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The Gut Microbiome and Mental Health: What Should We Tell Our Patients?: Le microbiote Intestinal et la Santé Mentale : que Devrions-Nous dire à nos Patients?
Butler, MI, Mörkl, S, Sandhu, KV, Cryan, JF, Dinan, TG
Canadian journal of psychiatry. Revue canadienne de psychiatrie. 2019;64(11):747-760
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The gut-brain axis is the bi-directional communication pathway and increasing evidence indicates its impact in neural health and disease. With the field of nutritional psychiatry actively developing, psychiatric patients have become increasingly aware of the therapeutic use of probiotics and mental health. This review aims to inform psychiatrists about the communication between the microbiome and brain and discuss its relevance to the management and treatment of psychiatric illness. In reviewing the common psychiatric illnesses, the current literature shows inconsistent results on specific microbiome compositions related to specific illnesses, yet shows promising effects for probiotic use in many disorders. These findings offer a novel paradigm for approaching mental illness through the lens of nutritional psychiatry. Authors conclude there is much work to be done translating laboratory findings into clinical practice, and highlight the necessity for clinicians to stay informed of the literature and make accurate recommendations to patients.
Abstract
The gut microbiome as a potential therapeutic target for mental illness is a hot topic in psychiatry. Trillions of bacteria reside in the human gut and have been shown to play a crucial role in gut-brain communication through an influence on neural, immune, and endocrine pathways. Patients with various psychiatric disorders including depression, bipolar disorder, schizophrenia, and autism spectrum disorder have been shown to have significant differences in the composition of their gut microbiome. Enhancing beneficial bacteria in the gut, for example, through the use of probiotics, prebiotics, or dietary change, has the potential to improve mood and reduce anxiety in both healthy people and patient groups. Much attention is being given to this subject in the general media, and patients are becoming increasingly interested in the potential to treat mental illness with microbiome-based therapies. It is imperative that those working with people with mental illness are aware of the rationale and current evidence base for such treatment strategies. In this review, we provide an overview of the gut microbiome, what it is, and what it does in relation to gut-brain communication and psychological function. We describe the fundamental principles and basic techniques used in microbiome-gut-brain axis research in an accessible way for a clinician audience. We summarize the current evidence in relation to microbiome-based strategies for various psychiatric disorders and provide some practical advice that can be given to patients seeking to try a probiotic for mental health benefit.
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Current Understanding of Gut Microbiota in Mood Disorders: An Update of Human Studies.
Huang, TT, Lai, JB, Du, YL, Xu, Y, Ruan, LM, Hu, SH
Frontiers in genetics. 2019;10:98
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The bidirectional communication between the brain and gastrointestinal tract has been established, and evidence suggests the gut microbiota can influence brain function. While the underlying cause of mood disorders is multifactorial and complex, the gut microbiota may play a role in the pathogenesis of disease. The aim of this review is to summarize the human studies of gut microbiota in mood disorders and discuss the cause-effect relationship between microbiota composition and mood disorders. Twelve studies were included and showed the microbiome diversity and composition of those experiencing mood disorders were significantly different compared with healthy individuals. They found an increase in the abundance of Actinobacteria, Enterobacteriaceae and a decrease in Faecalibacterium, suggesting a pro-inflammatory state. Based on these results, the authors conclude the gut microbiota plays an important role in mood disorders through the brain-gut-microbiota axis, and suggests it to be a target for improved diagnosis and therapeutic interventions.
