool studies and we used the Newcastle-Ottawa scale (NOS) to assess study quality and risk of bias.FindingsThe SR retrieved a total of nine studies, with mixed findings on the comparison of the CAR between children and adolescents with ASD and TD controls. The MA, based on four studies (ASD; n=117 and TD n=118), suggested no differences between the CAR in ASD and TD populations (SMD: −0.21, 95% CI −0.49 to 0.08). In terms of NOS items, no study specified Representativeness of the cases and Non-response rate.Discussion and clinical implicationsGiven the relatively few studies and lack of appropriately matched TD controls, additional research is needed to further understand and recommend the utility of the CAR as a reliable marker to differentiate ASD and TD.


2020 ◽  
Vol 27 (40) ◽  
pp. 6771-6786
Author(s):  
Geir Bjørklund ◽  
Nagwa Abdel Meguid ◽  
Maryam Dadar ◽  
Lyudmila Pivina ◽  
Joanna Kałużna-Czaplińska ◽  
...  

As a major neurodevelopmental disorder, Autism Spectrum Disorder (ASD) encompasses deficits in communication and repetitive and restricted interests or behaviors in childhood and adolescence. Its etiology may come from either a genetic, epigenetic, neurological, hormonal, or an environmental cause, generating pathways that often altogether play a synergistic role in the development of ASD pathogenesis. Furthermore, the metabolic origin of ASD should be important as well. A balanced diet consisting of the essential and special nutrients, alongside the recommended caloric intake, is highly recommended to promote growth and development that withstand the physiologic and behavioral challenges experienced by ASD children. In this review paper, we evaluated many studies that show a relationship between ASD and diet to develop a better understanding of the specific effects of the overall diet and the individual nutrients required for this population. This review will add a comprehensive update of knowledge in the field and shed light on the possible nutritional deficiencies, metabolic impairments (particularly in the gut microbiome), and malnutrition in individuals with ASD, which should be recognized in order to maintain the improved socio-behavioral habit and physical health.


2019 ◽  
Author(s):  
Sun Jae Moon ◽  
Jin Seub Hwang ◽  
Rajesh Kana ◽  
John Torous ◽  
Jung Won Kim

BACKGROUND Over the recent years, machine learning algorithms have been more widely and increasingly applied in biomedical fields. In particular, its application has been drawing more attention in the field of psychiatry, for instance, as diagnostic tests/tools for autism spectrum disorder. However, given its complexity and potential clinical implications, there is ongoing need for further research on its accuracy. OBJECTIVE The current study aims to summarize the evidence for the accuracy of use of machine learning algorithms in diagnosing autism spectrum disorder (ASD) through systematic review and meta-analysis. METHODS MEDLINE, Embase, CINAHL Complete (with OpenDissertations), PsyINFO and IEEE Xplore Digital Library databases were searched on November 28th, 2018. Studies, which used a machine learning algorithm partially or fully in classifying ASD from controls and provided accuracy measures, were included in our analysis. Bivariate random effects model was applied to the pooled data in meta-analysis. Subgroup analysis was used to investigate and resolve the source of heterogeneity between studies. True-positive, false-positive, false negative and true-negative values from individual studies were used to calculate the pooled sensitivity and specificity values, draw SROC curves, and obtain area under the curve (AUC) and partial AUC. RESULTS A total of 43 studies were included for the final analysis, of which meta-analysis was performed on 40 studies (53 samples with 12,128 participants). A structural MRI subgroup meta-analysis (12 samples with 1,776 participants) showed the sensitivity at 0.83 (95% CI-0.76 to 0.89), specificity at 0.84 (95% CI -0.74 to 0.91), and AUC/pAUC at 0.90/0.83. An fMRI/deep neural network (DNN) subgroup meta-analysis (five samples with 1,345 participants) showed the sensitivity at 0.69 (95% CI- 0.62 to 0.75), the specificity at 0.66 (95% CI -0.61 to 0.70), and AUC/pAUC at 0.71/0.67. CONCLUSIONS Machine learning algorithms that used structural MRI features in diagnosis of ASD were shown to have accuracy that is similar to currently used diagnostic tools.


