Article

Effects of a restricted elimination diet on the behaviour of children with attention-deficit hyperactivity disorder (INCA study): A randomised controlled trial

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Abstract

The effects of a restricted elimination diet in children with attention-deficit hyperactivity disorder (ADHD) have mainly been investigated in selected subgroups of patients. We aimed to investigate whether there is a connection between diet and behaviour in an unselected group of children. The Impact of Nutrition on Children with ADHD (INCA) study was a randomised controlled trial that consisted of an open-label phase with masked measurements followed by a double-blind crossover phase. Patients in the Netherlands and Belgium were enrolled via announcements in medical health centres and through media announcements. Randomisation in both phases was individually done by random sampling. In the open-label phase (first phase), children aged 4-8 years who were diagnosed with ADHD were randomly assigned to 5 weeks of a restricted elimination diet (diet group) or to instructions for a healthy diet (control group). Thereafter, the clinical responders (those with an improvement of at least 40% on the ADHD rating scale [ARS]) from the diet group proceeded with a 4-week double-blind crossover food challenge phase (second phase), in which high-IgG or low-IgG foods (classified on the basis of every child's individual IgG blood test results) were added to the diet. During the first phase, only the assessing paediatrician was masked to group allocation. During the second phase (challenge phase), all persons involved were masked to challenge allocation. Primary endpoints were the change in ARS score between baseline and the end of the first phase (masked paediatrician) and between the end of the first phase and the second phase (double-blind), and the abbreviated Conners' scale (ACS) score (unmasked) between the same timepoints. Secondary endpoints included food-specific IgG levels at baseline related to the behaviour of the diet group responders after IgG-based food challenges. The primary analyses were intention to treat for the first phase and per protocol for the second phase. INCA is registered as an International Standard Randomised Controlled Trial, number ISRCTN 76063113. Between Nov 4, 2008, and Sept 29, 2009, 100 children were enrolled and randomly assigned to the control group (n=50) or the diet group (n=50). Between baseline and the end of the first phase, the difference between the diet group and the control group in the mean ARS total score was 23·7 (95% CI 18·6-28·8; p<0·0001) according to the masked ratings. The difference between groups in the mean ACS score between the same timepoints was 11·8 (95% CI 9·2-14·5; p<0·0001). The ARS total score increased in clinical responders after the challenge by 20·8 (95% CI 14·3-27·3; p<0·0001) and the ACS score increased by 11·6 (7·7-15·4; p<0·0001). In the challenge phase, after challenges with either high-IgG or low-IgG foods, relapse of ADHD symptoms occurred in 19 of 30 (63%) children, independent of the IgG blood levels. There were no harms or adverse events reported in both phases. A strictly supervised restricted elimination diet is a valuable instrument to assess whether ADHD is induced by food. The prescription of diets on the basis of IgG blood tests should be discouraged. Foundation of Child and Behaviour, Foundation Nuts Ohra, Foundation for Children's Welfare Stamps Netherlands, and the KF Hein Foundation.

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... Several studies have shown that nutrition is a strong moderator of symptoms in ADHD (6)(7)(8)(9)(10)(11)(12)(13). Strong effects of the elimination diet or for food diet have been observed (6,7,10,(12)(13)(14)(15)(16). ...
... Several studies have shown that nutrition is a strong moderator of symptoms in ADHD (6)(7)(8)(9)(10)(11)(12)(13). Strong effects of the elimination diet or for food diet have been observed (6,7,10,(12)(13)(14)(15)(16). ...
... A symptom improvement of more than 40% between the two appointments T1 (before the diet) and T2 (after the diet) was defined as a response (7). As the study clinician spoke German to the participants and their parents, she used translated items of the ARS. ...
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Objectives The influence of food intake on behavioural disorders was already described in the early 20th century. Elimination of individually allergenic food items from individual diets [“oligoantigenic diet” (OD)] showed promise to improve attention-deficit/hyperactivity disorder (ADHD) symptoms. However, only few of the positive results were evaluated by blinded symptom rating. Therefore the present study’s purpose was to evaluate the reliability of a non-blinded rating of the ADHD Rating Scale IV (ARS) for the assessment of OD effects in comparison to a blinded rating of the ARS based on pseudonymized video recordings.Methods Ten children (8m/2f) aged 8 to 14 with ADHD according to ICD-10 participated in an uncontrolled, open-label dietary intervention study. Food items, commonly related to intolerances, were eliminated for four weeks. Participants with > 40% improvement in the ARS between T1 (before the diet) and T2 (after the diet) were defined as responders. Nutrients with individual relevance to ADHD symptoms were identified in a following reintroduction phase (T3–T4) lasting 8–16 weeks. The ARS was completed by a non-blinded child and adolescent psychiatrist (T0-T4). Sessions were recorded on video, pseudonymized, and evaluated by three blinded raters. Complete data were captured for eight children. The inter-rater reliability between the non-blinded therapist and every blinded rater was determined by the intra-class correlation coefficient (ICC). Correlations according to Pearson and Spearman between the non-blinded and blinded rating were calculated for each rater.ResultsTwo blinded raters and the non-blinded rater considered 5 of 8 (62.5%) children as responders, whereas one blinded rater disagreed as to the success of one case thus considering only 4 of 8 children as responders to the diet. Inter-rater reliability was assessed after each rater having scored 33 videos: The intra-class coefficients were >.9 for all raters (rater 1: ICC=.997, rater 2: ICC=.996, rater 3: ICC=.996) and the Spearman rho between the raters were high (n=33; rater 1: rho =.989, p<.0001, rater 2: rho=.987, p<.0001, rater 3: rho=.984, p<.0001), respectively.DiscussionAs both, blinded and non-blinded ratings of the ARS, revealed relevant significant improvement of ADHD scores in children following an OD in this uncontrolled trial, Randomized controlled trials appear as highly desirable in order to replicate these improvements and to establish reliable and unbiased effect sizes thereby fostering further more objective confirmatory measurements.
... Metaanalyses including double-blind placebo-controlled (DBPC) studies only showed that the clinical effects of fish oil and food additives were negligible to modest, while the effects of the FFD on ADHD were substantial (8), pointing to the existence of a food-induced subtype of ADHD. Subsequent single-blinded (9) and open (10,11) randomised controlled trials (RCT) investigating the effect of an optimal FFD-not having to moderate the diet as a consequence of the blinded design [see supplement S1Text (8)]-resulted in clinically relevant effect sizes as well. ...
... During the first 2 weeks a slightly extended FFD is followed, consistent with the few-foods diet procedure applied in previous RCTs (9,11): in addition to the most stringent FFD small portions of specific foods like wheat, lamb and butter (daily), and corn, potatoes, pear spread, mango and honey (twice a week) are allowed as well. Parents are given a schematic overview of which foods are permitted in which amount and on which days. ...
... Questionnaires An inventory of the child's behavior is made using three questionnaires; the Abbreviated Conners' Scale (ACS) and the ADHD Rating Scale (ARS) at T0, T1, and T2, and a DSM-IVbased structured psychiatric interview to assess Oppositional Defiant Disorder (ODD) at T1 and T2. The questionnaires, which have been described elsewhere (9), use a four-point scale: for the ACS and ARS from twice a week or less (0), more than twice a week but less than once a day (1), once per day (2) to more than once per day (3); for ODD from less than once a week (0), once or twice per week (1), thrice a week (2) to more than thrice a week (3). During each assessment parents and teachers are asked only to take into account the child's behavior in the week preceding the assessment. ...
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IntroductionDouble-blind placebo-controlled studies investigating the effect of a few-foods diet (FFD) on attention-deficit/hyperactivity disorder (ADHD) have provided consistent evidence that ADHD can be triggered by foods, indicating the existence of a food-induced ADHD subtype. In 2001 the “few-foods” approach was included in an ADHD treatment protocol. This approach consists of (a) determining, by means of an FFD, whether food is a trigger of ADHD; (b) reintroducing, in FFD responders, foods to assess which foods are incriminated; (c) finally composing a personalised diet eliminating the involved foods only. In the Netherlands the few-foods approach is applied in practice. We aimed to retrospectively assess its effectiveness on ADHD and oppositional defiant disorder (ODD) in real life.Methods Data from all children who started the few-foods approach in three specialised healthcare facilities during three consecutive months were included. Behavior was assessed at start and end of the 5-week FFD, using the ADHD Rating Scale and a structured psychiatric interview. Clinical responders (behavioral improvements ≥40%) proceeded with the reintroduction phase.ResultsData of 57 children, 27 taking medication and 15 following some elimination diet at start, were available. No differences were noted between parental scores of children with and without medication or some elimination diet at start. 21/27 (78%) children stopped taking medication during the FFD. 34/57 (60%) children were ADHD responders, 20/29 (65%) children meeting ODD criteria were ODD responders. 26/34 (76%) ADHD responders started the reintroduction phase; 14/26 (54%) still participated at six months. Teacher data were available of 18/57 (32%) children. 9/18 (50%) children were ADHD responders.Conclusion The FFD, if applied by trained specialists, may lead to clinically relevant reduction of ADHD and ODD symptoms in general practice, and a concomitant decrease of ADHD medication. These results corroborate the existence of an ADHD subgroup with food-induced ADHD. Defining and eliminating the incriminated foods, i.e. the underlying causal triggers, may result in secondary prevention of food-induced ADHD. Research into underlying mechanism(s) is of vital importance: finding an easier method or biomarkers for diagnosing food-induced ADHD and ascertaining the incriminated foods may lead to redundancy of the few-foods approach.
... Although controversial, dietary therapies have been suggested to play a major role in ADHD and should be considered in the evaluation and management of children with ADHD [20][21][22]. Nutritional deficiencies from a " Western " diet, food insecurity, artificial food additives and dyes, and food sensitivities and allergies have been implicated in ADHD [23][24][25][26][27][28]. Most research related to dietary constituents has focused on restricted elimination diets (RED), sugar restriction, and artificial food color exclusion diets in the treatment of ADHD. ...
... Although adherence is difficult and time consuming, RED has been shown to benefit children with ADHD. The Impact of Nutrition in Children with ADHD (INCA) was a double-blind crossover research study that showed children ages 4–8 years old improve on the abbreviated Conners' scale by 11.6 after being placed on a tailored RED for five weeks [26]. Furthermore, 63% of the children relapsed with ADHD symptoms after a food challenge. ...
... This study was well designed with good methodology, large sample size, and correlation with IgG food antigen blood tests. In addition, the diets were specifically tailored to each participant, which helped improve adherence [26]. Due to the recurrence of ADHD symptoms after a five-week RED, more research trials need to investigate how long children with ADHD need to stay on a RED in order to prevent recurrence of symptoms during a food challenge. ...
Article
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Attention deficit hyperactivity disorder (ADHD) is the most common neuropsychiatric disorder in children and is increasing in prevalence. There has also been a related increase in prescribing stimulant medication despite some controversy whether ADHD medication makes a lasting difference in school performance or achievement. Families who are apprehensive about side effects and with concerns for efficacy of medication pursue integrative medicine as an alternative or adjunct to pharmacologic and cognitive behavioral treatment approaches. Integrative medicine incorporates evidence-based medicine, both conventional and complementary and alternative therapies, to deliver personalized care to the patient, emphasizing diet, nutrients, gut health, and environmental influences as a means to decrease symptoms associated with chronic disorders. Pediatric integrative medicine practitioners are increasing in number throughout the United States because of improvement in patient health outcomes. However, limited funding and poor research design interfere with generalizable treatment approaches utilizing integrative medicine. The use of research designs originally intended for drugs and procedures are not suitable for many integrative medicine approaches. This article serves to highlight integrative medicine approaches in use today for children with ADHD, including dietary therapies, nutritional supplements, environmental hygiene, and neurofeedback.
... A systematic review of metaanalyses of double-blind placebo-controlled trials found no convincing evidence of therapeutic efficacy of artificial food color elimination, while the few-foods diet, which excludes many foods and additives, may offer new treatment options (19). The hypothesis of a relationship between food hypersensitivity and ADHD is supported by several studies (44)(45)(46)(47)(48). A strictly supervised restricted elimination diet has been demonstrated to be a valuable tool in examining whether ADHD symptoms are induced by individual foods (47). ...
... The hypothesis of a relationship between food hypersensitivity and ADHD is supported by several studies (44)(45)(46)(47)(48). A strictly supervised restricted elimination diet has been demonstrated to be a valuable tool in examining whether ADHD symptoms are induced by individual foods (47). Moreover, in a randomized controlled trial, considerable effects of this diet were observed in an unselected group of children with ADHD (47). ...
... A strictly supervised restricted elimination diet has been demonstrated to be a valuable tool in examining whether ADHD symptoms are induced by individual foods (47). Moreover, in a randomized controlled trial, considerable effects of this diet were observed in an unselected group of children with ADHD (47). A recent open nonblinded pilot study has shown a high level of compliance to an oligoantigenic diet in children with ADHD in an out-patient setting, demonstrating its feasibility 1 . ...
... 25 During an FFD, children follow a restricted diet for several weeks, in which they consume only a few types of food (eg, rice, meat, vegetables, pear and water), initially complemented with foods like potato, several fruits and wheat. [26][27][28][29] The FFD is not intended as a long-term treatment, but functions as a diagnostic tool to determine whether a child responds to dietary restriction. If a child is responsive to the diagnostic FFD, an individually tailored and more diverse diet can be designed after repeated challenges have identified the foods that trigger ADHD symptoms. ...
... 36 In the most recent RCT, 64% of a selected subgroup of young children with ADHD responded favourably to the FFD. 26 However, an FFD is burdensome, and adherence is most often successful in motivated and highly structured families. 37 For large-scale implementation, simplified dietary treatments should be developed. ...
... Thereafter, participants will follow a 5-week FFD preceded by a 1-week transition period. 26 27 54 To improve adherence, parents will receive a diet plan and a recipe book. During the 5-week period, parents and FFD researcher will discuss the child's diet and behaviour regularly (at least once a week). ...
Article
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Introduction Attention deficit hyperactivity disorder (ADHD) is the most common childhood behavioural disorder, causing significant impediment to a child’s development. It is a complex disorder with numerous contributing (epi)genetic and environmental factors. Currently, treatment consists of behavioural and pharmacological therapy. However, ADHD medication is associated with several side effects, and concerns about long-term effects and efficacy exist. Therefore, there is considerable interest in the development of alternative treatment options. Double-blind research investigating the effects of a few-foods diet (FFD) has demonstrated a significant decrease in ADHD symptoms following an FFD. However, an FFD requires a considerable effort of both child and parents, limiting its applicability as a general ADHD treatment. To make FFD intervention less challenging or potentially obsolete, we need to understand how, and in which children, an FFD affects ADHD behaviour and, consequently, the child’s well-being. We hypothesise that an FFD affects brain function, and that the nutritional impact on ADHD is effectuated by a complex interplay between the microbiota, gut and brain, that is, the microbiota–gut–brain axis. Methods and analysis The Biomarker Research in ADHD: the Impact of Nutrition (BRAIN) study is an open-label trial with researchers blinded to changes in ADHD symptoms during sample processing and initial data analyses. Ethics and dissemination The Medical Research and Ethics Committee of Wageningen University has approved this study (NL63851.081.17, application 17/24). Results will be disseminated through peer-reviewed journal publications, conference presentations, (social) media and the BRAIN study website. A summary of the findings will be provided to the participants. Trial registration number NCT03440346 . Study dates Collection of primary outcome data started in March 2018 and will be ongoing until 100 children have participated in the study. Sample data analysis will start after all samples have been collected.
