Therapeutic Effects of Probiotics on Symptoms of Anxiety in Children and Adolescents: A Systematic Review and Meta-Analysis of Placebo-Controlled Trials.

Attention-deficit hyperactivity disorder (ADHD) is a neurodevelopmental condition typified by inattention, hyperactivity, and impulsivity. Comorbid psychiatric disorders are common among children and adolescents with ADHD. In this study, it was aimed to examine anxiety and somatic symptoms in children and adolescents with ADHD and the effect of methylphenidate treatment on these symptoms. Three groups were formed, consisting of 37 children and adolescents diagnosed with ADHD and received methylphenidate treatment, 37 newly diagnosed, treatment-naive children and adolescents with ADHD diagnosis, and 37 children and adolescents without the diagnosis of ADHD. The symptoms of ADHD in children were examined by using the DSM-IV-based child and adolescent behavior disorders screening and rating scale, the symptoms of anxiety were examined by using the screen for child anxiety-related disorders (SCARED), and somatic symptoms were examined by using the DSM-5 level 2 somatic symptom scale. In the newly diagnosed, treatment-naive with ADHD group, anxiety and somatic symptoms were found to be significantly higher compared to the ADHD group with methylphenidate treatment and the non-ADHD group. It was shown that the symptoms of panic disorder, generalized anxiety, and social phobia were observed more in the newly diagnosed, treatment-naive with ADHD group compared to the treatment group with ADHD. It was determined that children and adolescents diagnosed with ADHD had more anxiety and somatic symptoms. Anxiety and somatic symptoms increased as the severity of ADHD symptoms increased. Anxiety and somatic symptoms were lower than in ADHD children receiving methylphenidate treatment. Clinicians should keep in mind to evaluate anxiety and somatic symptoms in children and adolescents with ADHD before the treatment.

Neurodevelopmental disorders [NDDs, including attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and tic disorder] usually arise during childhood or adolescence, but impact quality of life throughout the whole life cycle. Therefore, early diagnosis of NDDs is necessary; however, its etiology remains unclear. This study aimed to evaluate levels of thyroid, growth, and appetite hormones between children and adolescents with NDDs and healthy controls (HCs) by a meta-analysis of all evidence that demonstrated the importance of these indicators, but yielded controversial results. Five online databases were searched to retrieve relevant articles published before March 1, 2025. Mean and standard deviation data were collected and pooled using Stata 15.0 software to generate standardized mean difference (SMD) with 95% confidence intervals (CIs) as the effect size (ES) measure. Fifty-four studies were included. The overall meta-analysis, subgroup, and trim-and-fill adjusting revealed that compared with HCs, levels of thyroid hormone free triiodothyronine (FT3) (SMD = 0.22; 95% CI = 0.04 to 0.40; pES = 0.015), total triiodothyronine (TT3) (SMD = 0.82; 95% CI = 0.36 to 1.28; pES < 0.001), and thyroid peroxidase antibody (TPO-Ab) (SMD = 0.37; 95% CI = 0.08 to 0.67; pES = 0.014) were significantly increased, while free thyroxine (FT4) (SMD = -0.67; 95% CI = -0.69 to -0.64; pES < 0.001), total thyroxine (TT4) (SMD = -0.35; 95% CI = -0.50 to -0.20; pES < 0.001), and thyroid stimulating hormone (TSH) (SMD = -0.22; 95% CI = -0.41 to -0.03; pES = 0.026) were significantly decreased in children and adolescents with NDDs. These changes were mainly observed in ADHD patients, with TPO-Ab increased only in ASD patients. Levels of the appetite hormone leptin were significantly elevated in male NDDs (SMD = 0.74; 95% CI = 0.10 to 1.38; pES = 0.023) and ASD patients (SMD = 0.46; 95% CI = 0.17 to 0.74; pES = 0.002) relative to HCs, but not in ADHD cases. Growth factor IGF-1 (insulin-like growth factor-1) was only significantly lower in the cerebrospinal fluids of ASD patients when compared with HCs (SMD = -0.89; 95% CI = -1.42 to -0.36; pES = 0.001). Thyroid hormones and IGF-1/leptin may respectively represent promising biomarkers for predicting ADHD and ASD in children and adolescents.