Abstract
Gut microbiota plays an important role in the bidirectional communication between the gut and the central nervous system. Mounting evidence suggests that gut microbiota can influence the brain function via neuroimmune and neuroendocrine pathways as well as the nervous system. Advances in gene sequencing techniques further facilitate investigating the underlying relationship between gut microbiota and psychiatric disorders. In recent years, researchers have preliminarily explored the gut microbiota in patients with mood disorders. The current review aims to summarize the published human studies of gut microbiota in mood disorders. The findings showed that microbial diversity and taxonomic compositions were significantly changed compared with healthy individuals. Most of these findings revealed that short-chain fatty acids-producing bacterial genera were decreased, while pro-inflammatory genera and those involved in lipid metabolism were increased in patients with depressive episodes. Interestingly, the abundance of Actinobacteria, Enterobacteriaceae was increased and Faecalibacterium was decreased consistently in patients with either bipolar disorder or major depressive disorder. Some studies further indicated that specific bacteria were associated with clinical characteristics, inflammatory profiles, metabolic markers, and pharmacological treatment. These studies present preliminary evidence of the important role of gut microbiota in mood disorders, through the brain-gut-microbiota axis, which emerges as a promising target for disease diagnosis and therapeutic interventions in the future.
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Role of Ketogenic Diets in Neurodegenerative Diseases (Alzheimer's Disease and Parkinson's Disease).
Włodarek, D
Nutrients. 2019;11(1)
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The ketogenic diet (KD) is characterised by a low-carbohydrate, high-fat content that induces a fasting-like state in the body. The KD has been used clinically for children with epilepsy and recent studies have shed light on potential neuro-protective effects. The aim of this systematic review was to evaluate the role of the KD in prevention of Parkinson's disease (PD) and Alzheimer's disease (AD). Among the existing literature, there is very limited data on long-term application of the KD in patients with neurodegenerative disease. The research using animal models or in-vitro models look very promising however the use of KD in elderly adults with neurodegenerative disease is very complex. Based on these results, the authors conclude there is a need for further research to evaluate the suitability of KD for patients with AD or PD.
Expert Review
Conflicts of interest:
None
Take Home Message:
- The studies into the effectiveness of ketogenic diets in neurodegenerative diseases tend to be too small and heterogeneous to draw firm conclusions.
- Specific elements of ketogenic diets may be useful for individual cases, however healthcare practitioners are encouraged to take an individualised approach to the clinical management of neurodegenerative conditions, drawing from different approaches that suit the individual living with the disease.
Evidence Category:
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A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
The role of ketogenic diets for the management of a number of conditions has become a discussion subject, not only for scientists and clinicians, but also for the general public, however the evidence of their effectiveness in neurodegenerative diseases is patchy. Studies are either too small to be good enough to draw conclusions from, or the interventions are too mixed / heterogeneous to be able to attribute any potential benefit to the ketogenic dietary component alone. This highlights the need to take an individualised approach to the clinical management of neurodegenerative conditions, drawing from different approaches that suit the individual living with the disease.
Clinical practice applications:
Specific elements of ketogenic diets might be useful for individual cases. However clinicians should be encouraged to draw from a wide array of approaches and not be limited to one single method when it comes to dealing with complex conditions such as Alzheimer's and Parkinson's Disease. Patient-centred care where dietary recommendations revolve around the individual's needs - based on biochemical markers but also on subjective experience of their own quality of life / wellbeing - should be the basis upon which to tailor nutrition programmes that support those living with neurodegenerative conditions.
Considerations for future research:
Good methodological quality studies with placebo / control groups and clear outcomes are needed in order to contribute to the evidence base of the potential role of ketogenic diets in the support of patients living with neurodegenerative conditions.
Abstract
The goal of this review was to assess the effectiveness of ketogenic diets on the therapy of neurodegenerative diseases. The ketogenic diet is a low-carbohydrate and fat-rich diet. Its implementation has a fasting-like effect, which brings the body into a state of ketosis. The ketogenic diet has, for almost 100 years, been used in the therapy of drug-resistant epilepsy, but current studies indicate possible neuroprotective effects. Thus far, only a few studies have evaluated the role of the ketogenic diet in the prevention of Parkinson's disease (PD) and Alzheimer's disease (AD). Single studies with human participants have demonstrated a reduction of disease symptoms after application. The application of the ketogenic diet to elderly people, however, raises certain concerns. Persons with neurodegenerative diseases are at risk of malnutrition, while food intake reduction is associated with disease symptoms. In turn, the ketogenic diet leads to a reduced appetite; it is not attractive from an organoleptic point of view, and may be accompanied by side effects of the gastrointestinal system. All this may lead to further lowering of consumed food portions by elderly persons with neurodegenerative diseases and, in consequence, to further reduction in the supply of nutrients provided by the diet. Neither data on the long-term application of the ketogenic diet in patients with neurodegenerative disease or data on its effects on disease symptoms are available. Further research is needed to evaluate the suitability of the ketogenic diet in the therapy of AD- or PD-affected persons.
