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Frontiers in Pediatrics 2024Developmental language disorder (DLD) is a common childhood condition negatively influencing communication and psychosocial development. An increasing number of... (Review)
Review
INTRODUCTION
Developmental language disorder (DLD) is a common childhood condition negatively influencing communication and psychosocial development. An increasing number of pathogenic variants or chromosomal anomalies possibly related to DLD have been identified. To provide a base for accurate clinical genetic diagnostic work-up for DLD patients, understanding the specific genetic background is crucial. This study aims to give a systematic literature overview of pathogenic variants or chromosomal anomalies causative for DLD in children.
METHODS
We conducted a systematic search in PubMed and Embase on available literature related to the genetic background of diagnosed DLD in children. Included papers were critically appraised before data extraction. An additional search in OMIM was performed to see if the described DLD genes are associated with a broader clinical spectrum.
RESULTS
The search resulted in 15,842 papers. After assessing eligibility, 47 studies remained, of which 25 studies related to sex chromosome aneuploidies and 15 papers concerned other chromosomal anomalies (SCAs) and/or Copy Number Variants (CNVs), including del15q13.1-13.3 and del16p11.2. The remaining 7 studies displayed a variety of gene variants. 45 (candidate) genes related to language development, including , , , and . After an additional search in the OMIM database, 22 of these genes were associated with a genetic disorder with a broader clinical spectrum, including intellectual disability, epilepsy, and/or autism.
CONCLUSION
Our study illustrates that DLD can be related to SCAs and specific CNV's. The reported (candidate) genes ( = 45) in the latter category reflect the genetic heterogeneity and support DLD without any comorbidities and syndromic language disorder have an overlapping genetic etiology.
PubMed: 38298611
DOI: 10.3389/fped.2024.1315229 -
BMC Psychiatry Jan 2024To review the relationship between adiponectin levels and autism spectrum disorders (ASDs) in children.
OBJECTIVE
To review the relationship between adiponectin levels and autism spectrum disorders (ASDs) in children.
BACKGROUND
ASDs are associated with pervasive social interaction and communication abnormalities. Researchers have studied various pathophysiological mechanisms underlying ASDs to identify predictors for an early diagnosis to optimize treatment outcomes. Immune dysfunction, perhaps mediated by a decrease in anti-inflammatory adipokine, adiponectin, along with changes in other adipokines, may play a central role in increasing the risk for ASDs. However, other factors, such as low maternal vitamin D levels, atherosclerosis, diabetes, obesity, cardio-metabolic diseases, preterm delivery, and oxytocin gene polymorphism may also contribute to increased risk for ASDs.
METHODS
Searches on the database; PubMed, Google Scholar, and Cochrane using keywords; adiponectin, adipokines, ASD, autism, autistic disorder, included English-language studies published till September 2022. Data were extracted on mean differences between adiponectin levels in children with and without ASDs.
RESULTS
The search yielded six studies providing data on adiponectin levels in young patients with ASDs. As can be seen from Table 1, four of the six studies were positive for an inverse correlation between ASD and adiponectin levels. In addition, two of the four positive and one negative studies found low adiponectin levels associated with and the severity of autistic symptoms. However, results from one reviewed study were insignificant.
CONCLUSION
Most studies reviewed yielded lower adiponectin levels in children with ASDs as well as the severity of autistic symptoms.
Topics: Child; Infant, Newborn; Humans; Adiponectin; Autism Spectrum Disorder; Autistic Disorder; Child Development Disorders, Pervasive; Communication
PubMed: 38297246
DOI: 10.1186/s12888-024-05529-1 -
Frontiers in Psychiatry 2023Autism spectrum disorder (ASD) is a multifaceted developmental condition that commonly appears during early childhood. The etiology of ASD remains multifactorial and not...
A comparison between children and adolescents with autism spectrum disorders and healthy controls in biomedical factors, trace elements, and microbiota biomarkers: a meta-analysis.
INTRODUCTION
Autism spectrum disorder (ASD) is a multifaceted developmental condition that commonly appears during early childhood. The etiology of ASD remains multifactorial and not yet fully understood. The identification of biomarkers may provide insights into the underlying mechanisms and pathophysiology of the disorder. The present study aimed to explore the causes of ASD by investigating the key biomedical markers, trace elements, and microbiota factors between children with autism spectrum disorder (ASD) and control subjects.
