-
1.
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
-
-
-
Free full text
Plain language summary
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.
-
2.
Effects of a Synbiotic on Plasma Immune Activity Markers and Short-Chain Fatty Acids in Children and Adults with ADHD-A Randomized Controlled Trial.
Yang, LL, Stiernborg, M, Skott, E, Xu, J, Wu, Y, Landberg, R, Arefin, S, Kublickiene, K, Millischer, V, Nilsson, IAK, et al
Nutrients. 2023;15(5)
-
-
-
Free full text
Plain language summary
Attention deficit hyperactivity disorder (ADHD) is a common childhood-onset neurodevelopmental psychiatric disorder. The core symptoms of the disorder are inattention and hyperactivity/impulsivity. The aim of this study was to explore the effects of Synbiotic 2000 on concentrations of plasma immune activity markers and short-chain fatty acids (SCFAs) in ADHD. This study is a double-blind randomised controlled trial over a period of 9-weeks. Patients (n= 248) were randomly allocated to one of the two treatments: Synbiotic 2000 or placebo. Results show that there was no statistically significant overall effect of Synbiotic 2000 compared to placebo on any analyte analysing all the paediatric and all adult participants as one group. However, age-group stratified analyses showed that plasma levels of several of the analytes were at baseline different in the children compared to in the adults. Authors conclude that Synbiotic 2000, in children with ADHD, reduces markers of intestinal and vascular inflammation, the latter in part through increasing SCFAs levels. Furthermore, they suggest that the findings warrant further studies to determine if persons with ADHD would benefit inflammation-wise from dietary intake of Synbiotic 2000 or a similar synbiotic.
Abstract
Synbiotic 2000, a pre + probiotic, reduced comorbid autistic traits and emotion dysregulation in attention deficit hyperactivity disorder (ADHD) patients. Immune activity and bacteria-derived short-chain fatty acids (SCFAs) are microbiota-gut-brain axis mediators. The aim was to investigate Synbiotic 2000 effects on plasma levels of immune activity markers and SCFAs in children and adults with ADHD. ADHD patients (n = 182) completed the 9-week intervention with Synbiotic 2000 or placebo and 156 provided blood samples. Healthy adult controls (n = 57) provided baseline samples. At baseline, adults with ADHD had higher pro-inflammatory sICAM-1 and sVCAM-1 and lower SCFA levels than controls. Children with ADHD had higher baseline sICAM-1, sVCAM-1, IL-12/IL-23p40, IL-2Rα, and lower formic, acetic, and propionic acid levels than adults with ADHD. sICAM-1, sVCAM-1, and propionic acid levels were more abnormal in children on medication. Synbiotic 2000, compared to placebo, reduced IL-12/IL-23p40 and sICAM-1 and increased propionic acid levels in children on medication. SCFAs correlated negatively with sICAM-1 and sVCAM-1. Preliminary human aortic smooth-muscle-cell experiments indicated that SCFAs protected against IL-1β-induced ICAM-1 expression. These findings suggest that treatment with Synbiotic 2000 reduces IL12/IL-23p40 and sICAM-1 and increases propionic acid levels in children with ADHD. Propionic acid, together with formic and acetic acid, may contribute to the lowering of the higher-than-normal sICAM-1 levels.
-
3.
Micronutrients for Attention-Deficit/Hyperactivity Disorder in Youths: A Placebo-Controlled Randomized Clinical Trial.