... This divergence in conclusions might be explained by the fact that in previous reviews the results of uncontrolled and un-blinded studies [40], of studies amalgamating different types of diet interventions [40][41][42] and of meta-analyses not specifically aimed at children with ADHD or hyperactive behavior [41, 42] were included. Also, two reviews [41, 42] discussed studies [48,49] as meta-analyses although the reported results were not derived from meta-analytic research, while none of three reviews [40-42] mentioned a study [50] that was a meta-analysis. The differences between the three previously published reviews and this review are listed in S1 Table. ...
... The higher FFD ESs might also be the consequence of parental investments necessary to apply the intervention, specifically since the FFD is considered a strenuous intervention [48,70,72,74,82,83]. However, in adequately conducted DBPC trials parental investments are deemed commensurable in verum and placebo groups. ...
... The actual treatment is the individually tailored diet designed after repeated challenges have identified which food items should be avoided' [40]. Research has shown that this 'few-foods approach'-i.e. a short-term FFD followed by food challenges in children showing clinically relevant behavioral improvements (diet responders), eventually resulting in a personalized diet advice-would be achievable but may take at least one year [70,72], is considered burdensome [48,70,72,74,82,83], is feasible only in motivated families with good family structure [112] and would be easier to apply in younger children [113]. Hence, large-scale implementation of the few-foods approach would not be a realistic recommendation. ...
Article
Full-text available
Introduction Attention-deficit/hyperactivity disorder (ADHD) is a debilitating mental health problem hampering the child’s development. The underlying causes include both genetic and environmental factors and may differ between individuals. The efficacy of diet treatments in ADHD was recently evaluated in three reviews, reporting divergent and confusing conclusions based on heterogeneous studies and subjects. To address this inconsistency we conducted a systematic review of meta-analyses of double-blind placebo-controlled trials evaluating the effect of diet interventions (elimination and supplementation) on ADHD. Methods Our literature search resulted in 14 meta-analyses, six of which confined to double-blind placebo-controlled trials applying homogeneous diet interventions, i.e. artificial food color (AFC) elimination, a few-foods diet (FFD) and poly-unsaturated fatty acid (PUFA) supplementation. Effect sizes (ES) and Confidence intervals (CI) of study outcomes were depicted in a forest plot. I² was calculated to assess heterogeneity if necessary and additional random effects subgroup meta-regression was conducted if substantial heterogeneity was present. Results The AFC ESs were 0.44 (95% CI: 0.16–0.72, I² = 11%) and 0.21 (95% CI: -0.02–0.43, I² = 68%) [parent ratings], 0.08 (95% CI: -0.07–0.24, I² = 0%) [teacher ratings] and 0.11 (95% CI: -0.13–0.34, I² = 12%) [observer ratings]. The FFD ESs were 0.80 (95% CI: 0.41–1.19, I² = 61%) [parent ratings] and 0.51 (95% CI: -0.02–1.04, I² = 72%) [other ratings], while the PUFA ESs were 0.17 (95% CI: -0.03–0.38, I² = 38%) [parent ratings], -0.05 (95% CI: -0.27–0.18, I² = 0%) [teacher ratings] and 0.16 (95% CI: 0.01–0.31, I² = 0%) [parent and teacher ratings]. Three meta-analyses (two FFD and one AFC) resulted in high I² without presenting subgroup results. The FFD meta-analyses provided sufficient data to perform subgroup analyses on intervention type, resulting in a decrease of heterogeneity to 0% (diet design) and 37.8% (challenge design). Conclusion Considering the small average ESs PUFA supplementation is unlikely to provide a tangible contribution to ADHD treatment, while further research is required for AFC elimination before advising this intervention as ADHD treatment. The average FFD ES is substantial, offering treatment opportunities in subgroups of children with ADHD not responding to or too young for medication. Further FFD research should focus on establishing the underlying mechanisms of food (e.g. incrimination of gut microbiota) to simplify the FFD approach in children with ADHD.
... The oligoantigenic diet typically involves an elimination phase (usually two to five weeks) in which the specific food items are excluded completely. The food items in the elimination phase could, for instance, consist of only a few hypoallergenic foods such as rice, turkey, lettuce, pears, and water [34]. If the patient reacts by a substantial decrease of symptoms indicating 'food sensitivity', a reintroduction phase, which could take as long as eighteen months, could be applied to find out what specific food items trigger the symptoms. ...
... it was concluded that about one third of the children with ADHD show an excellent (>40% symptom reduction) response [51]. This meta-analysis excluded two studies by Pelsser et al. with an outlier effect size and the use of nonblinded ratings [34,52]. Another meta-analysis including these two studies estimated an effect size of 1.48 that, however, dropped substantially to 0.51 (95% confidence interval −0.02 to 1.04) when probably blinded raters were used [18]. ...
... The observed effects for food additives exclusion diets in children with ADHD are small, and may not be specific for children with ADHD. Although a few select studies using most proximal assessment demonstrated large effects of oligoantigenic diets in children with ADHD [34,52], an overall small effect of this diet was shown by other studies using probably blinded assessments. Furthermore, it remains unknown whether children will have a consolidated diet after the elimination phase of the oligoantigenic diet. ...
Article
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Nutrition plays an important role in neurodevelopment. This insight has led to increasing research into the efficacy of nutrition-related interventions for treating neurodevelopmental disorders. This review discusses an elimination diet as a treatment for attention deficit hyperactivity disorder and autism spectrum disorder, with a focus on the efficacy of the food additives exclusion diet, gluten-free/casein-free diet and oligoantigenic diet. Furthermore, we discuss the potential mechanisms of elimination diets’ effects in these neurodevelopmental disorders. The main candidate mechanism is the microbiome–gut–brain axis possibly involving complex interactions between multiple systems, including the metabolic, immune, endocrine, and neural system. We conclude with practical implications and future directions into the investigation of an elimination diet’s efficacy in the treatment of attention deficit hyperactivity disorder and autism spectrum disorder.
... This divergence in conclusions might be explained by the fact that in previous reviews the results of uncontrolled and un-blinded studies [40], of studies amalgamating different types of diet interventions [40][41][42] and of meta-analyses not specifically aimed at children with ADHD or hyperactive behavior [41, 42] were included. Also, two reviews [41, 42] discussed studies [48,49] as meta-analyses although the reported results were not derived from meta-analytic research, while none of three reviews [40-42] mentioned a study [50] that was a meta-analysis. The differences between the three previously published reviews and this review are listed in S1 Table. ...
... The higher FFD ESs might also be the consequence of parental investments necessary to apply the intervention, specifically since the FFD is considered a strenuous intervention [48,70,72,74,82,83]. However, in adequately conducted DBPC trials parental investments are deemed commensurable in verum and placebo groups. ...
... The actual treatment is the individually tailored diet designed after repeated challenges have identified which food items should be avoided' [40]. Research has shown that this 'few-foods approach'-i.e. a short-term FFD followed by food challenges in children showing clinically relevant behavioral improvements (diet responders), eventually resulting in a personalized diet advice-would be achievable but may take at least one year [70,72], is considered burdensome [48,70,72,74,82,83], is feasible only in motivated families with good family structure [112] and would be easier to apply in younger children [113]. Hence, large-scale implementation of the few-foods approach would not be a realistic recommendation. ...
Article
p>Introduction: Attention-deficit/hyperactivity disorder (ADHD) is a debilitating mental health problem hampering the child's development. The underlying causes include both genetic and environmental factors and may differ between individuals. The efficacy of diet treatments in ADHD was recently evaluated in three reviews, reporting divergent and confusing conclusions based on heterogeneous studies and subjects. To address this inconsistency we conducted a systematic review of meta-analyses of double-blind placebo-controlled trials evaluating the effect of diet interventions (elimination and supplementation) on ADHD. Methods: Our literature search resulted in 14 meta-analyses, six of which confined to double-blind placebo-controlled trials applying homogeneous diet interventions, i.e. artificial food color (AFC) elimination, a few-foods diet (FFD) and poly-unsaturated fatty acid (PUFA) supplementation. Effect sizes (ES) and Confidence intervals (CI) of study outcomes were depicted in a forest plot. I<sup>2</sup> was calculated to assess heterogeneity if necessary and additional random effects subgroup meta-regression was conducted if substantial heterogeneity was present. Results: The AFC ESs were 0.44 (95% CI: 0.16-0.72, I<sup>2</sup> = 11%) and 0.21 (95% CI: -0.02-0.43, I<sup>2</sup> = 68%) [parent ratings], 0.08 (95% CI: -0.07-0.24, I<sup>2</sup> = 0%) [teacher ratings] and 0.11 (95% CI: -0.13-0.34, I<sup>2</sup> = 12%) [observer ratings]. The FFD ESs were 0.80 (95% CI: 0.41-1.19, I<sup>2</sup> = 61%) [parent ratings] and 0.51 (95% CI: -0.02-1.04, I<sup>2</sup> = 72%) [other ratings], while the PUFA ESs were 0.17 (95% CI: -0.03-0.38, I<sup>2</sup> = 38%) [parent ratings], -0.05 (95% CI: -0.27-0.18, I<sup>2</sup> = 0%) [teacher ratings] and 0.16 (95% CI: 0.01-0.31, I<sup>2</sup> = 0%) [parent and teacher ratings]. Three meta-analyses (two FFD and one AFC) resulted in high I<sup>2</sup> without presenting subgroup results. The FFD meta-analyses provided sufficient data to perform subgroup analyses on intervention type, resulting in a decrease of heterogeneity to 0% (diet design) and 37.8% (challenge design). Conclusion: Considering the small average ESs PUFA supplementation is unlikely to provide a tangible contribution to ADHD treatment, while further research is required for AFC elimination before advising this intervention as ADHD treatment. The average FFD ES is substantial, offering treatment opportunities in subgroups of children with ADHD not responding to or too young for medication. Further FFD research should focus on establishing the underlying mechanisms of food (e.g. incrimination of gut microbiota) to simplify the FFD approach in children with ADHD.</p
... The relationship between certain foods and ADHD was also not related to IgE, which is normally involved in food allergies. Involvement of IgG was not found either [75]. ADHD might thus be a (non) allergic hypersensitivity disorder caused by an environmental trigger, based on a non-IgE dependent histamine release from mast cells and basophilic granulocytes, since the histamine H3 receptor is involved in hyperactivity and promotes dopamine release in the frontal cortex. ...
... Beneficial effects were found in children with ADHD when they were restricted from certain foods and food colorings. Atopic subjects responded more often, which points towards allergic hypersensitivity [75,121]. Moreover, maternal reports suggested an increased risk in individuals with food allergy to have symptoms of depression, anxiety or ADHD. ...
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Increasing understanding arises regarding disadvantages of stimulant medication in children with ADHD (Attention-Deficit Hyperactivity Disorder). This review presents scientific findings supporting dietary antioxidant treatment of ADHD and describes substantial alterations in the immune system, epigenetic regulation of gene expression, and oxidative stress regulation in ADHD. As a result, chronic inflammation and oxidative stress could develop, which can lead to ADHD symptoms, for example by chronic T-cell-mediated neuroinflammation, as well as by neuronal oxidative damage and loss of normal cerebral functions. Therefore, modulation of immune system activity and oxidant-antioxidant balance using nutritional approaches might have potential in ADHD treatment. The use of natural antioxidants against oxidative conditions is an emerging field in the management of neurodegenerative diseases. Dietary polyphenols, for example, have antioxidant capacities as well as immunoregulatory effects and, therefore, appear appropriate in ADHD therapy. This review can stimulate the development and investigation of dietary antioxidant treatment in ADHD, which is highly desired.
... Based on current studies, diets that reduce the symptoms associated with ADHD include restricting or eliminating the detrimental dietary factors that are associated with the risk of ADHD and supplementing the beneficial dietary factors that protect against ADHD [10][11][12][13][14][15][16]. For the detrimental dietary factors, the proposed dietary treatments include restricting sugar and ensuring additive/preservative-free foods (Feingold Diet) and an oligoantigenic diet (elimination) [11][12][13]. ...
... Based on current studies, diets that reduce the symptoms associated with ADHD include restricting or eliminating the detrimental dietary factors that are associated with the risk of ADHD and supplementing the beneficial dietary factors that protect against ADHD [10][11][12][13][14][15][16]. For the detrimental dietary factors, the proposed dietary treatments include restricting sugar and ensuring additive/preservative-free foods (Feingold Diet) and an oligoantigenic diet (elimination) [11][12][13]. ...
Article
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Dietary or nutrient patterns represent the combined effects of foods or nutrients, and elucidate efficaciously the impact of diet on diseases. Because the pharmacotherapy on attention deficit hyperactivity disorder (ADHD) was reported be associated with certain side effects, and the etiology of ADHD is multifactorial, this study investigated the association of dietary and nutrient patterns with the risk of ADHD. We conducted a case-control study with 592 Chinese children including ADHD (n = 296) and non-ADHD (n = 296) aged 6–14 years old, matched by age and sex. Dietary and nutrient patterns were identified using factor analysis and a food frequency questionnaire. Blood essential elements levels were measured using atomic absorption spectrometry. A fish-white meat dietary pattern rich in shellfish, deep water fish, white meat, freshwater fish, organ meat and fungi and algae was inversely associated with ADHD (p = 0.006). Further analysis found that a mineral-protein nutrient pattern rich in zinc, protein, phosphorus, selenium, calcium and riboflavin was inversely associated with ADHD (p = 0.014). Additionally, the blood zinc was also negatively related to ADHD (p = 0.003). In conclusion, the fish-white meat dietary pattern and mineral-protein nutrient pattern may have beneficial effects on ADHD in Chinese children, and blood zinc may be helpful in distinguishing ADHD in Chinese children.
... ADHD is a developmental disorder that affects approximately 7.2% of children 31 , where pharmacological treatments can reduce symptoms, but are often unsatisfactory due to side effects, failure to prevent or alter long-term course and discontinuance due to patient and family preferences 32 . Growing evidence is suggesting that nutrition plays an important role in ADHD behaviour 33,34 , with long-term studies showing that early malnutrition is an important risk factor 35 . ...
... Alpha and Beta diversity were calculated using the q2-diversity plugin and included Faith's Phylogenetic Diversity, and weighted and unweighted Unifrac distances. The feature table was rarefied to a sampling depth of 273,465, which retained 50.18% (9,297,810) of sequences and all samples (34). This sampling depth was selected as it was approaching the maximum depth which retained all samples for our analysis. ...
