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Epidemiology and Psychiatric Sciences Jul 2023This study aimed to summarize the evidence on sleep alterations in medication-naïve children and adolescents with autism spectrum disorder (ASD). (Meta-Analysis)
Meta-Analysis
AIMS
This study aimed to summarize the evidence on sleep alterations in medication-naïve children and adolescents with autism spectrum disorder (ASD).
METHODS
We systematically searched PubMed/Medline, Embase and Web of Science databases from inception through March 22, 2021. This study was registered with PROSPERO (CRD42021243881). Any observational study was included that enrolled medication-naïve children and adolescents with ASD and compared objective (actigraphy and polysomnography) or subjective sleep parameters with typically developing (TD) counterparts. We extracted relevant data such as the study design and outcome measures. The methodological quality was assessed through the Newcastle-Ottawa Scale (NOS). A meta-analysis was carried out using the random-effects model by pooling effect sizes as Hedges' . To assess publication bias, Egger's test and -curve analysis were done. A priori planned meta-regression and subgroup analysis were also performed to identify potential moderators.
RESULTS
Out of 4277 retrieved references, 16 studies were eligible with 981 ASD patients and 1220 TD individuals. The analysis of objective measures showed that medication-naïve ASD patients had significantly longer sleep latency (Hedges' 0.59; 95% confidence interval [95% CI] 0.26 to 0.92), reduced sleep efficiency (Hedges' -0.58; 95% CI -0.87 to -0.28), time in bed (Hedges' -0.64; 95% CI -1.02 to -0.26) and total sleep time (Hedges' -0.64; 95% CI -1.01 to -0.27). The analysis of subjective measures showed that they had more problems in daytime sleepiness (Hedges' 0.48; 95% CI 0.26 to 0.71), sleep latency (Hedges' 1.15; 95% CI 0.72 to 1.58), initiating and maintaining sleep (Hedges' 0.86; 95% CI 0.39 to 1.33) and sleep hyperhidrosis (Hedges' 0.48; 95% CI 0.29 to 0.66). Potential publication bias was detected for sleep latency, sleep period time and total sleep time measured by polysomnography. Some sleep alterations were moderated by age, sex and concurrent intellectual disability. The median NOS score was 8 (interquartile range 7.25-8.75).
CONCLUSION
We found that medication-naïve children and adolescents with ASD presented significantly more subjective and objective sleep alterations compared to TD and identified possible moderators of these differences. Future research requires an analysis of how these sleep alterations are linked to core symptom severity and comorbid behavioural problems, which would provide an integrated therapeutic intervention for ASD. However, our results should be interpreted in light of the potential publication bias.
Topics: Humans; Child; Adolescent; Autism Spectrum Disorder; Sleep; Comorbidity; Outcome Assessment, Health Care; Observational Studies as Topic
PubMed: 37469173
DOI: 10.1017/S2045796023000574 -
Molecular Autism Apr 2024This meta-analysis aimed to explore the most robust findings across numerous existing resting-state functional imaging and voxel-based morphometry (VBM) studies on the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
This meta-analysis aimed to explore the most robust findings across numerous existing resting-state functional imaging and voxel-based morphometry (VBM) studies on the functional and structural brain alterations in individuals with autism spectrum disorder (ASD).
METHODS
A whole-brain voxel-wise meta-analysis was conducted to compare the differences in the intrinsic functional activity and gray matter volume (GMV) between individuals with ASD and typically developing individuals (TDs) using Seed-based d Mapping software.
RESULTS
A total of 23 functional imaging studies (786 ASD, 710 TDs) and 52 VBM studies (1728 ASD, 1747 TDs) were included. Compared with TDs, individuals with ASD displayed resting-state functional decreases in the left insula (extending to left superior temporal gyrus [STG]), bilateral anterior cingulate cortex/medial prefrontal cortex (ACC/mPFC), left angular gyrus and right inferior temporal gyrus, as well as increases in the right supplementary motor area and precuneus. For VBM meta-analysis, individuals with ASD displayed decreased GMV in the ACC/mPFC and left cerebellum, and increased GMV in the left middle temporal gyrus (extending to the left insula and STG), bilateral olfactory cortex, and right precentral gyrus. Further, individuals with ASD displayed decreased resting-state functional activity and increased GMV in the left insula after overlapping the functional and structural differences.
