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Efficacy of non-pharmacological interventions on executive functions in children and adolescents with ADHD: A systematic review and meta-analysis.
Qiu, H, Liang, X, Wang, P, Zhang, H, Shum, DHK
Asian journal of psychiatry. 2023;87:103692
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Attention-deficit/hyperactivity disorder (ADHD) symptoms are thought to reflect underlying executive function (EF) impairments. EFs are comprised of three core functions (viz., inhibitory control [IC], working memory [WM], and cognitive flexibility [CF]) and higher-level functions (reasoning, planning, and problem-solving). Children with ADHD commonly show developmental delays in core EFs (vs. typically developing peers) which can persist throughout individuals’ lifetimes if not treated. The aim of this study was to investigate the effects of non-pharmacological interventions on EFs in children and adolescents with ADHD. This study is a systematic review and meta-analysis of sixty-seven articles. Results showed that non-pharmacological interventions had positive moderate to large effects on overall EFs; small to moderate effects on CF, IC, WM, and planning; non-existent on reasoning skills. Authors conclude that their findings underpin the importance of non-pharmacological treatments for improving core EFs in this clinical population.
Abstract
OBJECTIVE Although front-line doctors recommend medications, this kind of treatment has limited efficacy in improving executive functions (EFs) in children and adolescents with attention-deficit/hyperactivity disorder (ADHD). This study explored the effects of non-pharmacological intervention on EFs in children and adolescents with ADHD. METHODS In accordance with the Preferred Reporting Items for Systematic Review and Meta-analyses guidelines, we searched seven electronic databases: APA PsycINFO, CINAHL Complete, EMBASE, ERIC, Medline, Pubmed, and Web of Science, from inception to March 2022. Two authors independently screened studies for eligibility, extracted data, and assessed bias risk using the Physiotherapy Evidence Database scale. Our analyses included randomized controlled trials and non-randomized comparison studies of non-pharmacological interventions and assessed EFs through neurocognitive tasks in children and adolescents between 5 and 18 years. RESULTS Sixty-seven studies with 3147 participants met the inclusion criteria. The final meta-analysis included 74 independent interventions categorized into six categories: cognitive training, EF-specific curriculum, game-based training, mindfulness practice, neurofeedback training, and physical exercise. Overall, non-pharmacological interventions (combined) produced significant moderate to large effects on overall EFs in children and adolescents with ADHD (g=0.673). Physical exercise had a large positive effect on domain-specific EFs, including inhibitory control (g=0.900) and cognitive flexibility (g=1.377). Cognitive training had a large training effect on working memory (g=0.907), and an EF-specific curriculum had a small to moderate beneficial effect on planning performance (g=0.532). CONCLUSION Non-pharmacological interventions, particularly physical exercise, cognitive training, and an EF-specific curriculum, appear to have beneficial effects on EFs in children and adolescents with ADHD.
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The relationship between diabetes mellitus and attention deficit hyperactivity disorder: A systematic review and meta-analysis.
Ai, Y, Zhao, J, Liu, H, Li, J, Zhu, T
Frontiers in pediatrics. 2022;10:936813
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Attention deficit hyperactivity disorder (ADHD) is the most common neurodevelopmental disorder characterised by inattention and/or hyperactivity/impulsivity. Several studies have found bidirectional associations between ADHD and diabetes mellitus (DM). The aims of this study were to assess the prevalence of ADHD in DM patients as well as the prevalence of DM in ADHD patients compared with those without ADHD, and to explore the impacts of ADHD on glycaemic control in patients with DM. This study is a systematic review and meta-analysis of 17 articles; five were cohort studies, three were case-control studies, and nine were cross-sectional studies. Results through the pooled analyses suggest an important comorbid relationship between diabetes and ADHD. Overall, there was an increase in T2DM of 166% and 51% in children and adults with ADHD, respectively, relative to those without ADHD. Furthermore, there was an overall 37% increase in T1DM in children with ADHD. Authors conclude that further studies are needed to better understand the relationship between ADHD and DM. Additionally, it is important to take into consideration the type of DM if this association is different in various age groups (children and adults).