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It has been widely hypothesized that both diet and the microbiome play a role in the regulation of attention-deficit/hyperactivity disorder (ADHD) behaviour. However, there has been very limited scientific investigation into the potential biological connection. We performed a 10-week pilot study investigating the effects of a broad spectrum micronutrient administration on faecal microbiome content, using 16S rRNA gene sequencing. The study consisted of 17 children (seven in the placebo and ten in the treatment group) between the ages of seven and 12 years, who were diagnosed with ADHD. We found that micronutrient treatment did not drive large-scale changes in composition or structure of the microbiome. However, observed OTUs significantly increased in the treatment group, and showed no mean change in the placebo group. The differential abundance and relative frequency of Actinobacteria significantly decreased post- micronutrient treatment, and this was largely attributed to species from the genus Bifidobacterium. This was compensated by an increase in the relative frequency of species from the genus Collinsella. Further research is required to establish the role that Bifidobacterium contribute towards neuropsychiatric disorders; however, these findings suggest that micronutrient administration could be used as a safe, therapeutic method to modulate Bifidobacterium abundance, which could have potential implications for modulating and regulating ADHD behaviour. Our pilot study provides an initial observation into this area of research, and highlights an interesting avenue for further investigation in a larger cohort. Furthermore, these novel results provide a basis for future research on the biological connection between ADHD, diet and the microbiome.
... Elimination diets considered for ADHD (de Theije et al., 2014) are linked with removal of cow's milk, wheat, chocolate, cheese, nuts and citrus fruits. An improvement in behavioral symptoms in 64% of children with ADHD was seen on the elimination diet (Pelsser et al., 2011). Drug therapy for IBS has shown limited efficacy, which meant that other avenues had to be explored. ...
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Many childhood diseases such as autism spectrum disorders, allergic disease, and obesity are on the increase. Although environmental factors are thought to play a role in this increase. The mechanisms at play are unclear but increasing evidence points to an interaction with the gastrointestinal microbiota as being potentially important. Recently this community of bacteria and perturbation of its colonization in early life has been linked to a number of diseases. Many factors are capable of influencing this colonization and ultimately leading to an altered gut microbiota which is known to affect key systems within the body. The impact of the microbial composition of our gastrointestinal tract on systems outside the gut is also becoming apparent. Here we highlight the factors that are capable of impacting on microbiota colonization in early-life and the developing systems that are affected and finally how this may be involved in the manifestation of childhood diseases. Birth Defects Research (Part C), 2015. © 2015 Wiley Periodicals, Inc.
... До настоящего времени остается много нерешенных вопросов о дозозависимой роли «защитных» и «патогенных» ИК в развитии клинически отсроченных реакций воспаления и инициации патогенеза известных иммунокомплексных заболеваний, на первый взгляд, не связанных с процессом неэффективного пищеварения (витилиго, тиреоидит, артрит, сахарный диабет, ожирение, энцефалопатия, мигрень и т.д.). Тем не менее, исследования последних лет (в том числе double-blindstudies) актуализируют корреляционную связь диагностируемых на основе теста ELISA IgG продуктов -антагонистов с особенностями патогенеза иммуноопосредованных хронических заболеваний [5][6][7][8][9][10][11][12][13][14][15][16][17]. В пользу существования подобной связи свидетельствуют многочисленные факты наблюдения положительной клинической картины, вплоть до полного исчезновения симптомов различных неинфекционных хронических заболеваний, в результате использования персонифицированной «элиминационной диеты» как нефармакологического инструмента. ...
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A new methodological approach to analysis and interpretation of data from a multifaceted analysis ELISA IgG has been provided. The possibility for identification of a “norma-pathology” criterion, on the basis of research yielding a frequency spectrum (or probability density function-PDF) of IgG-immune responses in the integral IgG-immune reply is shown. The possibility for unified diagnostic of hypersensi-tivity type III in patients with varying levels of food disadaptation and symptoms of pathological reac-tions to food antigens is shown too.NEW METHODOLOGICAL APPROACH TO THE CREATION OF A PERSONALIZED ELIMINATION DIET IN FOOD INTOLERANCE CAUSED BY TYPE III IMMUNOPATHOLOGICAL REACTIONS Rosensteyn M.Yu.1, Rosensteyn A.Z.1, Kondakov S.E.2, Cherevko N.A.3 1 ImmunoHealthInt., New York, USA 2 M.V. Lomonosov Moscow State University, Moscow, Russian Federation 3 Siberian State Medical University, Tomsk, Russian Federation ABSTRACT A new methodological approach to analysis and interpretation of data from a multifaceted analysis ELISA IgG has been provided. The possibility for identification of a “norma-pathology” criterion, on the basis of research yielding a frequency spectrum (or probability density function-PDF) of IgG-immune responses in the integral IgG-immune reply is shown. The possibility for unified diagnostic of hypersensi- tivity type III in patients with varying levels of food disadaptation and symptoms of pathological reac- tions to food antigens is shown too. KEY WORDS: food intolerance, hypersensitivity type III, ELISA IgG, immunoglobulins G, adverse reactions to food, fooddisadaptation. Bulletin of Siberian Medicine, 2015, vol. 14, no. 4, pp. 60–67 References 1. Voeykov V.L., Rozental V.M. Metody podbora individu- al'nogo pitaniya [Methods of selection of individual nutri- 66 Бюллетень сибирской медицины, 2015, том 14, № 4, с. 60–67
... Few years ago a study showed considerable improvement effects of a restricted elimination diet in a group of children with ADHD [84]. In addition, a recent systematic review and meta-analysis indicated that artificial food color exclusion, and to a lesser extent free fatty acid supplementation, significantly reduce symptom severity in ADHD [85]. ...
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A bidirectional communication between the gut and the brain (gut–brain axis) is well recognized with the gut microbiota viewed as a key regulator of this cross-talk. Currently, a body of preclinical and to a lesser extent epidemiological evidence supports the notion that host–microbe interactions play a key role in brain development and function and in the etiology of neurodevelopmental disorders. Early life events and shifts away from traditional lifestyles are known to impact gut microbiota composition and function and, thereby, may increase the risk of developing neurodevelopmental disorders. Attention deficit hyperactivity disorder (ADHD) is nowadays the most prevalent neurodevelopmental disorder. Despite many years of research its etiology is unclear and its diagnosis and treatment are still challenging. Different factors reported to be associated with the risk of developing ADHD and/or linked to different ADHD manifestations have also been linked to shifts in gut microbiota composition, suggesting a link between the microbiota and the disorder. Evidence from preliminary human studies also suggests that dietary components that modulate gut microbiota may also influence ADHD development or symptoms, although further studies are warranted to confirm this hypothesis. Here, we firstly review the potential mechanisms by which the gut microbiota may regulate the brain–gut axis and influence behavior and neurodevelopmental disorders. Secondly, we discuss the current knowledge about the different factors and dietary components reported to be associated with the risk of developing ADHD or its manifestations and with shifts in gut microbiota composition. Finally, we briefly highlight the need to progress our understanding regarding the role of the gut microbiota in ADHD, since this could open new avenues for early intervention and improved management of the disease.
... Very frequently, however, parents consider using complementary and alternative medicine as a therapeutic option for controlling the core ADHD symptoms. Randomised trials and systematic reviews have evaluated the effects of pharmacological and non-pharmacological interventions in children and adolescents with ADHD [12][13][14][15][16][17][18][19], but most research has been limited to a particular treatment approach only without considering all available treatment alternatives, comparators and outcome measures of clinical importance. ...
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BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is one of the most commonly diagnosed psychiatric disorders in childhood. A wide variety of treatments have been used for the management of ADHD. We aimed to compare the efficacy and safety of pharmacological, psychological and complementary and alternative medicine interventions for the treatment of ADHD in children and adolescents. METHODS AND FINDINGS: We performed a systematic review with network meta-analyses. Randomised controlled trials (≥ 3 weeks follow-up) were identified from published and unpublished sources through searches in PubMed and the Cochrane Library (up to April 7, 2016). Interventions of interest were pharmacological (stimulants, non-stimulants, antidepressants, antipsychotics, and other unlicensed drugs), psychological (behavioural, cognitive training and neurofeedback) and complementary and alternative medicine (dietary therapy, fatty acids, amino acids, minerals, herbal therapy, homeopathy, and physical activity). The primary outcomes were efficacy (treatment response) and acceptability (all-cause discontinuation). Secondary outcomes included discontinuation due to adverse events (tolerability), as well as serious adverse events and specific adverse events. Random-effects Bayesian network meta-analyses were conducted to obtain estimates as odds ratios (ORs) with 95% credibility intervals. We analysed interventions by class and individually. 190 randomised trials (52 different interventions grouped in 32 therapeutic classes) that enrolled 26114 participants with ADHD were included in complex networks. At the class level, behavioural therapy (alone or in combination with stimulants), stimulants, and non-stimulant seemed significantly more efficacious than placebo. Behavioural therapy in combination with stimulants seemed superior to stimulants or non-stimulants. Stimulants seemed superior to behavioural therapy, cognitive training and non-stimulants. Behavioural therapy, stimulants and their combination showed the best profile of acceptability. Stimulants and non-stimulants seemed well tolerated. Among medications, methylphenidate, amphetamine, atomoxetine, guanfacine and clonidine seemed significantly more efficacious than placebo. Methylphenidate and amphetamine seemed more efficacious than atomoxetine and guanfacine. Methylphenidate and clonidine seemed better accepted than placebo and atomoxetine. Most of the efficacious pharmacological treatments were associated with harms (anorexia, weight loss and insomnia), but an increased risk of serious adverse events was not observed. There is lack of evidence for cognitive training, neurofeedback, antidepressants, antipsychotics, dietary therapy, fatty acids, and other complementary and alternative medicine. Overall findings were limited by the clinical and methodological heterogeneity, small sample sizes of trials, short-term follow-up, and the absence of high-quality evidence; consequently, results should be interpreted with caution. CONCLUSIONS: Clinical differences may exist between the pharmacological and non-pharmacological treatment used for the management of ADHD. Uncertainties about therapies and the balance between benefits, costs and potential harms should be considered before starting treatment. There is an urgent need for high-quality randomised trials of the multiple treatments for ADHD in children and adolescents. PROSPERO, number CRD42014015008.
... ADHD is highly heritable [8,9], and genetic studies have pointed to a role of dopamine-, noradrenaline-, and serotonin-related genes in ADHD [8], but these studies showed small effects suggesting that environmental factors also play a role in the etiology of ADHD. Meta-analyses of non-pharmacologic treatment interventions for ADHD showed that restriction diets for ADHD patients (usually directed at eliminating potential allergens) may lead to a significant reduction in ADHD symptoms, although there is heterogeneity across studies [10][11][12]. Conceivably, diet might influence behavior and ADHD symptoms by affecting gut microorganisms (i.e. the gut microbiome) [13]. The gut microbiome has an increasingly recognized impact on brain functioning and behavior [14]. ...
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Background Microorganisms in the human intestine (i.e. the gut microbiome) have an increasingly recognized impact on human health, including brain functioning. Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder associated with abnormalities in dopamine neurotransmission and deficits in reward processing and its underlying neuro-circuitry including the ventral striatum. The microbiome might contribute to ADHD etiology via the gut-brain axis. In this pilot study, we investigated potential differences in the microbiome between ADHD cases and undiagnosed controls, as well as its relation to neural reward processing. Methods We used 16S rRNA marker gene sequencing (16S) to identify bacterial taxa and their predicted gene functions in 19 ADHD and 77 control participants. Using functional magnetic resonance imaging (fMRI), we interrogated the effect of observed microbiome differences in neural reward responses in a subset of 28 participants, independent of diagnosis. Results For the first time, we describe gut microbial makeup of adolescents and adults diagnosed with ADHD. We found that the relative abundance of several bacterial taxa differed between cases and controls, albeit marginally significant. A nominal increase in the Bifidobacterium genus was observed in ADHD cases. In a hypothesis-driven approach, we found that the observed increase was linked to significantly enhanced 16S-based predicted bacterial gene functionality encoding cyclohexadienyl dehydratase in cases relative to controls. This enzyme is involved in the synthesis of phenylalanine, a precursor of dopamine. Increased relative abundance of this functionality was significantly associated with decreased ventral striatal fMRI responses during reward anticipation, independent of ADHD diagnosis and age. Conclusions Our results show increases in gut microbiome predicted function of dopamine precursor synthesis between ADHD cases and controls. This increase in microbiome function relates to decreased neural responses to reward anticipation. Decreased neural reward anticipation constitutes one of the hallmarks of ADHD.
... As has been observed in other studies [2,45], it may be that patients with high symptom scores have a more disordered lifestyle and possibly also a poorer nutritional status. There is now increasing interest in nutrition and possible effects on ADHD and related symptoms, and it has been shown that dietary interventions are able to reduce symptom burden in children with ADHD [46,47]. Signs of low activity in PLP dependent enzymes in ADHD patients suggest that pyridoxine treatment may have an effect [36]. ...
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Background: Prenatal inflammatory mechanisms may play a role in the pathogenesis of psychiatric disorders and could be relevant for attention-deficit/hyperactivity disorder (ADHD). We investigated maternal chronic somatic diseases with immune components as possible risk factors for ADHD in offspring. Methods: We performed a population-based nested case-control study by linking data from longitudinal Norwegian registers. We included all individuals born during the period 1967-2008 and alive at record linkage (2012). Individuals receiving ADHD medication during the years 2004-2012 were defined as patients with ADHD (N = 47,944), and all remaining individuals (N = 2,274,713) were defined as control subjects. The associations between maternal diseases and ADHD in offspring were analyzed using logistic regression models. Results: The following chronic diseases with immune components were related to ADHD in offspring: multiple sclerosis (adjusted odds ratio [OR] = 1.8; 95% confidence interval [CI] = 1.2-2.5), rheumatoid arthritis (adjusted OR = 1.7; 95% CI = 1.5-1.9), type 1 diabetes (adjusted OR = 1.6; 95% CI = 1.3-2.0), asthma (adjusted OR = 1.5; 95% CI = 1.4-1.6), and hypothyroidism (adjusted OR = 1.2; 95% CI = 1.1-1.4). In contrast, chronic hypertension and type 2 diabetes showed no significant associations. Estimates were almost unchanged with additional adjustment for parental ADHD, infant birth weight, and gestational age. Although point estimates for male and female offspring were different for some diseases (e.g., maternal asthma [adjusted OR = 1.7; 95% CI = 1.5-1.8 for female offspring and adjusted OR = 1.5; 95% CI = 1.4-1.6 for male offspring]), none of the associations differed significantly by offspring sex. Conclusions: Several maternal somatic diseases with immune components were found to increase the risk of ADHD in offspring. The associations could involve several causal pathways, including common genetic predisposition and environmental factors, and increased insight into the mechanisms behind these relationships could enhance our understanding of the etiology of ADHD.
... For adolescents, regardless of country of residence, obesity was positively correlated with the taste of fat and sugar-enriched food products [8]. Eliminating ultra-processed products from a diet can improve consumer health with studies reporting decreases in attention deficit hyperactivity disorder (ADHD) symptoms [9], a reduction in insulin resistance in children with Type 2 Diabetes [10], and decreased mineral deficiencies in children with autism [11]. ...