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Yoga for anxiety: A systematic review and meta-analysis of randomized controlled trials.
Cramer, H, Lauche, R, Anheyer, D, Pilkington, K, de Manincor, M, Dobos, G, Ward, L
Depression and anxiety. 2018;35(9):830-843
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While temporary anxiety is a natural response, excessive and prolonged anxiety can lead to a wide range of physical symptoms and behavior changes. Current treatment options include psychological approaches and medication, however many individuals experiencing anxiety choose to self-manage their condition. Yoga has become a popular approach to improve emotional well-being, and based on a recent study, yoga practitioners have reported managing stress and anxiety as one of the main reasons for practicing. The aim of this meta-analysis was to review the effectiveness and safety of yoga for anxiety. Eight studies with 319 participants were included in this systematic review. Among these studies, no effects were found for patients with anxiety disorders diagnosed by the Diagnostic and Statistical Manual (DSM) criteria, only for patients without a formal diagnosis. Based on these results, the authors conclude yoga may be beneficial in the short-term for individuals with elevated levels of anxiety, however there was no conclusive evidence for individuals when only DSM-diagnosed anxiety disorders were considered. These findings warrant further studies to better understand the connection between mindfulness practices and anxiety.
Abstract
Yoga has become a popular approach to improve emotional health. The aim of this review was to systematically assess and meta-analyze the effectiveness and safety of yoga for anxiety. Medline/PubMed, Scopus, the Cochrane Library, PsycINFO, and IndMED were searched through October 2016 for randomized controlled trials (RCTs) of yoga for individuals with anxiety disorders or elevated levels of anxiety. The primary outcomes were anxiety and remission rates, and secondary outcomes were depression, quality of life, and safety. Risk of bias was assessed using the Cochrane tool. Eight RCTs with 319 participants (mean age: 30.0-38.5 years) were included. Risk of selection bias was unclear for most RCTs. Meta-analyses revealed evidence for small short-term effects of yoga on anxiety compared to no treatment (standardized mean difference [SMD] = -0.43; 95% confidence interval [CI] = -0.74, -0.11; P = .008), and large effects compared to active comparators (SMD = -0.86; 95% CI = -1.56, -0.15; P = .02). Small effects on depression were found compared to no treatment (SMD = -0.35; 95% CI = -0.66, -0.04; P = .03). Effects were robust against potential methodological bias. No effects were found for patients with anxiety disorders diagnosed by Diagnostic and Statistical Manual criteria, only for patients diagnosed by other methods, and for individuals with elevated levels of anxiety without a formal diagnosis. Only three RCTs reported safety-related data but these indicated that yoga was not associated with increased injuries. In conclusion, yoga might be an effective and safe intervention for individuals with elevated levels of anxiety. There was inconclusive evidence for effects of yoga in anxiety disorders. More high-quality studies are needed and are warranted given these preliminary findings and plausible mechanisms of action.
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Anxiety, Depression, and the Microbiome: A Role for Gut Peptides.
Lach, G, Schellekens, H, Dinan, TG, Cryan, JF
Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics. 2018;15(1):36-59
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Hormones released in the gut can have an impact in the brain through a bidirectional relationship, known as the gut-brain axis. The release of these hormones may be controlled by the gut microbiota, however exact mechanisms are not fully understood. Most hormones originating in the gut may have a role in obesity development, which is often associated with psychiatric disorders. Understanding the relationship between gut microbiota and depression through gut derived signalling molecules may be of benefit and was the focus of this review. Diversity and stability of the gut microbiota is important for health, which is disrupted during depression and anxiety. The gut microbiota serves to produce brain, hormone and immune signals that can travel to the brain, and can be affected by poor gut health. For those with depression, side effects of anti-depressants can be a disruption of the gut microbiota, however how this impacts symptoms is not fully understood. It was concluded that although there is strong research on the gut microbiota and depression it is still in its infancy. The role of gut microbiota on signalling with the brain and the rest of the body seems to be important for depression and anxiety. This study could be used by healthcare professionals to understand how the gut microbiota can play a role in depression.