CONCLUSIONS
The present multimodal meta-analysis demonstrated that ASD exhibited similar alterations in both function and structure of the insula and ACC/mPFC, and functional or structural alterations in the default mode network (DMN), primary motor and sensory regions. These findings contribute to further understanding of the pathophysiology of ASD.
Topics: Humans; Autism Spectrum Disorder; Brain; Cerebral Cortex; Gray Matter; Gyrus Cinguli; Magnetic Resonance Imaging
PubMed: 38576034
DOI: 10.1186/s13229-024-00593-6 -
Brain Sciences May 2024Hyperserotonemia is one of the most studied endophenotypes in autism spectrum disorder (ASD), but there are still no unequivocal results about its causes or biological... (Review)
Review
Hyperserotonemia is one of the most studied endophenotypes in autism spectrum disorder (ASD), but there are still no unequivocal results about its causes or biological and behavioral outcomes. This systematic review summarizes the studies investigating the relationship between blood serotonin (5-HT) levels and ASD, comparing diagnostic tools, analytical methods, and clinical outcomes. A literature search on peripheral 5-HT levels and ASD was conducted. In total, 1104 publications were screened, of which 113 entered the present systematic review. Of these, 59 articles reported hyperserotonemia in subjects with ASD, and 26 presented correlations between 5-HT levels and ASD-core clinical outcomes. The 5-HT levels are increased in about half, and correlations between hyperserotonemia and clinical outcomes are detected in a quarter of the studies. The present research highlights a large amount of heterogeneity in this field, ranging from the characterization of ASD and control groups to diagnostic and clinical assessments, from blood sampling procedures to analytical methods, allowing us to delineate critical topics for future studies.
PubMed: 38790459
DOI: 10.3390/brainsci14050481 -
Frontiers in Psychology 2023In recent years, it has been described that the dysbiosis of the intestinal microbiota plays a transcendental role in several pathologies. In this sense, the importance...
INTRODUCTION
In recent years, it has been described that the dysbiosis of the intestinal microbiota plays a transcendental role in several pathologies. In this sense, the importance of the gut microbiota in the gut-brain axis, with a bidirectional communication, has been demonstrated. Furthermore, the gut microbiota has been linked with mood disorders and neuropsychiatric disorders.
METHODS
A systematic review of two databases - PubMed and Scopus - was carried out following PRISMA guidelines. We included original studies in humans with a control group published in the last 11 years, which were assessed by the Critical Appraisal Skills Program (CASP) to confirm their quality. Eighteen articles met all the selection criteria.
RESULTS
A review of the articles revealed an association between psychiatric disorders and different bacterial phyla. The studies we have reviewed have demonstrated differences between subjects with psychiatric disorders and controls and highlight a clear relationship between depression, stress, autism spectrum disorder (ASD), psychotic episodes, eating disorders, anxiety and brain function and the gut microbiota composition.
CONCLUSION
A reduction of fermentative taxa has been observed in different psychiatric disorders, resulting in a decrease in the production of short-chain fatty acids (SCFAs) and an increase in pro-inflammatory taxa, both of which may be consequences of the exacerbation of these pathologies.
PubMed: 37599717
DOI: 10.3389/fpsyg.2023.1215674 -
Neuropsychology Review Dec 2023To examine current clinical research on the use of transcranial magnetic stimulation (TMS) in the treatment of pediatric and young adult autism spectrum disorder in... (Meta-Analysis)
Meta-Analysis Review
Treatment Response of Transcranial Magnetic Stimulation in Intellectually Capable Youth and Young Adults with Autism Spectrum Disorder: A Systematic Review and Meta-Analysis.