2021 ◽  
pp. 116856
Author(s):  
Frédéric Dutheil ◽  
Aurélie Comptour ◽  
Roxane Morlon ◽  
Martial Mermillod ◽  
Bruno Pereira ◽  
...  

2021 ◽  
Vol 11 (6) ◽  
pp. 488
Author(s):  
Daniel A Rossignol ◽  
Richard E Frye

Autism spectrum disorder (ASD) is a neurodevelopmental disorder affecting approximately 2% of children in the United States. Growing evidence suggests that immune dysregulation is associated with ASD. One immunomodulatory treatment that has been studied in ASD is intravenous immunoglobulins (IVIG). This systematic review and meta-analysis examined the studies which assessed immunoglobulin G (IgG) concentrations and the therapeutic use of IVIG for individuals with ASD. Twelve studies that examined IgG levels suggested abnormalities in total IgG and IgG 4 subclass concentrations, with concentrations in these IgGs related to aberrant behavior and social impairments, respectively. Meta-analysis supported possible subsets of children with ASD with low total IgG and elevated IgG 4 subclass but also found significant variability among studies. A total of 27 publications reported treating individuals with ASD using IVIG, including four prospective, controlled studies (one was a double-blind, placebo-controlled study); six prospective, uncontrolled studies; 2 retrospective, controlled studies; and 15 retrospective, uncontrolled studies. In some studies, clinical improvements were observed in communication, irritability, hyperactivity, cognition, attention, social interaction, eye contact, echolalia, speech, response to commands, drowsiness, decreased activity and in some cases, the complete resolution of ASD symptoms. Several studies reported some loss of these improvements when IVIG was stopped. Meta-analysis combining the aberrant behavior checklist outcome from two studies demonstrated that IVIG treatment was significantly associated with improvements in total aberrant behavior and irritability (with large effect sizes), and hyperactivity and social withdrawal (with medium effect sizes). Several studies reported improvements in pro-inflammatory cytokines (including TNF-alpha). Six studies reported improvements in seizures with IVIG (including patients with refractory seizures), with one study reporting a worsening of seizures when IVIG was stopped. Other studies demonstrated improvements in recurrent infections, appetite, weight gain, neuropathy, dysautonomia, and gastrointestinal symptoms. Adverse events were generally limited but included headaches, vomiting, worsening behaviors, anxiety, fever, nausea, fatigue, and rash. Many studies were limited by the lack of standardized objective outcome measures. IVIG is a promising and potentially effective treatment for symptoms in individuals with ASD; further research is needed to provide solid evidence of efficacy and determine the subset of children with ASD who may best respond to this treatment as well as to investigate biomarkers which might help identify responsive candidates.


2019 ◽  
Vol 40 (6) ◽  
pp. 1421-1454 ◽  
Author(s):  
Tamar Kalandadze ◽  
Valentina Bambini ◽  
Kari-Anne B. Næss

AbstractIndividuals with autism spectrum disorder (ASD) often experience difficulty in comprehending metaphors compared to individuals with typical development (TD). However, there is a large variation in the results across studies, possibly related to the properties of the metaphor tasks. This preregistered systematic review and meta-analysis (a) explored the properties of the metaphor tasks used in ASD research, and (b) investigated the group difference between individuals with ASD and TD on metaphor comprehension, as well as the relationship between the task properties and any between-study variation. A systematic search was undertaken in seven relevant databases. Fourteen studies fulfilled our predetermined inclusion criteria. Across tasks, we detected four types of response format and a great variety of metaphors in terms of familiarity, syntactic structure, and linguistic context. Individuals with TD outperformed individuals with ASD on metaphor comprehension (Hedges’ g = −0.63). Verbal explanation response format was utilized in the study showing the largest effect size in the group comparison. However, due to the sparse experimental manipulations, the role of task properties could not be established. Future studies should consider and report task properties to determine their role in metaphor comprehension, and to inform experimental paradigms as well as educational assessment.


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