title: The theory of bipolar disorder as an illness of accelerated aging: implications for clinical care and research.
abstract: Bipolar Disorder (BD) has been conceptualized as both a cyclic and a progressive disorder. Mechanisms involved in neuroprogression in BD remain largely unknown although several non-mutually exclusive models have been proposed as explanatory frameworks. In the present paper, we propose that the pathophysiological changes observed in BD (e.g. brain structural alterations, cognitive deficits, oxidative stress imbalance, amyloid metabolism, immunological deregulation, immunosenescence, neurotrophic deficiencies and telomere shortening) converge on a model of accelerated aging (AA). Aging can be understood as a multidimensional process involving physical, neuropsychological, and social changes, which can be highly variable between individuals. Determinants of successful aging (e.g environmental and genetic factors), may also confer differential vulnerability to components of BD pathophysiology and contribute to the clinical presentation of BD. Herein we discuss how the understanding of aging and senescence can contribute to the search for new and promising molecular targets to explain and ameliorate neuroprogression in BD. We also present the strengths and limitations of this concept.
authors.affiliation: Program for Recognition and Intervention in Individuals in At-Risk Mental States (PRISMA), Department of Psychiatry, Federal University of São Paulo, São Paulo, Brazil; Interdisciplinary Laboratory of Clinical Neuroscience (LINC), Department of Psychiatry, Federal University of São Paulo, São Paulo, Brazil.
authors.forename: Lucas Bortolotto
authors.initials: LB
authors.lastname: Rizzo
authors.affiliation: Program for Recognition and Intervention in Individuals in At-Risk Mental States (PRISMA), Department of Psychiatry, Federal University of São Paulo, São Paulo, Brazil; Interdisciplinary Laboratory of Clinical Neuroscience (LINC), Department of Psychiatry, Federal University of São Paulo, São Paulo, Brazil.
authors.forename: Leonardo Gazzi
authors.initials: LG
authors.lastname: Costa
authors.affiliation: Program for Recognition and Intervention in Individuals in At-Risk Mental States (PRISMA), Department of Psychiatry, Federal University of São Paulo, São Paulo, Brazil; Interdisciplinary Laboratory of Clinical Neuroscience (LINC), Department of Psychiatry, Federal University of São Paulo, São Paulo, Brazil; Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, Ontario, Canada.
authors.forename: Rodrigo B
authors.initials: RB
authors.lastname: Mansur
authors.affiliation: Sunnybrook Research Institute, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Walter
authors.initials: W
authors.lastname: Swardfager
authors.affiliation: Interdisciplinary Laboratory of Clinical Neuroscience (LINC), Department of Psychiatry, Federal University of São Paulo, São Paulo, Brazil; Department of Morphology and Genetics, Federal University of São Paulo, São Paulo, Brazil.
authors.forename: Síntia Iole
authors.initials: SI
authors.lastname: Belangero
authors.affiliation: Institute of Biomedical Research and Faculty of Biosciences, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Grassi-Oliveira
authors.affiliation: Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, Ontario, Canada; Sunnybrook Research Institute, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Roger S
authors.initials: RS
authors.lastname: McIntyre
authors.affiliation: Institute of Biomedical Research and Faculty of Biosciences, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Moisés E
authors.initials: ME
authors.lastname: Bauer
authors.affiliation: Program for Recognition and Intervention in Individuals in At-Risk Mental States (PRISMA), Department of Psychiatry, Federal University of São Paulo, São Paulo, Brazil; Interdisciplinary Laboratory of Clinical Neuroscience (LINC), Department of Psychiatry, Federal University of São Paulo, São Paulo, Brazil. Electronic address: elisabrietzke@hotmail.com.
authors.forename: Elisa
authors.initials: E
authors.lastname: Brietzke
mesh_terms: D019588:Aging, Premature / Q000503:physiopathology*; D000818:Animals; D001714:Bipolar Disorder / Q000503:physiopathology* / Q000628:therapy*; D001921:Brain / Q000503:physiopathology*; D006801:Humans; D008959:Models, Neurological
keywords: Aging; Amyloid; BDNF; Biomarkers; Bipolar disorder; Cognition; Immunosenescence; Inflammation; Molecular imaging; Neuroprogression; Oxidative stress; Telomeres