The purpose of this study was to investigate whether there are elevated symptoms of anxiety or depression in children and adolescents (aged 2-18 years) who stutter, and to identify potential moderators of increased symptom severity. We conducted a preregistered systematic review of databases and gray literature; 13 articles met criteria for inclusion. A meta-analysis using robust variance estimation was conducted with 11 cohort studies comparing symptoms of anxiety in children and adolescents who do and do not stutter. Twenty-six effect sizes from 11 studies contributed to the summary effect size for anxiety symptoms (851 participants). Meta-analysis of depression outcomes was not possible due to the small number of studies. The summary effect size indicates that children and adolescents who stutter present with increased anxiety symptoms (g = 0.42) compared with nonstuttering peers. There were insufficient studies to robustly analyze depression symptoms, and qualitative review is provided. No significant between-groups differences were reported in any of the depression studies. Preliminary evidence indicates elevated symptoms of anxiety in some children and adolescents who stutter relative to peers. There was a tendency toward higher depression scores in this population, although reported between-groups differences did not reach statistical significance. These findings require replication in larger, preferably longitudinal studies that consider factors that may moderate risk. Nevertheless, our findings highlight a need for careful monitoring of mental health and well-being in young people who stutter. Supplemental Materials: http://osf.io/5m6zv.

BackgroundThe efficacy of probiotics as a therapeutic alternative for attention-deficit hyperactivity disorder (ADHD) remain unclear.AimsTo investigate the effectiveness of probiotics for symptoms of ADHD and identify possible factors affecting their efficacy.MethodRandomised placebo-controlled trials were identified through searching major databases from inception to April 2023, using the main keywords ‘probiotics’ and ‘ADHD’ without limitation on languages or geographic locations. The outcome of interest included improvement in total symptoms of ADHD, symptoms of inattention and hyperactivity/impulsivity, and drop-out rate. Continuous and categorical data were expressed as effect sizes based on standardised mean differences (SMDs) and odds ratios, respectively, with 95% confidence intervals.ResultsMeta-analysis of seven trials involving 379 participants (mean age 10.37 years, range 4–18 years) showed no significant improvement in total symptoms of ADHD (SMD = 0.25; P = 0.12), symptoms of inattention (SMD = 0.14; P = 0.3) or hyperactivity/impulsivity (SMD = 0.08; P = 0.54) between the probiotic and placebo groups. Despite non-significance on subgroup analyses, there was a large difference in effect size between studies using probiotics as an adjunct to methylphenidate and those using probiotics as supplementation (SMD = 0.84 v. 0.07; P = 0.16), and a moderate difference in effect size between studies using multiple strains of probiotics and those using single-strain regimens (SMD = 0.45 v. 0.03; P = 0.19).ConclusionsCurrent evidence shows no significant difference in therapeutic efficacy between probiotics and placebos for treatment of ADHD symptoms. However, albeit statistically non-significant, higher therapeutic efficacies associated with multiple-strain probiotics or combining probiotics with methylphenidate may provide direction for further research.