Johnstone, JM, Hatsu, I, Tost, G, Srikanth, P, Eiterman, LP, Bruton, AM, Ast, HK, Robinette, LM, Stern, MM, Millington, EG, et al
Journal of the American Academy of Child and Adolescent Psychiatry. 2022;61(5):647-661
-
-
-
-
Free full text
-
Plain language summary
Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental condition that affects about 5-7% of children. Characteristics of ADHD are age-inappropriate hyperactivity, impulsivity, and difficulties in focusing attention which arise from an impaired ability to regulate executive and emotional functions. The condition often persists into adulthood, where it presents an increased risk for poor educational achievements, substance abuse, incarceration, and mental health problems. In many cases, drug treatment can improve ADHD symptoms, yet concern remains about the side effects of these treatments. Some research has investigated the impact of nutrient supplementation on ADHD management, as many nutrients are essential for healthy brain function and are also involved in the production of neurotransmitters. In previous studies, supplementation with nutrients has shown some benefits but likewise also inconsistent results. This eight-week randomised placebo-controlled clinical trial evaluated the effects of a multi-nutrient supplement in 135 children with ADHD, aged 6-12 years. The study specifically focused on irritable mood symptoms. The multi-nutrient formula contained vitamins, minerals, amino acids, and antioxidants. Outcomes were measured by scores rated by clinicians (Clinical Global Impression-Improvement aka CGI-I) and scores rated by parents (Child and Adolescent Symptom Inventory-5 aka CASI-5). The multi-nutrient formula showed overall benefit in the blinded clinician rating but not by parental reports. According to the parents, overall improvement was reported, both in the placebo and intervention groups. The authors discussed how this absence of difference can be explained. Yet, on a subscale, the multi-nutrient group parents were more likely to report improvements. In addition, children with the additional micronutrients demonstrated greater height growth during the intervention. The supplement was well tolerated with good adherence and the monitored blood markers demonstrated safety of use.
Expert Review
Conflicts of interest:
None
Take Home Message:
This fully-blinded RCT of micronutrients addresses several concerns related to existing ADHD treatment, including the possibility of counteracting height suppression and treating associated irritable mood, emotional dysregulation, and aggression.
Although further research is needed, multinutrient supplementation should be considered for children with ADHD.
Evidence Category:
-
X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
-
B: Systematic reviews including RCTs of limited number
-
C: Non-randomized trials, observational studies, narrative reviews
-
D: Case-reports, evidence-based clinical findings
-
E: Opinion piece, other
Summary Review:
Introduction
Attention-deficit hyperactivity disorder (ADHD) is a common psychiatric condition that can result in low educational performance and achievement. Around 5-7% of children are believed to be affected. Alongside inattention and hyperactivity, emotional dysregulation is a common feature of ADHD. Psychiatric problems can continue into adulthood and an increased risk of incarceration and substance abuse have been reported.
Treatment with prescription medications may improve symptoms of ADHD, however, potential side effects include mild growth suppression, and mood and emotional dysregulation. Non-pharmacological treatments are therefore being investigated.
Previous research on single nutrients have shown mixed results for emotional dysregulation and mood issues in ADHD. The aim of this study was to test whether supplementation with a multi-nutrient could be beneficial to children aged 6-12 years with ADHD and irritability.
Methods
126 unmedicated children from North America with ADHD (mean age 9.8 years) completed this 8-week study. All participants had at least 1 symptom of anger, irritability, peer conflict or Disruptive Mood Dysregulation Disorder (DMDD).
Randomisation was into an intervention (n=71) or placebo (N=55) group with a 3:2 ratio to promote enrolment. Participants were required to take 6-12 capsules daily, depending on age and tolerance, of micronutrients or a placebo. Micronutrient dosages were above the recommended dietary allowance (RDA). Outcomes were measured using clinician and parent rated assessments and by a further adult who knew the child well.
The trial was blinded to all participants, parents and study staff.
Results
The clinician-rated results found 54% of the micronutrient group and 18% of the placebo group had improvements in irritability symptoms (Risk ratio =2.97, 97.5% CI: 1.5, 5.90, p<0.001). This was not replicated in the parent/adult rated results. Children in the micronutrient group grew on average 6mm more than the placebo group (p=0.002). No serious adverse treatment effects were reported. Adherence to protocol was met by >74% of participants (n=93).
Conclusions
In this study, clinicians reported that micronutrients showed greater benefits than placebo for treating irritability and supporting growth in children with ADHD.