Abstract
BACKGROUND This study aims to investigate the prevalence estimate of diabetes mellitus (DM) among people with attention deficit hyperactivity disorder (ADHD) as well as the prevalence of ADHD among those with DM. In addition, the impact of ADHD on glycemic control in patients with DM was also assessed using a systematic review and meta-analysis of currently available published data. MATERIALS AND METHODS The PubMed, Embase, Web of Science, and PsycInfo databases were searched for potential studies. Two reviewers independently selected studies according to the inclusion and exclusion criteria. All pooled analyses were conducted using the random-effects models on Review Manager 5.3. RESULTS Seventeen observational studies were included. The pooled results showed an increase in the prevalence of DM among patients with ADHD versus those without ADHD [type 1 DM OR 1.37 (95% CI: 1.17-1.61); type 2 DM OR 2.05 (95% CI: 1.37-3.07)]. There was an overall 35% increase in the prevalence of ADHD among patients with type 1 DM [OR: 1.35 (95% CI: 1.08-1.73)]. Children with type 1 DM and ADHD had higher levels of hemoglobin A1c [standardized mean of differences: 0.67 (95% CI: 0.48-0.86)], and prevalence of hypoglycemic and ketoacidosis index compared with those without ADHD. CONCLUSION Our study revealed the bidirectional associations between ADHD and DM. Patients with ADHD and type 1 DM comorbidities were more likely to have poorer diabetes control. More studies are needed to confirm this association and elucidate the underlying mechanism.
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The Association between ADHD and Celiac Disease in Children.
Gaur, S
Children (Basel, Switzerland). 2022;9(6)
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Untreated coeliac disease (CeD) can be accompanied by an array of neurological symptoms. Some of these symptoms are similar to those observed in attention deficit hyperactive disorder (ADHD), like an inability to focus, lack of mental alertness, physical under-activity and clinically measurable under-activity in particular brain regions. The mechanism of such symptoms is not fully understood but is thought to be linked to low-grade inflammation in the brain as a result of permeability in the gut and blood-brain barrier, which could contribute to the presentation of ADHD-like symptoms. CeD can persist for many years in seemingly healthy people (silent CeD) without gut symptoms. In this period, ADHD-like symptoms are particularly common and may be treatment resistant if not accompanied by a gluten-free diet Since 2015, there have been several studies showing an association between CeD and ADHD. This is an updated systematic review including 23 studies of children and young adults, which found an association between ADHD and CeD, in contrast to previous reviews that found no clear association. This review paid particular attention to the diagnostic criteria of ADHD and its subtypes, highlighting the need to examine the subtypes of ADHD in future studies. Specifically, the inattentive subtype may be a behavioural ADHD phenotype that could respond to a gluten-free diet. The authors advocate screening ADHD patients for CeD and encourage the consideration of non-neurological symptoms in the assessment of ADHD to identify potential CeD cases.
Expert Review
Conflicts of interest:
None
Take Home Message:
- There is an association between celiac disease (CeD) and attention deficit hyperactive disorder (ADHD).
- Some children with ADHD may respond well to gluten-free diet.
Evidence Category:
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A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
This systematic review explored the association between coeliac disease (CeD) and attention deficit hyperactive disorder (ADHD).
Methods
The review was conducted following the PRISMA reporting guidelines.
Inclusion criteria for the search:
- Search terms of ADHD and CeD
- Participants < 18 years.
52 papers were retrieved and screened
23 met inclusion/exclusion criteria
Results
- 13 studies (out of the 23) demonstrated an association between ADHD and CeD
- Most studies reporting a positive association were published post 2015
- The largest study reported (112,240 patients with CeD) demonstrates that ADHD showed an association of OR = 1.75 in in CeD.
- The study was limited by several factors including study design of the studies included in the review, which were mostly observational and some without control.
The author declares no conflict of interest.