Abstract
The complex bidirectional communication between the gut and the brain is finely orchestrated by different systems, including the endocrine, immune, autonomic, and enteric nervous systems. Moreover, increasing evidence supports the role of the microbiome and microbiota-derived molecules in regulating such interactions; however, the mechanisms underpinning such effects are only beginning to be resolved. Microbiota-gut peptide interactions are poised to be of great significance in the regulation of gut-brain signaling. Given the emerging role of the gut-brain axis in a variety of brain disorders, such as anxiety and depression, it is important to understand the contribution of bidirectional interactions between peptide hormones released from the gut and intestinal bacteria in the context of this axis. Indeed, the gastrointestinal tract is the largest endocrine organ in mammals, secreting dozens of different signaling molecules, including peptides. Gut peptides in the systemic circulation can bind cognate receptors on immune cells and vagus nerve terminals thereby enabling indirect gut-brain communication. Gut peptide concentrations are not only modulated by enteric microbiota signals, but also vary according to the composition of the intestinal microbiota. In this review, we will discuss the gut microbiota as a regulator of anxiety and depression, and explore the role of gut-derived peptides as signaling molecules in microbiome-gut-brain communication. Here, we summarize the potential interactions of the microbiota with gut hormones and endocrine peptides, including neuropeptide Y, peptide YY, pancreatic polypeptide, cholecystokinin, glucagon-like peptide, corticotropin-releasing factor, oxytocin, and ghrelin in microbiome-to-brain signaling. Together, gut peptides are important regulators of microbiota-gut-brain signaling in health and stress-related psychiatric illnesses.
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Recognizing Depression from the Microbiota⁻Gut⁻Brain Axis.
Liang, S, Wu, X, Hu, X, Wang, T, Jin, F
International journal of molecular sciences. 2018;19(6)
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Emerging research indicates that major depression is not just a mental disorder but also a systemic disease. In depression, the brain-gut axis, the bidirectional pathway that connects the brain and gut, is thought to be disturbed. This disruption is hypothesised to be a major pathological basis of depression. The aim of this paper is to explore this hypothesis by reviewing the current literature. According to the current literature, the authors found research stating the gut microbiota of depressed patients is significantly different from that of healthy controls. Additionally, disturbances or abnormalities in the gut can influence the susceptibility of onset of depression, while restoration of the gut will alleviate depression. Based on these findings, the authors conclude depression is closely related with the condition of the brain-gut axis, and that restoring the normal condition of gut microbiota may aid in the therapy of depression. The authors expect therapies that target gut microbiota will play an important role in the treatment and prevention of depression in the future.
Abstract
Major depression is one of the leading causes of disability, morbidity, and mortality worldwide. The brain⁻gut axis functions are disturbed, revealed by a dysfunction of the brain, immune system, endocrine system, and gut. Traditional depression treatments all target the brain, with different drugs and/or psychotherapy. Unfortunately, most of the patients have never received any treatment. Studies indicate that gut microbiota could be a direct cause for the disorder. Abnormal microbiota and the microbiota⁻gut⁻brain dysfunction may cause mental disorders, while correcting these disturbance could alleviate depression. Nowadays, the gut microbiota modulation has become a hot topic in treatment research of mental disorders. Depression is closely related with the health condition of the brain⁻gut axis, and maintaining/restoring the normal condition of gut microbiota helps in the prevention/therapy of mental disorders.
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Zinc, Magnesium, Selenium and Depression: A Review of the Evidence, Potential Mechanisms and Implications.