BackgroundPhysical activity (PA) interventions have been shown to yield positive effects on cognitive functions. However, it is unclear which type of PA intervention is the most effective in children and adolescents with Neurodevelopmental Disorders (NDDs). This study aimed to compare the effectiveness of different types of PA interventions on cognitive functions in children and adolescents with NDDs, with additional analyses examining intervention effects across specific NDD types including attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD).MethodsIn this systematic review and network meta-analysis, seven databases (Web of Science, PubMed, Medline, APA PsycINFO, Embase, CINAHL, and SPORTDiscus) for randomized controlled trials from database inception to September 2023 were searched. Randomized controlled trials comparing the effectiveness of PA intervention with any non-pharmacological treatment or control group on cognitive functions in children and adolescents diagnosed with NDDs aged 5–17 years were included. Frequentist network meta-analyses were performed based on standardized mean differences (SMD) using random effects models to examine post-intervention differences in cognitive functions, including attention, memory, and executive functions. Intervention dropout was assessed as a measure of treatment acceptability.ResultsThirty-one randomized controlled trials (n = 1,403, mean age 10.0 ± 1.9 years) with 66 arms were included in the network. Mind-body exercise (MBE; SMD = 1.91 for attention; 0.92 for executive functions), exergaming (SMD = 1.58 for attention; 0.97 for memory; 0.94 for executive functions), and multi-component physical activity (MPA; SMD = 0.79 for executive functions) were associated with moderate to substantial cognitive improvements compared with usual care, whereas the effectiveness of aerobic exercise (AE) was non-significant. Exergaming (SMD = 0.78, 95%CI 0.12 to 1.45) and MPA (SMD = 0.64, 95%CI 0.11 to 1.18) were more effective than AE for executive functions. When analyzing specific NDD types, exergaming lost its superiority over usual care for attention and memory in ADHD, nor for executive functions in ASD. Instead, MPA demonstrated significant benefits across these domains and populations. The certainty of evidence for these comparisons was very low to low. No significant differences in acceptability were observed among MBE, exergaming, and MPA.ConclusionsThe findings in this study suggest that MBE, exergaming, and MPA were effective interventions for improving domain-specific cognitive functions in children and adolescents with NDDs. AE demonstrated non-significant effectiveness for all outcomes. MBE emerges as particularly advantageous for attention. MPA yielded consistent improvements in memory and executive functions across NDD types. Further high-quality randomized controlled trials of direct comparisons are needed to confirm and expand on the findings from this NMA.Trial registrationPROSPERO CRD42023409606.

Anxiety is common in neurodevelopmental disorders (NDD). The parent version of the Spence Children's Anxiety Scale (SCAS-P) is a widely used measure to assess anxiety across a broad range of childhood populations. However, assessment of the measurement properties of the SCAS-P in NDDs have been limited. The present study aimed to assess the psychometric properties of the SCAS-P in children with attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) using Rasch Measurement Theory. Data from the Province of Ontario Neurodevelopmental Disorders Network Registry were used in the analysis. Children (ages 6-13 years old) with a primary diagnosis of ADHD (n=146) or ASD (n=104) were administered the SCAS-P. Rasch Measurement Theory was used to assess measurement properties of the SCAS-P, including unidimensionality and item-level fit, category ordering, item targeting, person separation index and reliability and differential item functioning. The SCAS-P fit well to the Rasch model in both ADHD and ASD, including unidimensionality, satisfactory category ordering and goodness-of-fit. However, item-person measures showed poor precision at lower levels of anxiety. Some items showed differential item functioning, including items within the obsessive-compulsive, panic/agoraphobia and physical injury fears domains, suggesting that the presentation of anxiety may differ between ADHD and ASD. Overall, the results generally support the use of the SCAS-P to screen and monitor anxiety symptoms in children with ADHD and ASD. Future studies would benefit from examination of more severely anxious NDD cohort, including those with clinically diagnosed anxiety.