Clinical practice applications:
- Evidence from across the literature suggests that children with untreated or newly diagnosed CeD may find that following a gluten-free diet can help improve some symptoms associated with ADHD
- The author suggests that there may be a behavioural phenotype of ADHD that responds to a gluten-free diet. If this is the case, it suggests that screening of ADHD patients for celiac disease may be important.
Considerations for future research:
- The number of studies were relatively small and varied in design. Further large-scale studies would help further inform the understanding of the association and potential therapeutic benefits of gluten-free diet.
- It would be interesting to further explore how different subtypes of ADHD, especially the inattentive subtype, may be associated with CeD.
- In particular, it might be useful to consider how the clinical construct of sluggish cognitive tempo (SCT) is associated, since SCT symptoms overlap with the neurological manifestations of CeD.
Abstract
UNLABELLED Controversy around the association between celiac disease (CeD) and attention deficit hyperactive disorder (ADHD) was addressed by a systematic review in 2015, ultimately showing no association. Since 2015, there have been several studies showing an association between celiac disease and attention deficit hyperactive disorder. This is an updated systematic review. BACKGROUND Most experts agree on the recommendation to not screen as part of the standard of care for ADHD in persons with CeD or vice versa. Simultaneously, they propose that untreated patients with CeD and neurological symptoms such as chronic fatigue, inattention, pain, and headache could be predisposed to ADHD-like behavior, namely inattention (which may be alleviated by following a gluten-free diet). The inattentive subtype of ADHD that encompasses the symptoms of inattention is phenotypically heterogeneous, as it includes the clinical construct of sluggish cognitive tempo (SCT). SCT symptoms overlap with the neurological manifestations of CeD. METHODS A systematic search (PRISMA) of PubMed, Google Scholar, EMBASE, Web of Science, Stanford Lane, SCOPUS, and Ovid was conducted for articles up to 21 February 2022. Of these, 23 studies met the criteria. RESULTS Out of the 23 studies, 13 showed a positive association between ADHD and CeD. Most studies that showed a positive association had been published in the last five years. Inconsistencies in the results remain due to the heterogeneous methodology used, specifically for ADHD and the outcome questionnaires, as well as a lack of reporting on ADHD subtypes. CONCLUSION There is an association between ADHD and celiac disease. The current methodological limitations will be lessened if we examine the subtypes of ADHD.
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The Influence of Prenatal DHA Supplementation on Individual Domains of Behavioral Functioning in School-Aged Children: Follow-Up of a Randomized Controlled Trial.
Gould, JF, Anderson, PJ, Yelland, LN, Gibson, RA, Makrides, M
Nutrients. 2021;13(9)
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Omega-3 fatty acids such as docosahexaenoic acid (DHA) are thought to be beneficial for the development of the fetal brain. Women with a singleton pregnancy at <21 weeks’ gestation enrolled in this multicentre, double-blind, randomised controlled trial to assess the fetal neurodevelopment effects of 800 mg/day, which they took until the birth of their children. A follow-up assessment was arranged when the children reached age seven to evaluate their neurodevelopment. Children of women who took DHA supplements showed increased risk scores on hyperactivity, behavioural problems that may impact daily activities, ADHD, peer relationships, Metacognition Indexes, Shift, Inhibit, Monitor, Working Memory, and Organization of Materials scales. Supplementing with high doses of DHA during pregnancy might not have any protective effects on neurodevelopment in women with high baseline DHA levels. However, further robust studies are required to confirm the results to determine the clinical applicability of DHA supplementation in pregnant women. Healthcare professionals can use the results of this study to understand the dose-dependent therapeutic application of DHA and its impact on fetal neurodevelopment.