Wang, J, Um, P, Dickerman, BA, Liu, J
Nutrients. 2018;10(5)
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Adequate micronutrient consumption and mental health are of major public health importance. Recent findings suggest micronutrient deficiencies may play a role in the development and progression of depression, yet the findings remain unclear. The aim of this review is to present the recent evidence on the association between several micronutrients and depression and discuss the potential mechanisms and clinical implications. Based on the current literature, evidence shows an association between both zinc and magnesium deficiency and the risk of depression, with stronger evidence supporting zinc. Studies on selenium are limited or inconclusive. According to these findings, the authors support the importance of adequate micronutrient consumption for promoting mental health. They suggest future research should investigate the safety and efficacy of micronutrient supplementation as an adjunct treatment for depression to better inform current prevention and treatment strategies.
Abstract
Micronutrient deficiency and depression are major global health problems. Here, we first review recent empirical evidence of the association between several micronutrients—zinc, magnesium, selenium—and depression. We then present potential mechanisms of action and discuss the clinical implications for each micronutrient. Collectively, empirical evidence most strongly supports a positive association between zinc deficiency and the risk of depression and an inverse association between zinc supplementation and depressive symptoms. Less evidence is available regarding the relationship between magnesium and selenium deficiency and depression, and studies have been inconclusive. Potential mechanisms of action involve the HPA axis, glutamate homeostasis and inflammatory pathways. Findings support the importance of adequate consumption of micronutrients in the promotion of mental health, and the most common dietary sources for zinc and other micronutrients are provided. Future research is needed to prospectively investigate the association between micronutrient levels and depression as well as the safety and efficacy of micronutrient supplementation as an adjunct treatment for depression.
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Metabolic and Microbiota Measures as Peripheral Biomarkers in Major Depressive Disorder.
Horne, R, Foster, JA
Frontiers in psychiatry. 2018;9:513
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Though the connection between the gut microbiome, physical health and mental health is becoming more established, there remains a lack of understanding around the underlying cause of major depressive disorder (MDD). There is a need to identify biomarkers in MDD in order to help identify individual differences and improve treatment outcomes. The aim of this review is to investigate the link between metabolic biomarkers and the gut microbiota in individuals experiencing MDD. The current literature points to two potential biomarkers, leptin and ghrelin, which play a role in both metabolic disease and depression. Based on these findings, the authors conclude these biomarkers may help researchers and clinicians establish subgroups in depressed individuals in order to better predict treatment responses and develop more targeted therapies.
Abstract
Advances in understanding the role of the microbiome in physical and mental health are at the forefront of medical research and hold potential to have a direct impact on precision medicine approaches. In the past 7 years, we have studied the role of microbiota-brain communication on behavior in mouse models using germ-free mice, mice exposed to antibiotics, and healthy specific pathogen free mice. Through our work and that of others, we have seen an amazing increase in our knowledge of how bacteria signal to the brain and the implications this has for psychiatry. Gut microbiota composition and function are influenced both by genetics, age, sex, diet, life experiences, and many other factors of psychiatric and bodily disorders and thus may act as potential biomarkers of the gut-brain axis that could be used in psychiatry and co-morbid conditions. There is a particular need in major depressive disorder and other mental illness to identify biomarkers that can stratify patients into more homogeneous groups to provide better treatment and for development of new therapeutic approaches. Peripheral outcome measures of host-microbe bidirectional communication have significant translational value as biomarkers. Enabling stratification of clinical populations, based on individual biological differences, to predict treatment response to pharmacological and non-pharmacological interventions. Here we consider the links between co-morbid metabolic syndrome and depression, focusing on biomarkers including leptin and ghrelin in combination with assessing gut microbiota composition, as a potential tool to help identify individual differences in depressed population.
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Commissioning guidance for weight assessment and management in adults and children with severe complex obesity.