Background: Sex differences in the prevalence of neurodevelopmental disorders such as autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are well documented, but studies examining sex differences in social and communication function remain limited and inconclusive. Objectives: The objective of this study is to conduct a meta-analysis of sex differences in social-communication function in children with ASD or ADHD and typically developing controls. Methods: Using PRISMA, a search was performed on Medline and PSYCHINFO on English-language journals (2000–2017) examining sex differences in social and communication function in ASD and ADHD compared to controls. Inclusion criteria: 1) peer reviewed journal articles, 2) diagnosis of ASD or ADHD and controls, 3) age 6–18 years, 4) measures of social–communication function, and 5) means, standard deviations, and sample sizes reported in order to calculate standardized mean differences (SMD). Results: Eleven original/empirical studies met inclusion criteria for ASD and six for ADHD. No significant sex differences were found between ASD and controls in social (SMD = −0.43; p = 0.5; CI: −1.58–0.72), or communication function (SMD = 0.86; p = 0.5 CI; −1.57–−3.30) and between ADHD and controls in social function (SMD = −0.68: p = 0.7, CI: −4.17–2.81). No studies evaluated sex differences in communication in ADHD. Significant heterogeneity was noted in all analyses. Type of measure may have partially accounted for some variability between studies. Conclusions: The meta-analysis did not detect sex differences in social and communication function in children with ASD and ADHD; however, significant heterogeneity was noted. Future larger studies, controlling for measure and with adequate numbers of female participants are required to further understand sex differences in these domains.

Systematic Umbrella Review and Meta-Meta-Analysis: Effectiveness of Physical Activity in Improving Depression and Anxiety in Children and Adolescents.

The aim of this systematic review and meta-analysis was to examine the evidence for the effectiveness of exercise interventions on attention deficit hyperactivity disorder (ADHD)-related symptoms such as inattention, hyperactivity/impulsivity, anxiety and cognitive functions in children and adolescents. Five databases covering the period up to November 2014 (PubMed, Scopus, EMBASE, EBSCO [E-journal, CINAHL, SportDiscus] and The Cochrane Library) were searched. Methodological quality was assessed using the Cochrane tool of bias. Standardized mean differences (SMD) and 95% confidence intervals were calculated, and the heterogeneity of the studies was estimated using Cochran's Q-statistic. Eight randomized controlled trials (n = 249) satisfied the inclusion criteria. The studies were grouped according to the intervention programme: aerobic and yoga exercise. The meta-analysis suggests that aerobic exercise had a moderate to large effect on core symptoms such as attention (SMD = 0.84), hyperactivity (SMD = 0.56) and impulsivity (SMD = 0.56) and related symptoms such as anxiety (SMD = 0.66), executive function (SMD = 0.58) and social disorders (SMD = 0.59) in children with ADHD. Yoga exercise suggests an improvement in the core symptoms of ADHD. The main cumulative evidence indicates that short-term aerobic exercise, based on several aerobic intervention formats, seems to be effective for mitigating symptoms such as attention, hyperactivity, impulsivity, anxiety, executive function and social disorders in children with ADHD.