METHODS
Medline, PubMed, ProQuest, EMBASE, Cochrane Library, PsycINFO, Web of Science, and EMBSCO databases have been searched for publications from 2012 to 2023 with no language restrictions using the population, intervention, control, and outcome (PICO) approach. Keywords including "autism spectrum disorder," "oxytocin," "GABA," "Serotonin," "CRP," "IL-6," "Fe," "Zn," "Cu," and "gut microbiota" were used for the search. The Joanna Briggs Institute (JBI) critical appraisal checklist was used to assess the article quality, and a random model was used to assess the mean difference and standardized difference between ASD and the control group in all biomedical markers, trace elements, and microbiota factors.
RESULTS
From 76,217 records, 43 studies met the inclusion and exclusion criteria and were included in this meta-analysis. The pooled analyses showed that children with ASD had significantly lower levels of oxytocin (mean differences, MD = -45.691, 95% confidence interval, CI: -61.667, -29.717), iron (MD = -3.203, 95% CI: -4.891, -1.514), and zinc (MD = -6.707, 95% CI: -12.691, -0.722), lower relative abundance of (MD = -1.321, 95% CI: -2.403, -0.238) and (MD = -0.081, 95% CI: -0.148, -0.013), higher levels of c-reactive protein, CRP (MD = 0.401, 95% CI: 0.036, 0.772), and GABA (MD = 0.115, 95% CI: 0.045, 0.186), and higher relative abundance of (MD = 1.386, 95% CI: 0.717, 2.055) and (MD = 0.281, 95% CI: 0.035, 0.526) when compared with controls. The results of the overall analyses were stable after performing the sensitivity analyses. Additionally, no substantial publication bias was observed among the studies.
INTERPRETATION
Children with ASD have significantly higher levels of CRP and GABA, lower levels of oxytocin, iron, and zinc, lower relative abundance of and , and higher relative abundance of , and when compared with controls. These results suggest that these indicators may be a potential biomarker panel for the diagnosis or determining therapeutic targets of ASD. Furthermore, large, sample-based, and randomized controlled trials are needed to confirm these results.
PubMed: 38283894
DOI: 10.3389/fpsyt.2023.1318637 -
Journal of Psychiatric Research Mar 2024It is plausible that exposure to cannabis in-utero could be associated with an increased risk of neurodevelopmental disorders such as attention deficit hyperactivity... (Meta-Analysis)
Meta-Analysis
BACKGROUND
It is plausible that exposure to cannabis in-utero could be associated with an increased risk of neurodevelopmental disorders such as attention deficit hyperactivity disorder (ADHD) symptoms and autism spectrum disorder (ASD) during childhood and adolescence; however, mixed results have been reported. This study investigated whether there is an association between prenatal cannabis use and ADHD symptoms and ASD in offspring using a systematic review and meta-analysis methodology.
METHODS
A systematic literature search was conducted in PubMed/Medline, Scopus, EMBASE, Web of Science, Psych-Info, and Google Scholar to identify relevant studies. The study protocol has been preregistered in the Prospective Register of Systematic Reviews (PROSPERO) (CRD42022345001), and the Newcastle-Ottawa Quality Assessment Scale (NOS) was used to assess the methodological quality of included studies. An inverse variance weighted random effect meta-analysis was conducted to pool the overall effect estimates from the included studies.
RESULTS
Fourteen primary studies, consisting of ten on ADHD and four on ASD, with a total of 203,783 participants, were included in this study. Our meta-analysis underscores an increased risk of ADHD symptoms and/or disorder [β = 0.39: 95 % CI (0.20-0.58), I = 66.85 %, P = 0.001)] and ASD [RR = 1.30: 95 % CI (1.03-1.64), I = 45.5 %, P = 0.14] associated with in-utero cannabis exposure in offspring compared to their non-exposed counterparts. Additionally, our stratified analysis highlighted an elevated risk of ADHD symptoms [β = 0.54: 95 % CI (0.26-0.82)] and a marginally significant increase in the risk of diagnostic ADHD among exposed offspring compared to non-exposed counterparts [RR = 1.13, 95 % CI (1.01, 1.26)].
CONCLUSION
This study indicated that maternal prenatal cannabis exposure is associated with a higher risk of ADHD symptoms and ASD in offspring.