Abstract
Docosahexaenoic acid (DHA) accumulates in the fetal brain during pregnancy and is thought to have a role in supporting neurodevelopment. We conducted a multicenter, double-blind, randomized controlled trial in women with a singleton pregnancy who were <21 weeks' gestation at trial entry. Women were provided with 800 mg DHA/day or a placebo supplement from trial entry until birth. When children reached seven years of age, we invited parents to complete the Strengths and Difficulties Questionnaire (SDQ), the Behavior Rating Inventory of Executive Function (BRIEF), and the Conners 3rd Edition Attention-Deficit Hyperactivity Disorder (ADHD) Index to assess child behavior and behavioral manifestations of executive dysfunction. There were 543 parent-child pairs (85% of those eligible) that participated in the follow-up. Scores were worse in the DHA group than the placebo group for the BRIEF Global Executive, Behavioral Regulation and Metacognition Indexes, and the Shift, Inhibit, Monitor, Working Memory, and Organization of Materials scales, as well as for the Conners 3 ADHD index, and the SDQ Total Difficulties score, Hyperactivity/Inattention score, and Peer Relationship Problems score. In this healthy, largely term-born sample of children, prenatal DHA supplementation conferred no advantage to childhood behavior, and instead appeared to have an adverse effect on behavioral functioning, as assessed by standardized parental report scales.
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Towards Tailored Gut Microbiome-Based and Dietary Interventions for Promoting the Development and Maintenance of a Healthy Brain.
Larroya, A, Pantoja, J, Codoñer-Franch, P, Cenit, MC
Frontiers in pediatrics. 2021;9:705859
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The cause of neurodevelopmental disorders (NDDs) is complex and multifactorial. Recent studies have indicated that early life disturbances of the gut microbiome can impact neurodevelopment, suggesting this critical window may play a key role in the prevention or progression of neurological disease. The growing field of personalized nutrition works on the basis of tailored dietary intervention strategies that consider individual variability based on genetics, diet, and the environment. The aim of this paper is to review the current evidence on the neurodevelopmental interaction between the gut microbiota, environment and host, and assess the efficacy of tailored, personalized nutrition interventions aimed at preventing or treating NDDs. The literature provides evidence that the gut microbiota is susceptible to influence by various factors early in life, and the health of the microbiome may modulate mental health consequences later in life. Additionally, key nutritional deficiencies and microbiome alterations have been linked to NDDs, suggesting potential markers that may lead to improved prevention and treatment. Based on the current literature, the authors emphasize the need for further research during the critical window of microbiome development in order to target the cause of neurodevelopmental impairments. They suggest these findings could help progress the field of Nutritional Psychiatry towards effective tailored nutrition and personalized medicine.
Abstract
Mental health is determined by a complex interplay between the Neurological Exposome and the Human Genome. Multiple genetic and non-genetic (exposome) factors interact early in life, modulating the risk of developing the most common complex neurodevelopmental disorders (NDDs), with potential long-term consequences on health. To date, the understating of the precise etiology underpinning these neurological alterations, and their clinical management pose a challenge. The crucial role played by diet and gut microbiota in brain development and functioning would indicate that modulating the gut-brain axis may help protect against the onset and progression of mental-health disorders. Some nutritional deficiencies and gut microbiota alterations have been linked to NDDs, suggesting their potential pathogenic implications. In addition, certain dietary interventions have emerged as promising alternatives or adjuvant strategies for improving the management of particular NDDs, at least in particular subsets of subjects. The gut microbiota can be a key to mediating the effects of other exposome factors such as diet on mental health, and ongoing research in Psychiatry and Neuropediatrics is developing Precision Nutrition Models to classify subjects according to a diet response prediction based on specific individual features, including microbiome signatures. Here, we review current scientific evidence for the impact of early life environmental factors, including diet, on gut microbiota and neuro-development, emphasizing the potential long-term consequences on health; and also summarize the state of the art regarding the mechanisms underlying diet and gut microbiota influence on the brain-gut axis. Furthermore, we describe the evidence supporting the key role played by gut microbiota, diet and nutrition in neurodevelopment, as well as the effectiveness of certain dietary and microbiome-based interventions aimed at preventing or treating NDDs. Finally, we emphasize the need for further research to gain greater insight into the complex interplay between diet, gut microbiome and brain development. Such knowledge would help towards achieving tailored integrative treatments, including personalized nutrition.