To examine current clinical research on the use of transcranial magnetic stimulation (TMS) in the treatment of pediatric and young adult autism spectrum disorder in intellectually capable persons (IC-ASD). We searched peer-reviewed international literature to identify clinical trials investigating TMS as a treatment for behavioral and cognitive symptoms of IC-ASD. We identified sixteen studies and were able to conduct a meta-analysis on twelve of these studies. Seven were open-label or used neurotypical controls for baseline cognitive data, and nine were controlled trials. In the latter, waitlist control groups were often used over sham TMS. Only one study conducted a randomized, parallel, double-blind, and sham controlled trial. Favorable safety data was reported in low frequency repetitive TMS, high frequency repetitive TMS, and intermittent theta burst studies. Compared to TMS research of other neuropsychiatric conditions, significantly lower total TMS pulses were delivered in treatment and neuronavigation was not regularly utilized. Quantitatively, our multivariate meta-analysis results report improvement in cognitive outcomes (pooled Hedges' g = 0.735, 95% CI = 0.242, 1.228; p = 0.009) and primarily Criterion B symptomology of IC-ASD (pooled Hedges' g = 0.435, 95% CI = 0.359, 0.511; p < 0.001) with low frequency repetitive TMS to the dorsolateral prefrontal cortex. The results of our systematic review and meta-analysis data indicate that TMS may offer a promising and safe treatment option for pediatric and young adult patients with IC-ASD. However, future work should include use of neuronavigation software, theta burst protocols, targeting of various brain regions, and robust study design before clinical recommendations can be made.
Topics: Humans; Adolescent; Young Adult; Child; Transcranial Magnetic Stimulation; Autism Spectrum Disorder; Research Design; Randomized Controlled Trials as Topic
PubMed: 36161554
DOI: 10.1007/s11065-022-09564-1 -
Frontiers in Psychiatry 2023Several reports suggest that altered mitochondrial DNA copy number (mtDNA-cn), a common biomarker for aberrant mitochondrial function, is implicated in autism spectrum... (Review)
Review
BACKGROUND
Several reports suggest that altered mitochondrial DNA copy number (mtDNA-cn), a common biomarker for aberrant mitochondrial function, is implicated in autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD), but the results are still elusive.
METHODS
A meta-analysis was performed to summarize the current indication and to provide a more precise assessment of the mtDNA-cn in ASD and ADHD. A search in the MEDLINE-PubMed, Scopus, and EMBASE databases was done to identify related studies up to the end of February 2023. The meta-analysis was conducted according to recommendations of the Cochrane Handbook of Systematic Reviews.
RESULTS
Fourteen studies involving 666 cases with ASD and ADHD and 585 controls were collected and judged relevant for the systematic review and meta-analysis. The pooled results by a random effects meta-analysis was reported as a geometric mean of the estimated average response ratio and 95% confidence interval. Overall analysis of studies reported differences in mtDNA-cn in blood samples ( = 10) and non-blood samples (brain tissues and oral samples; = 4) suggested significantly higher mtDNA-cn in patients compared to controls ( = 0.0275). Sub-analysis by stratifying studies based on tissue type, showed no significant increase in mtDNA-cn in blood samples among patients and controls ( = 0.284). Conversely, higher mtDNA-cn was observed in non-blood samples in patients than in controls ( = 0.0122). Further stratified analysis based on blood-cell compositions as potential confounds showed no significant difference in mtDNA-cn in peripheral blood samples of patients comparted to controls ( = 0.074). In addition, stratified analysis of aged-matched ASD and ADHD patients and controls revealed no significant difference in mtDNA-cn in blood samples between patients and controls ( = 0.214), whereas a significant increase in mtDNA-cn was observed in non-blood samples between patients and controls ( < 0.001). Finally, when the mtDNA-cn was analyzed in blood samples of aged-matched patients with ASD (peripheral blood, leukocytes, and PBMCs) or ADHD (peripheral blood), no significant difference in mtDNA-cn was observed between ASD patients and controls ( = 0.385), while a significant increase in mtDNA-cn was found between ADHD patients and controls ( = 0.033).