Topics: Pregnancy; Female; Adolescent; Humans; Attention Deficit Disorder with Hyperactivity; Cannabis; Autism Spectrum Disorder; Prenatal Exposure Delayed Effects; Maternal Exposure
PubMed: 38281464
DOI: 10.1016/j.jpsychires.2024.01.045 -
Frontiers in Psychiatry 2023Autism spectrum disorder (ASD) is characterized by impaired social interaction and communication skills, repetitive behaviors, restricted interests, and specific sensory...
Autism spectrum disorder (ASD) is characterized by impaired social interaction and communication skills, repetitive behaviors, restricted interests, and specific sensory processing. Particularly, adults with high-functioning ASD often remain unrecognized, presumably due to their high compensatory skills, but at the cost of high stress, which is often linked to anxiety and depression. This may further explain the significantly high suicide rates and reduced life expectancy among individuals with ASD. Thus, providing support to high-functioning autistic adults in managing core symptoms, as well as co-occurring anxiety and depression, appears essential. To date, only a limited number of evidence-based psychosocial therapeutic options are available, and very few of them have undergone rigorous evaluation in a clinical context. To obtain a comprehensive understanding, a systematic literature search was conducted according to the PRISMA checklist, and only studies demonstrating robust methodological quality were included and discussed in this review article. Although promising initial key factors and methods have been identified, additional evidence-based studies are imperative to ascertain the optimal treatment and evaluate the long-term outcomes for adults with high-functioning ASD.
PubMed: 38274434
DOI: 10.3389/fpsyt.2023.1265066 -
Molecular Autism Jan 2024Numerous interventions for irritability in autism spectrum disorder (ASD) have been investigated. We aimed to appraise the magnitude of pharmacological and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Numerous interventions for irritability in autism spectrum disorder (ASD) have been investigated. We aimed to appraise the magnitude of pharmacological and non-pharmacological interventions for irritability in ASD without any restrictions in terms of eligible interventions.
METHODS
We systematically searched PubMed/MEDLINE, Scopus, and Web of Science until April 15, 2023. We included randomized controlled trials (RCTs) with a parallel design that examined the efficacy of interventions for the treatment of irritability in patients of any age with ASD without any restrictions in terms of eligible interventions. We performed a random-effects meta-analysis by pooling effect sizes as Hedges' g. We classified assessed interventions as follows: pharmacological monotherapy, risperidone plus adjuvant therapy versus risperidone monotherapy, non-pharmacological intervention, and dietary intervention. We utilized the Cochrane tool to evaluate the risk of bias in each study and the GRADE approach to assess the certainty of evidence for each meta-analyzed intervention.
RESULTS
Out of 5640 references, we identified 60 eligible articles with 45 different kinds of interventions, including 3531 participants, of which 80.9% were males (mean age [SD] = 8.79 [3.85]). For pharmacological monotherapy, risperidone (Hedges' g - 0.857, 95% CI - 1.263 to - 0.451, certainty of evidence: high) and aripiprazole (Hedges' g - 0.559, 95% CI - 0.767 to - 0.351, certainty of evidence: high) outperformed placebo. Among the non-pharmacological interventions, parent training (Hedges' g - 0.893, 95% CI - 1.184 to - 0.602, certainty of evidence: moderate) showed a significant result. None of the meta-analyzed interventions yielded significant effects among risperidone + adjuvant therapy and dietary supplementation. However, several novel molecules in augmentation to risperidone outperformed risperidone monotherapy, yet from one RCT each.
LIMITATIONS
First, various tools have been utilized to measure the irritability in ASD, which may contribute to the heterogeneity of the outcomes. Second, meta-analyses for each intervention included only a small number of studies and participants.
CONCLUSIONS
Only risperidone, aripiprazole among pharmacological interventions, and parent training among non-pharmacological interventions can be recommended for irritability in ASD. As an augmentation to risperidone, several novel treatments show promising effects, but further RCTs are needed to replicate findings. Trial registration PROSPERO, CRD42021243965.
Topics: Male; Humans; Female; GRADE Approach; Aripiprazole; Risperidone; Autism Spectrum Disorder
PubMed: 38263251
DOI: 10.1186/s13229-024-00585-6 -
Systematic Reviews Jan 2024Children with autism spectrum disorders are frequent visitors to high technology environments, and their needs may differ from those of their typically developed peers....