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Food processing is used for transforming whole food ingredients into food commodities or edible products. The level of food processing occurs along a continuum from unprocessed to minimally processed, processed, and ultra-processed. Unprocessed foods use little to no processing and have zero additives. Minimally processed foods use finite processing techniques, including drying, freezing, etc., to make whole food ingredients more edible. Processed foods combine culinary ingredients with whole foods using processing and preservation techniques. Ultra-processed foods are manufactured using limited whole food ingredients and a large number of additives. Ultra-processed snack foods are increasing in food environments globally with detrimental implications for human health. This research characterizes the choices, consumption, and taste preferences of adolescents who were offered apple snack food items that varied along a processing level continuum (unprocessed, minimally processed, processed, and ultra-processed). A cross-sectional study was implemented in four elementary school classrooms utilizing a buffet of apple snack food items from the aforementioned four food processing categories. A survey was administered to measure students’ taste acceptance of the snacks. The study found that the students selected significantly (p < 0.0001) greater quantities of ultra-processed snack foods (M = 2.20 servings, SD = 1.23) compared to minimally processed (M = 0.56 servings, SD = 0.43) and unprocessed (M = 0.70 servings, SD = 0.37) snack foods. The students enjoyed the taste of ultra-processed snack foods (M = 2.72, SD = 0.66) significantly more (p < 0.0001) than minimally processed (M = 1.92, SD = 1.0) and unprocessed (M = 2.32, SD = 0.9) snack foods. A linear relationship was found between the selection and consumption quantities for each snack food item (R2 = 0.88). In conclusion, it was found that as processing levels increase in apple snack foods, they become more appealing and more heavily consumed by elementary school students. If applied broadly to snack foods, this conclusion presents one possible explanation regarding the high level of diet-related diseases and nutrient deficiencies across adolescents in America. Food and nutrition education, food product development, and marketing efforts are called upon to improve adolescent food choices and make less-processed snack food options more appealing and accessible to diverse consumers.
... Another commonly used dietary intervention for children with ADHD is an oligoantigenic (hypoallergenic/elimination) diet. Oligoantigenic diet eliminates most known sensitizing food antigens or allergens, such as cow's milk, cheese, wheat cereals, egg, chocolate, nuts, and citrus fruit, in an effort to identify and manage food allergies and intolerances that may be linked to neurologic dysfunction [57]. More recently known as an "elimination diet", these diets may vary in their specific contents. ...
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Complementary and alternative treatment approaches are becoming more common among children with chronic conditions. The prevalence of CAM use among US adults was estimated to be around 42% in 2015 and around 44% to 50% among adults with neurologic disorders. Studies demonstrate that children with certain chronic illnesses such as asthma, cancer, genetic disorders, attention-deficit/hyperactivity disorder (ADHD), and other neurodevelopmental disorders are treated with complementary and alternative treatments at higher rates. Dietary therapies are gaining increasing popularity in the mainstream population. Although the majority of “fad” diets do not have enough supporting evidence, some dietary therapies have been utilized for decades and have numerous published studies. The objective of this review is to describe the dietary interventions used in children with the specific chronic conditions, to evaluate their efficacy based on published data and to encourage pharmacist involvement in the management and care of such patients.
Article
Introduction: Attention deficit hyperactivity disorder (ADHD) is the most common psychiatric diagnosis in childhood and adolescence, with an estimated worldwide-pooled prevalence of 5,29%. The type of treatment depends on several factors. Psychopharmacological treatment entails undesirable side effects, with unclear long-term benefits, which has led the scientific community to investigate other therapeutic approaches, such as dietary interventions. Methods: The authors conducted a classical review on the current treatment recommended in individuals with ADHD diagnosis, their dietary patterns, as well as dietary factors possibly implicated in the etiology and treatment of this disorder. An extensive bibliographic research was carried out in the databases PubMed, The Cochrane Library and the National Guideline Clearinghouse. Discussion: The most common dietary interventions in the case of ADHD are food supplementation diets (e.g. PUFAs, vitamins) and elimination diets. Supplementation with omega-3 PUFAs lacks further studies that can validate them as an effective therapeutic approach in this disorder. Also, regarding vitamin supplementation, studies are not consistent as to their role in the etiology of ADHD. Elimination diets are unclear as to the benefits provided in individuals with ADHD. Children with ADHD are less likely to engage in healthy lifestyle behaviors than non-ADHD youth. Conclusion: There is no clear evidence that supports dietary interventions for the treatment of ADHD. The effects of unhealthy diet patterns in ADHD individuals are not yet fully understood and, like the general population, children with ADHD may benefit from a healthy lifestyle.
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We conducted genome-wide association studies (GWAS) of relative intake from the macronutrients fat, protein, carbohydrates, and sugar in over 235,000 individuals of European ancestries. We identified 21 unique, approximately independent lead SNPs. Fourteen lead SNPs are uniquely associated with one macronutrient at genome-wide significance (P < 5 × 10⁻⁸), while five of the 21 lead SNPs reach suggestive significance (P < 1 × 10⁻⁵) for at least one other macronutrient. While the phenotypes are genetically correlated, each phenotype carries a partially unique genetic architecture. Relative protein intake exhibits the strongest relationships with poor health, including positive genetic associations with obesity, type 2 diabetes, and heart disease (rg ≈ 0.15–0.5). In contrast, relative carbohydrate and sugar intake have negative genetic correlations with waist circumference, waist-hip ratio, and neighborhood deprivation (|rg| ≈ 0.1–0.3) and positive genetic correlations with physical activity (rg ≈ 0.1 and 0.2). Relative fat intake has no consistent pattern of genetic correlations with poor health but has a negative genetic correlation with educational attainment (rg ≈−0.1). Although our analyses do not allow us to draw causal conclusions, we find no evidence of negative health consequences associated with relative carbohydrate, sugar, or fat intake. However, our results are consistent with the hypothesis that relative protein intake plays a role in the etiology of metabolic dysfunction.
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The gut microbiota is a vast, complex, and fascinating ecosystem of microorganisms that resides in the human gastrointestinal tract. As an integral part of the microbiota–gut–brain axis, it is now being recognized that the microbiota is a modulator of brain and behavior, across species. Intriguingly, periods of change in the microbiota coincide with the development of other body systems and particularly the brain. We hypothesize that these times of parallel development are biologically relevant, corresponding to ‘sensitive periods’ or ‘critical windows’ in the development of the microbiota–gut–brain axis. Specifically, signals from the microbiota during these periods are hypothesized to be crucial for establishing appropriate communication along the axis throughout the life span. In other words, the microbiota is hypothesized to act like an expected input to calibrate the development of the microbiota–gut–brain axis. The absence or disruption of the microbiota during specific developmental windows would therefore be expected to have a disproportionate effect on specific functions or potentially for regulation of the system as a whole. Evidence for microbial modulation of neurocognitive development and neurodevelopmental risk is discussed in light of this hypothesis, finishing with a focus on the challenges that lay ahead for the future study of the microbiota–gut–brain axis during development.
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Objectives: Removing artificial food coloring (AFC) is a common dietary intervention for children with Attention-Deficit/Hyperactivity Disorder (ADHD), but has not been tested in young adults. This pilot study examined the effects of AFC on ADHD symptoms and electroencephalography (EEG) in college students with and without ADHD. Methods: At baseline, control and ADHD participants completed the Adult ADHD Self-Report Scale (ASRS), simple and complex attention measures, and resting-state EEG recordings. ADHD participants (n = 18) and a subset of controls (extended control group or EC, n = 11) avoided AFC in their diet for 2 weeks and then were randomized to a double-blind, placebo-controlled crossover challenge. Subjects received either 225 mg AFC disguised in chocolate cookies or placebo chocolate cookies for 3 days each week, with testing on the third day each week. Baseline comparisons were made using Student’s t-test or Wilcoxon rank sum tests and challenge period analyses were run using General Linear Modeling. Results: The ADHD group had significantly greater scores on the ASRS (p < 0.001), confirming a symptom differential between groups; however, there were no differences in attentional measures or EEG at baseline. The AFC challenge resulted in an increase in posterior mean gamma power (p = 0.05), a decrease in posterior relative alpha power (p = 0.04), and a marginal increase in inattentive symptoms (p = 0.08) in the ADHD group. There were no effects of AFC in the EC group. Discussion: This study indicates that AFC exposure may affect brainwave activity and ADHD symptoms in college students with ADHD. Larger studies are needed to confirm these findings.
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Data on the association between atopic diseases and attention-deficit/hyperactivity disorder (ADHD) have been inconclusive. To assess whether children with drug-treated ADHD are more likely to receive treatment for asthma, allergic rhinitis, or eczema before the start of ADHD medication use compared with controls and to examine the effect of parents receiving medication for ADHD and atopic diseases on ADHD medication use in their offspring. We conducted a retrospective nested case-control study among children (6-12 years of age) using the Groningen University prescription database. Cases were defined as children with at least 2 prescriptions of methylphenidate within 12 months. For each case, 4 controls were matched on age, sex, and regional area code. Parental prescription data were linked to cases and controls to assess the influence of parents receiving medication for ADHD and atopic diseases on ADHD medication use in their offspring. We identified 4257 cases and 17,028 matched controls. Drug treatment for asthma, allergic rhinitis, and eczema was more common in cases than controls (adjusted odds ratios [aORs], 1.4 [95% confidence interval (CI), 1.3-1.6], 1.4 [95% CI, 1.1-1.8], and 1.3 [95% CI, 1.1-1.5], respectively). Medication for allergic rhinitis and asthma among parents was associated with ADHD treatment in their children (aORs, 1.3 [95% CI, 1.1-1.5] and 1.2 [95% CI, 1.1-1.3], respectively). This study provides further evidence to support the hypothesis that atopic diseases are associated with ADHD. The parental-offspring association suggests a possible genetic and/or environmental component.
Chapter
There are a wide range of prevalence rates for attention deficit hyperactivity disorder (ADHD) cited in the world literature, with recent estimates converging on a figure of 5 % during the childhood years. The most recent figures from the British Child and Adolescent Mental Health Survey in the UK estimate a rate of 3.6 % in boys and 0.9 % in girls for any subtype of ADHD.
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Problem: There is a need to collect the many and varied data on AD/HD (Attention deficit hyper-activity disorder) into a meaningful overview. Method: Based on peer reviewed and published data as well as own research we try to make sense of the physiological mechanisms resulting in the relevant symptoms. Conclusion: AD/HD clearly has a genetic disposition, but as with many other genetic syndromes, the resulting proteomics must be stressed to become manifest as disease/ disorder. A common trait in the different etiologies is lower arousal.
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The microbial population residing within the human gut represents one of the most densely populated microbial niche in the human body with growing evidence showing it playing a key role in the regulation of behaviour and brain function. The bidirectional communication between the gut microbiota and the brain, the microbiota-gut-brain axis, occurs through various pathways including the vagus nerve, the immune system, neuroendocrine pathways and bacterial-derived metabolites. This axis has been shown to influence neurotransmission and behaviour that are often associated with neuropsychiatric conditions. Therefore, research targeting the modulation of this gut microbiota as a novel therapy for the treatment of various neuropsychiatric conditions is gaining interest. Numerous factors have been highlighted to influence gut microbiota composition, including genetics, health status, mode of birth and environment. However, it is diet composition and nutritional status that has repeatedly been shown to be one of the most critical modifiable factors regulating the gut microbiota at different time points across the lifespan and under various health conditions. Thus the microbiota is poised to play a key role in nutritional interventions for maintaining brain health.
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Food is essential for life. Yet, poor food choices may cause poor health. Dietary manipulation is frequently integrated into the management of common chronic pediatric conditions. Parents seek dietary information to have more control over child's condition and to avoid side effects of medicine. This article reviews selected diets for a few common pediatric disorders including eczema, attention deficit hyperactivity disorder, headache and migraine, non-celiac gluten sensitivity, and irritable bowel syndrome.
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All Indigenous communities have a time-tested child-rearing knowledge base that reflects and honors their cultural beliefs and historical experiences. Many of these communities emphasize group harmony and collaboration and respect for the natural environment—competencies that are increasingly important on our crowded and depleted planet. Unfortunately, Indigenous peoples are often marginalized within their own countries, and experience disproportionately high rates of poverty. Poverty and the associated lack of access to nutritious food, quality health care services, and education can prevent children from reaching their full potential. The authors of this article consider how to integrate Indigenous knowledge, spirituality, and priorities with research-based best practices for education and development. They describe a program that uses culturally relevant materials, storytelling, and music to encourage parent-child bonding and positive familial and community interactions, all designed to contribute to optimal child development in disadvantaged Aboriginal communities in Australia.
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Background: Food may trigger Attention-Deficit/Hyperactivity Disorder (ADHD) symptoms. Therefore, an elimination diet (ED) might be an effective treatment for children with ADHD. However, earlier studies were criticized for the nature of the control group, potential confounders explaining the observed effects, unsatisfactory blinding, potential risks of nutritional deficiencies and unknown long term and cost-effectiveness. To address these issues, this paper describes the rationale, study design and methods of an ongoing two arm randomized controlled trial (RCT) comparing the short (5 week) and long term (1 year) effects of an elimination diet and a healthy diet compared with care as usual (CAU) in children with ADHD. Methods: A total of N = 162 children (5-12 years) with ADHD will be randomized to either an ED or a healthy diet. A comparator arm including N = 60 children being solely treated with CAU (e.g. medication) is used to compare the effects found in both dietary groups. The two armed RCT is performed in two youth psychiatry centers in the Netherlands, with randomization within each participating center. The primary outcome measure is response to treatment defined as a ≥ 30% reduction on an ADHD DSM-5 rating scale (SWAN) and/or on an emotion dysregulation rating scale (SDQ: dysregulation profile). This is assessed after 5 weeks of dietary treatment, after which participants continue the diet or not. Secondary outcome measures include the Disruptive Behavior Diagnostic Observational Schedule (DB-DOS), parent and teacher ratings of comorbid symptoms, cognitive assessment (e.g. executive functions), school functioning, physical measurements (e.g. weight), motor activity, sleep pattern, food consumption, nutritional quality of the diet, adherence, parental wellbeing, use of health care resources and cost-effectiveness. Assessments take place at the start of the study (T0), after five weeks (T1), four months (T2), eight months (T3) and 12 months of treatment (T4). T0, T1 and T4 assessments take place at one of the psychiatric centers. T2 and T3 assessments consist of filling out online questionnaires by the parents only. Discussion: This RCT will likely contribute significantly to clinical practice for ADHD by offering insight into the feasibility, nutritional quality, (cost-)effectiveness and long term effects of dietary treatments for ADHD. Trial registration: www.trialregister.nl, NTR5434. Registered at October 11th, 2015.
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Preschool-age children with attention-deficit hyperactivity disorder (ADHD) have high rates of aggressive and disruptive behaviours. Although symptom improvement may be achieved with nonpharmacological management, there is often a need for pharmacological intervention, which is controversial, especially in very young children. Improvements in ADHD symptoms have been reported in preschoolers receiving methylphenidate or atomoxetine, but further studies are required.