CONCLUSION
In this first meta-analysis of the evaluation of mtDNA-cn in ASD/ADHD, our results show elevated mtDNA-cn in ASD and ADHD, further emphasizing the implication of mitochondrial dysfunction in neurodevelopmental disorders. However, our results indicate that the mtDNA-cn in blood is not reflected in other tissues in ASD/ADHD, and the true relationship between blood-derived mtDNA-cn and ASD/ADHD remains to be defined in future studies. The importance of blood-cell compositions as confounders of blood-based mtDNA-cn measurement and the advantages of salivary mtDNA-cn should be considered in future studies. Moreover, the potential of mtDNA-cn as a biomarker for mitochondrial malfunction in neurodevelopmental disorders deserves further investigations.
PubMed: 37484684
DOI: 10.3389/fpsyt.2023.1196035 -
Frontiers in Neuroscience 2024Critical phases of neurodevelopment and gut microbiota diversification occur in early life and both processes are impacted by genetic and environmental factors. Recent...
Functional contribution of the intestinal microbiome in autism spectrum disorder, attention deficit hyperactivity disorder, and Rett syndrome: a systematic review of pediatric and adult studies.
INTRODUCTION
Critical phases of neurodevelopment and gut microbiota diversification occur in early life and both processes are impacted by genetic and environmental factors. Recent studies have shown the presence of gut microbiota alterations in neurodevelopmental disorders. Here we performed a systematic review of alterations of the intestinal microbiota composition and function in pediatric and adult patients affected by autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and Rett syndrome (RETT).
METHODS
We searched selected keywords in the online databases of PubMed, Cochrane, and OVID (January 1980 to December 2021) with secondary review of references of eligible articles. Two reviewers independently performed critical appraisals on the included articles using the Critical Appraisal Skills Program for each study design.
RESULTS
Our systematic review identified 18, 7, and 3 original articles describing intestinal microbiota profiles in ASD, ADHD, and RETT, respectively. Decreased Firmicutes and increased Bacteroidetes were observed in the gut microbiota of individuals affected by ASD and ADHD. Proinflammatory cytokines, short-chain fatty acids and neurotransmitter levels were altered in ASD and RETT. Constipation and visceral pain were related to changes in the gut microbiota in patients affected by ASD and RETT. Hyperactivity and impulsivity were negatively correlated with (phylum Firmicutes) and positively correlated with sp. (phylum Bacteroidetes) in ADHD subjects. Five studies explored microbiota-or diet-targeted interventions in ASD and ADHD. Probiotic treatments with sp. and fecal microbiota transplantation from healthy donors reduced constipation and ameliorated ASD symptoms in affected children. Perinatal administration of sp. prevented the onset of Asperger and ADHD symptoms in adolescence. Micronutrient supplementation improved disease symptomatology in ADHD without causing significant changes in microbiota communities' composition.
DISCUSSION
Several discrepancies were found among the included studies, primarily due to sample size, variations in dietary practices, and a high prevalence of functional gastrointestinal symptoms. Further studies employing longitudinal study designs, larger sample sizes and multi-omics technologies are warranted to identify the functional contribution of the intestinal microbiota in developmental trajectories of the human brain and neurobehavior.
SYSTEMATIC REVIEW REGISTRATION
https://clinicaltrials.gov/, CRD42020158734.