Children with autistic spectrum disorder (ASD) frequently present with inattention, impulsivity and hyperactivity, which are the cardinal symptoms of attention deficit hyperactivity disorder (ADHD). The effectiveness of methylphenidate, a commonly used ADHD treatment, is therefore of interest in these children. To assess the effects of methylphenidate for symptoms of ADHD (inattention, impulsivity and hyperactivity) and ASD (impairments in social interaction and communication, and repetitive, restricted or stereotypical behaviours) in children and adolescents aged 6 to 18 years with ASD. In November 2016, we searched CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, 11 other databases and two trials registers. We also checked reference lists and contacted study authors and pharmaceutical companies. Randomised controlled trials (RCTs) that investigated the effect of methylphenidate versus placebo on the core symptoms of ASD or ADHD-like symptoms, or both, in children aged 6 to 18 years who were diagnosed with ASD or pervasive developmental disorder. The primary outcome was clinical efficacy, defined as an improvement in ADHD-like symptoms (inattention, impulsivity and hyperactivity) and in the core symptoms of ASD (impaired social interaction, impaired communication, and stereotypical behaviours), and overall ASD. Secondary outcomes examined were: rate of adverse events; caregiver well-being; need for institutionalisation, special schooling or therapy to achieve learning outcomes; and overall quality of life. We used standard Cochrane methodological procedures. We combined outcome measures that used different psychometric scales, where clinically appropriate. We used a coefficient of 0.6 to calculate standard deviations and adjust for the studies' cross-over design. We considered a standardised mean difference (SMD) of 0.52 as the minimum clinically relevant inter-treatment difference. We applied the GRADE rating for strength of evidence for each outcome. The studies: we included four cross-over studies, with a total of 113 children aged 5 to 13 years, most of whom (83%) were boys. We included two studies with five-year-old children since we were unable to obtain the disaggregated data for those aged six years and above, and all other participants were in our target age range. All participants resided in the USA. The duration of treatment in the cross-over phase was one week for each dose of methylphenidate. Studies used a range of outcome scales, rated by parents, teachers or both; clinicians; or programme staff. We report parent-rated outcomes separately. Risk of bias: we considered three trials to be at high risk of bias due to selective reporting and all trials to be at unclear risk of bias for blinding of participants and assessors, due to the potential for recognising the side effects of methylphenidate. We judged all trials to be at low or unclear risk of bias for other items. Primary outcomes: the meta-analysis suggested that high-dose methylphenidate (0.43 mg/kg/dose to 0.60 mg/kg/dose) had a significant and clinically relevant benefit on hyperactivity, as rated by teachers (SMD -0.78, 95% confidence interval (CI) -1.13 to -0.43; 4 studies, 73 participants; P no data were available for the secondary outcomes of caregiver well-being; need for institutionalisation, special schooling options or therapy to achieve learning outcomes; or overall quality of life. No trials reported serious adverse events. The only adverse effect that was significantly more likely with treatment was reduced appetite as rated by parents (risk ratio 8.28, 95% CI 2.57 to 26.73; 2 studies, 74 participants; P We found that short-term use of methylphenidate might improve symptoms of hyperactivity and possibly inattention in children with ASD who are tolerant of the medication, although the low quality of evidence means that we cannot be certain of the true magnitude of any effect. There was no evidence that methylphenidate has a negative impact on the core symptoms of ASD, or that it improves social interaction, stereotypical behaviours, or overall ASD. The evidence for adverse events is of very low quality because trials were short and excluded children intolerant of methylphenidate in the test-dose phase. Future RCTs should consider extending the duration of treatment and follow-up. The minimum clinically important difference also needs to be confirmed in children with ASD using outcome scales validated for this population.

In order to shed more light on the frequent co-occurrence of Autism Spectrum Disorder (ASD) and anxiety in children, the aims of the study were (a) to examine whether ASD and anxiety share familial transmission indicated by cross-symptom associations between parental and children's symptoms (e.g., parental anxiety predicting children's ASD) in addition to associations for similar symptoms; (b) to investigate the possibility that cross-assortative mating (i.e., whether ASD symptoms in one parent are positively associated with anxiety symptoms in the other parent) increases the risk for both ASD and anxiety in children. In 231 families of clinically referred children, parents rated both their own and the other parent's ASD and anxiety symptoms and one parent those of the index child and siblings (n=447, aged 2.5-18years). ASD symptoms were assessed using the Social Responsiveness Scale (SRS-2) and anxiety symptoms using the Achenbach System of Empirically Based Assessment (ASEBA) instruments. Parental ASD and anxiety symptoms predicted similar symptoms in children, dependent on the informant type. Additionally, parental anxiety symptoms across both self-report and informant-report predicted children's ASD symptoms and maternal self-reported ASD symptoms predicted children's anxiety symptoms. ASD and anxiety symptoms were correlated within parents, but we found only one cross-symptom association between parents. Cross-symptom associations between parental and children's ASD and anxiety symptoms suggest shared familial transmission of ASD and anxiety, but further research is needed to clarify the underlying mechanisms. Cross-assortative mating does not seem a likely explanation for the co-occurrence of ASD and anxiety in children.