The study and authors received funding from several research and association bodies. However, no funder was involved in the study design or reporting. No conflicts of interest were declared.
Clinical practice applications:
- Multinutrient supplementation including vitamins, minerals, amino acids, and antioxidants may support height growth in children who take pharmacologic treatment
- Multi nutrient supplementation may also help with irritable mood, emotional dysregulation, and aggression in ADHD children
- Micronutrients given at doses between the Recommended Dietary Allowance and Upper Tolerable Intake Level appear safe and may be developed into an alternative or complementary treatment for ADHD.
Considerations for future research:
- Further large scale research is needed into the potential benefits of micronutrients for children with ADHD and irritability
Abstract
OBJECTIVE To evaluate whether micronutrients (vitamins/minerals) benefit attention-deficit/hyperactivity disorder (ADHD) and irritability in a North American pediatric sample. METHOD A 3-site, 8-week, placebo-controlled, randomized clinical trial of micronutrients was conducted in nonmedicated children aged 6 to 12 years with ADHD and at least 1 impairing irritability symptom by parent report on the Child and Adolescent Symptom Inventory-5 (CASI-5). A priori-defined primary outcomes were Clinical Global Impression-Improvement (CGI-I) (CGI-I of 1 or 2 = treatment responder) and parent-rated CASI-5 composite score of ADHD, oppositional defiant, disruptive mood dysregulation, and peer conflict symptoms, including impairment scores. RESULTS Of 135 randomized (mean age 9.8 years), 126 youths (93%) comprised the modified intention-to-treat population. Blinding was maintained. For the CGI-I, 54% of the micronutrient and 18% of the placebo group were responders (risk ratio = 2.97, 97.5% CI = 1.50, 5.90, p < .001). CASI-5 composite scores improved significantly for both groups (p < .01), with a mean change of -0.31 (95% CI = -0.39, -0.23) in the micronutrient group and a mean change of -0.28 (95% CI = -0.38, -0.19) in the placebo group. However, the between-group difference was not significant (mean change = -0.02; 97.5% CI = -0.16, 0.12, effect size = 0.07, p = .70). The micronutrient group grew 6 mm more than the placebo group (p = .002). No serious adverse events or clinically significant changes from baseline in blood and urine tests occurred. CONCLUSION Micronutrients showed global benefit over placebo by blinded clinician rating, but not by parent-report CASI-5 composite rating in a population with ADHD and irritability. Micronutrients showed greater height growth. Micronutrients were well tolerated, and the majority of participants adhered to the number of capsules prescribed. This randomized controlled trial replicates safety and efficacy reported for ADHD in 2 smaller trials of a similar formula containing all vitamins and known essential minerals in amounts between the Recommended Dietary Allowance and Upper Tolerable Intake Level. CLINICAL TRIAL REGISTRATION INFORMATION Micronutrients for ADHD in Youth (MADDY) Study; https://clinicaltrials.gov; NCT03252522.
-
4.
Circulating levels of maternal vitamin D and risk of ADHD in offspring: results from the Vitamin D Antenatal Asthma Reduction Trial.
Chu, SH, Huang, M, Kelly, RS, Kachroo, P, Litonjua, AA, Weiss, ST, Lasky-Su, J
International journal of epidemiology. 2022;51(3):910-918
-
-
-
-
Free full text
-
Plain language summary
Acting as both a nutrient and a hormone, vitamin D has been found to play a critical role in neurodevelopment across sensitive periods in utero, infancy and early childhood. Among neurodevelopmental and behavioural disorders in early life, attention-deficit/hyperactivity disorder (ADHD) is the most common among children worldwide. Low levels of circulating 25-hydroxy-vitamin D [25(OH)D] have been shown to associate with prevalent ADHD. The aims of this study were to (i) determine the association between maternal vitamin D levels in the first and third trimesters of pregnancy and the risk of offspring ADHD by age 6 years or later; and (ii) to identify potential sensitive periods in utero during which vitamin D levels might be most important for reducing risk of ADHD. This is an ancillary study of the Vitamin D Antenatal Asthma Reduction Trial (VDAART). The VDAART was a randomised, double-blinded, multicentre, clinical trial in which 876 participating mothers were recruited between 10–18 weeks of gestation and assigned to receive either 4400 or 400 IU/day of vitamin D throughout pregnancy. Results show protective associations between maternal 25(OH)D sufficiency in the third trimester and child ADHD, but not at baseline. Furthermore, both at baseline and in the third trimester, there were higher odds of ADHD in male offspring as compared with female offspring with 25(OH)D insufficient mothers (analyses limited by small sample sizes) Authors conclude that higher levels of maternal vitamin D during pregnancy may play a protective role against risk of ADHD in offspring, but further studies are needed to confirm this association and any therapeutic potential therein.