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Attention-deficit hyperactivity disorder (ADHD) is one of the most common neuropsychiatric conditions of childhood and adolescence, and is also one of the best researched neurobiological conditions in medicine. The core symptoms of ADHD are manifest throughout the life cycle, from preschool through adult life; they interfere with a child's family and peer interactions, academic attainment, emotional development, self-esteem, and overall quality of life. The chapter begins with a resume of the medical history of ADHD, followed by a description of the core clinical criteria, which include poor sustained attention; difficulties in inhibiting impulses in social behavior and cognitive tasks; difficulties getting along with others; school underachievement; poor self-esteem; and other behavior disorders, learning disabilities, anxiety disorders, and depression. The epidemiology and etiology are then considered, before looking at the challenges of differential diagnosis and comorbidity. The basic elements of diagnosis and assessment are presented, and the main treatment options described; these include psychoeducation and pharmacotherapy. Psychostimulants are the first-line therapy, and their benefits and risks are detailed; other options considered include atomoxetine and adrenergic agents.
Chapter
ADHD is the most common psychiatric disorder of childhood. Overall, prevalence ranges from 5 to 12 % in school-aged children. Male to female ratio is around 3:1 in children and adolescents, but it is believed that females are under-diagnosed. Approximately 8–10 % of males, and 3–4 % of females, under the age of 18 have ADHD. Roughly 80 % of children with ADHD will continue to meet diagnostic criteria for ADHD into their adolescent years and 60 % will maintain core symptoms into adulthood (Wittchen et al. 2011; Dopheide and Pliszka 2009; Weyandt and Dupaul 2008).
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Over the last decades, the hypothesis has been raised that an atopic response could lead to the development of attention-deficit/hyperactivity disorder (ADHD). This study systematically reviews the observational cross-sectional and longitudinal studies that assessed the association between atopic disorders including asthma, atopic eczema, allergic rhinitis, and ADHD in children and adolescents. For longitudinal studies, a weighted Mantel-Haenszel odds ratio of these associations was estimated. The majority of cross-sectional and longitudinal studies reported a statistically significant positive association. The meta-analysis of longitudinal studies revealed an overall weighted odds ratio for asthma of 1.34 (95% confidence interval [CI] 1.24-1.44), 1.32 (95% CI 1.20-1.45) for atopic eczema, and 1.52 (95% CI 1.43-1.63) for allergic rhinitis. Heterogeneity of study data was low (I(2): 0%, p=.46 and p=.64, respectively) for both studies examining asthma and eczema but substantial for rhinitis studies (I(2): 82%, p=.004). This current systematic review provides strong evidence that ADHD is associated with atopic diseases and that individuals have a 30% to 50% greater chance of developing ADHD compared to controls.
Article
The importance of the gut-brain axis in maintaining homeostasis has long been appreciated. However, the past 15 yr have seen the emergence of the microbiota (the trillions of microorganisms within and on our bodies) as one of the key regulators of gut-brain function and has led to the appreciation of the importance of a distinct microbiota-gut-brain axis. This axis is gaining ever more traction in fields investigating the biological and physiological basis of psychiatric, neurodevelopmental, age-related, and neurodegenerative disorders. The microbiota and the brain communicate with each other via various routes including the immune system, tryptophan metabolism, the vagus nerve and the enteric nervous system, involving microbial metabolites such as short-chain fatty acids, branched chain amino acids, and peptidoglycans. Many factors can influence microbiota composition in early life, including infection, mode of birth delivery, use of antibiotic medications, the nature of nutritional provision, environmental stressors, and host genetics. At the other extreme of life, microbial diversity diminishes with aging. Stress, in particular, can significantly impact the microbiota-gut-brain axis at all stages of life. Much recent work has implicated the gut microbiota in many conditions including autism, anxiety, obesity, schizophrenia, Parkinson’s disease, and Alzheimer’s disease. Animal models have been paramount in linking the regulation of fundamental neural processes, such as neurogenesis and myelination, to microbiome activation of microglia. Moreover, translational human studies are ongoing and will greatly enhance the field. Future studies will focus on understanding the mechanisms underlying the microbiota-gut-brain axis and attempt to elucidate microbial-based intervention and therapeutic strategies for neuropsychiatric disorders.
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Children with attention-deficit/hyperactivity disorder (ADHD) show significant abnormalities on MR imaging in network communication and connectivity. The prefrontal-striatal-cerebella circuitry, involved in attention is particularly disrupted. Neurometabolites, the biochemical structures that support neurological structural integrity, particularly in the prefrontal cortex and striatum are associated with symptoms. This study aimed to explore changes in neurometabolite levels through treatment with vitamins and minerals (micronutrients), hypothesising that treatment would impact neural circuitry and correspond to a reduction in symptoms. Twenty-seven non-medicated children (M = 10.75 years) with DSM5 diagnosed ADHD were randomised to receive daily micronutrients or placebo for 10 weeks. Main outcome measures included the Clinical Global Impression-Improvement Scale and ADHD-RS-IV Clinician Ratings of ADHD symptoms. Magnetic resonance spectroscopy of the bilateral pre-frontal cortex and bilateral striatum, resting state fMRI and structural images were acquired 1 week pre-treatment, and in the last week of intervention. Results did not show any significant differences in the measured brain metrics and the levels of neurometabolites between treatment and placebo groups after ten weeks of treatment with micronutrients. In the treatment group there was a trend for: decreased choline in the striatum; decreased glutamate in the prefrontal cortex; increased grey matter in the anterior thalamus; increased white matter in the fornix and improved network integrity of the default mode network, dorsal attention network and frontal executive network. The small sample size of the current study limits results, future studies with higher power are warranted to explore any association between micronutrient treatment and neurological changes.
Article
Diets consisting of refined foods (REF) are associated with poor physical (e.g., obesity and diabetes) and mental (e.g., depression) health and impaired cognition. Few animal studies have explored the causal links between diet processing and health. Instead, most studies focus on the role of macronutrients, especially carbohydrate and fat concurrently with how processed are the ingredients. We previously showed that a REF low fat diet (LFD) caused greater adiposity and impaired motivation compared to an unrefined control (CON) diet consisting of similar macronutrient ratios (Blaisdell et al., 2014). Here we test the hypothesis that the same REF LFD adversely affects attentional processes and behavioral control relative to the CON diet.
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Background: Methylphenidate (MPH), the first choice medication for attention-deficit hyperactivity disorder (ADHD), is associated with serious adverse effects like arrhythmia. Evidence on the association of ADHD with immune and oxidant-antioxidant imbalances offers potential for antioxidant and/or immunomodulatory nutritional supplements as ADHD therapy. One small randomised trial in ADHD suggests, despite various limitations, therapeutic benefit from Pycnogenol®, a herbal, polyphenol-rich extract. Methods: This phase III trial is a 10-week, randomised, double-blind, placebo and active treatment controlled multicentre trial with three parallel treatment arms to compare the effect of Pycnogenol® to MPH and placebo on the behaviour of 144 paediatric ADHD and attention-deficit disorder (ADD) patients. Evaluations of behaviour (measured by the ADHD-Rating Scale (primary endpoint) and the Social-emotional Questionnaire (SEQ)), immunity (plasma cytokine and antibody levels, white blood cell counts and faecal microbial composition), oxidative stress (erythrocyte glutathione, plasma lipid-soluble vitamins and malondialdehyde and urinary 8-OHdG levels, as well as antioxidant enzyme activity and gene expression), serum zinc and neuropeptide Y level, urinary catecholamines and physical complaints (Physical Complaints Questionnaire) will be performed in week 10 and compared to baseline. Acceptability evaluations will be based on adherence, dropouts and reports of adverse events. Dietary habits will be taken into account. Discussion: This trial takes into account comorbid behavioural and physical symptoms, as well as a broad range of innovative immune and oxidative biomarkers, expected to provide fundamental knowledge on ADHD aetiology and therapy. Research on microbiota in ADHD is novel. Moreover, the active control arm is rather unseen in research on nutritional supplements, but of great importance, as patients and parents are often concerned with the side effects of MPH. Trial registration: Clinicaltrials.gov number: NCT02700685 . Registered on 18 January 2016. EudraCT 2016-000215-32 . Registered on 4 October 2016.
Article
Attention deficit hyperactivity disorder is a neurodevelopmental disorder marked by age-inappropriate deficits in attention or hyperactivity/impulsivity that interfere with functioning or development. It is highly correlated with other disorders, such as oppositional defiant disorder, conduct disorder, and mood symptoms. The etiology is multifactorial, and neuroimaging findings are nonspecific. Although assessment tools exist, there is variability among them, and historically, parent-teacher agreement has not been consistent. Treatment algorithm for attention deficit hyperactivity disorder in preschoolers includes behavioral interventions first followed by psychopharmacologic treatment when behavioral therapies fail. Other nonpharmacologic and nonbehavioral interventions are discussed including the role of exercise and nutrition.
Article
Background: For over forty years diet interventions have been investigated as a treatment of ADHD in children and adolescents and, with the new discoveries of the microbiota-gut-brain axis, this research becomes more relevant than ever. The aim of this systematic review was therefore to investigate the current knowledge of diet interventions as a treatment of ADHD in children and adolescents Methods: A systematic literature search in PubMed was conducted, identifying randomized controlled trials investigating diet interventions to treat ADHD in children and adolescents. Results: The study populations were generally small and the studies varied in duration and nature of the exposure. Overall 10 out of 12 studies spoke in favour of an elimination diet, 2 out of 6 of eliminating artificial food colourings from the diet and none in favour of eliminating sucrose or aspartame from the diet to treat ADHD. Conclusion: The current evidence is not enough to recommend treating ADHD with diet interventions, but a subgroup of children and adolescents might warrant from elimination of certain food-items. Further investigations of the mechanism and effect of diet interventions to treat ADHD is needed.
Article
The objective of this study is to compare oxidative stress and immune biomarkers between attention-deficit/hyperactivity disorder (ADHD) patients and controls without ADHD. A case–control comparison between 57 paediatric (6–12 years) untreated ADHD patients from the Antwerp University Hospital and 69 controls without ADHD from random schools in Flanders, Belgium, was conducted. Erythrocyte glutathione (GSH) and plasma lipid-soluble antioxidants (retinol, α-tocopherol, γ-tocopherol, retinyl palmitate, β-carotene, and co-enzyme Q10) were determined by HPLC with electrochemical detection, plasma malondialdehyde (MDA) by HPLC with fluorescence detection, plasma cytokines (interleukin (IL)-1β, IL-5, IL-6, IL-8, IL-10, tumour necrosis factor (TNF) and interferon (INF)-γ) and immunoglobulins (IgE, IgG and IgM) by flow cytometry and urinary 8-hydroxy-2′deoxyguanosine (8-OHdG) levels by ELISA assay. Dietary habits were determined by a food frequency questionnaire. Plasma MDA levels were on average 0.031 µM higher in patients than in controls (p < 0.05), and a trend for higher urinary 8-OHdG was observed. Erythrocyte GSH and plasma retinyl palmitate levels, as well as IgG and IgE levels, were higher in patients than in controls as well (on average 93.707 µg/ml, 0.006 µg/ml, 301.555 µg/ml and 125.004 µg/ml, resp., p < 0.05). Finally, a trend for lower plasma IL-5 levels was observed. After Bonferroni correction for multiple testing, the difference in GSH levels remained statistically significant (nominally significant for retinyl palmitate), while significance was lost for MDA, IgG and IgE levels. Dietary habits do not appear to cause the observed differences. These results point at the potential involvement of slight oxidative stress and immune disturbances in ADHD.
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Natural and artificial food colorants(AFC) are used for various purposes in foods as a food additive for many years. Their use are regulated by the legislations in the world. There are organizations authorized in this regard. In our country, food additives show no harmful effects on health when used according to the “Turkish Food Codex-Food Additives Regulation” AFC intake (per capita/day) has increased in parallel to the increase in the consumption of processed foods. AFCs are discussed for a long time to whether they cause to hyperactivity symptoms or attention-deficit/hyperactivity disorder(ADHD) in children in addition to the positive use of AFCs in foods as well. AFCs that their effects mostly researched are tartrazine, sunset yellow, quinoline yellow, ponso 4R, carmoisine, erythrosine and allura red AC. The results of the studies are inconsistent. AFCs are not the main reason of ADHD. It has been observed that these AFCs don’t cause hyperactivity directly; but promote existing symptoms in sensitive groups like children. There’s no consensus in such regard in the world. Further studies are needed to be made.
Article
Objective: Associations between nutritional/dietary factors and mental disorders have been suggested. This study was conducted to assess the relation of major dietary patterns determined by factor analysis with attention-deficit/hyperactivity disorder (ADHD) in a group of Iranian preschool- and school-aged children. Methods: This case-control study was conducted with 500 preschool- and school-aged children (4–12 years old) matched by age and sex, in Isfahan, Iran. Dietary intake was identified by a 168-item questionnaire, and major dietary patterns were identified by factor analysis. The multivariable logistic regression is used for the association of dietary patterns with the diagnosis of ADHD. ADHD diagnosis was carried out with the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Results: Two major dietary patterns were identified: healthy and Western. The healthy dietary pattern was rich in fruits, vegetables, vegetable oils, whole grains, legumes, and dairy products. The Western pattern was rich in processed meat, red meat, pizza, eggs, snacks, animal fat, hydrogenated fat, and salt. After controlling for potential confounders, children in the top quintile of the Western dietary pattern score had greater odds having ADHD, compared with those in the lowest quintile (odds ratio [OR] = 3.45; 95% confidence interval [CI], 1.17–18.3; ptrend = 0.03). The healthy pattern was inversely associated with ADHD (OR = 0.46; 95% CI, 0.38–0.91; ptrend = 0.01). Conclusions: A significant independent association was found between the Western dietary pattern and the odds of ADHD. The healthy dietary pattern was associated with lower odds of having ADHD. Prospective studies are needed to confirm these findings.
Article
Background: Evaluation of broad-spectrum micronutrient (vitamins and minerals) treatment for childhood ADHD has been limited to open-label studies that highlight beneficial effects across many aspects of psychological functioning. Method: This is the first fully blinded randomized controlled trial of medication-free children (n = 93) with ADHD (7-12 years) assigned to either micronutrients (n = 47) or placebo (n = 46) in a 1:1 ratio, for 10 weeks. All children received standardized ADHD assessments. Data were collected from clinicians, parents, participants and teachers across a range of measures assessing ADHD symptoms, general functioning and impairment, mood, aggression and emotional regulation. Results: Intent-to-treat analyses showed significant between-group differences favouring micronutrient treatment on the Clinical Global Impression-Improvement (ES = 0.46), with 47% of those on micronutrients identified as 'much' to 'very much' improved versus 28% on placebo. No group differences were identified on clinician, parent and teacher ratings of overall ADHD symptoms (ES ranged 0.03-0.17). However, according to clinicians, 32% of those on micronutrients versus 9% of those on placebo showed a clinically meaningful improvement on inattentive (OR = 4.9; 95% CI: 1.5-16.3), but no group differences on improvement in hyperactive-impulsive symptoms (OR = 1.0; 95% CI: 0.4-2.5). Based on clinician, parent and teacher report, those on micronutrients showed greater improvements in emotional regulation, aggression and general functioning compared to placebo (ES ranged 0.35-0.66). There were two dropouts per group, no group differences in adverse events and no serious adverse events identified. Blinding was successful with guessing no better than chance. Conclusions: Micronutrients improved overall function, reduced impairment and improved inattention, emotional regulation and aggression, but not hyperactive/impulsive symptoms, in this sample of children with ADHD. Although direct benefit for core ADHD symptoms was modest, with mixed findings across raters, the low rate of adverse effects and the benefits reported across multiple areas of functioning indicate micronutrients may be a favourable option for some children, particularly those with both ADHD and emotional dysregulation. Trial registered with the Australian New Zealand Clinical Trials Registry ACTRN12613000896774.
