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      A Review of Heterogeneity in Attention Deficit/Hyperactivity Disorder (ADHD)

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          Abstract

          Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder that affects approximately 8%–12% of children worldwide. Throughout an individual’s lifetime, ADHD can significantly increase risk for other psychiatric disorders, educational and occupational failure, accidents, criminality, social disability and addictions. No single risk factor is necessary or sufficient to cause ADHD. The multifactorial causation of ADHD is reflected in the heterogeneity of this disorder, as indicated by its diversity of psychiatric comorbidities, varied clinical profiles, patterns of neurocognitive impairment and developmental trajectories, and the wide range of structural and functional brain anomalies. Although evidence-based treatments can reduce ADHD symptoms in a substantial portion of affected individuals, there is yet no curative treatment for ADHD. A number of theoretical models of the emergence and developmental trajectories of ADHD have been proposed, aimed at providing systematic guides for clinical research and practice. We conducted a comprehensive review of the current status of research in understanding the heterogeneity of ADHD in terms of etiology, clinical profiles and trajectories, and neurobiological mechanisms. We suggest that further research focus on investigating the impact of the etiological risk factors and their interactions with developmental neural mechanisms and clinical profiles in ADHD. Such research would have heuristic value for identifying biologically homogeneous subgroups and could facilitate the development of novel and more tailored interventions that target underlying neural anomalies characteristic of more homogeneous subgroups.

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          Most cited references156

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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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            The age-dependent decline of attention deficit hyperactivity disorder: a meta-analysis of follow-up studies.

            This study examined the persistence of attention deficit hyperactivity disorder (ADHD) into adulthood. We analyzed data from published follow-up studies of ADHD. To be included in the analysis, these additional studies had to meet the following criteria: the study included a control group and it was clear from the methods if the diagnosis of ADHD included subjects who did not meet full criteria but showed residual and impairing signs of the disorder. We used a meta-analysis regression model to separately assess the syndromatic and symptomatic persistence of ADHD. When we define only those meeting full criteria for ADHD as having 'persistent ADHD', the rate of persistence is low, approximately 15% at age 25 years. But when we include cases consistent with DSM-IV's definition of ADHD in partial remission, the rate of persistence is much higher, approximately 65%. Our results show that estimates of ADHD's persistence rely heavily on how one defines persistence. Yet, regardless of definition, our analyses show that evidence for ADHD lessens with age. More work is needed to determine if this reflects true remission of ADHD symptoms or is due to the developmental insensitivity of diagnostic criteria for the disorder.
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              Analysis of shared heritability in common disorders of the brain

              Disorders of the brain can exhibit considerable epidemiological comorbidity and often share symptoms, provoking debate about their etiologic overlap. We quantified the genetic sharing of 25 brain disorders from genome-wide association studies of 265,218 patients and 784,643 control participants and assessed their relationship to 17 phenotypes from 1,191,588 individuals. Psychiatric disorders share common variant risk, whereas neurological disorders appear more distinct from one another and from the psychiatric disorders. We also identified significant sharing between disorders and a number of brain phenotypes, including cognitive measures. Further, we conducted simulations to explore how statistical power, diagnostic misclassification, and phenotypic heterogeneity affect genetic correlations. These results highlight the importance of common genetic variation as a risk factor for brain disorders and the value of heritability-based methods in understanding their etiology.
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                Author and article information

                Contributors
                Journal
                Front Hum Neurosci
                Front Hum Neurosci
                Front. Hum. Neurosci.
                Frontiers in Human Neuroscience
                Frontiers Media S.A.
                1662-5161
                11 February 2019
                2019
                : 13
                : 42
                Affiliations
                [1] 1Department of Biomedical Engineering, New Jersey Institute of Technology , Newark, NJ, United States
                [2] 2Department of Psychology, Queens College of the City University of New York , Flushing, NY, United States
                [3] 3Department of Electric and Computer Engineering, New Jersey Institute of Technology , Newark, NJ, United States
                Author notes

                Edited by: Juliana Yordanova, Institute of Neurobiology (BAS), Bulgaria

                Reviewed by: Bin Xuan, Anhui Normal University, China; Jia Huang, Institute of Psychology (CAS), China

                Article
                10.3389/fnhum.2019.00042
                6378275
                30804772
                a6b49c5c-5363-4acc-8a41-6ea95d345551
                Copyright © 2019 Luo, Weibman, Halperin and Li.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 08 June 2018
                : 25 January 2019
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 182, Pages: 12, Words: 11775
                Funding
                Funded by: National Institutes of Health 10.13039/100000002
                Award ID: MH109791, HD071593
                Categories
                Neuroscience
                Review

                Neurosciences
                adhd,heterogeneity,risk factors,cognitive impairments,structural mri,functional mri,dti,neuroscience model

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