Welbourn, R, Hopkins, J, Dixon, JB, Finer, N, Hughes, C, Viner, R, Wass, J
Obesity reviews : an official journal of the International Association for the Study of Obesity. 2018;19(1):14-27
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Treating severe and complex obesity requires specialist multi-professional teams for assessment, management and optimizing patients’ health outcomes. The aim of this study was to review existing evidence for defining commissioning and delivery of primary or secondary care weight assessment and management clinics to patients needing specialist care for severe and complex obesity. Twenty-two UK royal colleges and professional organizations were invited to develop the guidance revision according to the NICE-accreditation process. Fifty references were included in the final report. The following additions have been identified as new emergent developments to be included in the guidance: - multi-disciplinary team pathways for children/adolescent patients and their transition to adult care, and - anaesthetic assessment and recommendations for ongoing shared care with general practitioners, as a chronic disease management pathway. Authors indicate that the Guidance Development Group recommends the use of the NICE-accredited commissioning guidance as healthcare services in different countries develop services to manage patients with severe and complex obesity.
Abstract
The challenge of managing the epidemic of patients with severe and complex obesity disease in secondary care is largely unmet. In England, the National Institute of Health and Care Excellence and the National Health Service England have published guidance on the provision of specialist (non-surgical) weight management services. We have undertaken a systematic review of 'what evidence exists for what should happen in/commissioning of: primary or secondary care weight assessment and management clinics in patients needing specialist care for severe and complex obesity?' using an accredited methodology to produce a model for organization of multidisciplinary team clinics that could be developed in every healthcare system, as an update to a previous review. Additions to the previous guidance were multidisciplinary team pathways for children/adolescent patients and their transition to adult care, anaesthetic assessment and recommendations for ongoing shared care with general practitioners, as a chronic disease management pathway.
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Physical activity, diet and other behavioural interventions for improving cognition and school achievement in children and adolescents with obesity or overweight.
Martin, A, Booth, JN, Laird, Y, Sproule, J, Reilly, JJ, Saunders, DH
The Cochrane database of systematic reviews. 2018;3:CD009728
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Obesity in children and teenagers is markedly high worldwide and this has been linked to poor performance in school. While physical activity and diet are known to impact cognitive function, studies have not considered to what extent healthy lifestyle interventions can improve school performance in this cohort. The aim of this systematic review was to explore whether these interventions can improve school performance in children and teenagers with obesity. Based on the current literature, increased nutrition education and improved food offered within schools can lead to moderate improvements in school achievement when compared with standard school practice in children with obesity. The authors conclude that more high quality, school subject-specific research is needed to shed light on the extent of these benefits.
Abstract
BACKGROUND The global prevalence of childhood and adolescent obesity is high. Lifestyle changes towards a healthy diet, increased physical activity and reduced sedentary activities are recommended to prevent and treat obesity. Evidence suggests that changing these health behaviours can benefit cognitive function and school achievement in children and adolescents in general. There are various theoretical mechanisms that suggest that children and adolescents with excessive body fat may benefit particularly from these interventions. OBJECTIVES To assess whether lifestyle interventions (in the areas of diet, physical activity, sedentary behaviour and behavioural therapy) improve school achievement, cognitive function (e.g. executive functions) and/or future success in children and adolescents with obesity or overweight, compared with standard care, waiting-list control, no treatment, or an attention placebo control group. SEARCH METHODS In February 2017, we searched CENTRAL, MEDLINE and 15 other databases. We also searched two trials registries, reference lists, and handsearched one journal from inception. We also contacted researchers in the field to obtain unpublished data. SELECTION CRITERIA We included randomised and quasi-randomised controlled trials (RCTs) of behavioural interventions for weight management in children and adolescents with obesity or overweight. We excluded studies in children and adolescents with medical conditions known to affect weight status, school achievement and cognitive function. We also excluded self- and parent-reported outcomes. DATA COLLECTION AND ANALYSIS