Article
This study aimed to compare sugar intake in Australian children with current guidelines and determine if total sugar consumption as a percentage of energy (sugar %E) exacerbates the relationship between sleep and behaviour. A sample of 287 children aged 8–12 years (boys 48.8%, age: 10.7 ± 1.3 years), and their parents/guardians completed a battery of questionnaires. Children completed a food frequency questionnaire, and parents completed demographic, sleep, and behaviour questionnaires. Average sugar intake was 134.9 ± 71.7 g per day (sugar %E 26.0 ± 7.0%), and only 55 (19%) participants did not exceed the recommended sugar intake limit. Correlations and logistical regressions indicated that sugar %E was not associated with sleep or behavioural domains (r range = –0.07–0.08; p range = .173–.979) nor contributed to the prediction of sleep behaviour problems (p range = .16–.80). Whilst a high proportion of children consumed above the recommended amount of daily total sugar, total sugar consumption was not related to behavioural or sleep problems, nor affected the relationship between these variables.
Chapter
The prevalence of mental disorders between children and adolescents is 10–20% worldwide. Research has shown that most mental disorders begin at childhood and adolescence. Neurodevelopmental disorders are classified by which the development of the central nervous system is disturbed and are associated with varying degrees of consequences in one’s mental, emotional, physical, and economic states. Recently, research in mental health, neurobiology, and early childhood development supported the case for early intervention and prevention. The causes of mental disorders in children and adolescents are not currently known, but research suggests that a combination of factors that include heredity, biology, psychological trauma, spiritual well-being, and environmental stress might be involved. There are many factors that play into child and adolescent mental health and disorders; therefore, individualized, personalized, and integrative approaches are necessary in therapeutic interventions and prevention. Thus, by ensuring that the needed mental health care competencies are made available in each primary health care team and by assuring fully integrated mental health and other types of health care, primary health care teams would best provide early, efficient, effective, and optimal recovery-based care.
Comparing the strengths and diffi culties questionnaire and the child behavior checklist: is small beautiful? Prediction of clinical response to methylphenidate in children with attention-defi cit hyperactivity disorder
  • R Goodman
  • Scott
  • Jk
  • Van
  • Gaag Rj
  • H Swaab-Barneveld
  • Kuiper
Goodman R, Scott S. Comparing the strengths and diffi culties questionnaire and the child behavior checklist: is small beautiful? J Abnorm Child Psychol 1999; 27: 17. 23 Buitelaar JK, Van der Gaag RJ, Swaab-Barneveld H, Kuiper M. Prediction of clinical response to methylphenidate in children with attention-defi cit hyperactivity disorder. J Am Acad Child Adolesc Psychiatry 1995; 34: 1025–32.
Immune function, food allergies and food intolerance Human Nutrition 17 Food Allergy Testing with Nutritionally Yours Health Solutions. Metametrix: Allergix IgG " delayed " food allergy response
  • S Strobel
  • A Ferguson
16 Strobel S, Ferguson A. Immune function, food allergies and food intolerance. In: Geissler CA, Powers HJ, eds. Human Nutrition. London, UK: Elsevier, 2005: 493. 17 Food Allergy Testing with Nutritionally Yours Health Solutions. Metametrix: Allergix IgG " delayed " food allergy response. http:// www.foodallergytest.org/IgG4.html (accessed July 22, 2010).
Allergies and Nutrition Handbook of Nutrition and Immunity
  • C Chang
Chang C. Allergies and Nutrition. In: Gershwin ME, Nestel P, Keen CL, eds. Handbook of Nutrition and Immunity. Totowa, NJ, USA: Humana Press, 2004: 153.
Treatment alternatives for ADHD
  • Le Arnold
Arnold LE. Treatment alternatives for ADHD. J Attent Dis 1999; 3: 30–48.
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Background: Previous studies have demonstrated the short-term efficacy of pharmacotherapy and behavior therapy for attention-deficit/hyperactivity disorder (ADHD), but no longer-term tie, >4 months) investigations have compared these 2 treatments or their combination. Methods: A group of 579 children with ADHD Combined Type, aged 7 to 9.9 years, were assigned to 13 months of medication management (titration followed by monthly visits); intensive behavioral treatment (parent, school, and child components, with therapist involvement gradually reduced over time); the two combined; or standard community care (treatments by community providers). Outcomes were assessed in multiple domains before and during treatment and at treatment end point (with the combined treatment and medication management groups continuing medication at all assessment points). Data were analyzed through intent to-treat random-effects regression procedures. Results: All 4 groups showed sizable reductions in symptoms over time, with significant differences among them in degrees of change. For most ADHD symptoms, children in the combined treatment and medication management groups showed significantly greater improvement than those given intensive behavioral treatment and community care. Combined and medication management treatments did not differ significantly on any direct comparisons, but in several instances (oppositional/aggressive symptoms, internalizing symptoms, teacher-rated social skills, parent-child relations, and reading achievement) combined treatment proved superior to intensive behavioral treatment and/or community care while medication management did not. Study medication strategies were superior to community care treatments, despite the fact that two thirds of community-treated subjects received medication during the study period. Conclusions: For ADHD symptoms, our carefully crafted medication management was superior to behavioral treatment and to routine community care that included medication. Our combined treatment did not yield significantly greater benefits than medication management for core ADHD symptoms, but may have provided modest advantages for non-ADHD symptom and positive functioning outcomes.
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The Strengths and Difficulties Questionnaire (SDQ) is a brief behavioral screening questionnaire that can be completed in 5 minutes by the parents or teachers of children aged 4 to 16; there is a self-report version for 11- to 16-year-olds. In this study, mothers completed the SDQ and the Child Behavior Checklist (CBCL) on 132 children aged 4 through 7 and drawn from psychiatric and dental clinics. Scores from the SDQ and CBCL were highly correlated and equally able to discriminate psychiatric from dental cases. As judged against a semistructured interview, the SDQ was significantly better than the CBCL at detecting inattention and hyperactivity, and at least as good at detecting internalizing and externalizing problems. Mothers of low-risk children were twice as likely to prefer the SDQ.
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Food additives can exacerbate ADHD symptoms and cause non-immunoglobulin E-dependent histamine release from circulating basophils. However, children vary in the extent to which their ADHD symptoms are exacerbated by the ingestion of food additives. The authors hypothesized that genetic polymorphisms affecting histamine degradation would explain the diversity of responses to additives. In a double-blind, placebo-controlled crossover trial, challenges involving two food color additive and sodium benzoate (preservative) mixtures in a fruit drink were administered to a general community sample of 3-year-old children (N = 153) and 8/9-year-old children (N = 144). An aggregate ADHD symptom measure (based on teacher and parent blind ratings of behavior, blind direct observation of behavior in the classroom, and--for 8/9-year-old children only--a computerized measure of attention) was the main outcome variable. The adverse effect of food additives on ADHD symptoms was moderated by histamine degradation gene polymorphisms HNMT T939C and HNMT Thr105Ile in 3- and 8/9-year-old children and by a DAT1 polymorphism (short versus long) in 8/9-year-old children only. There was no evidence that polymorphisms in catecholamine genes COMT Val108Met, ADRA2A C1291G, and DRD4-rs7403703 moderated the effect on ADHD symptoms. Histamine may mediate the effects of food additives on ADHD symptoms, and variations in genes influencing the action of histamine may explain the inconsistency between previous studies. Genes influencing a range of neurotransmitter systems and their interplay with environmental factors, such as diet, need to be examined to understand genetic influences on ADHD symptoms.
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An increasing number of commercial tests for food allergies are marketed to consumers and healthcare practitioners with tenuous claims. The aim of this article is to provide an evidence-based review of the tests and procedures that currently are used for patients with suspected food allergy. A systematic review of the literature evaluating the validity of tests and procedures used in food reactions was performed using conventional search engines (eg, PubMed, Ovid) as well as consumer sites (eg, Google, Bing). The National Library of Medicine Medical Subject Headings (MeSH) term food hypersensitivity was used along with food allergy testing, food sensitivity testing, food intolerance testing, and adverse food reactions. Of the results obtained, testing for immunoglobulin E (IgE)-mediated food allergy was best represented in PubMed. IgE-based testing continues to be the gold standard for suspected food allergies. Among modalities used by many conventional and alternative practitioners, immunoglobulin G (IgG)-based testing showed promise, with clinically meaningful results. It has been proven useful as a guide for elimination diets, with clinical impact for a variety of diseases. Mediator release testing and antigen leukocyte cellular antibody testing were only represented on consumer sites. Further investigation into the validity and the clinical application of these tests and procedures is required. Disclosing the basis for food reactions continues to present a diagnostic challenge, and testing for food allergies in the context of an appropriate clinical history is paramount to making the correct diagnosis.
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Attention deficit/hyperactivity disorder (ADHD), a common behavioural disorder in children, may be associated with comorbid physical and sleep complaints. Dietary intervention studies have shown convincing evidence of efficacy in reducing ADHD symptoms in children. In this pilot study, we investigated the effects of an elimination diet on physical and sleep complaints in children with ADHD. A group of 27 children (3.8–8.5 years old), who all met the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for ADHD, were assigned randomly to either a diet group (15/27) or a control group (12/27). The diet group followed a 5-week elimination diet; the control group adhered to their normal diet. Parents of both groups had to keep an extended diary and had to monitor the behaviour and the physical and sleep complaints of their child conscientiously. The primary endpoint was the clinical response, i.e. a decrease of physical and sleep complaints, at the end of the trial, based on parent ratings on a Physical Complaints Questionnaire. The number of physical and sleep complaints was significantly decreased in the diet group compared to the control group (p
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To conduct a randomized, controlled trial to evaluate the efficacy of the Early Start Denver Model (ESDM), a comprehensive developmental behavioral intervention, for improving outcomes of toddlers diagnosed with autism spectrum disorder (ASD). Forty-eight children diagnosed with ASD between 18 and 30 months of age were randomly assigned to 1 of 2 groups: (1) ESDM intervention, which is based on developmental and applied behavioral analytic principles and delivered by trained therapists and parents for 2 years; or (2) referral to community providers for intervention commonly available in the community. Compared with children who received community-intervention, children who received ESDM showed significant improvements in IQ, adaptive behavior, and autism diagnosis. Two years after entering intervention, the ESDM group on average improved 17.6 standard score points (1 SD: 15 points) compared with 7.0 points in the comparison group relative to baseline scores. The ESDM group maintained its rate of growth in adaptive behavior compared with a normative sample of typically developing children. In contrast, over the 2-year span, the comparison group showed greater delays in adaptive behavior. Children who received ESDM also were more likely to experience a change in diagnosis from autism to pervasive developmental disorder, not otherwise specified, than the comparison group. This is the first randomized, controlled trial to demonstrate the efficacy of a comprehensive developmental behavioral intervention for toddlers with ASD for improving cognitive and adaptive behavior and reducing severity of ASD diagnosis. Results of this study underscore the importance of early detection of and intervention in autism.
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To investigate predictors and moderators of outcome of behavioral parent training (BPT) as adjunct to ongoing routine clinical care (RCC), versus RCC alone. We randomly assigned 94 referred children (4-12 years) with attention-deficit/hyperactivity disorder (ADHD) to BPT plus RCC or RCC alone. Outcome was based on parent-reported behavioral problems and ADHD symptoms. Predictor/moderator variables included children's IQ, age, and comorbidity profile, and maternal ADHD, depression, and parenting self-efficacy. Superior BPT treatment effects on behavioral problems and ADHD symptoms were present in children with no or single-type comorbidity-anxiety/depression or oppositional defiant disorder (ODD)/conduct disorder (CD)-and when mothers had high parenting self-efficacy, but absent in children with broad comorbidity (anxiety/depression and ODD/CD) and when mothers had low parenting self-efficacy. In older children ADHD symptoms tended to decrease more through BPT than in younger children. Adjunctive BPT is most useful when mothers have high parenting self-efficacy and in children with no or single-type comorbidity.
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Deep brain stimulation is an accepted treatment for advanced Parkinson disease (PD), although there are few randomized trials comparing treatments, and most studies exclude older patients. To compare 6-month outcomes for patients with PD who received deep brain stimulation or best medical therapy. Randomized controlled trial of patients who received either deep brain stimulation or best medical therapy, stratified by study site and patient age (< 70 years vs > or = 70 years) at 7 Veterans Affairs and 6 university hospitals between May 2002 and October 2005. A total of 255 patients with PD (Hoehn and Yahr stage > or = 2 while not taking medications) were enrolled; 25% were aged 70 years or older. The final 6-month follow-up visit occurred in May 2006. Bilateral deep brain stimulation of the subthalamic nucleus (n = 60) or globus pallidus (n = 61). Patients receiving best medical therapy (n = 134) were actively managed by movement disorder neurologists. The primary outcome was time spent in the "on" state (good motor control with unimpeded motor function) without troubling dyskinesia, using motor diaries. Other outcomes included motor function, quality of life, neurocognitive function, and adverse events. Patients who received deep brain stimulation gained a mean of 4.6 h/d of on time without troubling dyskinesia compared with 0 h/d for patients who received best medical therapy (between group mean difference, 4.5 h/d [95% CI, 3.7-5.4 h/d]; P < .001). Motor function improved significantly (P < .001) with deep brain stimulation vs best medical therapy, such that 71% of deep brain stimulation patients and 32% of best medical therapy patients experienced clinically meaningful motor function improvements (> or = 5 points). Compared with the best medical therapy group, the deep brain stimulation group experienced significant improvements in the summary measure of quality of life and on 7 of 8 PD quality-of-life scores (P < .001). Neurocognitive testing revealed small decrements in some areas of information processing for patients receiving deep brain stimulation vs best medical therapy. At least 1 serious adverse event occurred in 49 deep brain stimulation patients and 15 best medical therapy patients (P < .001), including 39 adverse events related to the surgical procedure and 1 death secondary to cerebral hemorrhage. In this randomized controlled trial of patients with advanced PD, deep brain stimulation was more effective than best medical therapy in improving on time without troubling dyskinesias, motor function, and quality of life at 6 months, but was associated with an increased risk of serious adverse events. clinicaltrials.gov Identifier: NCT00056563.