Expert Review
Conflicts of interest:
None
Take Home Message:
Ensure that women in pregnancy, and possibly also those seeking to conceive, have adequate vitamin D status in order to reduce the risk of ADHD in offspring.
Evidence Category:
-
X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
-
B: Systematic reviews including RCTs of limited number
-
C: Non-randomized trials, observational studies, narrative reviews
-
D: Case-reports, evidence-based clinical findings
-
E: Opinion piece, other
Summary Review:
Background
This paper describes a secondary data analysis from an RCT that looked at the effect of prenatal vitamin D supplementation on risk of childhood asthma in offspring. Enrolled women aged 18–39 years with a history of asthma, eczema or allergic rhinitis, or whose partner (biological father of child) had a history of the aforementioned condition, received either 400 IU or 4400 IU vitamin D daily for the duration of their pregnancy. Offspring follow-up is still ongoing.
Aims
The current study aims were twofold: (i) to determine the association between maternal vitamin D levels in trimesters 1 and 3 and the risk of attention deficit/hyperactivity disorder (ADHD) in offspring diagnosed by age 6 years or later; and (ii) to identify potentially sensitive periods during gestation in which vitamin D levels may be especially important for reducing risk of ADHD.
Methods
The analytical sample included 679 mother-child pairs, from the original sample of 876 participating mothers. No sample size calculation was reported, though the sample was considered representative of the overall RCT study population.
Maternal vitamin D (serum 25(OH)D) was classified as follows
- Highly deficient <12 ng/mL
- Deficient 12 ng/mL to 19.9 ng/mL
- Insufficient 20 ng/mL to 29.9 ng/mL
- Sufficient ≥30 ng/mL
ADHD status was assessed through parental reporting between ages 6 and 9 years.
Results
No baseline associations between a vitamin D sufficient status and offspring ADHD in maternal samples collected during trimester 1 were observed (OR 1.06, 95% CI 0.51–2.19; P.0.871), though this association became statistically significant at trimester 3 (OR 0.47, 95% CI 0.26–0.84; P.0.011). This translated to a 53% less chance of having a child with ADHD at age 6 or later among mothers with vitamin D sufficiency compared with children of mothers with vitamin D deficiency. There was also a linear trend in the protective association of vitamin D sufficiency (≥30 ng/mL) on reduced risk of offspring ADHD at age 6 years or later in data from trimester 3. Stratified analyses revealed a protective association for sufficient maternal vitamin D status and offspring ADHD among males (OR 0.47, 95% CI 0.23–0.94).
Conclusions
The authors concluded that vitamin D sufficiency (≥30 ng/mL) in the 3rd trimester of gestation may decrease the risk of ADHD development in offspring.
Notes: The authors reported no relevant conflicts of interest.
Clinical practice applications:
Ensuring a sufficient vitamin D status by the 3rd trimester of pregnancy may help to lessen the risk of ADHD in offspring. Nutritional therapists and other clinicians working with pregnant women or women looking to conceive should consider checking vitamin D status and providing corrective supplementation and lifestyle advice to augment vitamin D levels where indicated.