BackgroundAttention deficit hyperactivity disorder (ADHD) is a common psychiatric disorder in children that can extend into adulthood and that is often associated with a variety of comorbid psychiatric disorders.AimAssess the comorbidity of ADHD with anxiety disorders and depressive disorders in school-aged children, and the relationship of the severity of ADHD, anxiety, and depressive symptoms in children who have ADHD with the severity of the corresponding symptoms in their parents.MethodsA two-stage screening process identified children 7-10 years of age with and without ADHD treated at the Xin Hua Hospital in Shanghai. ADHD and other DSM-IV diagnoses were determined by a senior clinician using the Schedule for Affective Disorder and Schizophrenia for School-Aged Children (K-SADS-PL). One parent for each enrolled child completed three self-report scales: the ADHD Adult Self Report Scale (ASRS), the State-Trait Anxiety Inventory (STAI), and the Beck Depression Inventory (BDI). In total 135 children with ADHD and 65 control group children without ADHD were enrolled; parents for 94 of the children with ADHD and 63 of the children without ADHD completed the parental assessment scales.ResultsAmong the 135 children with ADHD, 27% had a comorbid anxiety disorder, 18% had a comorbid depressive disorder, and another 15% had both comorbid anxiety and depressive disorders. Parents of children with ADHD self-reported more severe ADHD inattention symptoms than parents of children without ADHD and were more likely to meet criteria for adult ADHD. Mothers (but not fathers) of children with ADHD had significantly more severe trait anxiety and depressive symptoms than mothers of children without ADHD. Among children with ADHD, the severity of ADHD symptoms was not significantly correlated with the severity of ADHD symptoms in parents, but depressive symptoms and anxiety symptoms in the children were significantly correlated with the corresponding symptoms in the parents.ConclusionSchool-aged children with ADHD commonly suffer from comorbid anxiety and depressive disorders, and the severity of these symptoms parallels the level of anxiety and depressive symptoms in their parents. Self-reported symptoms of ADHD are significantly more common in parents of children with ADHD than in parents of children without ADHD. Longitudinal studies are needed to disentangle the genetic, biological, and social factors responsible for these complex inter-relationships.

Therapeutic effects of probiotics on symptoms of irritability/emotional lability associated with neurodevelopmental conditions: A systematic review and meta-analysis of placebo-controlled trials.

BackgroundNo consensus on whether physical activity (PA) is related to physical and mental health among pediatric population remains has been reached to date. To further explore their association, our study assessed the effect of PA on physical and mental health of children and adolescents through a systematic review and meta-analysis of randomized controlled studies (RCTs).MethodsSeveral databases(Web of science, PubMed, Embase, Cochrane Central register of controlled trials, CINAHL) were searched from inception to 1st, December 2020 without language restrictions.Results38,236 records were identified primitively and 31 included studies with 1,255 participants eventually met our inclusion criteria, all of which exhibited a relatively low-moderate risk of bias of overall quality. In regard to mental health, the administration of PA, compared with the control group, led to moderate improvements in Autism Spectrum Disorder(ASD)[Standard mean difference (SMD) = −0.50, Confidence interval(CI): −0.87, −0.14)] and depression(SMD = −0.68, CI: −0.98, −0.38) among children and adolescents. Similarly, significant result was observed in obesity (SMD = −0.58, CI: −0.80, −0.36). No significant differences were observed in Attention deficit hyperactivity disorder (ADHD) (SMD = −0.29, CI: −0.59, 0.01).ConclusionAltogether, PA may have a beneficial effect on children and adolescents with ASD, depression and obesity; nevertheless, there is insufficient evidence to confirm its efficacy in ADHD. More large-scale population based randomized controlled trials are needed to explore more reliable evidence between them.

Behavioral outcomes after tDCS treatment during immediate post-intervention and follow-up periods in children and adolescents diagnosed with attention-deficit/hyperactivity disorder: a systematic review and meta-analysis on randomized sham-controlled trials.