BACKGROUND
Children with autism spectrum disorders are frequent visitors to high technology environments, and their needs may differ from those of their typically developed peers. Procedures in high technology environments can constitute a challenge for these children and their parents since the environment presents many challenges relevant to the child's impairments. This systematic review aimed to explore the experiences of children with autism spectrum disorders and their parents during procedures in a high technology environment.
METHODS
The following sources were searched for this systematic review: Cochrane CENTRAL Trials, CINAHL, Dentistry and Oral Sciences Source, MEDLINE, PsycINFO, Scopus, and Web of Science Core Collection. The search terms included variants of the following concepts: (1) children with autism spectrum disorder and/or their parents and (2) anesthesia or radiographic departments. Publications were not limited by date or study design.
RESULT
Out of 13,389 bibliographic records, nine studies were eligible for synthesis. After another search in October 2022, one additional study was eligible for synthesis.None of the studies reported children's experiences, and all ten reported their parents' experiences. Only one study was conducted in a radiographic context. Parents' experiences were both positive and negative and were categorized into two main categories: (1) challenges in a new environment and (2) health care professionals' approaches.
CONCLUSION
Studies describing children's experiences with procedures in high technology environments are lacking. The parents described a need for health care professionals to work in structured ways with their child and to be able to make suitable adaptations.
SYSTEMATIC REVIEW REGISTRATION
This systematic review was registered in advance on the Open Science Framework, https://doi.org/10.17605/OSF.IO/5TXWJ .
Topics: Child; Humans; Autism Spectrum Disorder; Parents; Health Personnel; Qualitative Research
PubMed: 38238824
DOI: 10.1186/s13643-023-02440-w -
Molecular Autism Jan 2024Gastrointestinal symptoms and inflammatory gastrointestinal diseases exist at higher rates in the autistic population. It is not clear however whether autism is... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Gastrointestinal symptoms and inflammatory gastrointestinal diseases exist at higher rates in the autistic population. It is not clear however whether autism is associated with elevated gastrointestinal inflammation as studies examining non-invasive faecal biomarkers report conflicting findings. To understand the research landscape and identify gaps, we performed a systematic review and meta-analysis of studies measuring non-invasive markers of gastrointestinal inflammation in autistic and non-autistic samples. Our examination focused on faecal biomarkers as sampling is non-invasive and these markers are a direct reflection of inflammatory processes in the gastrointestinal tract.
METHODS
We extracted data from case-control studies examining faecal markers of gastrointestinal inflammation. We searched PubMed, Embase, Cochrane CENTRAL, CINAHL, PsycINFO, Web of Science Core Collection and Epistemonikos and forward and backwards citations of included studies published up to April 14, 2023 (PROSPERO CRD42022369279).
RESULTS
There were few studies examining faecal markers of gastrointestinal inflammation in the autistic population, and many established markers have not been studied. Meta-analyses of studies examining calprotectin (n = 9) and lactoferrin (n = 3) were carried out. A total of 508 autistic children and adolescents and 397 non-autistic children and adolescents were included in the meta-analysis of calprotectin studies which found no significant group differences (ROM: 1.30 [0.91, 1.86]). Estimated differences in calprotectin were lower in studies with siblings and studies which did not exclude non-autistic controls with gastrointestinal symptoms. A total of 139 autistic participants and 75 non-autistic controls were included in the meta-analysis of lactoferrin studies which found no significant group differences (ROM: 1.27 [0.79, 2.04]).
LIMITATIONS
All studies included in this systematic review and meta-analysis examined children and adolescents. Many studies included non-autistic controls with gastrointestinal symptoms which limit the validity of their findings. The majority of studies of gastrointestinal inflammation focused on children under 12 with few studies including adolescent participants. Most studies that included participants aged four or under did not account for the impact of age on calprotectin levels. Future studies should screen for relevant confounders, include larger samples and explore gastrointestinal inflammation in autistic adolescents and adults.
CONCLUSIONS
There is no evidence to suggest higher levels of gastrointestinal inflammation as measured by calprotectin and lactoferrin are present in autistic children and adolescents at the population level. Preliminary evidence suggests however that higher calprotectin levels may be present in a subset of autistic participants, who may be clinically characterised by more severe gastrointestinal symptoms and higher levels of autistic traits.