Considerations for future research:
The authors of this study postulated that the statistically significant protective association between vitamin D at trimester 3 and ADHD in offspring was not significant in trimester 1 due to a low observed variability in vitamin D status (>75% of women were vitamin D insufficient), and thus the statistical test being underpowered to see difference between groups with sufficient or insufficient status.
Further research could expand upon this hypothesis to test whether vitamin D status in trimester 1, or preconceptually, may offer a protective association for ADHD and other related neurological conditions that may manifest in early life.
Abstract
BACKGROUND Low levels of circulating 25-hydroxy-vitamin D [25(OH)D] have been shown to associate with prevalent attention-deficit/hyperactivity disorder (ADHD), but few studies have examined the association between 25(OH)D during fetal development and risk of childhood ADHD. METHODS Maternal plasma 25(OH)D was measured at 10-18 and 32-38 weeks of gestation, with sufficiency defined as 25(OH)D ≥ 30 ng/ml. Offspring ADHD status between ages 6-9 years was measured by parent report of clinical ADHD diagnosis among 680 mother-child pairs from the Vitamin D Antenatal Asthma Reduction Trial. Association between maternal 25(OH)D and child ADHD was assessed using logistic regression, adjusting for maternal age, race and ethnicity. Effect modification by offspring sex was also assessed. RESULTS No associations between maternal 25(OH)D at 10-18 weeks of gestation and offspring ADHD were observed. In the third trimester, we observed associations between maternal vitamin D sufficiency and offspring ADHD [odds ratio (OR) 0.47, 95% confidence interval (CI) 0.26-0.84], in addition to maternal 25(OH)D sufficiency category, comparing the deficient (OR 0.34, 95% CI 0.12-0.94), insufficient (OR 0.41, 95% CI 0.15-1.10) and sufficient (OR 0.20, 95% CI 0.08-0.54) categories against highly deficient 25(OH)D, respectively. Stratified analyses revealed a protective association for sufficient maternal 25(OH)D and child ADHD among males (OR 0.47, 95% CI 0.23-0.94); the synergy index for additive effect modification of risk was 1.78 (95% CI 0.62-5.08). CONCLUSIONS Higher levels of maternal vitamin D in the third trimester are associated with lower risk of ADHD in offspring, with modest evidence for a stronger effect among male offspring. However, larger studies will be necessary to confirm these findings.
-
5.
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
-
-
-
Free full text
Plain language summary
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.
-
6.
The Association between ADHD and Celiac Disease in Children.
Gaur, S
Children (Basel, Switzerland). 2022;9(6)
-
-
-
-
Free full text
Plain language summary
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:
-
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
-
X
B: Systematic reviews including RCTs of limited number
-
C: Non-randomized trials, observational studies, narrative reviews
-
D: Case-reports, evidence-based clinical findings
-
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.
-
7.
Effect of Vitamin D Supplementation on Inflammatory Biomarkers in School-Aged Children with Attention Deficit Hyperactivity Disorder.
Samadi, M, Gholami, F, Seyedi, M, Jalali, M, Effatpanah, M, Yekaninejad, MS, Abdolahi, M, Chamari, M, Mohammadzadeh Honarvar, N
International journal of clinical practice. 2022;2022:1256408
-
-
-
Free full text
-
Plain language summary
Attention deficit hyperactivity disorder (ADHD) is one of the most prevalent psychiatric and developmental disorders among children and adolescents. Besides clinical impairments, these children have challenges with school performance and independent socioeconomic factors. The aim of this study was to assess the possible effects of vitamin D on inflammatory cytokines (tumour necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6)) levels in children with ADHD. This study is a randomised, double-blind, placebo-controlled clinical trial which was conducted on 86 children aged 6–12. Patients were randomly assigned to two groups to receive vitamin D3 or a placebo. Results show children with ADHD taking vitamin D supplementation for 3 months demonstrated a significant increase in serum levels of Vitamin D3. However, serum levels of IL-6 and TNF-α were not significantly influenced by vitamin D administration. Authors conclude that their findings failed to find a favourable effect of 3 months of supplementation with vitamin D on inflammatory cytokines. Thus, they highly recommend conducting further studies with different doses of vitamin D and various designs in addition to differences in the characteristics of participants.