PubMed: 38516317
DOI: 10.3389/fnins.2024.1341656 -
Sleep Medicine Reviews Apr 2024Pharmacological treatments (i.e., melatonin) and non-pharmacological therapies (e.g., parent-based sleep education programs and behavioural interventions) have been... (Meta-Analysis)
Meta-Analysis Review
Pharmacological treatments (i.e., melatonin) and non-pharmacological therapies (e.g., parent-based sleep education programs and behavioural interventions) have been found to result in improved sleep in children and adolescents with autism spectrum disorder (ASD). However, there are several limitations to these treatment approaches, including concerns about the possible side-effects and safety, high-cost and uncertainties of long-term effects. Physical activity (PA) intervention is a promising behavioural intervention that has received increasing attention. However, the effects of PA intervention on sleep are still unclear in this clinical group. This study aimed to synthesize available empirical studies concerning the effects of PA interventions on sleep in children and adolescents with ASD. Following PRISMA guidelines, seven electronic databases: APA PsychInfo, CINAHL Ultimate, ERIC, MEDLINE, PubMed, SPORTDiscus, and Web of Science, were searched from inception to March 2023. Randomized controlled trials/quasi-experimental designs with comparison groups were included. Initially, 444 articles were identified, 13 articles underwent systematic review, and 8 studies with control groups and sufficient statistical data were selected for meta-analysis. Compared to no-treatment control groups, PA interventions had a large positive effect on parent-reported general sleep problems, night awakenings, sleep resistance, sleep duration and actigraphy-assessed sleep efficiency in children and adolescents with ASD.
Topics: Child; Humans; Adolescent; Autism Spectrum Disorder; Sleep; Sleep Initiation and Maintenance Disorders; Behavior Therapy; Exercise
PubMed: 38442500
DOI: 10.1016/j.smrv.2024.101913 -
International Journal of Molecular... Apr 2024Autism Spectrum Disorder (ASD) is an early onset neurodevelopmental disorder characterized by impaired social interaction and communication, and repetitive patterns of... (Review)
Review
Autism Spectrum Disorder (ASD) is an early onset neurodevelopmental disorder characterized by impaired social interaction and communication, and repetitive patterns of behavior. Family studies show that ASD is highly heritable, and hundreds of genes have previously been implicated in the disorder; however, the etiology is still not fully clear. Brain imaging and electroencephalography (EEG) are key techniques that study alterations in brain structure and function. Combined with genetic analysis, these techniques have the potential to help in the clarification of the neurobiological mechanisms contributing to ASD and help in defining novel therapeutic targets. To further understand what is known today regarding the impact of genetic variants in the brain alterations observed in individuals with ASD, a systematic review was carried out using Pubmed and EBSCO databases and following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. This review shows that specific genetic variants and altered patterns of gene expression in individuals with ASD may have an effect on brain circuits associated with face processing and social cognition, and contribute to excitation-inhibition imbalances and to anomalies in brain volumes.
Topics: Humans; Autism Spectrum Disorder; Neuroimaging; Brain; Electroencephalography; Genetic Predisposition to Disease
PubMed: 38732157
DOI: 10.3390/ijms25094938 -
Frontiers in Endocrinology 2024Accumulating evidence suggests that the autism spectrum disorder (ASD) population exhibits altered hormone levels, including androgens. However, studies on the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Accumulating evidence suggests that the autism spectrum disorder (ASD) population exhibits altered hormone levels, including androgens. However, studies on the regulation of androgens, such as testosterone and dehydroepiandrosterone (DHEA), in relation to sex differences in individuals with ASD are limited and inconsistent. We conducted the systematic review with meta-analysis to quantitatively summarise the blood, urine, or saliva androgen data between individuals with ASD and controls.
METHODS
A systematic search was conducted for eligible studies published before 16 January 2023 in six international and two Chinese databases. We computed summary statistics with a random-effects model. Publication bias was assessed using funnel plots and heterogeneity using I statistics. Subgroup analysis was performed by age, sex, sample source, and measurement method to explain the heterogeneity.
RESULTS
17 case-control studies (individuals with ASD, 825; controls, 669) were assessed. Androgen levels were significantly higher in individuals with ASD than that in controls (SMD: 0.27, 95% CI: 0.06-0.48, =0.01). Subgroup analysis showed significantly elevated levels of urinary total testosterone, urinary DHEA, and free testosterone in individuals with ASD. DHEA level was also significantly elevated in males with ASD.
CONCLUSION
Androgen levels, especially free testosterone, may be elevated in individuals with ASD and DHEA levels may be specifically elevated in males.
Topics: Humans; Male; Androgens; Autism Spectrum Disorder; Case-Control Studies; Dehydroepiandrosterone; Testosterone; Female
PubMed: 38779452
DOI: 10.3389/fendo.2024.1371148