Topics: Adolescent; Child; Humans; Autistic Disorder; Biomarkers; Gastrointestinal Tract; Inflammation; Lactoferrin; Leukocyte L1 Antigen Complex
PubMed: 38233886
DOI: 10.1186/s13229-023-00575-0 -
Journal of Pain Research 2024Many studies have focused on the association between Autism spectrum disorder (ASD) and epidural labor analgesia (ELA), which is the most effective way to manage labor... (Review)
Review
PURPOSE
Many studies have focused on the association between Autism spectrum disorder (ASD) and epidural labor analgesia (ELA), which is the most effective way to manage labor pain. The purpose of this meta-analysis was to summarize the current state of the association between ELA and ASD.
METHODS
A search of the literature yielded 201 relevant studies, of which 7 cohort studies met our inclusion criteria. Two independent reviewers screened the inclusion results, extracted data, and assessed the risk of bias and quality of evidence.
RESULTS
Compared to parturient who did not receive ELA, parturient who received ELA had a slightly increased risk of ASD (adjusted hazard ratio [aHR], 1.12; 95% confidence interval [CI], 1.06-1.17; I2, 69%; P < 0.001; seven studies). After excluding one literature (aHR, 1.09; 95% CI, 1.06-1.12; I2, 4%; P < 0.001; six studies). The sensitivity analyses had consistent outcomes with the main analyses involving siblings (aHR 1.11; 95% CI 1.03-1.19), cesarean section and instrumental deliveries (aHR 1.07; 95% CI 1.03-1.10), non-overlapping populations (aHR 1.09; 95% CI 1.05-1.12), full-term birth populations (aHR 1.10; 95% CI 1.06-1.14), and studies assessed to have moderate risk of bias (aHR 1.09; 95% CI 1.02-1.16).
CONCLUSION
This meta-analysis revealed a modest positive association between ELA and ASD, acknowledging a slight potential risk. However, it is important to note that this risk cannot be completely dismissed due to the possibility of bias and this association is based on low-quality evidence. Future studies are required to assess and mitigate different confounding biases and investigate the time-dose-response relationship.
PubMed: 38230204
DOI: 10.2147/JPR.S442298 -
Frontiers in Nutrition 2023The potential impact of gut health on general physical and mental well-being, particularly in relation to brain function, has led to a growing interest in the potential...
BACKGROUND AND OBJECTIVE
The potential impact of gut health on general physical and mental well-being, particularly in relation to brain function, has led to a growing interest in the potential health advantages of prebiotics, probiotics, and synbiotics for the management of ASD. A comprehensive meta-analysis and systematic review was conducted in order to evaluate the effectiveness and protection of many drugs targeted at manipulating the microbiota in the treatment of ASD.
METHODS
The present study employed a comprehensive examination of various electronic databases yielded a total of 3,393 records that were deemed possibly pertinent to the study. RCTs encompassed a total of 720 individuals between the ages of 2 and 17, as well as 112 adults and participants ranging from 5 to 55 years old, all of whom had received a diagnosis of ASD.
RESULTS
Overall, 10 studies reported Autism-Related Behavioral Symptoms (ARBS). Regarding the enhancement of autism-related behavioral symptoms, there wasn't a statistically significant difference between the intervention groups (combined standardized mean difference = -0.07, 95% confidence interval: -0.39 to 0.24, = 0.46, = 0.65). We observed that in the patients with ASD treated with probiotic frontopolar's power decreased significantly from baseline to endpoints in beta band (Baseline: 13.09 ± 3.46, vs. endpoint: 10.75 ± 2.42, = 0.043, respectively) and gamma band (Baseline: 5.80 ± 2.42, vs. endpoint: 4.63 ± 1.39, = 0.033, respectively). Among all tested biochemical measures, a significant negative correlation was found between frontopolar coherence in the gamma band and -α ( = -0.30, = 0.04).
CONCLUSION
The existing body of research provides a comprehensive analysis of the developing evidence that indicates the potential of probiotics, prebiotics, and synbiotics as therapeutic therapies for ASD. Our findings revealed that those there was no significant effect of such therapy on autism-related behavioral symptoms, it has significant effect on the brain connectivity through frontopolar power in beta and gamma bands mediated by chemicals and cytokines, such as -α. The psychobiotics showed no serious side-effects.
PubMed: 38148790
DOI: 10.3389/fnut.2023.1294089