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Anxiety disorders are common psychiatric conditions affecting children and adolescents. Although cognitive behavioral therapy and selective serotonin-reuptake inhibitors have shown efficacy in treating these disorders, little is known about their relative or combined efficacy. In this randomized, controlled trial, we assigned 488 children between the ages of 7 and 17 years who had a primary diagnosis of separation anxiety disorder, generalized anxiety disorder, or social phobia to receive 14 sessions of cognitive behavioral therapy, sertraline (at a dose of up to 200 mg per day), a combination of sertraline and cognitive behavioral therapy, or a placebo drug for 12 weeks in a 2:2:2:1 ratio. We administered categorical and dimensional ratings of anxiety severity and impairment at baseline and at weeks 4, 8, and 12. The percentages of children who were rated as very much or much improved on the Clinician Global Impression-Improvement scale were 80.7% for combination therapy (P<0.001), 59.7% for cognitive behavioral therapy (P<0.001), and 54.9% for sertraline (P<0.001); all therapies were superior to placebo (23.7%). Combination therapy was superior to both monotherapies (P<0.001). Results on the Pediatric Anxiety Rating Scale documented a similar magnitude and pattern of response; combination therapy had a greater response than cognitive behavioral therapy, which was equivalent to sertraline, and all therapies were superior to placebo. Adverse events, including suicidal and homicidal ideation, were no more frequent in the sertraline group than in the placebo group. No child attempted suicide. There was less insomnia, fatigue, sedation, and restlessness associated with cognitive behavioral therapy than with sertraline. Both cognitive behavioral therapy and sertraline reduced the severity of anxiety in children with anxiety disorders; a combination of the two therapies had a superior response rate. (ClinicalTrials.gov number, NCT00052078.)
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A 10-week study was conducted in which all food was provided for the families of 24 hyperactive preschool-aged boys whose parents reported the existence of sleep problems or physical signs and symptoms. A within-subject crossover design was used, and the study was divided into three periods: a baseline period of 3 weeks, a placebo-control period of 3 weeks, and an experimental diet period of 4 weeks. The experimental diet was broader than those studied previously in that it eliminated not only artificial colors and flavors but also chocolate, monosodium glutamate, preservatives, caffeine, and any substance that families reported might affect their specific child. The diet was also low in simple sugars, and it was dairy free if the family reported a history of possible problems with cow's milk. According to the parental report, more than half of the subjects exhibited a reliable improvement in behavior and negligible placebo effects. In addition, several nonbehavioral variables tended to improve while the children received the experimental diet, particularly halitosis, night awakenings, and latency to sleep onset.
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The attention deficit hyperactive disorder (ADHD) is a neurophysiologic problem that is detrimental to children and their parents. Despite previous studies on the role of foods, preservatives and artificial colorings in ADHD this issue remains controversial. This investigation evaluated 26 children who meet the criteria for ADHD. Treatment with a multiple item elimination diet showed 19 children (73%) responded favorably, P < .001. On open challenge, all 19 children reacted to many foods, dyes, and/or preservatives. A double-blind placebo controlled food challenge (DBPCFC) was completed in 16 children. There was a significant improvement on placebo days compared with challenge days (P = .003). Atopic children with ADHD had a significantly higher response rate than the nonatopic group. This study demonstrates a beneficial effect of eliminating reactive foods and artificial colors in children with ADHD. Dietary factors may play a significant role in the etiology of the majority of children with ADHD.
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Seventy-eight children, referred to a diet clinic because of hyperactive behaviour, were placed on a 'few foods' elimination diet. Fifty nine improved in behaviour during this open trial. For 19 of these children it was possible to disguise foods or additives, or both, that reliably provoked behavioural problems by mixing them with other tolerated foods and to test their effect in a placebo controlled double blind challenge protocol. The results of a crossover trial on these 19 children showed a significant effect for the provoking foods to worsen ratings of behaviour and to impair psychological test performance. This study shows that observations of change in behaviour associated with diet made by parents and other people with a role in the child's care can be reproduced using double blind methodology and objective assessments. Clinicians should give weight to the accounts of parents and consider this treatment in selected children with a suggestive medical history.
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We present an auditable protocol for attention deficit/hyperactivity disorder (ADHD) or hyperkinetic disorder. The protocol is derived from standard recommendations and evidence, and is intended for outpatient medical clinic practice in secondary care. Suggested side effect rating scales are included.
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This article reports on the outcome of a randomized controlled trial of cognitive group therapy (CT) to prevent relapse/recurrence in a group of high-risk patients diagnosed with recurrent depression. Recurrently depressed patients (N = 187) currently in remission following various types of treatment were randomized to treatment as usual, including continuation of pharmacotherapy, or to treatment as usual augmented with brief CT. Relapse/recurrence to major depression was assessed over 2 years. Augmenting treatment as usual with CT resulted in a significant protective effect, which intensified with the number of previous depressive episodes experienced. For patients with 5 or more previous episodes (41% of the sample), CT reduced relapse/recurrence from 72% to 46%. Our findings extend the accumulating evidence that cognitive interventions following remission can be useful in preventing relapse/recurrence in patients with recurrent depression.
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In the intent-to-treat analysis of the Multimodal Treatment Study of Children With ADHD (MTA), the effects of medication management (MedMgt), behavior therapy (Beh), their combination (Comb), and usual community care (CC) differed at 14 and 24 months due to superiority of treatments that used the MTA medication algorithm (Comb+MedMgt) over those that did not (Beh+CC). This report examines 36-month outcomes, 2 years after treatment by the study ended. For primary outcome measures (attention-deficit/hyperactivity disorder [ADHD] and oppositional defiant disorder [ODD] symptoms, social skills, reading scores, impairment, and diagnostic status), mixed-effects regression models and orthogonal contrasts examined 36-month outcomes. At 3 years, 485 of the original 579 subjects (83.8%) participated in the follow-up, now at ages 10 to 13 years, (mean 11.9 years). In contrast to the significant advantage of MedMgt+Comb over Beh+CC for ADHD symptoms at 14 and 24 months, treatment groups did not differ significantly on any measure at 36 months. The percentage of children taking medication >50% of the time changed between 14 and 36 months across the initial treatment groups: Beh significantly increased (14% to 45%), MedMed+Comb significantly decreased (91% to 71%), and CC remained constant (60%-62%). Regardless of their treatment use changes, all of the groups showed symptom improvement over baseline. Notably, initial symptom severity, sex (male), comorbidity, public assistance, and parental psychopathology (ADHD) did not moderate children's 36-month treatment responses, but these factors predicted worse outcomes over 36 months, regardless of original treatment assignment. By 36 months, the earlier advantage of having had 14 months of the medication algorithm was no longer apparent, possibly due to age-related decline in ADHD symptoms, changes in medication management intensity, starting or stopping medications altogether, or other factors not yet evaluated.
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The aim of this study is to assess the efficacy of a restricted elimination diet in reducing symptoms in an unselected group of children with Attention deficit/hyperactivity disorder (ADHD). Dietary studies have already shown evidence of efficacy in selected subgroups. Twenty-seven children (mean age 6.2) who all met the DSM-IV criteria for ADHD, were assigned randomly to either an intervention group (15/27) or a waiting-list control group (12/27). Primary endpoint was the clinical response, i.e. a decrease in the symptom scores by 50% or more, at week 9 based on parent and teacher ratings on the abbreviated ten-item Conners Scale and the ADHD-DSM-IV Rating Scale. The intention-to-treat analysis showed that the number of clinical responders in the intervention group was significantly larger than that in the control group [parent ratings 11/15 (73%) versus 0/12 (0%); teacher ratings, 7/10 (70%) versus 0/7 (0%)]. The Number of ADHD criteria on the ADHD Rating Scale showed an effect size of 2.1 (cohen's d) and a scale reduction of 69.4%. Comorbid symptoms of oppositional defiant disorder also showed a significantly greater decrease in the intervention group than it did in the control group (cohens's d 1.1, scale reduction 45.3%). A strictly supervised elimination diet may be a valuable instrument in testing young children with ADHD on whether dietary factors may contribute to the manifestation of the disorder and may have a beneficial effect on the children's behaviour.
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342 Caucasian subjects with attention deficit/hyperactivity disorder (ADHD) were recruited from pediatric and behavioral health clinics for a genetic study. Concurrent comorbidity was assessed to characterize the clinical profile of this cohort. Subjects 6 to 18 years were diagnosed with the Schedule for Affective Disorders & Schizophrenia for School aged Children (K-SADS-P IVR). The most prevalent diagnoses co-occurring with ADHD were Oppositional Defiant Disorder (ODD) (40.6%), Minor Depression/Dysthymia (MDDD) (21.6%), and Generalized Anxiety Disorder (GAD) (15.2%). In Inattentive ADHD (n = 106), 20.8% had MDDD, 20.8% ODD, and 18.6% GAD; in Hyperactive ADHD (n = 31) 41.9% had ODD, 22.2% GAD, and 19.4% MDDD. In Combined ADHD, (n = 203), 50.7% had ODD, 22.7% MDDD and 12.4% GAD. MDDD and GAD were equally prevalent in the ADHD subtypes but, ODD was significantly more common among Combined and Hyperactive ADHD compared to Inattentive ADHD. The data suggested a subsample of Irritable prepubertal children exhibiting a diagnostic triad of ODD, Combined ADHD, and MDDD may account for the over diagnosing of Bipolar Disorder. Almost 2/3rd of ADHD children have impairing comorbid diagnoses; Hyperactive ADHD represents less than 10% of an ADHD sample; ODD is primarily associated with Hyperactive and Combined ADHD; and, MDDD may be a significant morbidity for ADHD youths from clinical samples.
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This chapter provides an overview of recent developments in the design and analysis of cross-over trials. We first consider the analysis of the trial that compares two treatments, A and B, over two periods and where the subjects are randomized to the treatment sequences AB and BA. We make the distinction between fixed and random effects models and show how these models can easily be fitted using modern software. Issues with fitting and testing for a difference in carry-over effects are described and the use of baseline measurements is discussed. Simple methods for testing for a treatment difference when the data are binary are also described. Various designs with two or more treatments but with three or four periods are then described and compared. These include the balanced and partially balanced designs for three or more treatments and designs for factorial treatment combinations. Also described are nearly balanced and nearly strongly balanced designs. Random subject-effects models for the designs with two or more treatments are described and methods for analysing non-normal data are also given. The chapter concludes with a description of the use of cross-over designs in the testing of bioequivalence.
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Objective: To review alternate treatments (Tx) of Attention-Deficit/Hyperactivity Disorder (ADHD)—those other than psychoactive medication and behavioral/psychosocial Tx—for the November, 1998 National Institute of Health (NIH) Consensus Development Conference on ADHD. Method: The literature was searched on Medline and Psychlnfo 1963-1998 and investigators known to be interested in alternate Tx were contacted for unpublished data. Results: Twenty-three alternate Tx were identified, ranging in scientific documentation from discrediting controlled studies through mere hypotheses to positive controlled double-blind clinical trials. Many of them are applicable only to a restricted etiological subgroup. The oligoantigenic or few-foods diet has convincing double-blind evidence of efficacy in multiple trials for a properly selected subgroup. Enzyme-potentiated desensitization to foods, relaxation/EMG biofeedback, and deleading also have controlled evidence of efficacy. Glyconutritional supplementation, iron supplementation, magnesium supplementation, Chinese herbals, EEG biofeedback, meditation, mirror feedback, channel-specific perceptual training, and vestibular stimulation all have promising prospective pilot data. Single-vitamin megadosage has some intriguing pilot trial data. Zinc supplementation is hypothetically supported by systematic case-control data but has no systematic clinical trial. Laser acupuncture has promising unpublished pilot data. Essential fatty acid supplementation has promising systematic case-control data but clinical trials are equivocal. Recommended-Daily-Allowance vitamin supplementation, nonChinese herbals, homeopathic remedies, and antifungal therapy have no systematic data in ADHD. Megadose multivitamin combinations are probably ineffective for most patients and possibly dangerous. Simple sugar restriction and hypnosis seem ineffective. Amino acid supplementation, though mildly effective in the short term, is not effective beyond a few weeks. Thyroid Tx is effective in the presence of documented thyroid abnormality, but not otherwise. Conclusion: Some alternate Tx of ADHD are effective or probably effective, but mainly for restricted etiologic subgroups. In some cases they are the Tx of choice, and initial evaluation should consider the relevant etiologies. A few have failed to prove effective in controlled trials. Most need research to determine whether they are effective and/or to define the applicable subgroup. Some of them, though not safer than standard Tx, may be preferable for an etiologic subgroup.
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Obtained data from parents and teachers for a large sample of urban school children aged 6 to 12 years on the attention deficit hyperactivity disorder (ADHD) Rating Scale, and collected criterion measures (e.g., direct observations of classroom behavior, academic achievement scores) on a smaller subsample. The ADHD Rating Scale was found to be a highly reliable questionnaire with adequate criterion-related validity. Strong differences between boys and girls were evident with respect to the frequency of ADHD symptomatology. The ADHD Rating Scale should be useful as one component of a multimodal assessment approach that would include rating scales surveying both general and specific areas of psychopathology.
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We present an auditable protocol for attention deficit/hyperactivity disorder (ADHD) or hyperkinetic disorder. The protocol is derived from standard recommendations and evidence, and is intended for outpatient medical clinic practice in secondary care. Suggested side effect rating scales are included.
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Control of blood pressure is a key component of cardiovascular disease prevention, but is difficult to achieve and until recently has been the sole preserve of health professionals. This study assessed whether self-management by people with poorly controlled hypertension resulted in better blood pressure control compared with usual care. This randomised controlled trial was undertaken in 24 general practices in the UK. Patients aged 35-85 years were eligible for enrolment if they had blood pressure more than 140/90 mm Hg despite antihypertensive treatment and were willing to self-manage their hypertension. Participants were randomly assigned in a 1:1 ratio to self-management, consisting of self-monitoring of blood pressure and self-titration of antihypertensive drugs, combined with telemonitoring of home blood pressure measurements or to usual care. Randomisation was done by use of a central web-based system and was stratified by general practice with minimisation for sex, baseline systolic blood pressure, and presence or absence of diabetes or chronic kidney disease. Neither participants nor investigators were masked to group assignment. The primary endpoint was change in mean systolic blood pressure between baseline and each follow-up point (6 months and 12 months). All randomised patients who attended follow-up visits at 6 months and 12 months and had complete data for the primary outcome were included in the analysis, without imputation for missing data. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN17585681. 527 participants were randomly assigned to self-management (n=263) or control (n=264), of whom 480 (91%; self-management, n=234; control, n=246) were included in the primary analysis. Mean systolic blood pressure decreased by 12.9 mm Hg (95% CI 10.4-15.5) from baseline to 6 months in the self-management group and by 9.2 mm Hg (6.7-11.8) in the control group (difference between groups 3.7 mm Hg, 0.8-6.6; p=0.013). From baseline to 12 months, systolic blood pressure decreased by 17.6 mm Hg (14.9-20.3) in the self-management group and by 12.2 mm Hg (9.5-14.9) in the control group (difference between groups 5.4 mm Hg, 2.4-8.5; p=0.0004). Frequency of most side-effects did not differ between groups, apart from leg swelling (self-management, 74 patients [32%]; control, 55 patients [22%]; p=0.022). Self-management of hypertension in combination with telemonitoring of blood pressure measurements represents an important new addition to control of hypertension in primary care. Department of Health Policy Research Programme, National Coordinating Centre for Research Capacity Development, and Midlands Research Practices Consortium.