Abstract
METHOD This randomized double-blind, placebo-controlled trial was conducted on 75 school-aged children with a diagnosis of ADHD based on DSM-V criteria. Children were randomly allocated to receive either vitamin D3 (2000 IU/day) or a placebo for 3 months. Serum IL-6, TNF-α, and 25(OH) D were assessed before and after the intervention to determine the effects of vitamin D on the highlighted parameters. RESULTS Serum levels of 25(OH) D increased significantly in the vitamin D group (P=0.01). However, no significant differences in serum IL-6 and TNF-α were found between both groups at the baseline and at the end of the intervention. CONCLUSION The findings revealed that vitamin D supplementation for 3 months is not efficacious in reducing inflammatory cytokines in children with ADHD. Further studies are required to confirm these results.
-
8.
The effect of vitamin D and magnesium supplementation on the mental health status of attention-deficit hyperactive children: a randomized controlled trial.
Hemamy, M, Pahlavani, N, Amanollahi, A, Islam, SMS, McVicar, J, Askari, G, Malekahmadi, M
BMC pediatrics. 2021;21(1):178
-
-
-
Free full text
Plain language summary
Attention-Deficit/Hyperactivity Disorder (ADHD) is a common neurodevelopmental disorder and studies have found it to be associated with nutrient deficiencies, namely magnesium and vitamin D. The aim of this randomized, controlled study is to assess the effect of vitamin D and magnesium supplementation on mental health and behavioral outcomes in children with ADHD. Sixty-six children with ADHD were randomly allocated to receive both vitamin D plus magnesium or placebo for eight weeks, and a validated children’s mental health questionnaire was assessed. After eight weeks, serum vitamin D and magnesium, as well as various behavioural outcomes (emotional problem, peer problem, total difficulties and internalising), were all significantly improved among the treatment group compared to placebo. Based on these results, the authors conclude co-supplementing vitamin D and magnesium can improve the behavioral function and mental health of children with ADHD. They suggest larger, well-designed studies are needed to both validate these findings and further explore whether micronutrient deficiencies in ADHD are a cause or effect of the disorder.
Abstract
BACKGROUND Attention-Deficit / Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder, characterized by varying severity in attention deficit and hyperactivity. Studies have shown deficiencies in the serum level of magnesium and vitamin D in people with ADHD. The aim of this study is to determine the effect of vitamin D and magnesium supplementation on mental health in children with ADHD. METHODS We conducted a randomized, double blind, placebo-controlled clinical trial of 66 children with ADHD. Participants were randomly allocated to receive both vitamin D (50,000 IU/week) plus magnesium (6 mg/kg/day) supplements (n = 33) or placebos (n = 33) for 8-weeks. Strengths and difficulties questionnaire was used to evaluate children's mental health at baseline and the end of the study. RESULTS After eight weeks of intervention, the serum levels of 25-hydroxy-vitamin D3 and magnesium increased significantly in the intervention group compared with the control group. Also, children receiving vitamin D plus magnesium showed a significant reduction in emotional problems (p = 0.001), conduct problems (p = 0.002), peer problems (p = 0.001), prosocial score (p = 0.007), total difficulties (p = 0.001), externalizing score (p = 0.001), and internalizing score (p = 0.001) compared with children treated with the placebo. CONCLUSION Vitamin D (50,000 IU/week) and magnesium (6 mg/kg/day) co-supplementation for a duration of 8-weeks could improve the behavioral function and mental health of children with ADHD. However, further well-designed studies with a larger sample size are needed. TRIAL REGISTRATION IRCT2016030326886N1 .
-
9.
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)
-
-
-
Free full text
Plain language summary
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.
-
10.
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
-
-
-
Free full text
Plain language summary
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.