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      Live fast, die young? A review on the developmental trajectories of ADHD across the lifespan

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          Abstract

          Attention-deficit/hyperactivity disorder (ADHD) is highly heritable and the most common neurodevelopmental disorder in childhood. In recent decades, it has been appreciated that in a substantial number of cases the disorder does not remit in puberty, but persists into adulthood. Both in childhood and adulthood, ADHD is characterised by substantial comorbidity including substance use, depression, anxiety, and accidents. However, course and symptoms of the disorder and the comorbidities may fluctuate and change over time, and even age of onset in childhood has recently been questioned. Available evidence to date is poor and largely inconsistent with regard to the predictors of persistence versus remittance. Likewise, the development of comorbid disorders cannot be foreseen early on, hampering preventive measures. These facts call for a lifespan perspective on ADHD from childhood to old age. In this selective review, we summarise current knowledge of the long-term course of ADHD, with an emphasis on clinical symptom and cognitive trajectories, treatment effects over the lifespan, and the development of comorbidities. Also, we summarise current knowledge and important unresolved issues on biological factors underlying different ADHD trajectories. We conclude that a severe lack of knowledge on lifespan aspects in ADHD still exists for nearly every aspect reviewed. We encourage large-scale research efforts to overcome those knowledge gaps through appropriately granular longitudinal studies.

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          Most cited references199

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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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            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
                Journal
                Eur Neuropsychopharmacol
                Eur Neuropsychopharmacol
                European Neuropsychopharmacology
                Elsevier
                0924-977X
                1873-7862
                1 October 2018
                October 2018
                : 28
                : 10
                : 1059-1088
                Affiliations
                [a ]Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands
                [b ]Department of Psychiatry, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands
                [c ]King's College London, Institute of Psychiatry, Psychology & Neuroscience, Social, Genetic & Developmental Psychiatry Centre, London, UK
                [d ]Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
                [e ]Attention Deficit Disorder Information and Support Service (ADDISS), Edgware, UK
                [f ]ADHD-Europe, Brussels, Belgium
                [g ]Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Department of Cognitive Neuroscience, Nijmegen, The Netherlands
                [h ]Department of Genetics, Microbiology and Statistics, Faculty of Biology, Universitat de Barcelona, Barcelona, Catalonia, Spain
                [i ]Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Spain
                [j ]Institut de Biomedicina de la Universitat de Barcelona (IBUB), Barcelona, Catalonia, Spain
                [k ]Institut de Recerca Sant Joan de Déu (IR-SJD), Esplugues de Llobregat, Catalonia, Spain
                [l ]Departments of Psychiatry and of Neuroscience and Physiology, State University of New York Upstate Medical University, New York, USA
                [m ]K.G. Jebsen Centre for Neuropsychiatric Disorders, Department of Biomedicine, University of Bergen, Bergen, Norway
                [n ]Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
                [o ]Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden
                [p ]Division of Psychiatry, Haukeland University Hospital, Bergen, Norway
                [q ]Division of Molecular Psychiatry, Center of Mental Health, University of Würzburg, Würzburg, Germany
                [r ]Laboratory of Psychiatric Neurobiology, Institute of Molecular Medicine, I.M. Sechenov First Moscow State Medical University, Moscow, Russia
                [s ]Department of Translational Neuroscience, School for Mental Health and Neuroscience (MHeNS), Maastricht University, Maastricht, The Netherlands
                [t ]Department of Psychiatry, Hospital Universitari Vall d'Hebron, Barcelona, Catalonia, Spain
                [u ]Psychiatric Genetics Unit, Vall d'Hebron Research Institute (VHIR), Barcelona, Catalonia, Spain
                [v ]Biomedical Network Research Centre on Mental Health (CIBERSAM), Barcelona, Catalonia, Spain
                [w ]Department of Psychiatry and Legal Medicine, Universitat Autònoma de Barcelona, Barcelona, Catalonia, Spain
                [x ]Department of Psychiatry and Psychotherapy, Semmelweis University, Budapest, Hungary
                [y ]MTA-SE NAP-B Molecular Psychiatry Research Group, Hungarian Academy of Sciences, Budapest, Hungary
                [z ]Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Frankfurt am Main, Germany
                Author notes
                [* ]Corresponding author at: Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, 6500 HB Nijmegen, The Netherlands. Barbara.Franke@ 123456radboudumc.nl
                Article
                S0924-977X(18)30303-1
                10.1016/j.euroneuro.2018.08.001
                6379245
                30195575
                5a3cc4e7-927b-4470-b643-bb74307a2a8f
                © 2018 Radboud University Medical Center

                This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

                History
                : 19 November 2017
                : 25 June 2018
                : 7 August 2018
                Categories
                Article

                Pharmacology & Pharmaceutical medicine
                developmental trajectory,treatment,comorbidity,cognitive impairment,genetics,adult-onset adhd

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