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Major depressive disorder (MDD) was projected to rank second on a list of 15 major diseases in terms of burden in 2030. A crucial part of the treatment of depression is the prevention of relapse/recurrence in high-risk groups, ie, recurrently depressed patients. The long-term preventive effects of group cognitive therapy (CT) in preventing relapse/recurrence in recurrent depression are not known. This article reports on the long-term (5.5-year) outcome of a randomized controlled trial to prevent relapse/recurrence in patients with recurrent depression. We specifically evaluated the long-term effects of CT in relation to the number of previous episodes experienced. From February through September 2000, patients with recurrent depression (DSM-IV-diagnosed) who were in remission (N = 172) were recruited from primary and specialty care facilities. They were randomly assigned to treatment as usual (TAU) versus TAU augmented with brief group CT. The primary outcome measure was time to relapse/recurrence, which was assessed over 5.5 years. Over 5.5 years, augmenting TAU with CT resulted in a significant protective effect (P = .003), which intensified with the number of previous depressive episodes experienced. For patients with 4 or more previous episodes (52% of the sample), CT significantly reduced cumulative relapse/recurrence from 95% to 75% (medium effect size). Our findings indicate that brief CT, started after remission from a depressive episode on diverse types of treatment in patients with multiple prior episodes, has long-term preventive effects for at least 5.5 years. Implementation of brief relapse prevention CT should be considered in the continued care of patients with recurrent depression. ccmo-online.nl Identifier: NTR454.
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To assay if plasma antibody levels in children with autism or developmental delays (DD) differ from those with typical development as an indicator of immune function and to correlate antibody levels with severity of behavioral symptoms. Plasma was collected from children with autistic disorder (AU; n=116), DD but not autism (n=32), autism spectrum disorder but not full autism (n=27), and age-matched typically developing (TD) controls (n=96). Samples were assayed for systemic levels of immunoglobulin (IgG, IgM, IgA, and IgE) by enzyme-linked immunosorbent assay. Subjects with autism were evaluated using the Autism Diagnostic Observation Schedule and the Autism Diagnostic Interview-Revised, and all subjects were scored on the Aberrant Behavior Checklist (ABC) by the parents. Numerical scores for each of the ABC subscales as well as the total scores were then correlated with Ig levels. Children with AU have a significantly reduced level of plasma IgG (5.39+/-0.29 mg/mL) compared to the TD (7.72+/-0.28 mg/mL; P<0.001) and DD children (8.23+/-0.49 mg/mL; P<0.001). Children with autism also had a reduced level of plasma IgM (0.670.06 mg/mL) compared to TD (0.79+/-0.05 mg/mL; P<0.05). Ig levels were negatively correlated with ABC scores for all children (IgG: r=-0.334, P<0.0001; IgM: r=-0.167, P=0.0285). Children with AU have significantly reduced levels of plasma IgG and IgM compared to both DD and TD controls, suggesting an underlying defect in immune function. This reduction in specific Ig levels correlates with behavioral severity, where those patients with the highest scores in the behavioral battery have the most reduced levels of IgG and IgM.
To determine any long-term effects, 6 and 8 years after childhood enrollment, of the randomly assigned 14-month treatments in the NIMH Collaborative Multisite Multimodal Treatment Study of Children With Attention-Deficit/Hyperactivity Disorder (MTA; N = 436); to test whether attention-deficit/hyperactivity disorder (ADHD) symptom trajectory through 3 years predicts outcome in subsequent years; and to examine functioning level of the MTA adolescents relative to their non-ADHD peers (local normative comparison group; N = 261). Mixed-effects regression models with planned contrasts at 6 and 8 years tested a wide range of symptom and impairment variables assessed by parent, teacher, and youth report. In nearly every analysis, the originally randomized treatment groups did not differ significantly on repeated measures or newly analyzed variables (e.g., grades earned in school, arrests, psychiatric hospitalizations, other clinically relevant outcomes). Medication use decreased by 62% after the 14-month controlled trial, but adjusting for this did not change the results. ADHD symptom trajectory in the first 3 years predicted 55% of the outcomes. The MTA participants fared worse than the local normative comparison group on 91% of the variables tested. Type or intensity of 14 months of treatment for ADHD in childhood (at age 7.0-9.9 years) does not predict functioning 6 to 8 years later. Rather, early ADHD symptom trajectory regardless of treatment type is prognostic. This finding implies that children with behavioral and sociodemographic advantage, with the best response to any treatment, will have the best long-term prognosis. As a group, however, despite initial symptom improvement during treatment that is largely maintained after treatment, children with combined-type ADHD exhibit significant impairment in adolescence. Innovative treatment approaches targeting specific areas of adolescent impairment are needed.
Article
A better understanding of the long-term scope and impact of the comorbidity with oppositional defiant disorder (ODD) in girls with attention-deficit/hyperactivity disorder (ADHD) has important clinical and public health implications. However, most of the available information on the subject derives from predominantly male samples. This study evaluated the longitudinal course and impact of comorbid ODD in a large sample of girls with ADHD. Subjects were pediatrically and psychiatrically referred girls with and without ADHD assessed blindly at baseline (mean age = 11.6 years), and 5 years later (mean age = 16.6 years) by mid to late adolescence. The subjects' diagnostic status of ADHD with and without comorbid ODD at baseline was used to define three groups (controls [N = 107], ADHD [N = 77], ADHD + ODD [N = 37]). Outcomes were examined using logistic regression (for binary outcomes) and linear regression (for continuous outcomes). Compared with girls who had ADHD only, those with ADHD + ODD at baseline had a significantly increased risk for ODD and major depression at follow-up. Both groups of girls with ADHD had an increased risk for conduct disorder and bipolar disorder at follow-up. These longitudinal findings in girls with ADHD support and extend previously reported findings in boys indicating that ODD heralds a compromised outcome for girls with ADHD in adolescence.
Article
A double-blind crossover trial involving a control diet and a diet eliminating artificial flavors, colors, and natural salicylates as recommended by Feingold was conducted on 15 hyperkinetic children. Teachers and parents observed the children for one month prior to treatment, using standardized rating scales. Both parents and teachers reported fewer hyperkinetic symptoms on the K-P diet as compared to the pretreatment baseline. The teachers noted a highly significant reduction of symptoms on the K-P diet as compared to the control diet but the parents did not. The control diet ratings did not differ from the baseline period ratings for either parents or teachers. It is concluded that the K-P diet may reduce hyperkinetic symptoms, though this result is put forth with caution in view of several features inherent in the present study which need further evaluation, including objective measures of change, manipulation of the independent variable, and reducing the independent variable to more specific components.
Article
This paper presents a general statistical methodology for the analysis of multivariate categorical data arising from observer reliability studies. The procedure essentially involves the construction of functions of the observed proportions which are directed at the extent to which the observers agree among themselves and the construction of test statistics for hypotheses involving these functions. Tests for interobserver bias are presented in terms of first-order marginal homogeneity and measures of interobserver agreement are developed as generalized kappa-type statistics. These procedures are illustrated with a clinical diagnosis example from the epidemiological literature.
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76 selected overactive children were treated with an oligoantigenic diet, 62 improved, and a normal range of behaviour was achieved in 21 of these. Other symptoms, such as headaches, abdominal pain, and fits, also often improved. 28 of the children who improved completed a double-blind, crossover, placebo-controlled trial in which foods thought to provoke symptoms were reintroduced. Symptoms returned or were exacerbated much more often when patients were on active material than on placebo. 48 foods were incriminated. Artificial colorants and preservatives were the commonest provoking substances, but no child was sensitive to these alone.
Article
To examine the pattern of individual responses to to methylphenidate (MPH) in children with attention-deficit hyperactivity disorder and to examine factors that predict drug response. Individual drug response was defined on the basis of changes on the Abbreviated Conners Rating Scales completed by parents and teachers. These scales were the main outcome measures in a double-blind, placebo-controlled trial of MPH. Response prediction was examined in stepwise discriminant analyses, in which baseline variables and the response to a single, 10-mg dose of MPH were entered. Predictors of a strong MPH response were a high IQ, considerable inattentiveness, young age, low severity of disorder, and low rates of anxiety. A positive response to a single dose of MPH significantly improved the prediction of less stringently defined levels of MPH response. Only strong levels of response could be predicted by baseline characteristics. Severity of disorder based on clinical judgment and improvement after a single dose of MPH are found to be important contributors to response prediction.
Article
A crossover 'placebo'-controlled, double-blind design was used to examine the effectiveness of an oligoantigenic diet in 49 children with hyperactive/disruptive behavior disorder. Effects of diet were compared with those yielded by stimulant medication (methylphenidate). The study was conducted in an inpatient unit at the Department of Child and Adolescent Psychiatry, Central Institute of Mental Health, Mannheim. Change in behavior was measured in standardized situations by trained raters, including behavior assessment when testing with CPT and PAT, during a free play situation, and at school. Twelve children (24%) showed significant behavioral improvement in two behavior ratings during diet relative to control diet conditions. Methylphenidate used in 36 children yielded more responders (44%) than diet. The amount of positive changes in behavior in those who received both treatments was about the same. Although only effective in a minority of children, dietary treatment cannot be neglected as a possible access to treating hyperactive/disruptive children and merits further investigation.
Article
The influence of an oligoantigenic diet on different dimensions of the behavior of 21 children diagnosed as having attention-deficit hyperactivity disorder (ADHD) was examined. Treatment effects were assessed with three subjective measures (two questionnaires and an interview) and three objective measures (two attention tests and actometer). The study was divided into three phases: baseline, diet and provocation, each lasting three weeks. A crossover design was used. A significant effect was found for the subjective measures, but not for the objective measures. The results are discussed in terms of possible types of effects, e. g. rater effects and environmental effects. It may be that the oligoantigenic diet influences only certain dimensions of hyperactivity.
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Psychiatric research has benefited from attention to measurement theories of reliability, and reliability/agreement statistics for psychopathology ratings and diagnoses are regularly reported in empirical reports. Nevertheless, there are still controversies regarding how reliability should be measured, and the amount of resources that should be spent on studying measurement quality in research programs. These issues are discussed in the context of recent theoretical and technical contributions to the statistical analysis of reliability. Special attention is paid to statistical studies published since Kraemer's 1992 review of reliability methods in this journal.
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The nomenclature proposed in the October 2003 report of the Nomenclature Review Committee of the World Allergy Organization is an update of the European Academy of Allergology and Clinical Immunology Revised Nomenclature for Allergy Position Statement published in 2001. The nomenclature can be used independently of target organ or patient age group and is based on the mechanisms that initiate and mediate allergic reactions. It is assumed that as knowledge about basic causes and mechanisms improves, the nomenclature will need further review.
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The accurate diagnosis of food allergy is crucial not only for the right treatment but also for the avoidance of unnecessary diets. The diagnostic work-up of suspected food allergy includes the measurement of food-specific IgE antibodies using serologic assays, the skin prick test, elimination diets and oral provocation tests. In addition, some approaches are either under further rigorous investigation (the atopy patch test) or are already in widespread use, particularly by practitioners of alternative or complementary medicine, but are considered unproven. These diagnostic methods include specific IgG to foods, provocation/neutralization testing, kinesiology, cytotoxic tests and electrodermal testing. This review covers some of the most common scientifically validated and unproven approaches used in the diagnosis of food allergy. For specific serum IgE and the SPT, decision points have been established for some foods, allowing prediction of clinical relevance. The APT may be helpful, especially when considered in combination with defined levels of specific IgE. In regard to other approaches, most scientific studies do refute the usefulness of these approaches. In most patients, controlled oral food challenges remain the gold standard in the diagnostic work-up of suspected food allergy. The skin prick test and measurement of specific IgE antibodies to food extracts, individual allergens or allergenic peptides are helpful in the diagnostic approach. Food-specific IgG continues to be an unproven or experimental test. The other alternative and complementary techniques have no proven benefit and may endanger patients via misdiagnosis.
Article
Attention-deficit hyperactivity disorder (ADHD) is a disorder of inattention, impulsivity, and hyperactivity that affects 8-12% of children worldwide. Although the rate of ADHD falls with age, at least half of children with the disorder will have impairing symptoms in adulthood. Twin, adoption, and molecular genetic studies show ADHD to be highly heritable, and other findings have recorded obstetric complications and psychosocial adversity as predisposing risk factors. Converging evidence from animal and human studies implicates the dysregulation of frontal-subcortical-cerebellar catecholaminergic circuits in the pathophysiology of ADHD, and molecular imaging studies suggest that abnormalities of the dopamine transporter lead to impaired neurotransmission. Studies during the past decade have shown the safety and effectiveness of new non-stimulant drugs and long-acting formulations of methylphenidate and amfetamine. Other investigations have also clarified the appropriate role of targeted psychosocial treatments in the context of ongoing pharmacotherapy.
Article
We undertook a randomised, double-blinded, placebo-controlled, crossover trial to test whether intake of artificial food colour and additives (AFCA) affected childhood behaviour. 153 3-year-old and 144 8/9-year-old children were included in the study. The challenge drink contained sodium benzoate and one of two AFCA mixes (A or B) or a placebo mix. The main outcome measure was a global hyperactivity aggregate (GHA), based on aggregated z-scores of observed behaviours and ratings by teachers and parents, plus, for 8/9-year-old children, a computerised test of attention. This clinical trial is registered with Current Controlled Trials (registration number ISRCTN74481308). Analysis was per protocol. 16 3-year-old children and 14 8/9-year-old children did not complete the study, for reasons unrelated to childhood behaviour. Mix A had a significantly adverse effect compared with placebo in GHA for all 3-year-old children (effect size 0.20 [95% CI 0.01-0.39], p=0.044) but not mix B versus placebo. This result persisted when analysis was restricted to 3-year-old children who consumed more than 85% of juice and had no missing data (0.32 [0.05-0.60], p=0.02). 8/9-year-old children showed a significantly adverse effect when given mix A (0.12 [0.02-0.23], p=0.023) or mix B (0.17 [0.07-0.28], p=0.001) when analysis was restricted to those children consuming at least 85% of drinks with no missing data. Artificial colours or a sodium benzoate preservative (or both) in the diet result in increased hyperactivity in 3-year-old and 8/9-year-old children in the general population.
Research data concerning the causal association between attention deficit hyperactivity disorder (ADHD) and allergies are conflicting. Allergic disorders, like asthma and eczema are clinical syndromes in which both genetic predisposition and environmental factors (pets, pollen and foods) contribute to its development. The hypothesis of ADHD, in some children also being an allergic disorder, is postulated based on comparison of the mechanisms underlying the development of ADHD and allergic disorders. According to the accepted terminology, ADHD may comply with the criteria of hypersensitivity, allergy and atopy. This hypothesis has to be thoroughly tested by randomized controlled trials using environmental triggers and immunologic research. As genes related to the immune system may be associated with ADHD, further genetic research is compulsory. Immunotherapeutic approaches, using immunotherapy and probiotics, can subsequently be implicated in the treatment of ADHD. If hypersensitivity to environmental stimuli like foods contributes to the development of ADHD, the assessment and treatment of ADHD will have to be reconsidered, thereby improving the quality of care for these patients.