Four review authors independently selected studies for inclusion. Two review authors extracted data, assessed quality and risks of bias, and evaluated the quality of the evidence using the GRADE approach. We contacted study authors to obtain additional information. We used standard methodological procedures expected by Cochrane. Where the same outcome was assessed across different intervention types, we reported standardised effect sizes for findings from single-study and multiple-study analyses to allow comparison of intervention effects across intervention types. To ease interpretation of the effect size, we also reported the mean difference of effect sizes for single-study outcomes. MAIN RESULTS We included 18 studies (59 records) of 2384 children and adolescents with obesity or overweight. Eight studies delivered physical activity interventions, seven studies combined physical activity programmes with healthy lifestyle education, and three studies delivered dietary interventions. We included five RCTs and 13 cluster-RCTs. The studies took place in 10 different countries. Two were carried out in children attending preschool, 11 were conducted in primary/elementary school-aged children, four studies were aimed at adolescents attending secondary/high school and one study included primary/elementary and secondary/high school-aged children. The number of studies included for each outcome was low, with up to only three studies per outcome. The quality of evidence ranged from high to very low and 17 studies had a high risk of bias for at least one item. None of the studies reported data on additional educational support needs and adverse events.Compared to standard practice, analyses of physical activity-only interventions suggested high-quality evidence for improved mean cognitive executive function scores. The mean difference (MD) was 5.00 scale points higher in an after-school exercise group compared to standard practice (95% confidence interval (CI) 0.68 to 9.32; scale mean 100, standard deviation 15; 116 children, 1 study). There was no statistically significant beneficial effect in favour of the intervention for mathematics, reading, or inhibition control. The standardised mean difference (SMD) for mathematics was 0.49 (95% CI -0.04 to 1.01; 2 studies, 255 children, moderate-quality evidence) and for reading was 0.10 (95% CI -0.30 to 0.49; 2 studies, 308 children, moderate-quality evidence). The MD for inhibition control was -1.55 scale points (95% CI -5.85 to 2.75; scale range 0 to 100; SMD -0.15, 95% CI -0.58 to 0.28; 1 study, 84 children, very low-quality evidence). No data were available for average achievement across subjects taught at school.There was no evidence of a beneficial effect of physical activity interventions combined with healthy lifestyle education on average achievement across subjects taught at school, mathematics achievement, reading achievement or inhibition control. The MD for average achievement across subjects taught at school was 6.37 points lower in the intervention group compared to standard practice (95% CI -36.83 to 24.09; scale mean 500, scale SD 70; SMD -0.18, 95% CI -0.93 to 0.58; 1 study, 31 children, low-quality evidence). The effect estimate for mathematics achievement was SMD 0.02 (95% CI -0.19 to 0.22; 3 studies, 384 children, very low-quality evidence), for reading achievement SMD 0.00 (95% CI -0.24 to 0.24; 2 studies, 284 children, low-quality evidence), and for inhibition control SMD -0.67 (95% CI -1.50 to 0.16; 2 studies, 110 children, very low-quality evidence). No data were available for the effect of combined physical activity and healthy lifestyle education on cognitive executive functions.There was a moderate difference in the average achievement across subjects taught at school favouring interventions targeting the improvement of the school food environment compared to standard practice in adolescents with obesity (SMD 0.46, 95% CI 0.25 to 0.66; 2 studies, 382 adolescents, low-quality evidence), but not with overweight. Replacing packed school lunch with a nutrient-rich diet in addition to nutrition education did not improve mathematics (MD -2.18, 95% CI -5.83 to 1.47; scale range 0 to 69; SMD -0.26, 95% CI -0.72 to 0.20; 1 study, 76 children, low-quality evidence) and reading achievement (MD 1.17, 95% CI -4.40 to 6.73; scale range 0 to 108; SMD 0.13, 95% CI -0.35 to 0.61; 1 study, 67 children, low-quality evidence). AUTHORS' CONCLUSIONS Despite the large number of childhood and adolescent obesity treatment trials, we were only able to partially assess the impact of obesity treatment interventions on school achievement and cognitive abilities. School and community-based physical activity interventions as part of an obesity prevention or treatment programme can benefit executive functions of children with obesity or overweight specifically. Similarly, school-based dietary interventions may benefit general school achievement in children with obesity. These findings might assist health and education practitioners to make decisions related to promoting physical activity and healthy eating in schools. Future obesity treatment and prevention studies in clinical, school and community settings should consider assessing academic and cognitive as well as physical outcomes.