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      Reduced microbiome alpha diversity in young patients with ADHD

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          Abstract

          ADHD is a psychiatric disorder which is characterized by hyperactivity, impulsivity and attention problems. Due to recent findings of microbial involvement in other psychiatric disorders like autism and depression, a role of the gut microbiota in ADHD pathogenesis is assumed but has not yet been investigated. In this study, the gut microbiota of 14 male ADHD patients (mean age: 11.9 yrs.) and 17 male controls (mean age: 13.1 yrs.) was examined via next generation sequencing of 16S rDNA and analyzed for diversity and biomarkers. We found that the microbial diversity (alpha diversity) was significantly decreased in ADHD patients compared to controls (p Shannon = 0.036) and that the composition (beta diversity) differed significantly between patients and controls (p ANOSIM = 0.033, p ADONIS = 0.006, p betadisper = 0.002). In detail, the bacterial family Prevotellacae was associated with controls, while patients with ADHD showed elevated levels of Bacteroidaceae, and both Neisseriaceae and Neisseria spec. were found as possible biomarkers for juvenile ADHD. Our results point to a possible link of certain microbiota with ADHD, with Neisseria spec. being a very promising ADHD-associated candidate. This finding provides the basis for a systematic, longitudinal assessment of the role of the gut microbiome in ADHD, yielding promising potential for both prevention and therapeutic intervention.

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          Most cited references58

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          Annual research review: A meta-analysis of the worldwide prevalence of mental disorders in children and adolescents.

          The literature on the prevalence of mental disorders affecting children and adolescents has expanded significantly over the last three decades around the world. Despite the field having matured significantly, there has been no meta-analysis to calculate a worldwide-pooled prevalence and to empirically assess the sources of heterogeneity of estimates.
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            ADHD prevalence estimates across three decades: an updated systematic review and meta-regression analysis.

            Previous studies have identified significant variability in attention-deficit / hyperactivity disorder (ADHD) prevalence estimates worldwide, largely explained by methodological procedures. However, increasing rates of ADHD diagnosis and treatment throughout the past few decades have fuelled concerns about whether the true prevalence of the disorder has increased over time. We updated the two most comprehensive systematic reviews on ADHD prevalence available in the literature. Meta-regression analyses were conducted to test the effect of year of study in the context of both methodological variables that determined variability in ADHD prevalence (diagnostic criteria, impairment criterion and source of information), and the geographical location of studies. We identified 154 original studies and included 135 in the multivariate analysis. Methodological procedures investigated were significantly associated with heterogeneity of studies. Geographical location and year of study were not associated with variability in ADHD prevalence estimates. Confirming previous findings, variability in ADHD prevalence estimates is mostly explained by methodological characteristics of the studies. In the past three decades, there has been no evidence to suggest an increase in the number of children in the community who meet criteria for ADHD when standardized diagnostic procedures are followed.
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              Molecular genetics of attention-deficit/hyperactivity disorder.

              Results of behavioral genetic and molecular genetic studies have converged to suggest that both genetic and nongenetic factors contribute to the development of attention-deficit/hyperactivity disorder (ADHD). We review this literature, with a particular emphasis on molecular genetic studies. Family, twin, and adoption studies provide compelling evidence that genes play a strong role in mediating susceptibility to ADHD. This fact is most clearly seen in the 20 extant twin studies, which estimate the heritability of ADHD to be .76. Molecular genetic studies suggest that the genetic architecture of ADHD is complex. The few genome-wide scans conducted thus far are not conclusive. In contrast, the many candidate gene studies of ADHD have produced substantial evidence implicating several genes in the etiology of the disorder. For the eight genes for which the same variant has been studied in three or more case-control or family-based studies, seven show statistically significant evidence of association with ADHD on the basis of the pooled odds ratio across studies: DRD4, DRD5, DAT, DBH, 5-HTT, HTR1B, and SNAP-25.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SupervisionRole: Writing – original draft
                Role: ConceptualizationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: SoftwareRole: ValidationRole: VisualizationRole: Writing – original draft
                Role: Data curationRole: ValidationRole: Writing – review & editing
                Role: ResourcesRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: ResourcesRole: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: MethodologyRole: ResourcesRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: MethodologyRole: Project administrationRole: ValidationRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                12 July 2018
                2018
                : 13
                : 7
                : e0200728
                Affiliations
                [1 ] Department of Child and Adolescent Psychiatry and Psychotherapy, Centre for Integrative Psychiatry, University Hospital Schleswig-Holstein, Kiel, Germany
                [2 ] Institute of Clinical Molecular Biology, University Hospital Schleswig-Holstein, Kiel, Germany
                [3 ] Institute for Epidemiology, University Hospital Schleswig-Holstein, Kiel, Germany
                [4 ] Clinic of Internal Medicine I, University Hospital Schleswig-Holstein, Kiel, Germany
                Kunming Institute of Zoology, Chinese Academy of Sciences, CHINA
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0002-3510-9888
                Article
                PONE-D-17-28985
                10.1371/journal.pone.0200728
                6042771
                30001426
                c00c2240-ab4d-4eef-8f7e-4d459e43003a
                © 2018 Prehn-Kristensen et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 4 August 2017
                : 2 July 2018
                Page count
                Figures: 4, Tables: 1, Pages: 19
                Funding
                This study was funded by an intramural grant of the medical faculty of the University Hospital Schleswig-Holstein.
                Categories
                Research Article
                Biology and Life Sciences
                Neuroscience
                Developmental Neuroscience
                Neurodevelopmental Disorders
                Adhd
                Medicine and Health Sciences
                Neurology
                Neurodevelopmental Disorders
                Adhd
                Medicine and Health Sciences
                Mental Health and Psychiatry
                Neuropsychiatric Disorders
                Adhd
                Biology and Life Sciences
                Microbiology
                Medical Microbiology
                Microbiome
                Biology and Life Sciences
                Genetics
                Genomics
                Microbial Genomics
                Microbiome
                Biology and Life Sciences
                Microbiology
                Microbial Genomics
                Microbiome
                Biology and Life Sciences
                Ecology
                Ecological Metrics
                Species Diversity
                Ecology and Environmental Sciences
                Ecology
                Ecological Metrics
                Species Diversity
                Biology and Life Sciences
                Ecology
                Ecological Metrics
                Species Diversity
                Shannon Index
                Ecology and Environmental Sciences
                Ecology
                Ecological Metrics
                Species Diversity
                Shannon Index
                Biology and Life Sciences
                Biochemistry
                Biomarkers
                Biology and Life Sciences
                Psychology
                Personality
                Personality Traits
                Impulsivity
                Social Sciences
                Psychology
                Personality
                Personality Traits
                Impulsivity
                Biology and Life Sciences
                Organisms
                Bacteria
                Neisseria
                Biology and Life Sciences
                Organisms
                Bacteria
                Gut Bacteria
                Custom metadata
                Data are available from popgen, University Hospital Schleswig-Holstein, Kiel, Germany. Data cannot be made publicly available due to ethical restrictions defined in the informed consent form for the patients and implemented by the ethics committee. For researchers who meet the criteria for access to confidential data, however, the data can be accessed via a structured application procedure for research projects. This procedure has been implemented to ensure that all data usage is preceded by appropriate ethical review and complies with the consent provided by the participants. Further information can be found at: https://www.uksh.de/p2n/Information+for+Researchers.html and here https://www.uksh.de/p2n/Information+for+Researchers/Material+Data+Access+Form.html.

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